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Τετάρτη, 3 Απριλίου 2019

Neurotherapeutic potential of erythropoietin after ischemic injury

 of the central nervous system
Florian Simon, Nicolaos Floros, Wiebke Ibing, Hubert Schelzig, Artis Knapsis

Neural Regeneration Research 2019 14(8):1309-1312

Erythropoietin (EPO) is one of the most successful biopharmaceuticals in history and is used for treating anemia of different origins. However, it became clear that EPO could also work in a neuroprotective, antiapoptotic, antioxidative, angiogenetic and neurotropic way. It causes stimulation of cells to delay cell apoptosis, especially in the central nervous system. In rodent models of focal cerebral ischemia, EPO showed an impressive reduction of infarct size by 30% and improvement of neurobehavioral outcome by nearly 40%. A large animal model dealing with ischemia and reperfusion of the spinal cord showed that EPO could reduce the risk of spinal cord injury significantly. In addition, some clinical studies tested whether EPO works in real live clinical settings. One of the most promising studies showed the innocuousness and improvements in follow-up, outcome scales and in infarct size, of EPO-use in humans suffering from ischemic stroke. Another study ended unfortunately in a negative outcome and an increased overall death rate in the EPO group. The most possible reason was the involvement of patients undergoing simultaneously systemic thrombolysis with recombinant tissue plasminogen activator. An experimental study on rats demonstrated that administration of EPO might exacerbate tissue plasminogen activator-induced brain hemorrhage without reducing the ischemic brain damage. This case shows clearly how useful animal models can be to check negative side effects of a treatment before going into clinical trials. Other groups looked in human trials at the effects of EPO on the outcome after ischemic stroke, relation to circulating endothelial progenitor cells, aneurysmal subarachnoid hemorrhage, traumatic brain injury, hemoglobin transfusion thresholds and elective first-time coronary artery bypass surgery. Most of the results were positive, but are based mostly on small group sizes. However, some of the most neglected facts when focusing on experimental setups of ischemia of the central nervous system are issues like age and comorbidities. It might be extremely worthy to consider these points for future projects, because EPO might influence all these factors. 

Hypertension and sleep duration and water intake

Association between hypertension and sleep duration and water intake in Indian young adults
Umeshwar Pandey, Tanu Midha, Yashwant Kumar Rao

Journal of Clinical and Preventive Cardiology 2019 8(2):50-55

Context: The prevalence of hypertension is on the rise in developing countries like India. Physiological parameters such as sleep duration and water intake may be associated with hypertension in young adults. Aims: The aim is to study the association between hypertension and day and nighttime sleep duration and water intake among young adults. Setting and Design: The study was a cross-sectional study, conducted among 596 students of Government Medical College, Kannauj, aged between 17 and 22 years. Materials and Methods: Participants were classified using the diagnostic criteria of the American Heart Association. Data were recorded on a pre-designed and pretested questionnaire. Data analysis was performed using SPSS 22.0. Receiver operator characteristic curve analysis and multiple logistic regression analysis were applied. Results: The prevalence of hypertension was 34.9%, 35.9% among boys, and 33.5% among girls, respectively. Less water intake and shorter sleep duration at nighttime were found to be independent predictors of hypertension. Cutoff of sleep duration at nighttime for predicting hypertension was ≤7.6 h among boys and ≤7.1 h among girls. The sensitivity and specificity of the cutoff for sleep duration at night time in boys was 79.3% and 74.2%, respectively, and that in girls was 81.5% and 75.6%, respectively. The cutoff for water intake for predicting hypertension was ≤2.1 L for boys and ≤1.5 L for girls, respectively. The sensitivity and specificity of the cutoff for water intake in boys was 74.8% and 70.3%, and in girls was 78.3% and 71.5%, respectively. Conclusions: Young adults with longer duration of sleep during night time and more water intake had a lesser risk of hypertension. 

Ankle–brachial pressure index/carotid intima-media thickness ratio in predicting presence and severity of coronary artery disease

Utility of ankle–brachial pressure index/carotid intima-media thickness ratio in predicting presence and severity of coronary artery disease: A study from major center in Northeastern India
Farhin Iqbal, Amol Vasantrao Patil, Jogesh Chandra Barkataki

Journal of Clinical and Preventive Cardiology 2019 8(2):44-49

Background: Studies have shown that carotid intima-media thickness (CIMT) and ankle–brachial pressure index (ABI) can be used as surrogate markers of coronary artery disease (CAD). However, whether studying the ratio of ABI and CIMT has any added value in predicting CAD when compared to either of them alone, has not been studied. Aims: The aim of the study is to compare CIMT and ABI as surrogate markers for the presence and extent of CAD and to investigate whether studying the ratio of ABI and CIMT has any incremental value in predicting CAD than either of them. Methods: We prospectively enrolled 235 stable, non-ACS patients who underwent CIMT and ABI measurements followed by diagnostic coronary angiography. Results: The mean age of the study population was 56.32 ± 10.14 years. CIMT was significantly higher in the CAD group compared to non-CAD group (0.91 ± 0.22 vs. 0.66 ± 0.15, P ≤ 0.0001). ABI was significantly lower in the CAD group compared to non-CAD group (1.07 ± 0.19 vs. 1.18 ± 0.14, P ≤ 0.0001). At an optimal cutoff value of ≥0.75 mm, CIMT showed better predictive values (sensitivity and specificity –72.3% and 79%, respectively) compared to ABI ≤0.9 (sensitivity and specificity – 21.53% and 96.19%, respectively). CIMT was the strongest independent predictor of CAD (P < 0.0001) followed by ABI (P = 0.006) by multiple regression. ABI/CIMT ratio of ≤1.55 had better predictive value (sensitivity and specificity –75.4% and 78.1%, respectively) and stronger correlation with CAD severity (R = 0.42), than either of them. Conclusion: CIMT is a better surrogate marker of CAD compared to ABI. Studying ABI/CIMT ratio has an incremental value in predicting CAD. 

Neural Regeneration Research

Tandem pore TWIK-related potassium channels and neuroprotection
J Antonio Lamas, Diego Fernández-Fernández

Neural Regeneration Research 2019 14(8):1293-1308

TWIK-related potassium channels (TREK) belong to a subfamily of the two-pore domain potassium channels family with three members, TREK1, TREK2 and TWIK-related arachidonic acid-activated potassium channels. The two-pore domain potassium channels is the last big family of channels being discovered, therefore it is not surprising that most of the information we know about TREK channels predominantly comes from the study of heterologously expressed channels. Notwithstanding, in this review we pay special attention to the limited amount of information available on native TREK-like channels and real neurons in relation to neuroprotection. Mainly we focus on the role of free fatty acids, lysophospholipids and other neuroprotective agents like riluzole in the modulation of TREK channels, emphasizing on how important this modulation may be for the development of new therapies against neuropathic pain, depression, schizophrenia, epilepsy, ischemia and cardiac complications. 


Neurotherapeutic potential of erythropoietin after ischemic injury of the central nervous system
Florian Simon, Nicolaos Floros, Wiebke Ibing, Hubert Schelzig, Artis Knapsis

Neural Regeneration Research 2019 14(8):1309-1312

Erythropoietin (EPO) is one of the most successful biopharmaceuticals in history and is used for treating anemia of different origins. However, it became clear that EPO could also work in a neuroprotective, antiapoptotic, antioxidative, angiogenetic and neurotropic way. It causes stimulation of cells to delay cell apoptosis, especially in the central nervous system. In rodent models of focal cerebral ischemia, EPO showed an impressive reduction of infarct size by 30% and improvement of neurobehavioral outcome by nearly 40%. A large animal model dealing with ischemia and reperfusion of the spinal cord showed that EPO could reduce the risk of spinal cord injury significantly. In addition, some clinical studies tested whether EPO works in real live clinical settings. One of the most promising studies showed the innocuousness and improvements in follow-up, outcome scales and in infarct size, of EPO-use in humans suffering from ischemic stroke. Another study ended unfortunately in a negative outcome and an increased overall death rate in the EPO group. The most possible reason was the involvement of patients undergoing simultaneously systemic thrombolysis with recombinant tissue plasminogen activator. An experimental study on rats demonstrated that administration of EPO might exacerbate tissue plasminogen activator-induced brain hemorrhage without reducing the ischemic brain damage. This case shows clearly how useful animal models can be to check negative side effects of a treatment before going into clinical trials. Other groups looked in human trials at the effects of EPO on the outcome after ischemic stroke, relation to circulating endothelial progenitor cells, aneurysmal subarachnoid hemorrhage, traumatic brain injury, hemoglobin transfusion thresholds and elective first-time coronary artery bypass surgery. Most of the results were positive, but are based mostly on small group sizes. However, some of the most neglected facts when focusing on experimental setups of ischemia of the central nervous system are issues like age and comorbidities. It might be extremely worthy to consider these points for future projects, because EPO might influence all these factors. 


Dendritic shrinkage after injury: a cellular killer or a necessity for axonal regeneration?
An Beckers, Lieve Moons

Neural Regeneration Research 2019 14(8):1313-1316

Dendrites form an essential component of the neuronal circuit have been largely overlooked in regenerative research. Nevertheless, subtle changes in the dendritic arbors of neurons are one of the first stages of various neurodegenerative diseases, leading to dysfunctional neuronal networks and ultimately cellular death. Maintaining dendrites is therefore considered an essential neuroprotective strategy. This mini-review aims to discuss an intriguing hypothesis, which postulates that dendritic shrinkage is an important stimulant to boost axonal regeneration, and thus that preserving dendrites might not be the ideal therapeutic method to regain a full functional network upon central nervous system damage. Indeed, our study in zebrafish, a versatile animal model with robust regenerative capacity recently unraveled that dendritic retraction is evoked prior to axonal regrowth after optic nerve injury. Strikingly, inhibiting dendritic pruning upon damage perturbed axonal regeneration. This constraining effect of dendrites on axonal regrowth has sporadically been proposed in literature, as summarized in this short narrative. In addition, the review discusses a plausible underlying mechanism for the observed antagonistic axon-dendrite interplay, which is based on energy restriction inside neurons. Axonal injury indeed leads to a high local energy demand in which efficient axonal energy supply is fundamental to ensure regrowth. At the same time, axonal lesion is known to induce mitochondrial depolarization, causing energy depletion in the axonal compartment of damaged neurons. Mitochondria, however, become mostly stationary after development, which has been proposed as a potential underlying reason for the low regenerative capacity of adult mammals. Per contra, upon reduced neuronal activity, mitochondrial mobility enhances. In this view, dendritic shrinkage after axonal injury in zebrafish could result in less synaptic input and hence, a release of mitochondria within the soma-dendrite compartment that then translocate to the axonal growth cone to stimulate axonal regeneration. If this hypothesis proofs to be correct, i.e. dendritic remodeling serving as fuel for axonal regeneration, we envision a major shift in the research focus within the neuroregenerative field and in the potential uncovering of various novel therapeutic targets. 


Regenerative biomarkers for Duchenne muscular dystrophy
Simon Guiraud, Kay E Davies

Neural Regeneration Research 2019 14(8):1317-1320

Skeletal muscle has an extraordinary capacity to regenerate after injury and trauma. The muscle repair mechanism is a complex process orchestrated by multiple steps. In neuromuscular disorders such as Duchenne muscular dystrophy (DMD), the pathological consequences of the lack of dystrophin and the loss of the dystrophin-associated protein complex are dramatic, with a progressive cascade of events, such as continual influx of inflammation, repeated cycles of degeneration and impaired regeneration. Thus, muscle regeneration is a hallmark of the disease and careful monitoring of regenerative processes with robust markers should provide useful information to the field. Since decades, several indices of regeneration such as centronucleation and fibre size have been commonly used. In the present review, we discuss the impaired regenerative process in DMD, the common and new indices of regeneration and their associated methodologies. We notably highlight the regenerative marker embryonic myosin as a robust indicator of muscle regeneration. We also describe new quantitative methodologies offering the possibility of using a panel of translational regenerative biomarkers to obtain a more complete view of the regeneration processes. Upregulation of utrophin, an autosomal and functional paralogue of dystrophin, is one of the most promising therapeutic strategies as it targets the primary cause of the disease and is applicable to all DMD patients regardless their genetic defects. As utrophin is a regeneration associated protein increased in dystrophic muscle, we discuss the correlation of utrophin levels after drug treatment with regeneration markers. The recent advances in technologies and complementary markers of muscle regeneration described in this review, provide an unprecedented opportunity to develop more robust utrophin DMD based strategies for all DMD patients. 


Exploring the efficacy of natural products in alleviating Alzheimer's disease
Prajakta Deshpande, Neha Gogia, Amit Singh

Neural Regeneration Research 2019 14(8):1321-1329

Alzheimer’s disease (hereafter AD) is a progressive neurodegenerative disorder that affects the central nervous system. There are multiple factors that cause AD, viz., accumulation of extracellular Amyloid-beta 42 plaques, intracellular hyper-phosphorylated Tau tangles, generation of reactive oxygen species due to mitochondrial dysfunction and genetic mutations. The plaques and tau tangles trigger aberrant signaling, which eventually cause cell death of the neurons. As a result, there is shrinkage of brain, cognitive defects, behavioral and psychological problems. To date, there is no direct cure for AD. Thus, scientists have been testing various strategies like screening for the small inhibitor molecule library or natural products that may block or prevent onset of AD. Historically, natural products have been used in many cultures for the treatment of various diseases. The research on natural products have gained importance as the active compounds extracted from them have medicinal values with reduced side effects, and they are bioavailable. The natural products may target the proteins or members of signaling pathways that get altered in specific diseases. Many natural products are being tested in various animal model systems for their role as a potential therapeutic target for AD, and to address questions about how these natural products can rescue AD or other neurodegenerative disorders. Some of these products are in clinical trials and results are promising because of their neuroprotective, anti-inflammatory, antioxidant, anti-amyloidogenic, anticholinesterase activities and easy availability. This review summarizes the use of animal model systems to identify natural products, which may serve as potential therapeutic targets for AD. 


Involvement of insulin receptor substrates in cognitive impairment and Alzheimer's disease
Daisuke Tanokashira, Wataru Fukuokaya, Akiko Taguchi

Neural Regeneration Research 2019 14(8):1330-1334

Type 2 diabetes—associated with impaired insulin/insulin-like growth factor-1 (IGF1) signaling (IIS)—is a risk factor for cognitive impairment and dementia including Alzheimer’s disease (AD). The insulin receptor substrate (IRS) proteins are major components of IIS, which transmit upstream signals via the insulin receptor and/or IGF1 receptor to multiple intracellular signaling pathways, including AKT/protein kinase B and extracellular-signal-regulated kinase cascades. Of the four IRS proteins in mammals, IRS1 and IRS2 play key roles in regulating growth and survival, metabolism, and aging. Meanwhile, the roles of IRS1 and IRS2 in the central nervous system with respect to cognitive abilities remain to be clarified. In contrast to IRS2 in peripheral tissues, inactivation of neural IRS2 exerts beneficial effects, resulting in the reduction of amyloid β accumulation and premature mortality in AD mouse models. On the other hand, the increased phosphorylation of IRS1 at several serine sites is observed in the brains from patients with AD and animal models of AD or cognitive impairment induced by type 2 diabetes. However, these serine sites are also activated in a mouse model of type 2 diabetes, in which the diabetes drug metformin improves memory impairment. Because IRS1 and IRS2 signaling pathways are regulated through complex mechanisms including positive and negative feedback loops, whether the elevated phosphorylation of IRS1 at specific serine sites found in AD brains is a primary response to cognitive dysfunction remains unknown. Here, we examine the associations between IRS1/IRS2-mediated signaling in the central nervous system and cognitive decline. 


Role of macrophages in peripheral nerve injury and repair
Ping Liu, Jiang Peng, Gong-Hai Han, Xiao Ding, Shuai Wei, Gang Gao, Kun Huang, Feng Chang, Yu Wang

Neural Regeneration Research 2019 14(8):1335-1342

Resident and inflammatory macrophages are essential effectors of the innate immune system. These cells provide innate immune defenses and regulate tissue and organ homeostasis. In addition to their roles in diseases such as cancer, obesity and osteoarthritis, they play vital roles in tissue repair and disease rehabilitation. Macrophages and other inflammatory cells are recruited to tissue injury sites where they promote changes in the microenvironment. Among the inflammatory cell types, only macrophages have both pro-inflammatory (M1) and anti-inflammatory (M2) actions, and M2 macrophages have four subtypes. The co-action of M1 and M2 subtypes can create a favorable microenvironment, releasing cytokines for damaged tissue repair. In this review, we discuss the activation of macrophages and their roles in severe peripheral nerve injury. We also describe the therapeutic potential of macrophages in nerve tissue engineering treatment and highlight approaches for enhancing M2 cell-mediated nerve repair and regeneration. 


Therapeutic strategies for peripheral nerve injury: decellularized nerve conduits and Schwann cell transplantation
Gong-Hai Han, Jiang Peng, Ping Liu, Xiao Ding, Shuai Wei, Sheng Lu, Yu Wang

Neural Regeneration Research 2019 14(8):1343-1351

In recent years, the use of Schwann cell transplantation to repair peripheral nerve injury has attracted much attention. Animal-based studies show that the transplantation of Schwann cells in combination with nerve scaffolds promotes the repair of injured peripheral nerves. Autologous Schwann cell transplantation in humans has been reported recently. This article reviews current methods for removing the extracellular matrix and analyzes its composition and function. The development and secretory products of Schwann cells are also reviewed. The methods for the repair of peripheral nerve injuries that use myelin and Schwann cell transplantation are assessed. This survey of the literature data shows that using a decellularized nerve conduit combined with Schwann cells represents an effective strategy for the treatment of peripheral nerve injury. This analysis provides a comprehensive basis on which to make clinical decisions for the repair of peripheral nerve injury. 


Role and prospects of regenerative biomaterials in the repair of spinal cord injury
Shuo Liu, Yuan-Yuan Xie, Bin Wang

Neural Regeneration Research 2019 14(8):1352-1363

Axonal junction defects and an inhibitory environment after spinal cord injury seriously hinder the regeneration of damaged tissues and neuronal functions. At the site of spinal cord injury, regenerative biomaterials can fill cavities, deliver curative drugs, and provide adsorption sites for transplanted or host cells. Some regenerative biomaterials can also inhibit apoptosis, inflammation and glial scar formation, or further promote neurogenesis, axonal growth and angiogenesis. This review summarized a variety of biomaterial scaffolds made of natural, synthetic, and combined materials applied to spinal cord injury repair. Although these biomaterial scaffolds have shown a certain therapeutic effect in spinal cord injury repair, there are still many problems to be resolved, such as product standards and material safety and effectiveness. 


The "Brain Stress Timing" phenomenon and other misinterpretations of randomized clinical trial on aneurysmal subarachnoid hemorrhage
Rafael Martinez-Perez, Natalia Rayo, Agustín Montivero, Jorge Marcelo Mura

Neural Regeneration Research 2019 14(8):1364-1366

Clipping and coiling are currently the two alternatives in treatment of ruptured cerebral aneurysms. In spite of some meritorious analysis, further discussion is helpful to understand the actual state of art. Retreatment and rebleeding rates clearly favors clipping, although short-term functional outcome seems to be beneficial for clipping, while this different is not such if we perform the comparison at a longer follow up. Long-term follow ups and cost analysis are mandatory to have a clear view of the current picture in treatment of subarachnoid hemorrhage. Treatment strategy should be made by a multi-disciplinary team in accredited centers with proficient experience in both techniques. 


Clinical and Preventive Cardiology

Editor's page April 2019
Ravi R Kasliwal

Journal of Clinical and Preventive Cardiology 2019 8(2):43-43



Utility of ankle–brachial pressure index/carotid intima-media thickness ratio in predicting presence and severity of coronary artery disease: A study from major center in Northeastern India
Farhin Iqbal, Amol Vasantrao Patil, Jogesh Chandra Barkataki

Journal of Clinical and Preventive Cardiology 2019 8(2):44-49

Background: Studies have shown that carotid intima-media thickness (CIMT) and ankle–brachial pressure index (ABI) can be used as surrogate markers of coronary artery disease (CAD). However, whether studying the ratio of ABI and CIMT has any added value in predicting CAD when compared to either of them alone, has not been studied. Aims: The aim of the study is to compare CIMT and ABI as surrogate markers for the presence and extent of CAD and to investigate whether studying the ratio of ABI and CIMT has any incremental value in predicting CAD than either of them. Methods: We prospectively enrolled 235 stable, non-ACS patients who underwent CIMT and ABI measurements followed by diagnostic coronary angiography. Results: The mean age of the study population was 56.32 ± 10.14 years. CIMT was significantly higher in the CAD group compared to non-CAD group (0.91 ± 0.22 vs. 0.66 ± 0.15, P ≤ 0.0001). ABI was significantly lower in the CAD group compared to non-CAD group (1.07 ± 0.19 vs. 1.18 ± 0.14, P ≤ 0.0001). At an optimal cutoff value of ≥0.75 mm, CIMT showed better predictive values (sensitivity and specificity –72.3% and 79%, respectively) compared to ABI ≤0.9 (sensitivity and specificity – 21.53% and 96.19%, respectively). CIMT was the strongest independent predictor of CAD (P < 0.0001) followed by ABI (P = 0.006) by multiple regression. ABI/CIMT ratio of ≤1.55 had better predictive value (sensitivity and specificity –75.4% and 78.1%, respectively) and stronger correlation with CAD severity (R = 0.42), than either of them. Conclusion: CIMT is a better surrogate marker of CAD compared to ABI. Studying ABI/CIMT ratio has an incremental value in predicting CAD. 


Association between hypertension and sleep duration and water intake in Indian young adults
Umeshwar Pandey, Tanu Midha, Yashwant Kumar Rao

Journal of Clinical and Preventive Cardiology 2019 8(2):50-55

Context: The prevalence of hypertension is on the rise in developing countries like India. Physiological parameters such as sleep duration and water intake may be associated with hypertension in young adults. Aims: The aim is to study the association between hypertension and day and nighttime sleep duration and water intake among young adults. Setting and Design: The study was a cross-sectional study, conducted among 596 students of Government Medical College, Kannauj, aged between 17 and 22 years. Materials and Methods: Participants were classified using the diagnostic criteria of the American Heart Association. Data were recorded on a pre-designed and pretested questionnaire. Data analysis was performed using SPSS 22.0. Receiver operator characteristic curve analysis and multiple logistic regression analysis were applied. Results: The prevalence of hypertension was 34.9%, 35.9% among boys, and 33.5% among girls, respectively. Less water intake and shorter sleep duration at nighttime were found to be independent predictors of hypertension. Cutoff of sleep duration at nighttime for predicting hypertension was ≤7.6 h among boys and ≤7.1 h among girls. The sensitivity and specificity of the cutoff for sleep duration at night time in boys was 79.3% and 74.2%, respectively, and that in girls was 81.5% and 75.6%, respectively. The cutoff for water intake for predicting hypertension was ≤2.1 L for boys and ≤1.5 L for girls, respectively. The sensitivity and specificity of the cutoff for water intake in boys was 74.8% and 70.3%, and in girls was 78.3% and 71.5%, respectively. Conclusions: Young adults with longer duration of sleep during night time and more water intake had a lesser risk of hypertension. 


Clinical presentation and 2-year mortality outcomes in acute heart failure in a tertiary care hospital in South India: A retrospective cohort study
Vengatesh Munusamy, Luxitaa Goenka, Masum Sharma, Thilagavathi Ramamoorthy, Durga Jha, S Solaipriya, VE Dhandapani, Melvin George

Journal of Clinical and Preventive Cardiology 2019 8(2):56-63

Background: Heart failure (HF) is one of the leading causes of mortality and morbidity worldwide. We sought to describe the clinical epidemiology of HF from a representative sample in a tertiary care setting and to evaluate the factors which could increase the mortality risk in the study patients. Methods: This retrospective cohort study was carried out among patients who had been admitted with a diagnosis of acute HF from 2013 to 2017. Demographic data, history, laboratory investigations, data on medication clinical variables, and in-hospital outcomes were obtained from the patient's hospital records. The patients were assessed through the telephonic interview for mortality outcomes. Data were analyzed using SPSS software version 16.0 (SPSS Inc., Chicago, IL) and all values of P < 0.05 was considered as statistically significant. Results: A total of 355 acute heart failure (AHF) patients were included in the study with a mean age of 57.78 ± 12.78 years. The most common etiologies among the study patients were ischemic heart disease (58%) and Dilated Cardiomyopathy (24.79%). The in-hospital and 2-year mortality was found to be 104 (29.3%) and 179 (50.4%), respectively. The 2-year mortality was significantly higher in patients with ischemic HF than that of nonischemic HF (119 [57.8%] vs. 58 [39.5%], P = 0.003). Multivariate Cox proportional hazard analysis demonstrated that elderly age, the presence of diastolic dysfunction and higher levels of total leukocyte count (TLC) were independent predictors of mortality. Conclusion: The mortality rate in AHF is higher among ischemic HF than nonischemic HF. The major factors contributing to the 2-year mortality rate among AHF were elderly age, diastolic dysfunction, and high-TLC. 


Stress echocardiography in aortic stenosis
Nitin Burkule

Journal of Clinical and Preventive Cardiology 2019 8(2):64-70

In apparently asymptomatic severe aortic stenosis (AS) group, stress echocardiography objectively identifies symptomatic, high-risk AS patients requiring early aortic valve replacement (AVR). The low-flow, low-gradient AS is well-characterized clinical entity with distinct diagnostic, management, and clinical outcome challenges. A comprehensive two-dimensional transthoracic echocardiography (2D echo) and Doppler and low-dose dobutamine stress echocardiography are of paramount importance for accurate diagnosis and timely decision of AVR. However, clinicians and imaging experts should be aware of the pitfalls and inaccuracies inherent in 2D echo/Doppler measurements and the effects of pathophysiological factors which impact the stroke volume and transvalvular gradient measurements. In appropriate clinical situations, clinicians should take additional help of cardiac computational tomography, cardiac magnetic resonance imaging, and biomarkers. 


QT interval – Its measurement and clinical significance
Sita Ram Mittal

Journal of Clinical and Preventive Cardiology 2019 8(2):71-79

QT interval extends from the beginning of QRS complex to the end of T wave. Thus, it includes the duration of ventricular depolarization (QRS) and repolarization (J point to end of T wave). It corresponds to the duration of cellular action potential. “long-” and “short”-QT intervals are considered as risk markers for cardiac arrhythmias and sudden death. In the last decade, there have been significant advances in our understanding about measurement and significance of QT interval. We have made an attempt to review the literature to find the limitations and queries surrounding the present status of measurement of QT interval and its significance as a risk marker for cardiac arrhythmias and sudden death. 


Republication- Indian academy of echocardiography guidelines and manual for performance of stress echocardiography in coronary artery disease
Nitin Burkule, Manish Bansal

Journal of Clinical and Preventive Cardiology 2019 8(2):80-112

Stress echocardiography is one of the most useful non-invasive diagnostic modalities for detection and evaluation of coronary artery disease (CAD). It is also very useful for assessment of cardiac response to hemodynamic stress in a variety of other cardiac and non-cardiac disorders. Given its cost-effectiveness, stress echocardiography is particularly suited for Indian scenario where the incidence of CAD is rising at an alarming rate and the astronomical expenditure required for its management is borne largely by the patients themselves. However, despite its unequivocal diagnostic value, stress echocardiography remains underutilized, particularly in India, due to the lack of adequate exposure and training in this modality. Unfortunately, while there is extensive literature available to document diagnostic accuracy of stress echocardiography, there are very few texts that actually describe how to perform stress echocardiography in real life. This Indian Academy of Echocardiography guideline document aims to fill this very void. This is a comprehensive 'how to do' document prepared with the objective of providing detailed description of the steps involved in performance and interpretation of stress echocardiography so that there is increased adoption of this important and clinically useful diagnostic modality in daily clinical practice. However, while stress echocardiography has several clinical applications, the present document is restricted to its main application, which is evaluation of CAD. Republished with permission from: Dr. Satish Govind, Editor-in-chief (Journal of the Indian Academy of Echocardiography & Cardiovascular Imaging). 


Pharmacognosy Reviews

A comprehensive review on eugenol's antimicrobial properties and industry applications: A transformation from ethnomedicine to industry
Kit-Kay Mak, Masnah Banu Kamal, Sunday Buru Ayuba, Raghavendra Sakirolla, Yew-Beng Kang, Kavitha Mohandas, Madhu Katyayani Balijepalli, Sazali Hamzah Ahmad, Mallikarjuna Rao Pichika

Pharmacognosy Reviews 2019 13(25):1-9

Eugenol and eugenol-containing plants are used in ethno and modern medicine for various biological activities including antimicrobial activity. This review article provides an insightful transformation of eugenol from being an ethnomedicine to being a food protectant in the food industry. Scientific publications on the antimicrobial activity of eugenol and its respective advancements were collected from scientific databases such as Scopus, PubMed, and Google Scholar published between 1995 and June 2018. The eugenol has shown significant broad-spectrum antimicrobial activities against Gram-positive, Gram-negative, fungi, and virus. The eugenol has also shown synergistic effects with conventional antimicrobials. Formulations, such as micro- and nanoemulsions, nanocapsules, and nanoparticles, are prepared to improve the aqueous solubility and efficacy of eugenol. Eugenol is used as a food protectant in storing plants, grains, fruits, and livestock. This review covers eugenol's antimicrobial activities, formulations to improve aqueous solubility, and applications in the food industry. Extensive scientific investigations validated the ethnomedicinal uses of eugenol as an antimicrobial agent. Its activity on multidrug-resistant pathogens should further be explored to identify the molecular mechanisms and synergistic/antagonistic effects with conventional antimicrobials. There were no studies on investigating eugenol's potential in in vivo infectious animal models. This is the first review on eugenol that details the antimicrobial potential of eugenol and its possible applications as a protectant in the food industry. 


Can medicinal properties of watercress be relevant to human health? A systematic review based on preclinical study in vivo
Mirna Clemente, Marilis Dallarmi Miguel, Karina Bettega Felipe, Gislene Mari Fujiwara, Luiz Claudio Fernandes, Joseane de Fatima Gaspari Dias, Sandra Maria Warumby Zenin, Beatriz Cristina Konopatzki Hirota, Obdulio Gomes Miguel

Pharmacognosy Reviews 2019 13(25):10-15

Nasturtium officinale (Watercress) is a perennial dicotyledonous herbaceous plant and a member of the Brassicaceae family. The leaves of this plant are used as a home remedy as expectorant and hypoglycemic. They can also be used in the treatment of hyperlipidemia, hypertension, as well as many other chronic diseases. This finding supports the idea of watercress being a health promoter. In addition, this study intends to provide recommendations for future research. This systematic review was performed by Science Direct, MEDLINE, Cochrane, and Scopus from July 2017 to August 2018. A total of 14 preclinical studies with watercress were selected by the inclusion and exclusion criteria, 13 were with rats and mice and 1 fish. The search terms used were “bioactive compounds,” “Nasturtium,” “preclinical study,” and “systematic review.” For the quality of the individual studies, we adopted the risk of bias. The results of the selected articles with Nasturtium in animals showed positive effects on the improvement of the immune system, hypoglycemic hypercholesterolemia, and anti-inflammatory activity, sex hormones synthesis, the preventive effect on the renal stone formation, and others. Since Nasturtium is widely used for therapeutic and nontherapeutic purposes that trigger its significant value, a new approach is necessary. Different combinations and the numerous medicinal properties of its extract juice and leaves, whether administrated orally or topically, demand further studies about other useful and unknown properties of this multipurpose plant. Finally, it is suggested by our reviewers that more studies with animals to be applied to human health, should be investigated of bioactive compounds from watercress. 


Mangifera and Impatiens from Sumatra: Phylogenetic positions and their modes of action as anticancer agents
Agustina Dwi Retno Nurcahyanti

Pharmacognosy Reviews 2019 13(25):16-23

Cancer has become a growing health threat due to the emergence of multidrug resistance and the increasing diversity of cancer cells. The continuous investigation into the development of anticancer agents and treatments is crucial because the current treatments can cause adverse side effects and are often ineffective. Anticancer derived medicinal plants are a potential source of treatment. However, the abundance of medicinal plant species can cause several problems, like the adulteration. The author aims to demonstrate DNA Barcoding technique as a tool to perform phylogenetic positions of Mangifera and Impatiens species grown in Sumatra. The phylogenetic positions of the plants are supported by the review on the active secondary metabolites from Mangifera and Impatiens. The current study is based on unpublished work on DNA Barcoding technique, an established modern technique to identify the phylogenetic position and also adulteration in medicinal plants. The review on the active secondary metabolites including the mechanism of action as anticancer is based on pertinent papers that were retrieved using relevant keywords in PubMed and Science Direct. Work using DNA Barcoding technique confirmed that Mangifera and Impatiens from Sumatra are closely related to Momordica foetida and Impatiens balsamina from other areas, indicating that they may share the same anticancer traits with those species. The mechanism of action of Mangifera and Impatiens includes inhibition of the cell cycle, cytotoxicity activity, apoptosis and leading to cell death, and anti-angiogenesis activity. Further research on both species is needed to identify their relevant chemical components to potentially develop anticancer drugs, either as a single compound or as a drug combination with minimal side effects and also to determine possible adverse reactions. 


The beneficial properties of virgin coconut oil in management of atopic dermatitis
Yik-Ling Chew

Pharmacognosy Reviews 2019 13(25):24-27

Atopic dermatitis (AD) is a chronic, inflammatory skin disease that is characterized by intense pruritus and eczematous lesions. It is an increasingly pruritic inflammatory skin disorder which can affect both children and adults. Natural products offer great hope in the identification of bioactive lead compounds and their development into topical cream or ointment in managing skin diseases which are associated with inflammatory response. One of the most popular natural products which have been vastly used in managing AD is virgin coconut oil (VCO). VCO is extracted from the fresh and mature kernel of the coconut (Cocos nucifera L.) through wet and dry methods, without altering the valuable phytochemicals and physiochemical properties of the oil. It possesses numerous health benefits from the retained physiochemical properties from its triglycerides and medium chain fatty acids. The use of VCO in the management of AD is one of the topical therapies which have been proven to have good therapeutic effects and it is safe for topical applications. Studies have been proven that VCO exhibits antioxidant, anti-inflammatory, antibacterial, wound healing, and moisturizing properties which were extremely important in the management of AD. 


The potential of xanthones as a therapeutic option in macrophage-associated inflammatory diseases
Ida May Jen Ng, Caroline Lin Lin Chua

Pharmacognosy Reviews 2019 13(25):28-33

Xanthones are well known for their significant biological activities and can be found in many herbal medicines. These compounds have the ability to regulate various inflammatory activities and signaling pathways in immune cells, especially macrophages. Macrophages are innate immune cells that can either fuel or dampen an inflammatory response depending on their activation states and play an active role in the development of inflammatory diseases such as atherosclerosis, arthritis, cancer, and diabetes. Many traditional medicines used as a remedy for these diseases contain xanthones, and their bioactivities may be partially attributed to their ability in regulating macrophage responses. In this review, we discuss the in vitro and in vivo findings on the effects of xanthones on different macrophage immune functions including nitric oxide and cytokine production, migration, polarization, and phagocytosis. Their specific modes of action are highlighted whenever known. We also discuss the potential and challenges in using xanthones as a therapeutic option in various inflammatory diseases. It is hoped that this review can pave the way for future research that focuses on developing xanthones as specific macrophage-targeted therapeutics. 


Medical Research

Family planning in India: The way forward
Poonam Muttreja, Sanghamitra Singh

Indian Journal of Medical Research 2018 148(7):1-9

Given the magnitude of the family planning programme in India, there is a need to strengthen the coordination of all its aspects, focusing on planning, programmes, monitoring, training and procurement. The quality of care in family planning must be a major focus area to ensure the success of family planning programmes. Despite serious efforts and progress, India has yet to achieve its family planning goals. Furthermore, there is a need for greater male participation both as enablers and beneficiaries and also address the sexual and reproductive needs of the youth. It is imperative for the government to ensure the prioritization of family planning in the national development agenda. Family planning is crucial for the achievement of the sustainable development goals, and subsequent efforts need to be made to improve access and strengthen quality of family planning services. 


Infertility & assisted reproduction: A historical & modern scientific perspective
Radhey Shyam Sharma, Richa Saxena, Rajeev Singh

Indian Journal of Medical Research 2018 148(7):10-14

Infertility has always been considered as a social stigma and has often been treated as socially, mentally and physically damaging experience for the childless women rather than man. Fatherhood was more a social rather than biological concept, thereby making childlessness a legitimate ground for divorce and a matter of disgrace for women. Every country has its own set of customs and traditional beliefs for the relief of childlessness. While introducing a second wife was one way to overcome the predicament of childlessness, divorce was also an available choice. There were several myths that contemplated the human concerns and their needs during ancient times. It is evident that types of the infertility and their treatment in the modern era have some historical background and different representations in the ancient civilizations. The present review discusses the historical and modern perspectives of infertility and assisted reproduction and their importance in different cultures. 


Mid-life fertility: Challenges & policy planning
Umesh N Jindal

Indian Journal of Medical Research 2018 148(7):15-26

This review highlights the challenges, priority areas of research and planning, strategies for regulation of services and the need to develop guidelines and laws for fertility treatments during mid-life. The success rate of all treatments is poor in advanced age women because of declining ovarian reserve and natural fertility. There is often a need of third-party involvement which has its own ethical, legal and medical issues. Welfare of children born to older women and early death of parents are important concerns. Most of the new techniques such as the pre-implantation genetic diagnosis, oocyte augmentation, use of stem cells or artificial gametes, ovarian tissue preservation and ovarian transplantation are directed to improve, preserve or replace the declining ovarian reserve. These techniques are costly and have limited availability, safety and efficacy data. Continued research and policies are required to keep pace with these techniques. The other important issues include the patients' personal autonomy and right of self-determination, welfare of offspring, public vs. private funding for research and development of new technologies vs. indiscriminate use of unproven technology. It is important that mid-life fertility is recognized as a distinct area of human reproduction requiring special considerations. 


Socio-economic correlates of bereavement among women - Examining the differentials on social axes
Sanghmitra S Acharya

Indian Journal of Medical Research 2018 148(7):27-37

Death, disease and disaster can inflict anyone, anywhere and at any time. While occurrence of such an event could be absolved of any selective strike, the outcome reflects otherwise. Historical deprivations experienced by certain populations have caused more bereavement and sorrow to them than those who have experienced lesser or no deprivation. Therefore, the process which shapes the factors to yield such a result is important and needs to be understood for any policy suggestions and programmatic inputs. Loss of pregnancy and newborn inflicts sorrow and bereavement across space, time and social labyrinth. The degree of bereavement is likely to reduce with time, but space and social context govern the response to it. Therefore, factors contributing to the differentials vary in their demographic, social and economic characteristics. The loss of pregnancy and newborn remains inadequately addressed. Family and community play a significant role in coping. While the developed countries have institutional structure to address coping with the loss, the South Asian countries rely heavily on the family and the community for such support. The present review examines these trajectories across social groups. 


Stem cells survive oncotherapy & can regenerate non-functional gonads: A paradigm shift for oncofertility
Deepa Bhartiya

Indian Journal of Medical Research 2018 148(7):38-49

A large proportion of patients who survive cancer are rendered infertile as an unwanted side effect of oncotherapy. Currently accepted approaches for fertility preservation involve banking eggs/sperm/embryos or ovarian/testicular tissue before oncotherapy for future use. Such approaches are invasive, expensive, technically challenging and depend on assisted reproductive technologies (ART). Establishing a gonadal tissue bank (for cancer patients) is also fraught with ethical, legal and safety issues. Most importantly, patients who find it difficult to meet expenses towards cancer treatment will find it difficult to meet expenses towards gonadal tissue banking and ART to achieve parenthood later on. In this review an alternative strategy to regenerate non-functional gonads in cancer survivors by targeting endogenous stem cells that survive oncotherapy is discussed. A novel population of pluripotent stem cells termed very small embryonic-like stem cells (VSELs), developmentally equivalent to late migratory primordial germ cells, exists in adult gonads and survives oncotherapy due to their quiescent nature. However, the stem-cell niche gets compromised by oncotherapy. Transplanting niche cells (Sertoli or mesenchymal cells) can regenerate the non-functional gonads. This approach is safe, has resulted in the birth of fertile offspring in mice and could restore gonadal function early in life to support proper growth and later serve as a source of gametes. This newly emerging understanding on stem cells biology can obviate the need to bank gonadal tissue and fertility may also be restored in existing cancer survivors who were earlier deprived of gonadal tissue banking before oncotherapy. 


Dendritic cell engineering for selective targeting of female reproductive tract cancers
Arpit Bhargava, Rupesh Kumar Srivastava, Dinesh Kumar Mishra, Rajnarayan R Tiwari, Radhey Shyam Sharma, Pradyumna Kumar Mishra

Indian Journal of Medical Research 2018 148(7):50-63

Female reproductive tract cancers (FRCs) are considered as one of the most frequently occurring malignancies and a foremost cause of death among women. The late-stage diagnosis and limited clinical effectiveness of currently available mainstay therapies, primarily due to the developed drug resistance properties of tumour cells, further increase disease severity. In the past decade, dendritic cell (DC)-based immunotherapy has shown remarkable success and appeared as a feasible therapeutic alternative to treat several malignancies, including FRCs. Importantly, the clinical efficacy of this therapy is shown to be restricted by the established immunosuppressive tumour microenvironment. However, combining nanoengineered approaches can significantly assist DCs to overcome this tumour-induced immune tolerance. The prolonged release of nanoencapsulated tumour antigens helps improve the ability of DC-based therapeutics to selectively target and remove residual tumour cells. Incorporation of surface ligands and co-adjuvants may further aid DC targeting (in vivo) to overcome the issues associated with the short DC lifespan, immunosuppression and imprecise uptake. We herein briefly discuss the necessity and progress of DC-based therapeutics in FRCs. The review also sheds lights on the future challenges to design and develop clinically effective nanoparticles-DC combinations that can induce efficient anti-tumour immune responses and prolong patients' survival. 


Postpartum uterine infection & ovarian dysfunction
Sunita Dahiya, Suman Kumari, Payal Rani, Suneel Kumar Onteru, Dheer Singh

Indian Journal of Medical Research 2018 148(7):64-70

Postpartum uterine infections such as metritis, endometritis and mastitis have been considered as underlying causes for ovarian dysfunction in mammals. Almost all mammals, particularly dairy animals are susceptible to postpartum uterine infections, resulting in impaired fertility and economic loss. One of the factors for low fertility in females is ovarian dysfunction, which is exhibited as impaired growth and function of ovarian follicles by the postpartum infection. Immune system of mammals provides a host defence mechanism against pathogenic microbes through the recognition of pathogen-associated molecular patterns (PAMPs) and forming inflammasomes. Like immune cells, ovarian granulosa cells also exhibit a similar pattern of cytokine gene expressions on exposure to PAMPs. Genome-wide transcriptomic approaches explored the molecular mechanisms underlying the immune function of buffalo granulosa cells during endotoxin exposure. Understanding the molecular mechanism of ovarian dysfunction due to uterine infection would be helpful to implement various strategies to handle the adverse effects of postpartum uterine disease on fertility by developing potential therapeutics. Therefore, this article focuses on key factors that are responsible for postpartum infection and particularly summarizes the molecular mechanism of infection underlying the ovarian dysfunction in dairy animals. 


Female genital tuberculosis: Revisited
Jai Bhagwan Sharma, Eshani Sharma, Sangeeta Sharma, Sona Dharmendra

Indian Journal of Medical Research 2018 148(7):71-83

Female genital tuberculosis (FGTB) is caused by Mycobacterium tuberculosis (rarely Mycobacterium bovis and/or atypical mycobacteria) being usually secondary to TB of the lungs or other organs with infection reaching through haematogenous, lymphatic route or direct spread from abdominal TB. In FGTB, fallopian tubes are affected in 90 per cent women, whereas uterine endometrium is affected in 70 per cent and ovaries in about 25 per cent women. It causes menstrual dysfunction and infertility through the damage of genital organs. Some cases may be asymptomatic. Diagnosis is often made from proper history taking, meticulous clinical examination and judicious use of investigations, especially endometrial aspirate (or biopsy) and endoscopy. Treatment is through multi-drug antitubercular treatment for adequate time period (rifampicin, isoniazid, pyrazinamide, ethambutol daily for 60 days followed by rifampicin, isoniazid, ethambutol daily for 120 days). Treatment is given for 18-24 months using the second-line drugs for drug-resistant (DR) cases. With the advent of increased access to rapid diagnostics and newer drugs, the management protocol is moving towards achieving universal drug sensitivity testing and treatment with injection-free regimens containing newer drugs, especially for new and previously treated DR cases. 


Redox regulation & sperm function: A proteomic insight
Gayatri Mohanty, Luna Samanta

Indian Journal of Medical Research 2018 148(7):84-91

Infertility affects nearly 15 per cent of all couples within the reproductive age worldwide, with about 50 per cent being exhibited in the male, called male factor infertility. Successful reproduction is dependent on sperm chromatin integrity. Spermatozoa are highly specialized cells that aim to transmit the paternal genomic blueprint to the oocyte. The spermatozoon is regulated by redox mechanisms during its epididymal transit to acquire fertilizing ability. While, at physiological levels, the production of reactive oxygen species (ROS) supports the spermatozoon to acquire its fertilizing ability, at high concentrations, it affects sperm function leading to infertility. Emerging proteomic technologies provide an opportunity to address these key issues that may solve many fertility-associated problems resulting from oxidative stress (OS). This review highlights the need for an efficient therapeutic approach to male infertility with the application of high-throughput OS-mediated proteomic technology, and also addresses the question as to whether targeting these altered sperm-specific proteins may help in designing an efficient and reversible male contraceptive. 


Effect of radiofrequency radiation on reproductive health
Rajeev Singh, Ravindra Nath, Ajit Kumar Mathur, Radhey Shyam Sharma

Indian Journal of Medical Research 2018 148(7):92-99

The development of cellular phone system has greatly increased the extent and magnitude of radiofrequency radiation (RFR) exposure. The RFR emitted from mobile phone and mobile phone base stations exerts thermal and non-thermal effects. The short-term and long-term exposure to RFR may have adverse effect on humans as well as animals. Most laboratory studies have indicated a direct link between exposure to RFR and adverse biological effects. Several in vitro studies have reported that RFR induces various types of cancer and DNA or chromosomal damage. On the other hand, some animal studies have not reported adverse effects of this radiation. The present review summarizes information available on the possible effects of RFR on the reproductive health. 


Endodontics

The smear layer in endodontic: To keep or remove – an updated overview
Ruaa A Alamoudi

Saudi Endodontic Journal 2019 9(2):71-81

During mechanical preparation, the use of hand or rotary instruments results in the production of considerable amount of smear layer. The smear layer consists of two parts: a superficial layer that covers the dentinal wall and a smear plug which occludes that dentinal tubules. Researchers had reached to different conclusions on the importance of removing or maintaining this layer. Removing the smear layer allows for more cleaning and disinfecting root canal walls and better adaptation of root canal filling materials. However, the presence of smear layer can act as a seal to the dentinal tubules and minimize the ability of bacteria and its toxins from penetrating the dentinal tubules. The ability to remove smear layer depends primarily on chemomechanical preparation. There are three main methods to remove smear layer: chemically, mechanically (ultrasonically), laser, or combinations. No one single irrigant has the ability to kill microorganisms, dissolve organic tissues, and demineralize smear layer. Thus, alternating between organic and inorganic solvents and the use of different methods and techniques have been recommended. Indeed, there is little relevance attributed to the influence of smear layer on the clinical treatment outcomes. Moreover, there is critical lack of clinical studies to determine the role of smear layer since all previous studies were carried out on laboratory based. Further experimental model with a longitudinal observational characteristic should be applied.


Parents' awareness and attitude toward urgent management of avulsed permanent tooth in AL-Baha city
M Sarhan Alzahrani, Fatmah Ali Almaqboul

Saudi Endodontic Journal 2019 9(2):82-87

Objective: This study was conducted to evaluate the parents' awareness and attitude toward emergency management of avulsed tooth in AL-Baha city. Materials and Methods: Eleven-item questionnaire form was designed and sent randomly to parents with different demographic characteristics in Al-Baha city. A total of 263 questionnaires were collected. Data were statistically analyzed using SPSS program. Results: The majority of the respondents (n = 227; 86.3%) were females. The result revealed insufficient awareness among parents regarding the emergency management of tooth avulsion. One hundred fifty-two (58%) of the respondents think that replantation of an avulsed tooth is impossible where 76% (n = 202) of the parents were not aware of the transportation medium for the avulsed tooth. The demographic characteristics showed a nonsignificant impact on the awareness and attitude toward emergency management of the avulsed tooth in this study (P < 0.05). Conclusion: This study showed an insufficient awareness regarding tooth avulsion among Saudi subpopulation.


Root canal treatment with postcore restoration versus implant restoration: Clinical and radiographic outcome and quality of life after treatment
Abed Al-Hadi Hamasha, Ashraf Fareed Nbhan

Saudi Endodontic Journal 2019 9(2):88-95

Introduction: The study intended to support the decision-making process regarding whether to save a compromised tooth by endodontic treatment with a subsequent postcore and crown or to extract such a tooth in favor of implant replacement. Therefore, the aim of this study is to explore differences between the two modalities of treatments in terms of clinical and radiographic outcomes and quality of life. Materials and Methods: A randomly selected 126 patients with 150 root canal treatment (RCT) teeth compared with 150 single-tooth implants in 129 patients was conducted at Jordan University of Science and Technology in Jordan. Participants were clinically and radiographically examined after 1 year of treatment. Administered questionnaires were filled on patient interview consisting of patient's characteristics and oral health impact profile (OHIP) instrument. Data analysis included descriptive statistics, bivariate analysis using Mann–Whitney tests and Chi-square tests. Results: Treatment outcomes for RCT and implant groups were as follows, respectively: success (75.3% and 56.7%), satisfactory survival (8.7% and 24.7%), compromised survival (4% and 10%), and failure (12% and 8.7%). Improvement of the subject's OHIP items reveals a notable improvement (67%–100%) following RCT (mean improvement = 96.32) and implant (mean improvement = 89.04) treatment. Conclusion: RCT and implant achieved equivalent proportion of cases having a good prognosis. However, implant restoration was associated with more postoperative complications. Both treatments achieved a predictable improvement in patient's OHIP.


Malondialdehyde expressions on pulp odontoblast cells after application of 2-hydroxyethyl methacrylate mixed with water, ethanol, and acetone solvents
Adioro Soetojo, KH Ekhtiyanto Cahyadi, Edhie Arif Prasetyo

Saudi Endodontic Journal 2019 9(2):96-100

Background: 2-hydroxyethyl methacrylate (HEMA) is a resin-based methacrylate material most widely used as an adhesive within dentistry. In order to reduce the level of HEMA toxicity, some ingredients such as water, ethanol, and acetone are used as solvent agents because they are readily available and inexpensive. However, significant concerns persist with regard to their biocompatibility. Purpose: The aim of this study was to compare and evaluate the biocompatibility of HEMA, HEMA with water solvent, HEMA with ethanol solvent, and HEMA with acetone solvent by measuring the oxidative stress parameters of malondialdehyde (MDA). Materials and Methods: Twenty-seven Wistar rats were equally divided into three groups. Three dental resin-based adhesive systems were subsequently applied to the dentin surface of their teeth. MDA assessment was conducted based on the levels of MDA expressions observable under microscope 24 h after initiation of the treatment. Results: There was a significant difference in MDA expression in the pulp odontoblast cells between Group 1 and Group 2 with a P = 0.000. Similarly, there was a significant difference in MDA expression in the pulp odontoblast cells between Group 1 and Group 3 with a = 0.000. Yet, there was no significant difference in MDA expression in the pulp odontoblast cells between Group 2 and Group 3 with a P = 0.082. Conclusion: HEMA with water solvent showed the least MDA expression compared to HEMA with ethanol and water solvent, therefore, HEMA with water solvent has the most suitable biocompatibility.


Impact of educational background on knowledge, attitude, and practice of root canal treatment among male university and high school students of Sakaka Province
Ravi Jothish, Mohammad Khursheed Alam, Fayyaz Alam

Saudi Endodontic Journal 2019 9(2):101-108

Aim: To determine the knowledge, attitude, and practice of root canal treatment (RCT) among male university and high school students of Sakaka province and to compare and analyze the impact of educational status on the three parameters mentioned earlier. Materials and Methods: A self-administered questionnaire prepared in Arabic and English was circulated among 600 male participants who consented to participate in the survey. Participants were divided into two groups – Group 1 (University) and Group 2 (high school) students. Pearson Chi-square test was used to analyze the data. Results: Data sheets were received from 500 participants only. Most of the participants, irrespective of the group, visit dentists only on the appearance of pain (84% and 82.8%, respectively). Substantial number of participants had a history of RCT (24.7% and 42.2%, respectively); 8.7 and 17% from respective groups reported that they were uncomfortable during the past RCT. However, majority of the participants (64.7% from either group) mentioned that they would opt for RCT in the future despite the slightly negative experience of the past. Conclusion: Young adults are reasonably well informed about RCT. Exposure to alternative sources like social media seems to be the reason behind this. Hence, internet platforms should be used to further popularize RCT among the youth.


Effect of chelating agents on the microhardness of Biodentine
Nidambur Vasudev Ballal, Preeti Mishra, Sheetal Rao, Sree Teja Upadhyay

Saudi Endodontic Journal 2019 9(2):109-112

Introduction: The objective of this study was to evaluate the effect of SmearOFF, 7% maleic acid (MA) and 17% ethylenediaminetetraacetic acid (EDTA), on the surface microhardness of Biodentine (BD). Materials and Methods: Forty BD cylindrical-shaped specimens were prepared using a split mold and were divided randomly into four groups (n = 10) based on the type of irrigant used for 1 min. In Group I, the specimens were treated with 17% EDTA, in Group II with 7% MA, in Group III with SmearOFF solution, and in Group IV with 5 mL distilled water. In all these groups, the irrigants were taken in a beaker and the samples were immersed with a magnetic stirrer placed to ensure complete wetting of the specimens. All the samples were then washed with distilled water and air-dried. The surface microhardness of the specimens was measured using Knoop hardness tester. Data were analyzed statistically using Kruskal–Wallis and Mann–Whitney U-test. The significant level was preset to P = 0.05. Results: MA significantly compromised the microhardness of BD followed by EDTA, SmearOFF, and distilled water which was statistically significant (P < 0.001). On comparison between 17% EDTA and SmearOFF, 17% EDTA reduced microhardness to maximum (P < 0.05). Conclusion: In conclusion, the present study demonstrated that microhardness of BD cement was generally affected by chelating agents.


Cone-beam computed tomographic evaluation of root canal morphology of mandibular canines in a Saudi subpopulation
Yousef Al-Dahman, Abdullah Alqedairi, Hussam Alfawaz, Faisal Alnassar, Asma Al-Jebaly

Saudi Endodontic Journal 2019 9(2):113-118

Introduction: The aim of the study was to investigate the root canal morphology of mandibular canines in a Saudi subpopulation using cone-beam computed tomography (CBCT). Materials and Methods: This retrospective cross-sectional study assessed CBCT images of 707 patients. A total of 454 mandibular canine teeth were evaluated. The number of roots and canal configuration was identified based on Vertucci's classification. The Fisher's exact test was used alongside the Chi-square test to analyze the association between gender and number of roots, as well as gender and root canal configuration. Results: Most patients had one root, 99.8%, while double-rooted mandibular canines were observed in 0.2%. Moreover, Type I, II, III, and IV canal configurations were observed in mandibular canines with Type I being the most prevalent canal configuration (95.4%). Fisher's exact and Chi-square tests showed no significant association between gender and number of roots (P = 0.463), while the presence of two canals was more frequent in men than in women with a statistically significant difference (P = 0.006). Conclusion: Single rooted with Type I canal configuration was the most prevalent in mandibular canines in the Saudi subpopulation. However, incidence of more than one root canal with different canal configurations was also detected.


Comparative evaluation of efficiency of single-file rotary and reciprocating systems in instrumenting severely curved mesial root canals of extracted mandibular first molars: A morphometric study using cone-beam computed tomography
Deepthi Santhosh, A Devadathan, Josey Mathew, Manuja Nair, Baby James

Saudi Endodontic Journal 2019 9(2):119-125

Aims and Objectives: The nickel–titanium multifile system is a viable tool in shaping severely curved canals as it reduces instrumentation errors. To eliminate the drawbacks with multifile systems, single-file systems were introduced. In this in vitro study, two single-file systems, One Shape and WaveOne, which work in a rotating and reciprocating motion, respectively, were compared with multifile systems for their efficiency in shaping severely curved mesial canals of extracted mandibular first molars, using cone-beam computed tomography (CBCT). Methodology: Fifty-two intact mesial roots of mandibular first molars with severely curved canals were selected using CBCT and divided into four groups of 13 samples each. Samples in Groups I, II, III, and IV, were instrumented using One Shape, WaveOne, ProTaper, and H and K-files, respectively. All the specimens were prepared up to working length to size 25 file using the manufacturer recommended technique along with standardized irrigation protocol. Pre- and postinstrumentation CBCT images were assessed at 8 mm, 5 mm, and 3 mm from apex to compare the changes in canal transportation (CT), canal centering (CC), and remaining dentin thickness. Results: All the groups showed CT with the statistically significant difference between the groups (P < 0.05). Except for ProTaper group at 5 mm (P < 0.05) none of the file systems showed CC. Except for Group I, a significant reduction in dentin thickness was noticed in Group II, III, and IV (P < 0.05). Conclusion: Among the two single-file systems compared, One Shape file in rotating motion prepared canals with fewer changes in canal anatomy than WaveOne file in the reciprocating motion.


Assessment of dental interns' knowledge toward managing endodontic emergency: A Survey of three dental schools in Jeddah city
Ruaa A Alamoudi

Saudi Endodontic Journal 2019 9(2):126-133

Introduction: Endodontic emergencies are about one-third of the total dental emergency cases. Treatment modalities of endodontic emergencies have shown a great controversy. Therefore, for dentists it is vital to have enough knowledge and information about the suitable treatment protocols to manage these situations properly. The primary goal of this study aimed to determine the knowledge of dental interns regarding the management of endodontic emergencies. Materials and Methods: This cross-sectional survey compromised of 20 closed-ended questions that was distributed among dental interns in three Dental schools; King Abdul-Aziz University, Ibn Sina National College, Batterjee Medical College; in academic year 2017–2018. Questionnaire divided into two parts. The first part assessed dental interns' background and training experience. The second part assessed their knowledge toward managing different endodontic emergencies which composed of 12 conditions of pulp/periapical emergencies, and thirteen modalities of treatment. Results: About 24.7% of dental interns answered correctly all endodontic emergency conditions according to the standard protocols. The correlation test showed that significant correlation between the correct answers and students who had high score of 6th year accumulative grade, 6th year endodontic grade, students who attended meeting or conferences related to endodontic emergency, and those who had exposed to any endodontic emergency during their clinical training (P > 0.001). Moreover, there is a significant difference between the knowledge of the three dental schools. King Abdul-Aziz University showed the higher percentage to answer correctly (39.6%) compared to 11.9% Ibn Sina National College and 15.4% Batterjee Medical College. Conclusions: This study showed that dental interns' knowledge and awareness were almost similar to previous studies except in few aspects. This emphasizes the importance of refreshing courses for dental interns to improve their competency in managing different endodontic emergencies.


Use of cone-beam computed tomography as a diagnostic aid in nonsurgical endodontic management of furcation perforations: Two case reports
Paras Mull Gehlot, Bastin Cherian, Mysore Krishnaswamy Manjunath

Saudi Endodontic Journal 2019 9(2):134-139

Iatrogenic furcation perforation is undesirable communication between the pulpal floor and the periodontium. This study reports nonsurgical endodontic management of iatrogenic furcation perforation in mandibular molars in two cases. Cone-beam computed tomography (CBCT) was used as an advanced diagnostic aid to accurately determine the location and extent of the perforation. The perforation was sealed with mineral trioxide aggregate, and the teeth were treated endodontically. Since the pulpal floor was weakened due to perforations, attempt was made to reinforce the coronal tooth structure using composite resin. Full crowns were placed as a definitive restoration. Two-year postoperative follow-up showed the absence of pain or swelling clinically, and radiographic examination revealed complete healing of furcation lesion. The use of CBCT in this report was a valuable diagnostic aid, which helped in better treatment planning and improved treatment outcome for the patient.


Otolaryngology

Research articleAbstract only
Expression of vimentin (VIM) and metastasis-associated 1 (MTA1) protein in laryngeal squamous cell carcinoma are associated with prognostic outcome of patients
Sotirios Karamagkiolas, Ioannis Giotakis, Efthimios Kyrodimos, Evangelos I. Giotakis, ... Andreas M. Lazaris
In Press, Accepted Manuscript, Available online 3 April 2019
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Abstract
Abstract
Purpose
Laryngeal squamous cell carcinoma (LSCC), a common type of head and neck cancer, is associated with high rates of metastasis and recurrence. In this study, we investigated the potential combinatorial prognostic value of NOTCH1, Vimentin (VIM), and Metastasis-associated 1 (MTA1) protein in LSCC, using immunohistochemistry.

Materials and methods
Tissue specimens from 69 patients with LSCC were immunohistochemically evaluated for the protein expression of NOTCH1, VIM, and MTA1. Then, biostatistical analysis was performed, in order to assess the prognostic value of the expression of each one of these proteins.

Results
NOTCH1 expression status was not a significant prognosticator in LSCC, as shown in Kaplan-Meier survival analysis. On the contrary, both VIM and MTA1 seem to have an important prognostic potential, independently of TNM staging and histological grade of the tumor. In fact, positive VIM expression was shown to predict patients' relapse and poor outcome regarding patients' overall survival, in contrast with MTA1, the positive expression of which predicts higher disease-free survival (DFS) and overall survival (OS) rates in LSCC.

Conclusions
VIM and MTA1 constitute potential tumor biomarkers in LSCC and could be integrated into a multiparametric prognostic model. Undoubtedly, their prognostic value needs further validation in larger cohorts of LSCC patients.

select article Spontaneous cervical chyle fistula: A case report
Case reportAbstract only
Spontaneous cervical chyle fistula: A case report
Swathi Appachi, Joseph B. Meleca, Paul C. Bryson
In Press, Accepted Manuscript, Available online 2 April 2019
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Abstract
Abstract
Background
Cervical chylous fistulae are rare complications usually occurring from iatrogenic injury to the thoracic duct. There have been no reported cases of spontaneous chyle leaks in surgical naïve necks.

Methods
Case report.

Results
A 50 year-old female presented with progressive left neck swelling without fever, dyspnea, or dysphagia. Imaging demonstrated extensive infiltrative changes of the left neck with retropharyngeal fluid extending into strap musculature and the mediastinum. Flexible laryngoscopy revealed posterior pharyngeal wall edema. Differential diagnosis included abscess versus necrotizing fasciitis. Broad-spectrum antibiotics were initiated and she was taken to the OR for neck exploration. Intra-operatively, milky fluid was present around the carotid sheath and in the retropharyngeal space. Fluid analysis demonstrated chylomicrons and triglycerides >2400 mg/dL. Repeat imaging of the neck, chest, and abdomen did not reveal malignancy or obstructive masses. A lymphangiogram showed dilated lymphatic vessels near the cervical thoracic duct. On post-operative day four, the patient was taken back to the OR for thoracic duct ligation and biopsy of nearby tissue. Pathology demonstrated benign lymph nodes with dilated sinusoids. A low-fat diet was started and she was discharged home on hospital day nine. She has followed up regularly with no signs of recurrence.

Conclusion
A cervical chylous fistula usually results from iatrogenic injury to the thoracic duct. To our knowledge, this is the first reported case of a spontaneous cervical chyle leak.

select article Does cervical range of motion affect the outcomes of canalith repositioning procedures for posterior canal benign positional paroxysmal vertigo?
Research articleAbstract only
Does cervical range of motion affect the outcomes of canalith repositioning procedures for posterior canal benign positional paroxysmal vertigo?
Salvatore Martellucci, Giuseppe Attanasio, Massimo Ralli, Vincenzo Marcelli, ... Andrea Gallo
In Press, Accepted Manuscript, Available online 2 April 2019
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Abstract
Abstract
Purpose
Canalith repositioning procedure (CRP) for posterior canal benign positional paroxysmal vertigo (BPPV), also known as Epley maneuver, is a common procedure for the treatment of BPPV. This maneuver entails flexion, extension and rotation of the patient's neck. This study aims to investigate the impact of cervical range of motion (C-ROM) on CRP efficacy.

Materials and methods
The study included 47 patients with posterior canal BPPV treated by CRP. The procedure was considered successful if vertigo and nystagmus disappeared at the post-treatment evaluation. If CRP resulted ineffective, it was repeated up to three times per session. C-ROM was measured at BPPV diagnosis before treatment. Patients were followed up for 30 days.

Results
The first CRP was successful in 29 patients (61.7%), while it was ineffective in 18 patients (38.3%) requiring multiple repositioning maneuvers. Patients who needed two or more CRP showed lower C-ROM in extension (p = .003) and flexion (p = .042), and earlier recurrences (p = .006). Univariate regression analysis showed that lower cervical extension was significantly associated with the failure of the first CRP (OR: 0.899, 95% CI 0.831–0.973, p = .008).

Conclusions
Our data suggest that a reduced C-ROM can require multiple CRPs to successfully treat BPPV and increase the risk of early recurrences.

select article Total vs hemithyroidectomy for intermediate risk papillary thyroid cancer: A 23 year retrospective study in a tertiary center
Research articleAbstract only
Total vs hemithyroidectomy for intermediate risk papillary thyroid cancer: A 23 year retrospective study in a tertiary center
Kwan Pok Tsui, Wai Yin Kwan, Tam Lin Chow
In Press, Accepted Manuscript, Available online 2 April 2019
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Abstract
Abstract
Background
There is much debate in the literature over the extent of surgery for patients with intermediate risk papillary thyroid cancer. We herein report our results in a local tertiary hospital.

Method
We identify from our database patients with papillary thyroid cancer who underwent surgery in our hospital and were stratified to be of intermediate risk from the GAMES stratification system. Patients' demographic data, surgical and pathological details were recorded. Primary end points were disease specific survival (DSS) and recurrence free survival (RFS).

Results
From January 1993 to December 2016, 231 patients with papillary thyroid cancer underwent surgery of which 137 (59%) were of intermediate risk. 45 (33%) patients had hemithyroidectomy and 92 (67%) patients had total thyroidectomy. In the total thyroidectomy group, patients had a higher tumor (T) (p value = 0.009) and nodal (N) staging (p value = 0.001). They were also predicted to have a higher risk of recurrence according to the American Thyroid Association (ATA) classification (p value = 0.005). The 5 year DSS in both groups were 100%. The 5 year RFS in the total thyroidectomy and hemithyroidectomy groups were 92% and 100% respectively and were significantly different by the log rank test (p value = 0.02). The median follow up time was 54 months (range 4–276 months).

Conclusion
The 5 year survival in intermediate risk papillary thyroid cancer is favorable. Hemithyroidectomy is an acceptable choice of operation in intermediate risk patients with a better risk profile.

select article Translation and validation of the Parotidectomy Outcome Inventory 8 (POI-8) to Spanish
Research articleAbstract only
Translation and validation of the Parotidectomy Outcome Inventory 8 (POI-8) to Spanish
Carlos Miguel Chiesa-Estomba, Elizabeth Ninchritz, Teresa Rivera Schmitz, Jose Angel González-García, ... Xabier Altuna-Mariezcurrena
In Press, Accepted Manuscript, Available online 2 April 2019
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Abstract
Abstract
Introduction
There are >400 million of native Spanish speakers around the world, being the second most spoken language in regard to the number of native speakers. For this reason, a valid questionnaire to access the quality of our patients after parotidectomy is necessary.

Material and methods
Validation and cross-cultural adaptation of the POI-8 questionnaire to the Spanish language. Internal consistency of Sp-POI 8 measured with Cronbach α.

Results
35 patients met the inclusion criteria during the mentioned period. Mean age was 59 ± 15,37 (Min: 18/Max: 87). 20 patients (57,1%) were male and 15 (42,9%) were female. Internal consistency with Cronbach α was 0.868. The intraclass correlation coefficient was 0.830 [CI] (95%: 0,791–925). Hypoesthesia was the most severely weighted problem (0,91) and xerostomia was the second (0,89). However, the high score was for fear of revision surgery (1,26).

Conclusion
The Spanish Language is the second most spoken language with regard to the number of native speakers and the Sp-POI 8 translation represents a valid option for the Spanish-speaking medical community, from which a large number of patients can benefit.

select article Sex-specific enlarged vestibular aqueduct morphology and audiometry
Research articleAbstract only
Sex-specific enlarged vestibular aqueduct morphology and audiometry
Jeremy Ruthberg, Mustafa S. Ascha, Armine Kocharyan, Amit Gupta, ... Todd D. Otteson
In Press, Accepted Manuscript, Available online 29 March 2019
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Abstract
Abstract
Objective
Enlargement of the vestibular aqueduct (EVA) is one of the most common congenital malformations in pediatric patients presenting with sensorineural or mixed hearing loss. The relationship between vestibular aqueduct (VA) morphology and hearing loss across sex is not well characterized. This study assesses VA morphology and frequency-specific hearing thresholds with sex as the primary predictor of interest.

Materials and methods
A retrospective, longitudinal, and repeated-measures study was used. 47 patients at an academic tertiary care center with hearing loss and a record of CT scan of the internal auditory canal were candidates, and included upon meeting EVA criteria after confirmatory measurements of vestibular aqueduct midpoint and operculum widths. Audiometric measures included pure-tone average and frequency-specific thresholds.

Results
Of the 47 patients (23 female and 24 male), 79 total ears were affected by EVA; the median age at diagnosis was 6.60 years. After comparing morphological measurements between sexes, ears from female patients were observed to have a greater average operculum width (3.25 vs. 2.70 mm for males, p = 0.006) and a greater average VA midpoint width (2.80 vs. 1.90 mm for males, p = 0.004). After adjusting for morphology, male patients' ears had pure-tone average thresholds 17.6 dB greater than female patients' ears (95% CI, 3.8 to 31.3 dB).

Conclusions
Though females seem to have greater enlargement of the vestibular aqueduct, this difference does not extend to hearing loss. Therefore, our results indicate that criteria for EVA diagnoses may benefit from re-evaluation. Further exploration into morphological and audiometric discrepancies across sex may help inform both clinician and patient expectations.

select article Clinical and audiometric outcomes of palisade cartilage myringoplasty under local anesthetic in an office setting
Research articleAbstract only
Clinical and audiometric outcomes of palisade cartilage myringoplasty under local anesthetic in an office setting
Nael M. Shoman
In Press, Accepted Manuscript, Available online 29 March 2019
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Abstract
Abstract
Objective
Assess clinical and functional outcomes of a modified palisade cartilage-perichondrium graft myringoplasty under local in an office setting.

Study design
Retrospective case series.

Setting
Tertiary care facility.

Patients
Patients with a tympanic membrane perforation presenting between March 2013 and October 2017. Inclusion criteria included age ≥ 7 years, entire perforation margin visualized through a transcanal view, and the ability to lie supine for up to 45 min. Exclusion criteria included a conductive hearing loss larger than expected, and presence of active infection.

Intervention
In-office modified myringoplasty technique under local anesthesia without sedation.

Main outcome measures
Complete perforation closure rate and audiometric outcomes.

Results
250 patients underwent the procedure, of whom 13 had bilateral sequential procedures (total 263 ears). Of those, 197 were primary and 66 revision. Average age was 46.3 years. Perforation sizes were categorized as small (32), moderate (109), large (78), and subtotal (44). Complete perforation closure was evident in 219 of the 250 cases (88%). Preoperative mean air pure tone average (PTA) was 56.7 dB and mean bone PTA was 27.5 dB (pre-operative ABG 29.2 dB). AC-PTA significantly improved to 35.0 dB (p < 0.0001), and ABG to 9.6 dB (p < 0.0001). Only subtotal perforations showed a statistically significant negative relationship with outcome (p = 0.04).

Conclusion
The modified palisade cartilage-perichondrium graft myringoplasty under local anesthetic is a highly successful procedure well tolerated by adult and pediatric patients with variable perforation sizes. This may have significant potential patient benefits, as well as cost savings to the health care system.

select article Cricoarytenoid joint abscess associated with rheumatoid arthritis
Case reportAbstract only
Cricoarytenoid joint abscess associated with rheumatoid arthritis
Megan J. Foggia, Henry T. Hoffman
In Press, Corrected Proof, Available online 28 March 2019
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Abstract
Abstract
Cricoarytenoid joint arthritis is an uncommon manifestation of rheumatoid arthritis. We encountered a 68-year-old woman with rheumatoid arthritis who presented with odynophagia, dysphagia, and progressive shortness of breath. Examination findings showed diminished mobility of the left vocal cord and right arytenoid swelling associated with an immobile right vocal cord. Computed tomography (CT) imaging identified a ring-enhancing lesion of the right lateral cricoarytenoid joint. Microdirect laryngoscopy with drainage of the cricoarytenoid abscess and tracheotomy were performed. Development of a laterally based cricoarytenoid joint abscess is identified as a complication of chronic rheumatoid arthritis with successful management described.

select article Delayed laryngeal implant infection and laryngocutaneous fistula after medialization laryngoplasty
Case reportAbstract only
Delayed laryngeal implant infection and laryngocutaneous fistula after medialization laryngoplasty
Joseph B. Meleca, Paul C. Bryson
In Press, Corrected Proof, Available online 27 March 2019
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Abstract
Abstract
Background
Medialization laryngoplasty is a common procedure for voice rehabilitation in patients with unilateral vocal fold paralysis. Complications are uncommon and delayed infections involving implants are rare. We report a delayed infectious complication following an animal scratch resulting in a laryngocutaneous fistula.

Methods
Case report.

Results
A 73-year-old female underwent a successful and uneventful medialization laryngoplasty for idiopathic unilateral vocal fold paralysis using a silastic implant. More than one year after surgery, she presented with an anterior neck infection following an animal scratch with CT neck findings of a left strap muscle abscess. After incision and drainage, cultures grew methicillin-resistant Staphylococcus aureus. Despite culture-directed antibiotic therapy, the neck continued to drain persistently. Laryngoscopy with stroboscopy revealed a medialized vocal fold with no obvious granulation tissue and normal mucosal pliability.

The patient underwent neck exploration revealing a laryngocutaneous fistula. Thus, both the fistulous tract and implant were removed. The wound was closed with a strap muscle advancement into the laryngoplasty window. One month after surgery and antibiotics, the patient had no signs of recurrent neck infection, with a well-healing wound and stroboscopic findings of complete glottic closure, symmetric vocal fold oscillation and acceptable phonation with mild supraglottic compression.

Conclusions
Delayed complications of medialization laryngoplasty are rarely reported. This case demonstrates a delayed infection of a laryngeal implant after an animal scratch requiring implant removal, local tissue reconstruction, and culture-directed antibiotic therapy.

select article Conservative thyroidectomy for papillary thyroid microcarcinoma
Research articleAbstract only
Conservative thyroidectomy for papillary thyroid microcarcinoma
Hyun Joo Nahm, Sung Jun Choi, Young Chang Lim
In Press, Corrected Proof, Available online 21 March 2019
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Abstract
Abstract
Objective
According to American Thyroid Association (ATA) guideline, thyroid lobectomy is recommended for the management of papillary thyroid microcarcinomas (PTMC) with a diameter lesser than 1 cm. However, this procedure is associated with a risk of potential complications such as vocal cord palsy. Thus, we considered the applicability of conservative thyroidectomy, involving partial removal of the thyroid cancer lesion, not the entire ipsilateral thyroid lobe.

Methods
A retrospective analysis of all PTMC patients who underwent conservative thyroidectomy at Konkuk University Hospital between August 2008 and February 2014 was performed. Oncologic results of these patients along with the incidence of postoperative complications were evaluated. Seventy-nine patients who underwent conservative thyroidectomy for the treatment of PTMC were enrolled in the present study.

Results
Four of the 79 patients (5.0%) showed recurrence, 2 local (2.5%) and 2 regional (2.5%), respectively. All of these patients consequently underwent surgery alone and were salvaged. Temporary postoperative complications such as vocal cord palsy and hypocalcemia developed in 1 and 1 case, respectively, but completely recovered over time.

Conclusions
Conservative thyroidectomy is an oncologically and functionally safe procedure for surgical treatment of PTMC and can be considered as an alternative to thyroid lobectomy for the surgical management of PTMC.

select article Histopathologic analysis in chronic rhinosinusitis: Impact on quality of life outcomes
Research articleAbstract only
Histopathologic analysis in chronic rhinosinusitis: Impact on quality of life outcomes
Feng Wang, Yang Yang, Qihan Wu, Haihong Chen
In Press, Corrected Proof, Available online 21 March 2019
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Abstract
Abstract
Objective
This study investigates the impact of histopathologic parameters on quality of life outcomes in patients with chronic rhinosinusitis.

Setting
Hospital of Zhejiang University.

Study design
Retrospective analysis of collected data.

Subjects and methods
One hundred and twenty patients with chronic rhinosinusitis (CRS) who underwent endoscopic sinus surgery were recruited. Clinical features, CT evaluation, pre and postoperative SNOT-22 scores and histopathologic findings were collected. Tissue eosinophils and mucosal remodeling were analyzed relative to clinical features and outcomes 12 months postoperatively.

Results
Symptom improvement was seen for the entire population. Eosinophilic CRS had significantly worse preoperative and postoperative SNOT-22 scores than non- eosinophilic CRS. Symptom improvement in eosinophilic CRS after surgery was less than that of non-eosinophilic CRS. There was no significant association between preoperative and postoperative SNOT-22 scores and remodeling markers. However, patients with basement membrane thickening showed less reductions of SNOT-22 score postoperatively.

Conclusions
Presence of mucosal eosinophilia and basal membrane thickening appear to be the main factors adversely affect the symptom control of surgical intervention. Routine histopathology analysis can provide meaningful information for prognostication of surgical outcome.

select article Vestibulotoxicity in a patient without renal failure after inhaled tobramycin
Case reportAbstract only
Vestibulotoxicity in a patient without renal failure after inhaled tobramycin
Adam C. Kaufman, Steven J. Eliades
In Press, Corrected Proof, Available online 19 March 2019
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Abstract
Abstract
Aminoglycoside antibiotics have a long history of use in the control of gram-negative bacterial infections, but their systemic use has been complicated by known ototoxicity and nephrotoxicity. Because of the utility of these medications in patients with frequent pulmonary infections, there has been a move towards the use of inhaled agents, in particular tobramycin, due to a lower rate of systemic complications. Inhaled tobramycin is generally consider to be safe from otologic complications, with only two previous reports of ototoxicity, both in patients who had underlying chronic renal disease. Here we present the first case of a patient developing isolated vestibular toxicity, without associated hearing loss or evidence of renal insufficiency, in a patient receiving inhaled tobramycin. This is an extremely rare complication of an inhaled aminoglycoside and underscores the importance of careful monitoring despite perceived safety.

select article Transdermal lidocaine as treatment for chronic subjective tinnitus: A pilot study
Research articleAbstract only
Transdermal lidocaine as treatment for chronic subjective tinnitus: A pilot study
Daniel C. O'Brien, Aaron D. Robinson, Nancy Wang, Rodney Diaz
In Press, Corrected Proof, Available online 18 March 2019
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Abstract
Abstract
Objective
To assess the efficacy of transdermal lidocaine as a treatment for chronic subjective tinnitus as measured by the Tinnitus Functional Index (TFI).

Study design
Pilot, prospective efficacy trial.

Setting
Tertiary care hospital.

Patients
Men and women, over the age of 18 with chronic subjective tinnitus for >6 months.

Intervention
Daily application of commercially available transdermal lidocaine patch.

Outcome measure
Change in the TFI.

Results
The average pre-treatment TFI score was 56.2. After 1 month the average TFI decreased to 41 (p < 0.05). The scores dropped to 34 and 35 after 2 and 3 months of treatment respectively. Despite improvement in symptoms of tinnitus, most patients did not continue the study after the first month, dropping out due to the size, discomfort, and appearance of the lidocaine patch, failure to follow-up and lack of perceived benefit from treatment.

Conclusions
In this preliminary study, 5% transdermal lidocaine appears to be a potential treatment for chronic subjective tinnitus. The majority of subjects who completed 1 month of treatment had clinically significantly improved tinnitus. These findings are confounded however by the small sample size and significant drop out rate.

select article PEAK PlasmaBlade versus monopolar electrocautery tonsillectomy in adults: A prospective double-blinded randomized controlled trial
Research articleAbstract only
PEAK PlasmaBlade versus monopolar electrocautery tonsillectomy in adults: A prospective double-blinded randomized controlled trial
Alvin Tan Kah Leong, Sanjay Ganhasan, Peter Lu Kuo Sun, Yuen Heng Wai, ... Chan Yiong Huak
In Press, Accepted Manuscript, Available online 18 March 2019
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Abstract
Abstract
Objective
To evaluate the efficacy and compare postoperative pain and recovery following PEAK PlasmaBlade and monopolar electrocautery tonsillectomy in adults.

Study design
Prospective double-blinded randomized controlled trial.

Methods
Fifty-eight patients were recruited and randomized into 2 groups: PEAK PlasmaBlade (n = 29) or monopolar electrocautery (n = 29) tonsillectomy. Postoperative pain, complications, patient satisfaction, number of tablets of analgesia taken and days taken to return to soft diet, normal diet, normal activities and achieve pain-free swallowing were compared and analysed, with the aid of a pain diary given to patients. Statistical analysis was performed with SPSS 13.0 with statistical significance set at P < 0.05.

Results
Patients in the PEAK PlasmaBlade group were able to achieve pain-free swallowing in a shorter time compared to the electrocautery group (13.28 versus 15.76 days, P = 0.035). Patients were also more satisfied with PEAK PlasmaBlade tonsillectomy (P = 0.046). No significant differences in the incidence of postoperative haemorrhage, daily visual analog score for pain, number of tablets of analgesia taken and time taken to return to soft diet, normal diet and activities were seen for both groups.

Conclusions
This study showed that PEAK PlasmaBlade tonsillectomy has a faster recovery period in terms of time taken to achieve pain-free swallowing and may offer advantages when compared to monopolar electrocautery tonsillectomy.

Level of evidence
1b.

select article Mild hypothermia is associated with improved outcomes in patients undergoing microvascular head and neck reconstruction
Research articleAbstract only
Mild hypothermia is associated with improved outcomes in patients undergoing microvascular head and neck reconstruction
Benjamin M. Laitman, Yue Ma, Bryan Hill, Marita Teng, ... Brett A. Miles
In Press, Accepted Manuscript, Available online 16 March 2019
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Abstract
Abstract
Objective
Microvascular free tissue transfer has become the standard for reconstruction for large defects. With long operative times and an increased surface area exposed, transient hypothermia is common, but it is unclear how this impacts surgical outcomes. This study evaluated the impact of core body temperature on free tissue flap outcomes in patients undergoing microvascular reconstruction.

Study design
Retrospective data analysis.

Setting
Mount Sinai Hospital; NYC, NY; 2007–2016.

Subjects and methods
Demographic information, mean/minimum/maximum body temperatures, and the presence of flap complications (venous thrombosis, arterial insufficiency, flap death, wound infection/dehiscence, fistula, chyle leak, hematoma/seroma) of 519 free tissue transfer patients were documented. Binomial logistic regression was used to examine associations between the presence of flap complications and mean temperature. Statistical analysis used SPSS, with p-values ≤0.05 deemed statistically significant.

Results
393 soft-tissue and 125 osteocutaneous flaps were included. 19.8% (n = 103) patients had the presence of ≥1 flap complication, while 80.2% (n = 416) did not. Average temperature for all patients was 36.12 ± 0.84 °C, with minimum at 34.43 ± 0.97 °C and maximum at 37.24 ± 1.23 °C. After controlling for several factors including: tumor stage, radiation, diabetes, BMI, age, sex, and flap type, there was a significant association between flap complications and mean intraoperative temperature (Exp(B) = 1.559, p = 0.004).

Conclusion
Higher intraoperative temperatures were associated with worse outcomes. A mild relative hypothermia may improve flap outcomes in this population. This represents the largest study to date evaluating the impact of intraoperative temperature on free tissue transfer outcomes.

select article Angiolymphoid hyperplasia with eosinophilia of the external ear
Case reportAbstract only
Angiolymphoid hyperplasia with eosinophilia of the external ear
Brian C. Deutsch, Zachary G. Schwam, Vivian Z. Kaul, George B. Wanna
In Press, Corrected Proof, Available online 12 March 2019
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Abstract
Abstract
Herein we present the rare case of angiolymphoid hyperplasia with eosinophilia of the external ear treated by surgical resection and full-thickness skin graft. Current diagnosis and management options are reviewed.

select article Thyroid cancer in patients undergoing surgery for hyperthyroidism
Research articleNo access
Thyroid cancer in patients undergoing surgery for hyperthyroidism
Yogesh More, Aly Bernard Khalil, Huda Mustafa, Manjiri Gupte, ... Shaikh Irfan Basha
In Press, Accepted Manuscript, Available online 11 March 2019
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select article Seed and soil? - Pharyngeal Merkel cell carcinoma after radiotherapy for laryngeal squamous cell carcinoma
Case reportOpen access
Seed and soil? - Pharyngeal Merkel cell carcinoma after radiotherapy for laryngeal squamous cell carcinoma
Monica K. Rossi, D. Anand Rajan Kanagasabapathy, Henry T. Hoffman
In Press, Corrected Proof, Available online 9 March 2019
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Abstract
Abstract
Merkel cell carcinoma (MCC) is a neuroendocrine cutaneous malignancy that may present as metastatic disease without a known primary site but, most commonly originates in the sun-exposed skin of the head, neck, and extremities. We present a 66-year-old male treated with chemo-radiation for T3N2cM0 laryngeal squamous cell carcinoma (SCCa) six years before he was diagnosed with MCC isolated to the radiated laryngopharynx. Mucosal MCC is rare and radiation-induced MCC has been hypothesized to occur in previously radiated tissue but, never before to the laryngopharynx. Implications regarding cancer biology and management is focused with discussion on relevant advances in pathologic assessment and immunotherapy.

select article A systematic review of the nasal septal turbinate: An overlooked surgical target
Review articleAbstract only
A systematic review of the nasal septal turbinate: An overlooked surgical target
William J. Moss, Farhoud Faraji, Aria Jafari, Adam S. DeConde
In Press, Accepted Manuscript, Available online 4 March 2019
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Abstract
Abstract
Objective
The nasal septal turbinate (NST) is a conspicuous structure located in the anterior nasal cavity that impacts the internal nasal valve. Its structure and function is often thought to be poorly characterized, and it is rarely addressed surgically. The authors perform a systematic review in an attempt to synthesize what has been learned of this structure and to evaluate its potential as a treatment target.

Methods
A query of the Medline, Embase, Web of Science and Cochrane databases was undertaken in search of studies evaluating the NST. This qualitative systematic review was performed in accordance with PRISMA guidelines. Study quality and risk of bias were assessed with established criteria.

Results
Of the initial 1069 hits from the four databases, 16 articles were ultimately included in the review, which varied in quality and risk of bias. The included articles consisted predominantly of radiographic and histopathologic studies. Four studies evaluated NST treatment outcomes. The NST represents a fusiform-shaped region of erectile tissue, similar in structure and function to that of the turbinates. Preliminary treatment outcomes suggest the NST represents an important surgical target in nasal airway surgery.

Conclusion
When evaluating nasal obstruction patients, surgeons should assess the NST and consider addressing it surgically.

select article The role of doxycycline in the management of chronic rhinosinusitis with nasal polyps
Research articleAbstract only
The role of doxycycline in the management of chronic rhinosinusitis with nasal polyps
Arjun K. Parasher, Sarah M. Kidwai, Neeraja Konuthula, Erden Goljo, ... Benjamin D. Malkin
In Press, Accepted Manuscript, Available online 4 March 2019
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Abstract
Abstract
Introduction
Many theories on the pathophysiology of chronic rhinosinusitis with nasal polyposis (CRSwNP) exist. The most effective management of CRSwNP has not been elucidated. Doxycycline, which has anti-inflammatory and anti-bacterial properties, has shown durable effects; however, its efficacy in combination with standard therapy has not been examined. We hypothesized that its addition to the standard anti-inflammatory regimen would improve patient outcomes.

Methods
We performed a double-blind, placebo-controlled trial at a tertiary level institution. Patients with moderate or severe CRSwNP were randomized into two groups, each receiving a 20-day course of oral corticosteroids and doxycycline or placebo. The 22-item Sinonasal Outcome Test (SNOT-22), nasal polyp scores, and visual analog scale (VAS) scores were recorded at the initial, 3-, 8- and 12-week visits.

Results
49 patients were enrolled, 24 in the experimental and 25 in the placebo group with 3 moderate disease patients in each group. There were 12 dropouts in the treatment group and 14 in the placebo group. The most common reasons for dropout were severe CRS and asthma exacerbations. There was no significant difference in SNOT-22 scores, nasal polyp scores, and VAS scores between the two arms.

Conclusions
Non-surgical management of patients with CRSwNP remains challenging. Our conclusions are limited given the high dropout rate and thus, limited sample size with inadequate power. This study is important, however, because a high dropout rate of mostly severe disease patients may illustrate that this patient population may not be optimally managed with medical therapy alone.