Δευτέρα, 10 Ιουνίου 2019

Cancer Cell


Genomic and Transcriptomic Profiling of Combined Hepatocellular and Intrahepatic Cholangiocarcinoma Reveals Distinct Molecular Subtypes

Publication date: Available online 23 May 2019

Source: Cancer Cell

Author(s): Ruidong Xue, Lu Chen, Chong Zhang, Masashi Fujita, Ruoyan Li, Shu-Mei Yan, Choon Kiat Ong, Xiwen Liao, Qiang Gao, Shota Sasagawa, Yanmeng Li, Jincheng Wang, Hua Guo, Qi-Tao Huang, Qian Zhong, Jing Tan, Lisha Qi, Wenchen Gong, Zhixian Hong, Meng Li

Summary

We performed genomic and transcriptomic sequencing of 133 combined hepatocellular and intrahepatic cholangiocarcinoma (cHCC-ICC) cases, including separate, combined, and mixed subtypes. Integrative comparison of cHCC-ICC with hepatocellular carcinoma and intrahepatic cholangiocarcinoma revealed that combined and mixed type cHCC-ICCs are distinct subtypes with different clinical and molecular features. Integrating laser microdissection, cancer cell fraction analysis, and single nucleus sequencing, we revealed both mono- and multiclonal origins in the separate type cHCC-ICCs, whereas combined and mixed type cHCC-ICCs were all monoclonal origin. Notably, cHCC-ICCs showed significantly higher expression of Nestin, suggesting Nestin may serve as a biomarker for diagnosing cHCC-ICC. Our results provide important biological and clinical insights into cHCC-ICC.

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Genomic and Transcriptomic Profiling of Combined Hepatocellular and Intr...

We performed genomic and transcriptomic sequencing of 133 combined hepatocellular and intrahepatic cholangiocarc...



Targeting Ferroptosis to Iron Out Cancer

Publication date: Available online 16 May 2019

Source: Cancer Cell

Author(s): Behrouz Hassannia, Peter Vandenabeele, Tom Vanden Berghe

One of the key challenges in cancer research is how to effectively kill cancer cells while leaving the healthy cells intact. Cancer cells often have defects in cell death executioner mechanisms, which is one of the main reasons for therapy resistance. To enable growth, cancer cells exhibit an increased iron demand compared with normal, non-cancer cells. This iron dependency can make cancer cells more vulnerable to iron-catalyzed necrosis, referred to as ferroptosis. The identification of FDA-approved drugs as ferroptosis inducers creates high expectations for the potential of ferroptosis to be a new promising way to kill therapy-resistant cancers.






Combination of Hypoglycemia and Metformin Impairs Tumor Metabolic Plasticity and Growth by Modulating the PP2A-GSK3β-MCL-1 Axis

Publication date: 13 May 2019

Source: Cancer Cell, Volume 35, Issue 5

Author(s): Mohamed Elgendy, Marco Cirò, Amir Hosseini, Jakob Weiszmann, Luca Mazzarella, Elisa Ferrari, Riccardo Cazzoli, Giuseppe Curigliano, Andrea DeCensi, Bernardo Bonanni, Alfredo Budillon, Pier Giuseppe Pelicci, Veerle Janssens, Manfred Ogris, Manuela Baccarini, Luisa Lanfrancone, Wolfram Weckwerth, Marco Foiani, Saverio Minucci

Summary

Tumor cells may adapt to metabolic challenges by alternating between glycolysis and oxidative phosphorylation (OXPHOS). To target this metabolic plasticity, we combined intermittent fasting, a clinically feasible approach to reduce glucose availability, with the OXPHOS inhibitor metformin. In mice exposed to 24-h feeding/fasting cycles, metformin impaired tumor growth only when administered during fasting-induced hypoglycemia. Synergistic anti-neoplastic effects of the metformin/hypoglycemia combination were mediated by glycogen synthase kinase 3β (GSK3β) activation downstream of PP2A, leading to a decline in the pro-survival protein MCL-1, and cell death. Mechanistically, specific activation of the PP2A-GSK3β axis was the sum of metformin-induced inhibition of CIP2A, a PP2A suppressor, and of upregulation of the PP2A regulatory subunit B56δ by low glucose, leading to an active PP2A-B56δ complex with high affinity toward GSK3β.

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Pervasive H3K27 Acetylation Leads to ERV Expression and a Therapeutic Vulnerability in H3K27M Gliomas

Publication date: 13 May 2019

Source: Cancer Cell, Volume 35, Issue 5

Author(s): Brian Krug, Nicolas De Jay, Ashot S. Harutyunyan, Shriya Deshmukh, Dylan M. Marchione, Paul Guilhamon, Kelsey C. Bertrand, Leonie G. Mikael, Melissa K. McConechy, Carol C.L. Chen, Sima Khazaei, Robert F. Koncar, Sameer Agnihotri, Damien Faury, Benjamin Ellezam, Alexander G. Weil, Josie Ursini-Siegel, Daniel D. De Carvalho, Peter B. Dirks, Peter W. Lewis

Summary

High-grade gliomas defined by histone 3 K27M driver mutations exhibit global loss of H3K27 trimethylation and reciprocal gain of H3K27 acetylation, respectively shaping repressive and active chromatin landscapes. We generated tumor-derived isogenic models bearing this mutation and show that it leads to pervasive H3K27ac deposition across the genome. In turn, active enhancers and promoters are not created de novo and instead reflect the epigenomic landscape of the cell of origin. H3K27ac is enriched at repeat elements, resulting in their increased expression, which in turn can be further amplified by DNA demethylation and histone deacetylase inhibitors providing an exquisite therapeutic vulnerability. These agents may therefore modulate anti-tumor immune responses as a therapeutic modality for this untreatable disease.

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Targeting TMEM176B Enhances Antitumor Immunity and Augments the Efficacy of Immune Checkpoint Blockers by Unleashing Inflammasome Activation

Publication date: 13 May 2019

Source: Cancer Cell, Volume 35, Issue 5

Author(s): Mercedes Segovia, Sofia Russo, Mathias Jeldres, Yamil D. Mahmoud, Valentina Perez, Maite Duhalde, Pierre Charnet, Matthieu Rousset, Sabina Victoria, Florencia Veigas, Cédric Louvet, Bernard Vanhove, R. Andrés Floto, Ignacio Anegon, Maria Cristina Cuturi, M. Romina Girotti, Gabriel A. Rabinovich, Marcelo Hill

Summary

Although immune checkpoint blockers have yielded significant clinical benefits in patients with different malignancies, the efficacy of these therapies is still limited. Here, we show that disruption of transmembrane protein 176B (TMEM176B) contributes to CD8+ T cell-mediated tumor growth inhibition by unleashing inflammasome activation. Lack of Tmem176b enhances the antitumor activity of anti-CTLA-4 antibodies through mechanisms involving caspase-1/IL-1β activation. Accordingly, patients responding to checkpoint blockade therapies display an activated inflammasome signature. Finally, we identify BayK8644 as a potent TMEM176B inhibitor that promotes CD8+ T cell-mediated tumor control and reinforces the antitumor activity of both anti-CTLA-4 and anti-PD-1 antibodies. Thus, pharmacologic de-repression of the inflammasome by targeting TMEM176B may enhance the therapeutic efficacy of immune checkpoint blockers.

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BCL2 Amplicon Loss and Transcriptional Remodeling Drives ABT-199 Resistance in B Cell Lymphoma Models

Publication date: 13 May 2019

Source: Cancer Cell, Volume 35, Issue 5

Author(s): Xiaohong Zhao, Yuan Ren, Matthew Lawlor, Bijal D. Shah, Paul M.C. Park, Tint Lwin, Xuefeng Wang, Kenian Liu, Michelle Wang, Jing Gao, Tao Li, Mousheng Xu, Ariosto S. Silva, Kaplan Lee, Tinghu Zhang, John M. Koomen, Huijuan Jiang, Praneeth R. Sudalagunta, Mark B. Meads, Fengdong Cheng

Summary

Drug-tolerant "persister" tumor cells underlie emergence of drug-resistant clones and contribute to relapse and disease progression. Here we report that resistance to the BCL-2 targeting drug ABT-199 in models of mantle cell lymphoma and double-hit lymphoma evolves from outgrowth of persister clones displaying loss of 18q21 amplicons that harbor BCL2. Further, persister status is generated via adaptive super-enhancer remodeling that reprograms transcription and offers opportunities for overcoming ABT-199 resistance. Notably, pharmacoproteomic and pharmacogenomic screens revealed that persisters are vulnerable to inhibition of the transcriptional machinery and especially to inhibition of cyclin-dependent kinase 7 (CDK7), which is essential for the transcriptional reprogramming that drives and sustains ABT-199 resistance. Thus, transcription-targeting agents offer new approaches to disable drug resistance in B-cell lymphomas.

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Ripretinib (DCC-2618) Is a Switch Control Kinase Inhibitor of a Broad Spectrum of Oncogenic and Drug-Resistant KIT and PDGFRA Variants

Publication date: 13 May 2019

Source: Cancer Cell, Volume 35, Issue 5

Author(s): Bryan D. Smith, Michael D. Kaufman, Wei-Ping Lu, Anu Gupta, Cynthia B. Leary, Scott C. Wise, Thomas J. Rutkoski, Yu Mi Ahn, Gada Al-Ani, Stacie L. Bulfer, Timothy M. Caldwell, Lawrence Chun, Carol L. Ensinger, Molly M. Hood, Arin McKinley, William C. Patt, Rodrigo Ruiz-Soto, Ying Su, Hanumaiah Telikepalli, Ajia Town

Summary

Ripretinib (DCC-2618) was designed to inhibit the full spectrum of mutant KIT and PDGFRA kinases found in cancers and myeloproliferative neoplasms, particularly in gastrointestinal stromal tumors (GISTs), in which the heterogeneity of drug-resistant KIT mutations is a major challenge. Ripretinib is a "switch-control" kinase inhibitor that forces the activation loop (or activation "switch") into an inactive conformation. Ripretinib inhibits all tested KIT and PDGFRA mutants, and notably is a type II kinase inhibitor demonstrated to broadly inhibit activation loop mutations in KIT and PDGFRA, previously thought only achievable with type I inhibitors. Ripretinib shows efficacy in preclinical cancer models, and preliminary clinical data provide proof-of-concept that ripretinib inhibits a wide range of KIT mutants in patients with drug-resistant GISTs.






Mitochondrial ClpP-Mediated Proteolysis Induces Selective Cancer Cell Lethality

Publication date: 13 May 2019

Source: Cancer Cell, Volume 35, Issue 5

Author(s): Jo Ishizawa, Sarah F. Zarabi, R. Eric Davis, Ondrej Halgas, Takenobu Nii, Yulia Jitkova, Ran Zhao, Jonathan St-Germain, Lauren E. Heese, Grace Egan, Vivian R. Ruvolo, Samir H. Barghout, Yuki Nishida, Rose Hurren, Wencai Ma, Marcela Gronda, Todd Link, Keith Wong, Mark Mabanglo, Kensuke Kojima

Summary

The mitochondrial caseinolytic protease P (ClpP) plays a central role in mitochondrial protein quality control by degrading misfolded proteins. Using genetic and chemical approaches, we showed that hyperactivation of the protease selectively kills cancer cells, independently of p53 status, by selective degradation of its respiratory chain protein substrates and disrupts mitochondrial structure and function, while it does not affect non-malignant cells. We identified imipridones as potent activators of ClpP. Through biochemical studies and crystallography, we show that imipridones bind ClpP non-covalently and induce proteolysis by diverse structural changes. Imipridones are presently in clinical trials. Our findings suggest a general concept of inducing cancer cell lethality through activation of mitochondrial proteolysis.



The Fire within: Cell-Autonomous Mechanisms in Inflammation-Driven Cancer

Publication date: 13 May 2019

Source: Cancer Cell, Volume 35, Issue 5

Author(s): Jelena Todoric, Michael Karin

Inflammatory cells are important for tumor initiation and promotion, providing cancer cells with cytokines that enhance cell proliferation and survival. Although malignant epithelial cells were traditionally considered to be on the receiving end of these microenvironmental interactions, recent studies show that epithelial cells can undergo inflammatory reprogramming on their own. Such epigenetic switches are often triggered by chronic tissue injury and play important roles in tissue repair. By converting terminally differentiated cells that harbor even a single oncogenic mutation to a less differentiated state with a higher proliferative potential, cell-autonomous inflammation is an important contributor to tumor initiation.






Lung Cancer Evolution: What's Immunity Got to Do with It?

Publication date: 13 May 2019

Source: Cancer Cell, Volume 35, Issue 5

Author(s): Luc G.T. Morris, Timothy A. Chan

During the development and progression of tumors, cancer cells undergo clonal selection due to a variety of genetic and microenvironmental factors. A recent report presents insights demonstrating the interplay between neoantigens and the immune system in untreated non-small-cell lung cancers.








ALEXANDROS SFAKIANAKIS ANAPAFSEOS 5 AGIOS NIKOLAOS CRETE 72100 GREECE +306932607174 +302841026182

Postgraduate Medical Journal

Contemporary management of retinoblastoma in the context of a low-resource country
Dupe S Ademola-Popoola, Enrico Opocher, M Ashwin Reddy

Nigerian Postgraduate Medical Journal 2019 26(2):69-79

Retinoblastoma (RB) is the most common ocular cancer, and it typically presents before the age of 5 years in over 90% of cases. In high resource countries, RB patients tend to survive and retain their sight. This is not the case in low-resource countries because of late presentation and delayed intervention arising mostly from sociocultural and socioeconomic challenges. RB has no gender or racial predilection; the incidence is estimated as 1:16,000–1:18,000 live-births or 11/1 million children under 5 years. Most of the world's RB cases are found in Asia and Africa while most RB treatment centres are in America and Europe. RB is easy to detect by caregivers as a glowing white 'cat eye reflex' at night or when captured on camera. Health workers at primary care level can detect RB in early life if red reflex test and/or squint (Hirschberg) tests are deployed as part of wellness checks done especially during routine immunisation and well-baby clinics in the first 24 months of life. In most cases of RB, biopsies for histological confirmation are not required for diagnosis and treatment decisions to be made. Clinical information, ophthalmic evaluation and imaging modalities are typically used. There have been significant changes in the management of RB using various treatment modalities such as enucleation with orbital implant, use of chemotherapy delivered through intravenous, intravitreal, periocular and intra-arterial routes and targeted treatment with laser, cryotherapy and brachytherapy. Algorithm for management and development of the national RB program within the context of a low-resource country is presented from review of data extracted from Mendeley library, PubMed library, Google Scholar and One Network; full-text articles were mostly retrieved through the American Academy of Ophthalmology.


Pattern of prevalent Hepatitis B virus genotypes in Zaria, Nigeria
Abdurrahman Elfulaty Ahmad, Adamu Girei Bakari, Bolanle Olufunke Priscilla Musa, Shettima Kagu Mustapha, Bello Yusuf Jamoh, Idris Nasir Abdullahi, Mohammed Ibrahim Tahir, Abdulqadri Olarenwaju Olatunji, Sumayya Hamza Maishanu, Ahmed Babangida Suleiman, Afolaranmi Tolulope, Claudia Hawkins, Atiene Solomon Sagay, Ayuba Zoakah, Adebola Tolulope Olayinka

Nigerian Postgraduate Medical Journal 2019 26(2):80-86

Background: Hepatitis B virus (HBV) is hyperendemic in Nigeria. Available literature reveal genotype E as being predominant in West Africa. This study aimed at identifying the current pattern and prevalent genotypes of HBV in Zaria, Nigeria. Materials and Methods: Four millilitre of blood was collected in ethylenediaminetetraacetic acid-container from each of 165 HBV surface antigen-positive participants recruited purposively from the gastroenterology clinic from May to August, 2017. Plasma was separated and frozen at −20°C till analysis. Multiplex-nested polymerase chain reaction using type-specific primers was used to identify the various HBV genotypes. Results: Median (and interquartile range) age of the participants was 31.0 (25.5–39.0) years, with males constituting 107 (64.8%). Majority (83.6%) of the samples analysed were HBV-DNA-positive with 82.6% of the HBV-DNA-positive samples being mixed genotype infections. Irrespective of mode of occurrence, five HBV genotypes were identified with HBV/E (97.1%) being the most predominant, followed by HBV/B (82.6%), HBV/A (24.6%), then HBV/C (17.4%), while HBV/D (0.7%) was the least prevalent. Conclusion: In most (99.1%) of the mixed-infection were a combination of genotype E, the predominant genotype, with other genotypes predominantly genotype B. HBV genotypes E, B, A, C and D are the prevalent genotypes in Zaria, Nigeria, as they occur in single genotype and in mixed-genotypes pattern.


Patient–Doctor relationship in underserved environment: A cross-sectional study of attitudinal orientation, practice inclination, barriers and benefits among medical practitioners in Abia State, Nigeria
Gabriel Uche Pascal Iloh, Obianma Nneka Onya, Uche Ngozi Nwamoh, Prince Ezenwa Ndubueze Onyemachi, Miracle Erinma Chukwuonye, Ezinne Uchamma Godswill-Uko

Nigerian Postgraduate Medical Journal 2019 26(2):87-93

Background: Healthcare has become complex requiring balance of ever-increasing demands on physicians against humanness of medicine. As the impetus for the delivery of patient-centred care grows, there is need to study the attitude and practice orientations of medical practitioners to patient–doctor relationship (PDR). The study was aimed at describing the attitude, practice, barriers and benefits of PDR among medical practitioners in Abia State. Participants and Methods: A descriptive cross-sectional study was carried out on 210 medical practitioners in Abia State who were consecutively recruited for the study. Data were collected using self-administered questionnaire that elicited information on attitude, practice, barriers and benefits of PDR. Attitude was assessed with the 18-item Patient-Practitioner Orientation Scale (PPOS) with subscales of caring and sharing. Results: The age of the participants ranged from 26 to 77 years with the mean of 36 ± 8.4 years. There were 173 (82.4%) male. The caring attitude score (mean = 3.57 ± 0.80) was higher than sharing (mean = 3.42 ± 0.65) (P = 0.036). Practice was predominantly doctor-centred (86.7%) than patient-centred (64.3%, P < 0.0001). The most common barrier to PDR was patient–doctor communication, while the most common benefit of PDR was improvement in patient satisfaction. Medical practitioners with duration of practice <10 years had significantly higher mean scores in attitudinal subscale of caring when compared with those with duration of practice ≥10 years (P < 0.0001). The study participants with duration of practice ≥10 years had significantly higher adequate practice (75.0%) of patient-centred care when compared with their counterparts with duration of practice <10 years (47.6%) (P = 0.00005). Conclusion: The attitude to caring did not translate to comparative disposition to sharing. The practice was more doctor-centred than patient-centred. The most common barrier and benefit of PDR were communication drawbacks and improvement in patient satisfaction, respectively. Duration of practice was associated with caring attitude and practice of patient-centred care, respectively.


Mycology-related dissertations from the faculty of pathology, national postgraduate medical college of Nigeria (1980-2017): output and scientific communication
Iriagbonse Iyabo Osaigbovo

Nigerian Postgraduate Medical Journal 2019 26(2):94-99

Background: The actual burden of fungal infections in Nigeria is uncertain due to the dearth of research in medical mycology. Evidence generated from dissertations is often overlooked, becoming moribund if not appropriately disseminated. The objectives of this study were to assess dissertations submitted to the Faculty of Pathology, National Postgraduate Medical College of Nigeria, for medical mycology-centred research and ascertain their dissemination by scientific communication. Materials and Methods: Dissertations accepted by the faculty of pathology from 1980 to 2017 were analysed and categorised into respective subdisciplines. Medical microbiology dissertations were further categorised into bacteriology, parasitology, virology and mycology. The proportion of titles under each subcategory was determined. A literature search was conducted to determine if mycology-related dissertations were published in peer-reviewed journals. Results: Six hundred dissertations were indexed under the faculty of pathology. There were 95 (15.8%) medical microbiology dissertations. The distribution of subject matter was bacteriology 62 (65.3%), parasitology 13 (13.7%), virology 15 (15.8%) and mycology 5 (5.3%). Two dissertations in anatomic pathology dealt with fungi. Mycology-related dissertations accounted for 0.8% of all dissertations submitted. Research focused on Candida, Histoplasma capsulatum var. duboisii, dermatophytes and others. At least 57.1% of mycology-related dissertations were disseminated by means of publication in peer-reviewed journals and/or abstract at scientific conferences. Conclusion: Mycology is a neglected research domain amongst post-graduates in the faculty. Scientific communication of research findings was above average.


Surgical outcome of cutting diathermy versus scalpel skin incisions in uncomplicated appendectomy: A comparative study
Chukwuma Eze Okereke, Aba I Katung, Abdulrashid Kayode Adesunkanmi, Olusegun Isaac Alatise

Nigerian Postgraduate Medical Journal 2019 26(2):100-105

Background: It is traditionally believed that diathermy skin incisions produce a comparatively poorer surgical outcome despite recent evidences to the contrary. This study set out to compare diathermy and scalpel skin incisions with respect to immediate post-operative pain, surgical-site infection and surgical scar cosmesis. Methodology: This was a randomised, double-blinded study comparing cutting diathermy and scalpel skin incisions in patients undergoing open appendectomies for uncomplicated appendicitis. The post-operative pain was rated with the Visual Analogue Pain Scale 6, 12 and 24 h postoperatively, and 30 day wound infection was rated with the Southampton score. Scar cosmesis was assessed at 3 months, by a plastic surgery trainee, using the Patient and Observer Scar Assessment Scale (POSAS). The patients also self-evaluated their scars using POSAS. Results: A total of 64 patients were randomised to cutting diathermy (32) and scalpel (32) skin incision groups. The mean pain score was higher in the diathermy incised wounds, but this was not statistically significant (P = 0.094). There was one wound infection recorded in the scalpel incision group and none in the diathermy incision group (P = 0.524). At 3 months post-surgery, there was no difference between the diathermy and scalpel incised wounds in mean (±SD) objective POSAS scores (15.64 [±5.98] vs. 17.79 [±6.37], P = 0.228) or subjective POSAS scores (22.44 [±13.13] vs. 22.21 [±13.17], P = 0.951), respectively. The mean scar satisfaction score, as assessed by the patients, was better for the diathermy incised wounds, but this was not statistically significant (P = 0.406). Conclusion: In patients undergoing open appendectomy for uncomplicated acute appendicitis, skin incision with a cutting diathermy is not inferior to the scalpel in surgical outcome, with respect to post-operative pain, wound infection and surgical scar cosmesis.


Uterine and umbilical artery doppler in women with pre-eclampsia and their pregnancy outcomes
Ademola Joseph Adekanmi, Adebola Roberts, Janet Adetinuke Akinmoladun, Abiodun Oludotun Adeyinka

Nigerian Postgraduate Medical Journal 2019 26(2):106-112

Background: Pre-eclampsia (PE) is an important public health menace in both developed and developing countries with high maternal and perinatal morbidity and mortality globally. A major goal towards improving antenatal management of PE is to develop accurate prediction models that identify women at high risk of this disease for appropriate interventions. Methodology: In a longitudinal cohort study, high-risk singleton pregnant women enroled between April 2015 and February 2016 had uterine and umbilical artery Doppler sonography at 22–24 weeks and 32–34 weeks gestation and had their delivery outcomes documented by the obstetrician and gynaecologist. The peak systolic velocity (PSV), end-diastolic velocity (EDV), Resistivity Index (RI), Pulsatility Index (PI) and the systolic-diastolic ratio (S/D) were recorded. Results: Among the ninety-eight high-risk pregnant women, 61 (62.2%) developed PE and 32 (32.8%) did not have PE. In the PE cases, 15 (24.5%) were mild and 46 (74.5%) were severe PE. The uterine artery PI was significantly associated with PE. A unit increase in uterine PI in high-risk pregnancies, increases the odd of PE by 37.37 times (95% confidence interval; odds ratio = 6.09, 241.9; P < 0.001). The combination of the uterine and umbilical PSV predicted 80.3% of severe PE. All three spontaneous abortions were in women who developed PE, more caesarean section (48.4%) and 69.2% of 45 pre-term deliveries occurred in women with severe PE. Conclusion: The findings from this study show significantly lower uterine and umbilical arteries PSV and EDV but higher RI, PI and S/D in cases that developed PE. The uterine artery PI is the best predictor of PE, whereas the combinations of uterine and umbilical arteries PSV best predict severity of PE among high-risk pregnant Nigeria women.


Factors influencing the outcome of spontaneous intracerebral haematoma in a Neurosurgical Hospital in South-East Nigeria
Chika Anele Ndubuisi, Mark Oseghale Okhueleigbe, Tobechi Nwankwo Mbadugha, Kelechi Onyenekeya Ndukuba, Moses Osaodion Inojie, Samuel Chukwunoyerem Ohaegbulam

Nigerian Postgraduate Medical Journal 2019 26(2):113-117

Introduction: Spontaneous intracerebral haemorrhage (SICH) is a major cause of stroke worldwide. SICH management is still challenging, especially in developing countries. This study highlights certain factors affecting outcome of SICH managed in a Nigerian Neurosurgical centre, on a background of the modernisation of the patient care facilities. Materials and Methods: Retrospective analysis of patients managed for SICH at Memfys Hospital for Neurosurgery and Neurology in Enugu from years 2009–2016. All patients had computed tomography or magnetic resonance imaging for diagnosis. Treatment included medical, surgical and intensive care unit (ICU) care. Patients with aneurysmal subarachnoid haemorrhage and trauma were excluded. Factors analysed include age, admission Glasgow Coma Score (GCS), haematoma location, complications encountered during admission, duration of hospital stay and 6-month Glasgow Outcome Score (GOS). Results: There were 66 cases, age range of 21–85 years (mean 57 years). A total of 30 (45.5%) patients were admitted with GCS ≤ 8/15; 63.3% of these died within 6 months. The proportion of mortalities was 63.6% (>70 years) and 35.6% (41–70 years). Most commonly associated complication was chest infection 27 (40.9%), with 56.6% mortality. Common haematoma locations were basal ganglia (43.9%) and lobar haemorrhage (40.9%) with a similar effect on outcome (P = 0.098). Outcomes were GOS 1: (43.9%), GOS 5: (30.3%) and GOS 4: (13.6%). Among 42 (63.3%) admitted to ICU, 25 (59.5%) died, while 11 (26.2%) achieved GOS of ≥ 4 at 6 months. Those discharged between days 11 and 20 had 26.7% mortality while 53.3% were independent. Conclusion: Good admission GCS, absence of chest infections, younger age group are predictors of good outcome following SICH. Anatomical location of haemorrhage alone does not have a significant impact on 6 months' mortality.


The effect of the coinheritance of Glucose-6-phosphate dehydrogenase deficiency on the severity of sickle cell disease
Foluke Atinuke Fasola, Florence Olamide Fowodu, Wuraola Adebola Shokunbi, Taiwo Rachel Kotila

Nigerian Postgraduate Medical Journal 2019 26(2):118-122

Background: Sickle cell disease (SCD) and glucose-6-phosphate dehydrogenase (G6PD) deficiency are inherited disorders associated with chronic haemolysis. Therefore, coinheritance of both disorders could worsen haemolysis in the former and compound a haemolytic crisis. This study compared clinical and laboratory features of deficient and non-deficient SCD patients and the G6PD activities of SCD patients and apparently healthy controls. Materials and Methods: This is a case–control study of 175 SCD patients and 166 non-SCD controls. G6PD assay was carried out on haemolysate from washed red cells. The G6PD activity was measured by spectrophotometry. Results: The mean age of patients and controls was 27.3 ± 9.4 and 35.9 ± 9.7 years, respectively, with 75 (46.2%) and 87 (52.4%) being males, respectively. G6PD activity was similar in cases and controls (6.7 ± 3.3 vs. 6.9 ± 3.0 IU/gHb), respectively (P = 0.6). The prevalence of G6PD deficiency was higher in patients than controls (28.6% vs. 22.3%, P = 0.18), and SCD patients were twice more likely to have enzyme activities below 3.0 IU/gHb. No significant difference was observed in the clinical parameters between deficient and non-deficient patients. Deficient patients were more likely to have lower haematocrit (22.8 ± 3.9% vs. 24.5 ± 5%, P = 0.04) and non-significantly higher bilirubin and reticulocyte counts. Furthermore, in patients, severe deficiency resulted in higher bilirubin than in those with mild deficiency (60.5 vs. 21.7 IU/L, P < 0.001). G6PD activity correlated positively with haematocrit (r = 0.91, P = 0.01) and mean corpuscular haemoglobin concentration (r = 0.17, P = 0.02). Conclusions: Coinheritance of both disorders could worsen haemolysis in SCD patients, and care should, therefore, be taken in the choice of drugs in deficient SCD patients.


Distal symmetrical polyneuropathy and cardiovascular autonomic neuropathy among diabetic patients in Ilorin: Prevalence and predictors
Abiodun Bello, Sikiru Biliaminu, Kolawole Wahab, Emmanuel Sanya

Nigerian Postgraduate Medical Journal 2019 26(2):123-128

Background: Peripheral neuropathy contributes to morbidity and mortality among diabetic patients. Objectives: We aimed to determine the prevalence of distal symmetrical polyneuropathy (DSP) and cardiovascular autonomic neuropathy (CAN) and their predictors among diabetic patients in Ilorin, North-central Nigeria. Materials and Methods: This was a cross-sectional study in which 175 consenting diabetic patients were recruited consecutively. We assessed DSP using the Michigan Neuropathy Screening Instrument (MNSI), and it was defined by MNSI symptom score ≥7 or physical examination score ≥2. CAN was assessed using five tests of cardiovascular autonomic function, and abnormalities in ≥2 tests defined CAN. Logistic regression analysis was used to identify the predictors of DSP and CAN. Results: The prevalence of DSP and CAN was 41.7% and 26.9%, respectively, while 19.4% had both. Hypertension (odds ratio [OR]: 2.401; 95% confidence interval [CI]: 1.169–4.930, P = 0.017) and poor glycaemic control (OR: 2.957; 95% CI: 1.488–5.878, P = 0.002) independently predicted DSP. Hypertension (OR: 2.215; 95% CI: 1.023–4.414, P = 0.043) and serum creatinine (OR: 1.035; 95% CI: 1.014–1.056, P ≤ 0.001) were independent predictors of CAN. Conclusion: DSP and CAN are common among diabetic patients, and thus efforts should be made to prevent their occurrence by intensifying blood pressure and glucose control while regularly monitoring renal function.


Medication adherence and patient satisfaction among hypertensive patients attending outpatient clinic in Lagos University Teaching Hospital, Nigeria
Esther O Oluwole, Olatokunbo Osibogun, Oluseyi Adegoke, Adebola A Adejimi, Ajoke M Adewole, Akin Osibogun

Nigerian Postgraduate Medical Journal 2019 26(2):129-137

Background of the Study: Low adherence is an essential element responsible for impaired effectiveness and efficiency in the pharmacological treatment of hypertension. Patient satisfaction is an important measure of healthcare quality and is a crucial determinant of patients' perspective on behavioural intention. Aims: This study determined the association between medication adherence and treatment satisfaction among hypertensive patients attending hypertension outpatient clinic in Lagos University Teaching Hospital (LUTH), Nigeria. Materials and Methods: Setting – The study setting was LUTH; a descriptive cross-sectional study was conducted. Study design – Hypertensive patients were consecutively recruited from the outpatient clinic. Medication adherence was assessed using the 8-item Morisky Medication Adherence Scale and treatment satisfaction was assessed using the 14-item Treatment Satisfaction Questionnaire for Medication. Statistical Analysis: Univariate and linear regression analyses were conducted using STATA software version 14.1 (StataCorp LP, College Station, TX, USA). Statistical significance was set at P ≤ 0.05. Results: A total of 500 respondents with a mean age of 58.9 ± 13.3 years participated in the study. Overall, majority (446 [89.2%]) of the respondents in this study had 'moderate' adherence to antihypertensive medication. However, only five (1.0%) respondents reported 'high' adherence. Mean scores were highest in the moderate adherence category for all satisfaction domains and overall domain. Treatment satisfaction was associated with medication adherence, and was statistically significant (P = 0.000). Conclusion: One in every hundred patients had high adherence to hypertensive medication in this study, and there was a positive association between treatment satisfaction and medication adherence. Continuous patient-specific and tailored adherence education and counselling for hypertensive patients is recommended.




ALEXANDROS SFAKIANAKIS ANAPAFSEOS 5 AGIOS NIKOLAOS CRETE 72100 GREECE +306932607174 +302841026182

Otolaryngology


Outcomes in surgically resectable oropharynx cancer treated with transoral robotic surgery versus definitive chemoradiation,Head and neck involvement with histoplasmosis,Treatment for lymphedema following head and neck cancer therapy,Morbidity after tonsillectomy in children with autism spectrum disorders,What is the evidence for cannabis use in otolaryngology?,New wand coblation turbinator vs coblation radiofrequency,Post-operative treatment patterns after functional endoscopic sinus surgery,Comparison of the effects of the temperature of intratympanic dexamethasone injections on vertigo,Craniofacial injuries related to motorized scooter use,Buteyko breathing technique for obstructive Eustachian tube dysfunction.

Outcomes in surgically resectable oropharynx cancer treated with transoral robotic surgery versus definitive chemoradiation

Publication date: Available online 4 June 2019

Source: American Journal of Otolaryngology

Author(s): Bhaswanth Dhanireddy, Nicolas P. Burnett, Sreeja Sanampudi, Charles E. Wooten, Jon Slezak, Brent Shelton, Lauren Shelton, Andrew Shearer, Susanne Arnold, Mahesh Kudrimoti, Thomas J. Gal

Abstract
Purpose

Optimal treatment strategies for the management of oropharyngeal squamous cell carcinoma (OPSCC) remain unclear. The objective of this study is to examine the role of transoral robotic surgery (TORS) on functional and treatment outcomes.

Materials and methods

A retrospective review of patients with OPSCC (tonsil/base of tongue) who underwent TORS with neck dissection± adjuvant therapy between January 2011 to December 2016 were compared to a stage matched cohort of patients treated with primary chemoradiation. Demographic, treatment, and outcome data were collected.

Results

54 patients received primary chemoradiation and 65 patients (surgical group) received TORS ± adjuvant therapy for clinically staged disease meeting study criteria. 25% (N = 17) were treated with surgery alone. The remainder of the surgical group received postoperative radiation (N = 48), half of which received adjuvant chemotherapy (N = 24) in addition to radiation. 63% (N = 41) of the patients did not have risk factors for chemotherapy. No differences in overall or disease free survival were observed with TORS compared to chemoradiation (p = 0.9), although Charlson Comorbidity Index (CCI) was higher in the surgical group (p = 0.01). The strongest predictor of prolonged gastrostomy tube use was not treatment, but rather co-morbidity (p = 0.03), with no significant differences beyond 12 months.

Conclusion

Although no significant survival differences were observed across treatment groups, this was maintained despite increased comorbidity index in the surgical patients. Given the ability to de-escalate and/or eliminate adjuvant therapy, particularly in a less healthy population, TORS would appear to be the viable treatment option it has become.



Outcomes in surgically resectable oropharynx cancer treated with transor...

Optimal treatment strategies for the management of oropharyngeal squamous cell carcinoma (OPSCC) remain unclear....



Head and neck involvement with histoplasmosis; the great masquerader

Publication date: Available online 3 June 2019

Source: American Journal of Otolaryngology

Author(s): A. Singh, M. Gauri, P. Gautam, D. Gautam, M. Haq, A.C. Handa, K.K. Handa

Abstract
Introduction

Head and neck involvement with histoplasmosis usually occurs as a part of the disseminated illness. There are no pathognomic features of the upper aerodigestive tract involvement and the lesion may mimic a host of other conditions. The current report presents our experience with head and neck histoplasmosis in a non-endemic tertiary care center.

Materials and methods

We present a case of disseminated histoplasmosis with oral symptoms and lesions as the chief complaints. A 10 years' retrospective institutional database search was undertaken to identify the patients with histoplasmosis affecting head and neck region treated at our institution. The demographic and treatment details of the patients were reviewed.

Results

In addition to the index patient, four more patients (two with gingivobuccal and one each with nasal and laryngeal histoplasmosis) were found. Out of the five patients, only one patient was found to have underlying immunosuppression. All of the patients were diagnosed with biopsy showing typical appearance of the intracellular organism. All the patients were satisfactorily treated with systemic antifungal treatment.

Conclusion

Upper aerodigestive tract involvement with histoplasmosis can present as an intriguing clinical puzzle. A high index of suspicion is needed and biopsy is the gold standard for the diagnosis. Intravenous Liposomal Amphotericin B and oral Itraconazole are standard treatment agents of choice and are highly efficacious in achieving cure.






Treatment for lymphedema following head and neck cancer therapy: A systematic review

Publication date: Available online 30 May 2019

Source: American Journal of Otolaryngology

Author(s): Albina Tyker, Joel Franco, Sean T. Massa, Shaun C. Desai, Scott G. Walen

Abstract
Objective

To perform the first systematic review evaluating all established treatment modalities of head and neck lymphedema resulting from head and neck cancer therapy. Since craniofacial lymphedema treatment represents unique challenges not addressed by extremity lymphedema therapies, a systematic review and evaluation of treatment modalities specific to this area is needed to guide clinical management and further research.

Data sources

Four electronic databases were searches from inception to September 2018. These included Scopus (Embase), PubMed (Medline), Clinicaltrials.gov, and Cochrane Databases.

Review methods

A search string was developed, and all databases queried for keywords on three subjects: head and neck cancer, lymphedema, and therapy. Results were uploaded to an EndNote database where relevant items were identified by hand-searching all titles and abstracts. Subsequently results were combined, duplicates removed, and full papers screened according to eligibility criteria.

Results

Of a total 492 search results, twenty-six items met eligibility criteria for this review. These included fourteen cohort studies, seven case reports, two randomized controlled trials, two systematic reviews, and one narrative review totaling 1018 study subjects. The manual lymph drainage group had the largest number of studies and participants, with fewer studies investigating selenium, liposuction, and lymphaticovenular anastomosis.

Conclusion

Evidence for the efficacy of all types of lymphedema therapy is limited by paucity of large randomized controlled trials. While manual lymph drainage is best studied, liposuction and surgical treatments have also been effective in a small number of patients.






Morbidity after tonsillectomy in children with autism spectrum disorders

Publication date: Available online 30 May 2019

Source: American Journal of Otolaryngology

Author(s): Jillian N. Printz, Katelin A. Mirkin, Christopher S. Hollenbeak, Michele M. Carr

Abstract
Objectives

As the incidence of autism spectrum disorder (ASD) increases, otolaryngologists are more likely to encounter patients from this population during tonsillectomy. The purpose of this study was to examine whether outcomes differ between pediatric patients with and without ASD in a national cohort of children undergoing tonsillectomy. Understanding these differences may be used to inform future approaches to improve clinical outcomes and healthcare costs.

Methods

Data for this study were obtained from the Kids Inpatient Database (KID) of the Healthcare Cost Utilization Project. We studied pediatric patients who underwent tonsillectomy during 2003, 2006, 2009, and 2012. Tonsillectomy was identified using ICD-9-CM diagnosis codes 28.2 (tonsillectomy without adenoidectomy) and 28.3 (tonsillectomy with adenoidectomy). ASD was identified using ICD-9-CM diagnosis code 299 (autism). Outcomes including complications, length of hospital stay, and total hospitalization costs. Analyses were performed using multivariable models. Propensity score matching was used to control for covariate imbalance between patients with and without ASD.

Results

In our sample of 27,040 patients, 322 (1.2%) had a diagnosis of ASD. After controlling for potential confounders, multivariable modeling suggested patients with ASD had a shorter LOS of 0.50 days (p < 0.0001), were less likely to experience complications (odds ratio 0.57, p = 0.001), and had lower associated costs of $1308 less (p < 0.0001). Propensity score matching confirmed the findings of the multivariable modeling.

Conclusion

Although ASD alone does not appear to confer additional costs or morbidity, differences between children with and without ASD suggest the need for providers to address patients with ASD uniquely.






What is the evidence for cannabis use in otolaryngology?: A narrative review

Publication date: Available online 30 May 2019

Source: American Journal of Otolaryngology

Author(s): William L. Valentino, Brian J. McKinnon

Abstract
Objectives

Review of the English literature for all studies involving cannabis and Otolaryngology.

Methods

PubMed was searched using a combination of the terms cannabis, marijuana, otolaryngology, hearing, tinnitus, vestibular, rhinology, sinusitis, laryngology, voice, airway, head and neck, head and neck cancer, facial trauma, spasm, pediatric otolaryngology, sleep medicine, obstructive sleep apnea, and other variations. Literature included in the review provided substantive research on cannabis in Otolaryngology.

Results

Seventy-nine unique publications were found in the literature. The majority were published in the last decade and pertain to the subspecialty of Head and Neck; specifically, its association with incident cancers. A small number of studies exist that suggest cannabis may be a useful therapy for Otolaryngological patients suffering from blepharospasm, the effects of radiation, and the psychological sequelae of receiving a cancer diagnosis.

Conclusion

Further research is required to determine the potential therapeutic roles and adverse effects of cannabis on conditions related to Otolaryngology. This study serves the Otolaryngological researcher with the most current, comprehensive literature review for the exploration into possible projects to undertake.






New wand coblation turbinator vs coblation radiofrequency

Publication date: Available online 21 May 2019

Source: American Journal of Otolaryngology

Author(s): Yuce Islamoglu, Gulın Gokcen Kesici, Kadır Sınası Bulut, Ebubekır Alper Ozer, Yagmur Canan Teleke, Mehmet Ali Babademez

Abstract
Introduction

İnferior turbinate hypertrophy is a common reason of nasal obstruction. One of the most preferred surgical metod is radiofrequency tecnique. Coblation submucosal reduction turbinator (SCT);new surgical device; started to use recently. Since the method is new, very few study has been done yet. We compare coblation radiofrequency (CR) with SCT.

Material and methods

Patients with only inferior turbinate hypertrophy but no other diseases included in study. Paranasal CT was made to all patient to rule out turbinate bone hypertrophy. Group 1 32 patient; performed CR. Group 2 25 patients performed SCT. To all patients preoperative and 3 weeks later post operative mucosiliary activity test was performed. Nasal flow was measured with nasal flow meter preoperatively and 3 weeks post operatively. VAS and NOSE was measured. Results compared between two groups. SCT performed under general; CR performed under local anesthesia.

Results

There was significant nasal flow changes in CR group. (p < 0.001) There was no difference in pre-and-post operatively saccharin test results in CR group. (p = 0.385) There was slightly nasal flow gain in SCT group but this was not statistically significant. (p < 0.192) Also there was no statistically significant changes in pre-and-post operatively saccharin test results in SCT group. (p = 0.167) There was no difference between two groups in terms of post operative nasal flow values and mucociliary activity. (respectively p = 0.562, p = 0.355). (Table 2). Both two tecnique has significant increase in VAS and NOSE scores. (p < 0.001).

Conclusions

According to our study two tecnique is suitable and safe for nasal mucociliary activity. Tecniques has positive effect on nasal flow, VAS and NOSE scores.






Post-operative treatment patterns after functional endoscopic sinus surgery: A survey of the American Rhinologic Society

Publication date: Available online 21 May 2019

Source: American Journal of Otolaryngology

Author(s): Samuel N. Helman, Benjamin M. Laitman, Mingyang Gray, Brian Deutsch, Michael Setzen, Satish Govindaraj, Alfred M.C. Iloreta, Anthony Del Signore






Comparison of the effects of the temperature of intratympanic dexamethasone injections on vertigo

Publication date: Available online 20 May 2019

Source: American Journal of Otolaryngology

Author(s): Nurdoğan Ata, Kayhan Öztürk, Bahri Gezgin

Abstract
Objective

This study aimed to compare if vertigo improved in patients when the dexamethasone used in the intratympanic (IT) injection was applied at body temperature or at room temperature.

Methods

The study included 54 patients who had undergone intratympanic treatment due to sudden hearing loss and tinnitus. The IT injection was administered to all patients, 2 times with 1-day intervals. Two different IT injection techniques were used for each patient: injecting dexamethasone at room temperature and injecting it at body temperature. Patients were asked to report the vertigo they felt immediately, and at 15 min after the injection using the visual analogue scale (VAS) and the four-point categorical rating scale (CRS-4).

Results

The level of vertigo immediately after injection was lower when the dexamethasone was injected at body temperature rather that at room temperature for both the VAS and CRS-4 (p < 0.05). However, no statistical differences in the VAS and CRS-4 self-report values between the two methods were found 15 min after the injection (p > 0.05).

Conclusion

Vertigo due to IT decreases within minutes. When the IT drugs are administered at body temperature, temporal vertigo due to injection is lower than when they are administered at room temperature.






Craniofacial injuries related to motorized scooter use: A rising epidemic

Publication date: Available online 20 May 2019

Source: American Journal of Otolaryngology

Author(s): Amishav Y. Bresler, Curtis Hanba, Peter Svider, Michael A. Carron, Wayne D. Hsueh, Boris Paskhover

Abstract
Objectives

Over the last decade, there has been increased interest in utilizing motorized scooters for transportation. The limited regulation of this modernized vehicle raises numerous safety concerns. This analysis examines a national database to describe the yearly incidence of craniofacial injuries and patterns of injury related to motorized scooter use.

Methods

The Consumer Product Safety Commission's National Electronic Injury Surveillance system was queried for craniofacial injuries associated with motorized scooter use. Patient demographics, injury type, anatomic location, injury pattern, and helmet status were extracted for analysis.

Results

From 2008 to 2017, there were 990 recorded events for craniofacial injuries secondary to motorized scooters extrapolating to an estimated 32,001 emergency department (ED) visits. The annual incidence was noted to triple over that 10-year period. The majority of patients were male (62.1%) and the common age groups at presentation were young children 6–12 years old (33.3%), adolescents 13–18 years old (16.1%) and young adults 19–40 years old (18.0%). The most common injury pattern was a closed head injury (36.1%) followed by lacerations (20.5%). Facial fractures were only present in 5.2% of cases. In cases in which helmet use was recorded, 66% of the patients were not helmeted.

Conclusion

The incidence of motorized scooter related craniofacial trauma is rising, resulting in thousands of ED visits annually. Many patients are experiencing morbid traumatic injuries and may not be wearing appropriate protective equipment. This study highlights the importance of public awareness and policy to improve safety and primarily prevent craniofacial trauma.






Buteyko breathing technique for obstructive Eustachian tube dysfunction: Preliminary results from a randomized controlled trial

Publication date: Available online 17 May 2019

Source: American Journal of Otolaryngology

Author(s): Haicang Zeng, Xiaoxin Chen, Yaodong Xu, Yiqing Zheng, Hao Xiong

Abstract
Purpose

To assess the effectiveness of Buteyko breathing technique in patients with obstructive Eustachian tube dysfunction (ETD).

Materials and methods

Fifty-one patients (77 ears) aged between 21 and 62 years were randomized to Buteyko breathing in conjunction with medical management (nasal steroid) group or medical management alone group. The Eustachian Tube Dysfunction Questionnaire (ETDQ-7) symptom scores, tympanogram, positive Valsalva maneuver were evaluated at baseline, 6-week and 12-week follow-up.

Results

Normalization of ETDQ-7 symptom scores at 6-week follow-up was observed in 30.0% (12/40) of the Buteyko breathing group versus 16.2% (6/37) of the controls (P > 0.05). At 12-week follow-up, the ratio rose to 50.0% (20/40) in the Buteyko breathing group and 24.3% (9/37) in the controls (P < 0.05). Tympanogram normalization at 12-week follow-up was observed in 53.6% (15/28) of the Buteyko breathing group versus 26.9% (7/26) of the controls (P < 0.05). The Buteyko breathing group showed slight improvement in positive Valsalva maneuver at 6- and 12-week follow-up (P > 0.05).

Conclusions

Our study shows that Buteyko breathing technique might be an effective adjunctive intervention in treatment of obstructive ETD, especially for those patients who are refractory to medical treatment and cannot afford Eustachian tube balloon dilation surgery.







ALEXANDROS SFAKIANAKIS ANAPAFSEOS 5 AGIOS NIKOLAOS CRETE 72100 GREECE +306932607174 +302841026182

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