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! # Ola via Alexandros G.Sfakianakis on Inoreader

Πέμπτη, 8 Ιουνίου 2017

Randomized Controlled Trial of Adding Telephone Follow-Up to an Occupational Rehabilitation Program to Increase Work Participation

Abstract

Purpose Transfer from on-site rehabilitation to the participant's daily environment is considered a weak link in the rehabilitation chain. The main objective of this study is to see if adding boosted telephone follow-up directly after completing an occupational rehabilitation program effects work participation. Methods A randomized controlled study included participants with chronic pain, chronic fatigue or common mental disorders on long-term sick leave. After completing 3½ weeks of acceptance and commitment therapy based occupational rehabilitation, participants were randomized to boosted follow-up or a control group before returning to their daily environment. The intervention was delivered over 6 months by on-site RTW coordinators mainly via telephone. Primary outcome was RTW categorized as participation in competitive work ≥1 day per week on average over 8 weeks. Results There were 213 participants of mean age 42 years old. Main diagnoses of sick leave certification were mental disorders (38%) and musculoskeletal disorders (30%). One year after discharge the intervention group had 87% increased odds (OR 1.87, 95% confidence interval 1.06–3.31, p = 0.031), of (re)entry to competitive work ≥1 day per week compared with the controls, with similar positive results for sensitivity analysis of participation half time (≥2.5 days per week). The cost of boosted follow-up was 390.5 EUR per participant. Conclusion Participants receiving boosted RTW follow-up had higher (re)entry to competitive work ≥1 day per week at 1 year when compared to the control group. Adding low-cost boosted follow-up by telephone after completing an occupational rehabilitation program augmented the effect on return-to-work.



http://ift.tt/2rRWVpm

Role of Inflammatory Diseases in Hypertension

Abstract

Chronic inflammatory diseases (CID) are characterized by an increased risk of cardiovascular (CV) morbidity and mortality. Several mechanisms, including early acceleration of subclinical atherosclerotic damage, inflammatory markers and immune system deregulation factors, have been demonstrated to strictly interplay for development and progression of atherosclerosis. Moreover, traditional CV risk factors are likely to explain at least some of the excess of CV risk in these patients. Among traditional CV risk factors, compelling evidence suggests a higher incidence and prevalence of hypertension in patients with CID in comparison to the general population. Moreover, hypertension represents an important predictor of CV events in these patients. Pathogenic mechanisms underlying the rise of blood pressure in CID are multifactorial and still poorly investigated. Indeed, multiple disease-related factors may affect blood pressure control in these patients and hypertension may affect disease prognosis and increase CV risk. Better knowledge of the complex interplay between hypertension and CID will be important to elucidate pathogenic mechanisms and to improve CV outcome in these patients. Aim of this review is to highlight available evidence on the relationship between hypertension and CID and to elucidate the multiple factors that may affect blood pressure control in these disorders.



http://ift.tt/2r8sAWk

Minimal Device Encrustation on Vesair Intravesical Balloons in the Treatment of Stress Urinary Incontinence: Analysis of Balloons Removed from Women in the SOLECT Trial

Abstract

Introduction

Encrustation of urinary biomaterials is common; however, the incidence of surface deposition on the Vesair® intravesical pressure-attenuation balloon has not been previously reported. The purpose of this analysis is to determine the incidence and potential risk factors for encrustation of the Vesair intravesical balloon.

Methods

The SOLECT trial is a prospective randomized controlled trial conducted at several European centers to evaluate the safety and efficacy of the Vesair balloon for the treatment of female stress urinary incontinence (SUI). Women included in the study demonstrated SUI symptoms for more than 12 months without complicating factors, such as history of recurrent urinary tract infections or nephrolithiasis. All balloons removed from women enrolled in the SOLECT trial were analyzed for surface characteristics and encrustation. Surface deposition severity was quantified and composition analyzed with infrared spectroscopy and scanning electron microscopy. Incidence of surface deposition was tabulated and risk factors analyzed.

Results

One hundred and five balloons removed from 75 women were included in this analysis. Measurable stone deposition of less than 1.5 mm was found on four balloons (3.8%), surface granules were noted on 42 (40.0%), surface film on 11 (10.5%), and both granules and film on two (1.9%). Analysis identified calcium oxalate both in measurable encrustation deposits as well as those with surface granulation. Pooled analysis found that dwell time was a risk factor for calcium deposition.

Conclusion

The rate of encrustation on the Vesair intravesical balloon is low and does not appear to increase the rate of adverse outcomes or reduce clinical efficacy.

Funding

Solace Therapeutics, Inc.



http://ift.tt/2rShIsU

Problems, interventions, and their outcomes during the routine work of hospital pharmacists in Bosnia and Herzegovina

Abstract

Background In the last 30 years, activities of hospital pharmacists have gone through significant changes. Pharmacists are increasingly involved in patient care. Objectives To explore drug-related and logistic problems, interventions, and their outcomes during routine everyday work of hospital pharmacists. Setting Institute for physical medicine and rehabilitation, Banja Luka, Bosnia and Herzegovina. Methods In the period of January 2013–October 2015 a prospective observational study was performed. Medical doctors, nurses, therapists, and patients addressed pharmacists, face-to-face or by telephone, with drug-related problems (DRPs) and/or logistic issues. Main outcome measure Type of DRP or logistic issue, intervention, outcome, initiator and time spent for solving the problem were documented for each consultation. Results Out of 1515 interventions, 48.8% were aimed at solving DRPs. The most common DRPs were the recommendation of a drug or dose and need for additional information about drugs. Drug price and supply were the most prevalent logistic issues. DRPs were more frequently initiated by medical doctors and required more time to solve the problem compared to logistic issues (Mann–Whitney U test, p ≤ 0.001, respectively). The acceptance rate of interventions to solve DRPs (83.7%) was lower compared to logistic issues (95.2%; p ≤ 0.001). Conclusions Hospital pharmacists were faced with an approximately equal number of DRPs and logistic issues during their routine everyday work. The overall acceptance rate of pharmacists' interventions was high, and the results of our study indicate that there is a need for more involvement of hospital pharmacists in Bosnia and Herzegovina in clinical activities. Impact on practice.



http://ift.tt/2sJA2EI

Letter to the Editor concerning “The surgical algorithm for the AOSpine thoracolumbar spine injury classification system” by A. R. Vaccaro et al. Eur Spine J (2016);25(4):1087–1094



http://ift.tt/2rSnQRJ

Utility of Arterial Spin Labeling MRI in Pediatric Neuroimaging: A Pictorial Essay

Abstract

Purpose of Review

With advances in magnetic field strength, multichannel coils and parallel imaging, arterial spin labeling (ASL) magnetic resonance imaging (MRI) is now widely available for clinical use. There is a growing body of literature on the utility of ASL in a variety of pediatric diseases that feature alterations in blood flow as part of the pathophysiologic process.

Recent Findings

ASL can help discriminate high-grade tumors from low-grade tumors, and is especially useful to identify characteristic hyperperfusion seen in hemangioblastoma and choroid plexus tumors. In moyamoya, ASL coupled with acetazolamide challenge provides quantitative cerebral blow flow data that can inform decisions regarding revascularization surgery. In both migraine headaches and hypoxic ischemic injury (HII), there is early hypoperfusion on ASL imaging followed by hyperperfusion. Global or medial occipital hyperperfusion in the setting of HII is a poor prognostic factor. ASL can identify hypoperfusion in seizure foci, but is more useful for seizure localization with hyperperfusion in the acute setting.

Summary

ASL perfusion imaging is a useful adjunct to conventional brain MRI in children, and should be applied in a wide variety of clinical scenarios.



http://ift.tt/2r7F293

Working Towards an Appropriate Use of Ibuprofen in Children: An Evidence-Based Appraisal

Abstract

Ibuprofen is the most widely used non-steroidal anti-inflammatory drug (NSAID) for the treatment of inflammation, mild-to-moderate pain and fever in children, and is the only NSAID approved for use in children aged ≥3 months. Its efficacy and safety profile have led to its increasing use in paediatric care, even without medical prescription. However, an increase of suspected adverse reactions to ibuprofen has been noted in concomitance with the raised, often medically unsupervised, consumption of the drug. The purpose of this work was a critical review of the paediatric literature over the last 15 years on side effects and adverse events associated with ibuprofen, in order to highlight circumstances associated with higher risks and to promote safe and appropriate use of this drug. The literature from 2000 to date demonstrates that gastrointestinal events are rare, but (when they occur) include both upper and lower digestive tract lesions. Dehydration plays an important role in triggering renal damage, so ibuprofen should not be given to patients with diarrhoea and vomiting, with or without fever. Likewise, ibuprofen should never be administered to patients who are sensitive to it or to other NSAIDs. It is contraindicated in neonates and in children with wheezing and persistent asthma and/or during varicella. Most of the analysed studies reported adverse events when ibuprofen was being used for fever symptoms or flu-like syndrome. Ibuprofen should not be used as an antipyretic, except in rare cases. Ibuprofen remains the drug of first choice in the treatment of inflammatory pain in children.



http://ift.tt/2sJfKev

Dermoscopic images of malignant and benign skin lesions

http://sfaki.blogspot.com/2017/06/using-watson-to-diagnose-skin-cancer.html
Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Tilt-induced cardio-inhibitory reflex syncope (BIOSync trial) : 12-item questionnaire to distinguish between complete transient loss of consciousness (i.e., syncope) and pre-syncope or other minor symptoms and, additionally, to provide a standardized categorical description of the clinical presentation of syncope including duration, reproducibility with previous episodes, presence of prodromes, presence of witnesses, context, and consequences of the episode.

http://sfaki.blogspot.com/2017/06/12-item-questionnaire-to-distinguish.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Monoclonal antibodies against IL-5 or IL-5 receptor alpha (mepolizumab, reslizumab, benralizumab), IL-13 (lebrikizumab, tralokinumab), IL-4 receptor alpha (dupilumab), Immune globuline E (IgE) (omalizumab), anti-Thymic Stromal Lymphopoitin (TSLP) (tezepelumab) and small molecule therapies such as prostaglandin D2 blockers (fevipiprant, timapiprant). New Anti-Eosinophil Drugs for asthma and COPD

http://sfaki.blogspot.com/2017/06/monoclonal-antibodies-against-il-5-or.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Maintenance of remission with combination etanercept–DMARD therapy versus DMARDs alone in active rheumatoid arthritis: results of an international treat-to-target study conducted in regions with limited biologic access

Abstract

In this transglobal, randomized, double-blind, placebo-controlled, treat-to-target study, the maintenance of efficacy was compared between biologic–and biologic-free–disease-modifying antirheumatic drug (DMARD) combination regimens after low disease activity (LDA) was achieved with biologic DMARD induction therapy. Patients with moderate-to-severe rheumatoid arthritis despite methotrexate therapy received open-label etanercept 50 mg subcutaneously once weekly plus methotrexate with or without other conventional synthetic (cs) DMARDs for 24 weeks. Patients achieving LDA [disease activity score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) <3.2] at week 24 were randomized to receive etanercept–methotrexate combination therapy or placebo–methotrexate combination therapy, with or without other csDMARDs, for 28 weeks. In the open-label period, 72% of patients achieved DAS28-ESR LDA at week 24. Patients enrolled in the double-blind period had long-standing rheumatoid arthritis and high disease activity at baseline (mean duration, 8.1 years; DAS28-ESR, 6.4). In the etanercept and placebo combination groups, 44% versus 17% achieved DAS28-ESR LDA and 34 versus 13% achieved DAS28-ESR remission at week 52 (p < 0.001). Adverse events were reported in 37 and 43%, serious adverse events in 0 and 4%, and serious infections in 0 and 2% in these groups, respectively, in the double-blind period. After induction of response with etanercept combination therapy following a treat-to-target approach in patients with long-standing rheumatoid arthritis and high disease activity at baseline, the etanercept combination regimen was significantly more effective in maintaining LDA and remission than a biologic-free regimen.

ClinicalTrials.gov identifier. NCT01578850.



http://ift.tt/2t06WQI

Unlicensed and off-label use of drugs in pediatric surgical units at tertiary care hospitals of Pakistan

Abstract

Background Unlicensed and off-label prescribing practice is global dilemma around the world. This pioneering study was designed to determine unlicensed and off-label use of drug in surgical wards of tertiary care hospitals of Pakistan. Objective To assess unlicensed and off-label use of drugs in pediatric surgical unit at three tertiary care hospitals in Peshawar, Pakistan. Setting Two government and one private tertiary care hospitals in Pakistan. Method Drug profiles of 895 patients from three different clinical settings were evaluated for unlicensed and off-label use of drugs using Micromedex DRUGDEX. Main outcome measure Characteristics of the unlicensed and off-label drug prescriptions. Result Total of 3168 prescribed drugs were analyzed in this study. Indication (38.7%) and dose (34.8%) were the most frequent off-label categories. In comparison with the corresponding reference categories, infants and children, male patients and having less than five prescribed drugs were significant predictors of unlicensed prescriptions. In comparison with the corresponding reference categories, significant predictors of off-label drug prescribing were children younger than two year, children between 2–12 years, patient staying at hospital less than 5 days and patients having less than five prescribed drugs. Conclusion The prevalence of unlicensed and off-label drug prescriptions are high at pediatric surgical ward of tertiary care hospitals. More awareness of the efficacy and safety of drugs are required in pediatrics. In addition, new formulations with advanced dosing for children are also required to minimize the risk of adverse outcomes.



http://ift.tt/2saiOmy

Problems, interventions, and their outcomes during the routine work of hospital pharmacists in Bosnia and Herzegovina

Abstract

Background In the last 30 years, activities of hospital pharmacists have gone through significant changes. Pharmacists are increasingly involved in patient care. Objectives To explore drug-related and logistic problems, interventions, and their outcomes during routine everyday work of hospital pharmacists. Setting Institute for physical medicine and rehabilitation, Banja Luka, Bosnia and Herzegovina. Methods In the period of January 2013–October 2015 a prospective observational study was performed. Medical doctors, nurses, therapists, and patients addressed pharmacists, face-to-face or by telephone, with drug-related problems (DRPs) and/or logistic issues. Main outcome measure Type of DRP or logistic issue, intervention, outcome, initiator and time spent for solving the problem were documented for each consultation. Results Out of 1515 interventions, 48.8% were aimed at solving DRPs. The most common DRPs were the recommendation of a drug or dose and need for additional information about drugs. Drug price and supply were the most prevalent logistic issues. DRPs were more frequently initiated by medical doctors and required more time to solve the problem compared to logistic issues (Mann–Whitney U test, p ≤ 0.001, respectively). The acceptance rate of interventions to solve DRPs (83.7%) was lower compared to logistic issues (95.2%; p ≤ 0.001). Conclusions Hospital pharmacists were faced with an approximately equal number of DRPs and logistic issues during their routine everyday work. The overall acceptance rate of pharmacists' interventions was high, and the results of our study indicate that there is a need for more involvement of hospital pharmacists in Bosnia and Herzegovina in clinical activities. Impact on practice.



http://ift.tt/2sJA2EI

Ectopic ACTH-secreting tumor of the thymus revealed by a Cushing’s syndrome: case report and review of literature

Abstract

Tumors of the thymus are rare. Neuroendocrine tumors are extremely rare. We report a case of a 39-year-old man, referred to our hospital for a paraneoplastic Cushing syndrome with a thymic tumor. Despite bilateral adrenalectomy, the patient still had signs of hypercorticism. A CT scan revealed a 25-mm nodule in the thymic compartment. A resection was indicated and surgery was successful. No adjuvant therapy was administrated. After 10 months, the patient was in good health and his clinical symptoms resolved, with no signs of recurrence. Lung and thymic neuroendocrine carcinomas with Cushing syndrome are aggressive with a high risk of recurrence even after a complete resection. A close follow-up is recommended.



http://ift.tt/2rSyU1u

Maintenance of remission with combination etanercept–DMARD therapy versus DMARDs alone in active rheumatoid arthritis: results of an international treat-to-target study conducted in regions with limited biologic access

Abstract

In this transglobal, randomized, double-blind, placebo-controlled, treat-to-target study, the maintenance of efficacy was compared between biologic–and biologic-free–disease-modifying antirheumatic drug (DMARD) combination regimens after low disease activity (LDA) was achieved with biologic DMARD induction therapy. Patients with moderate-to-severe rheumatoid arthritis despite methotrexate therapy received open-label etanercept 50 mg subcutaneously once weekly plus methotrexate with or without other conventional synthetic (cs) DMARDs for 24 weeks. Patients achieving LDA [disease activity score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) <3.2] at week 24 were randomized to receive etanercept–methotrexate combination therapy or placebo–methotrexate combination therapy, with or without other csDMARDs, for 28 weeks. In the open-label period, 72% of patients achieved DAS28-ESR LDA at week 24. Patients enrolled in the double-blind period had long-standing rheumatoid arthritis and high disease activity at baseline (mean duration, 8.1 years; DAS28-ESR, 6.4). In the etanercept and placebo combination groups, 44% versus 17% achieved DAS28-ESR LDA and 34 versus 13% achieved DAS28-ESR remission at week 52 (p < 0.001). Adverse events were reported in 37 and 43%, serious adverse events in 0 and 4%, and serious infections in 0 and 2% in these groups, respectively, in the double-blind period. After induction of response with etanercept combination therapy following a treat-to-target approach in patients with long-standing rheumatoid arthritis and high disease activity at baseline, the etanercept combination regimen was significantly more effective in maintaining LDA and remission than a biologic-free regimen.

ClinicalTrials.gov identifier. NCT01578850.



http://ift.tt/2t06WQI

Relative Ascites Polymorphonuclear Cell Count Indicates Bacterascites and Risk of Spontaneous Bacterial Peritonitis

Abstract

Background and Aims

Absolute polymorphonuclear (PMN) counts in ascites define spontaneous bacterial peritonitis (SBP), a severe form of bacterial infection in liver cirrhosis. Bacterascites, another form of ascites infection, can progress to SBP or may resolve spontaneously but is not reflected by absolute PMN counts. We investigated whether the relative ascites PMN count (the absolute PMN count divided by the absolute leukocyte count) provides additional information to detect bacterascites or predict SBP.

Methods

Hospitalized patients with liver cirrhosis requiring paracentesis were stratified with respect to a diagnosis of bacterascites and SBP with a prospective follow-up for 1 year. Diagnostic power of relative PMN counts in ascites was evaluated by receiver operating characteristics curves.

Results

At inclusion, we observed 28/269 (10%) and 43/269 (16%) episodes of BA and SBP, respectively. Unlike absolute PMN counts, relative PMN counts in ascites were significantly elevated in bacterascites (p = 0.001). During follow-up, 16 and 30 further episodes of BA and SBP were detected, respectively. Relative PMN counts increased significantly once patients developed BA (p = 0.001). At a threshold of 0.20 for the relative PMN count, sensitivity, specificity, positive and negative predictive values for bacterascites which required antibiotic treatment were 83, 75, 26 and 98%, respectively (p < 0.001). Furthermore, a relative PMN count in ascites ≥0.13 and MELD score >17 was independent factors associated with occurrence of SBP during follow-up.

Conclusion

The relative PMN count is a cheap immunological marker linked to bacterascites and future SBP, which may help to stratify patients according to their risk of infection.



http://ift.tt/2skTRo8

Microscopic Colitis Evolved Into Inflammatory Bowel Diseases Is Characterized by Increased Th1/Tc1 Cells in Colonic Mucosal Lamina Propria

Abstract

Background

An association between microscopic colitis (MC), i.e., lymphocytic colitis (LC) and collagenous colitis (CC), and inflammatory bowel diseases (IBD) has been noticed. A subset of MC cases may evolve into IBD, and IBD in remission may present as MC in a histologic pattern. Moreover, MC and IBD may coexist in different regions of the bowel. A link between MC and IBD in their pathogenesis is, therefore, suggested. Abnormal mucosal immunity is likely the key.

Methods

We reviewed 2324 MC cases in Calgary over 14 years and identified 20 cases evolved into IBD (IBD transformers). 13 of them were further investigated for colonic mucosal lamina propria mononuclear cells (LPMNCs), as opposed to 22 cases whose MC resolved. On their index colonic biopsy immunohistochemistry was performed to detect major T cell subsets characterized by key cytokines and master transcription factors (IFNγ and T-bet for Th1/Tc1, GATA-3 for Th2/Tc2, IL-17 and RORc for Th17/Tc17, FoxP3 for Treg/Tcreg) as well as TNFα+ cells (partly representing Th1). LPMNCs positive for each marker were counted (average number per high-power field).

Results

IBD transformers had increased IFNγ+, T-bet+, TNF-α+, and GATA-3+ LPMNCs compared to the MC-resolved cases. The LC-to-IBD subgroup had increased IFNγ+ and GATA-3+ cells compared to the LC-resolved subgroup. The CC-to-IBD subgroup had increased T-bet+, TNF-α+, and GATA-3+ cells compared to the CC-resolved subgroup. Among MC-resolved patients, more TNF-α+ and RORc+ cells were seen in LC than in CC.

Conclusion

Th1/Tc1- and TNFα-producing cells, and likely a subset of Th2/Tc2 cells as well, may be involved in the MC-to-IBD transformation.



http://ift.tt/2r1Qr5U

Maintenance of remission with combination etanercept–DMARD therapy versus DMARDs alone in active rheumatoid arthritis: results of an international treat-to-target study conducted in regions with limited biologic access

Abstract

In this transglobal, randomized, double-blind, placebo-controlled, treat-to-target study, the maintenance of efficacy was compared between biologic–and biologic-free–disease-modifying antirheumatic drug (DMARD) combination regimens after low disease activity (LDA) was achieved with biologic DMARD induction therapy. Patients with moderate-to-severe rheumatoid arthritis despite methotrexate therapy received open-label etanercept 50 mg subcutaneously once weekly plus methotrexate with or without other conventional synthetic (cs) DMARDs for 24 weeks. Patients achieving LDA [disease activity score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) <3.2] at week 24 were randomized to receive etanercept–methotrexate combination therapy or placebo–methotrexate combination therapy, with or without other csDMARDs, for 28 weeks. In the open-label period, 72% of patients achieved DAS28-ESR LDA at week 24. Patients enrolled in the double-blind period had long-standing rheumatoid arthritis and high disease activity at baseline (mean duration, 8.1 years; DAS28-ESR, 6.4). In the etanercept and placebo combination groups, 44% versus 17% achieved DAS28-ESR LDA and 34 versus 13% achieved DAS28-ESR remission at week 52 (p < 0.001). Adverse events were reported in 37 and 43%, serious adverse events in 0 and 4%, and serious infections in 0 and 2% in these groups, respectively, in the double-blind period. After induction of response with etanercept combination therapy following a treat-to-target approach in patients with long-standing rheumatoid arthritis and high disease activity at baseline, the etanercept combination regimen was significantly more effective in maintaining LDA and remission than a biologic-free regimen.

ClinicalTrials.gov identifier. NCT01578850.



http://ift.tt/2t06WQI

Advances in renal genetic diagnosis

Abstract

Most genetic disorders are clinically and genetically heterogeneous. Next-generation sequencing (NGS) has revolutionized the field and is providing rapidly growing insights into the pathomechanism of hereditary nephropathies. Current best-practice guidelines for most hereditary nephropathies include genetic diagnostics. The increasing number of genes that have to be considered in patients with hereditary nephropathies is often challenging when addressed by conventional techniques and largely benefits from NGS-based approaches that allow the parallel analysis of all disease genes in a single test at relatively low cost, e.g., by the use of multi-gene panels. Knowledge of the underlying genotype is of advantage in discussions with regard to transplantation and therapeutic options. Further, genetics may aid the early detection and treatment of renal and extrarenal complications and the reduction of invasive procedures. An accurate genetic diagnosis is crucial for genetic counselling, provides information about the recurrence risk and may help to improve the clinical management of patients and their families. The bottleneck in genetics is no longer the primary wet lab process but the interpretation of the obtained genetic data, which is by far the most challenging and work-intensive part of the analysis. This can only be managed in a multidisciplinary setting that brings together expert knowledge in genetics and the respective medical field. In the future, bench and bedside benefits can be expected from this kind of digitized medicine.



http://ift.tt/2rRTxe5

Erratum to: Sarcopenic overweight is associated with early acute limiting toxicity of anti-PD1 checkpoint inhibitors in melanoma patients



http://ift.tt/2s9oAF2

Outcomes and prognostic factors for relapsed or refractory lymphoma patients in phase I clinical trials

Summary

Background Although safety and prognostic factors for overall survival (OS) have been extensively studied in Phase I clinical trials on patients with solid tumours, data on lymphoma trials are scarce. Here, we investigated safety, outcomes and prognostic factors in relapsed or refractory lymphoma patients included in a series of Phase I trials. Method and patients All consecutive adult patients with recurrent/refractory lymphoma enrolled in 26 Phase I trials at a single cancer centre in France between January 2008 and June 2016 were retrospectively assessed. Results 133 patients (males: 65%) were included in the analysis. The median (range) age was 65 (23–86). Aggressive non-Hodgkin, indolent non-Hodgkin and Hodgkin types accounted for 64%, 25% and 11% of the patients, respectively. The patients had received a median (range) of 3 (1–13) lines of treatment prior to trial entry. The median [95% confidence interval] progression-free survival and OS times were 3.0 [1.8–3.6] and 17.8 [12.7–30.4] months, respectively. High-grade toxicity (grade 3 or higher, according to the National Cancer Institute's Common Terminology Criteria for Adverse Events classification) was experienced by 56 of the 133 patients (42%) and was related to the investigational drug in 44 of these cases (79%). No toxicity-related deaths occurred. Dose-limiting toxicity (DLT) was encountered in 11 (9%) of the 116 evaluable patients. High-grade toxicity occurred during the DLT period for 34 of the 56 patients (61%) and after the DLT period in the remaining 22 (39%). The main prognostic factors for poor OS were the histological type (i.e. tumour aggressiveness), an elevated serum LDH level, and a low serum albumin level. Early withdrawal from a trial was correlated with the performance status score, the histological type and the serum LDH level. The overall objective response and disease control rates were 24% and 57%, respectively. Conclusion Performance status, LDH, albumin and histological type (tumour aggressiveness) appear to be the most relevant prognostic factors for enrolling Phase I participants with relapsed or refractory lymphoma. 39% of the patients experienced a first high-grade toxic event after the dose-limiting toxicity period, suggesting that the conventional concept of dose-limiting toxicity (designed for chemotherapy) should be redefined in the era of modern cancer therapies.



http://ift.tt/2rc0bKf

Erratum to: Sarcopenic overweight is associated with early acute limiting toxicity of anti-PD1 checkpoint inhibitors in melanoma patients



http://ift.tt/2s9oAF2

Outcomes and prognostic factors for relapsed or refractory lymphoma patients in phase I clinical trials

Summary

Background Although safety and prognostic factors for overall survival (OS) have been extensively studied in Phase I clinical trials on patients with solid tumours, data on lymphoma trials are scarce. Here, we investigated safety, outcomes and prognostic factors in relapsed or refractory lymphoma patients included in a series of Phase I trials. Method and patients All consecutive adult patients with recurrent/refractory lymphoma enrolled in 26 Phase I trials at a single cancer centre in France between January 2008 and June 2016 were retrospectively assessed. Results 133 patients (males: 65%) were included in the analysis. The median (range) age was 65 (23–86). Aggressive non-Hodgkin, indolent non-Hodgkin and Hodgkin types accounted for 64%, 25% and 11% of the patients, respectively. The patients had received a median (range) of 3 (1–13) lines of treatment prior to trial entry. The median [95% confidence interval] progression-free survival and OS times were 3.0 [1.8–3.6] and 17.8 [12.7–30.4] months, respectively. High-grade toxicity (grade 3 or higher, according to the National Cancer Institute's Common Terminology Criteria for Adverse Events classification) was experienced by 56 of the 133 patients (42%) and was related to the investigational drug in 44 of these cases (79%). No toxicity-related deaths occurred. Dose-limiting toxicity (DLT) was encountered in 11 (9%) of the 116 evaluable patients. High-grade toxicity occurred during the DLT period for 34 of the 56 patients (61%) and after the DLT period in the remaining 22 (39%). The main prognostic factors for poor OS were the histological type (i.e. tumour aggressiveness), an elevated serum LDH level, and a low serum albumin level. Early withdrawal from a trial was correlated with the performance status score, the histological type and the serum LDH level. The overall objective response and disease control rates were 24% and 57%, respectively. Conclusion Performance status, LDH, albumin and histological type (tumour aggressiveness) appear to be the most relevant prognostic factors for enrolling Phase I participants with relapsed or refractory lymphoma. 39% of the patients experienced a first high-grade toxic event after the dose-limiting toxicity period, suggesting that the conventional concept of dose-limiting toxicity (designed for chemotherapy) should be redefined in the era of modern cancer therapies.



http://ift.tt/2rc0bKf

Identification and description of three families with familial Alzheimer disease that segregate variants in the SORL1 gene

Abstract

Alzheimer disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. The majority of AD cases are sporadic, while up to 5% are families with an early onset AD (EOAD). Mutations in one of the three genes: amyloid beta precursor protein (APP), presenilin 1 (PSEN1) or presenilin 2 (PSEN2) can be disease causing. However, most EOAD families do not carry mutations in any of these three genes, and candidate genes, such as the sortilin-related receptor 1 (SORL1), have been suggested to be potentially causative. To identify AD causative variants, we performed whole-exome sequencing on five individuals from a family with EOAD and a missense variant, p.Arg1303Cys (c.3907C > T) was identified in SORL1 which segregated with disease and was further characterized with immunohistochemistry on two post mortem autopsy cases from the same family. In a targeted re-sequencing effort on independent index patients from 35 EOAD-families, a second SORL1 variant, c.3050-2A > G, was found which segregated with the disease in 3 affected and was absent in one unaffected family member. The c.3050-2A > G variant is located two nucleotides upstream of exon 22 and was shown to cause exon 22 skipping, resulting in a deletion of amino acids Gly1017- Glu1074 of SORL1. Furthermore, a third SORL1 variant, c.5195G > C, recently identified in a Swedish case control cohort included in the European Early-Onset Dementia (EU EOD) consortium study, was detected in two affected siblings in a third family with familial EOAD. The finding of three SORL1-variants that segregate with disease in three separate families with EOAD supports the involvement of SORL1 in AD pathology. The cause of these rare monogenic forms of EOAD has proven difficult to find and the use of exome and genome sequencing may be a successful route to target them.



http://ift.tt/2rRRg2x

Human IκBα Gain of Function: a Severe and Syndromic Immunodeficiency

Abstract

Germline heterozygous gain-of-function (GOF) mutations of NFKBIA, encoding IκBα, cause an autosomal dominant (AD) form of anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID). Fourteen unrelated patients have been reported since the identification of the first case in 2003. All mutations enhanced the inhibitory activity of IκBα, by preventing its phosphorylation on serine 32 or 36 and its subsequent degradation. The mutation certainly or probably occurred de novo in 13 patients, whereas it was inherited from a parent with somatic mosaicism in one patient. Eleven mutations, belonging to two groups, were identified: (i) missense mutations affecting S32, S36, or neighboring residues (8 mutations, 11 patients) and (ii) nonsense mutations upstream from S32 associated with the reinitiation of translation downstream from S36 (3 mutations, 3 patients). Thirteen patients had developmental features of EDA, the severity and nature of which differed between cases. All patient cells tested displayed impaired NF-κB-mediated responses to the stimulation of various surface receptors involved in cell-intrinsic (fibroblasts), innate (monocytes), and adaptive (B and T cells) immunity, including TLRs, IL-1Rs, TNFRs, TCR, and BCR. All patients had profound B-cell deficiency. Specific immunological features, found in some, but not all patients, included a lack of peripheral lymph nodes, lymphocytosis, dysfunctional α/β T cells, and a lack of circulating γ/δ T cells. The patients had various pyogenic, mycobacterial, fungal, and viral severe infections. Patients with a missense mutation tended to display more severe phenotypes, probably due to higher levels of GOF proteins. In the absence of hematopoietic stem cell transplantation (HSCT), this condition cause death before the age of 1 year (one child). Two survivors have been on prophylaxis (at 9 and 22 years). Six children died after HSCT. Five survived, four of whom have been on prophylaxis (3 to 21 years post HSCT), whereas one has been well with no prophylaxis. Heterozygous GOF mutations in IκBα underlie a severe and syndromic immunodeficiency, the interindividual variability of which might partly be ascribed to the dichotomy of missense and nonsense mutations, and the hematopoietic component of which can be rescued by HSCT.



http://ift.tt/2s2o7E1

Potential impact of climate change on the risk of windthrow in eastern Canada’s forests

Abstract

Climate change is likely to affect windthrow risks at northern latitudes by potentially changing high wind probabilities and soil frost duration. Here, we evaluated the effect of climate change on windthrow risk in eastern Canada's balsam fir (Abies balsamea [L.] Mill.) forests using a methodology that accounted for changes in both wind speed and soil frost duration. We used wind speed and soil temperature projections at the regional scale from the CRCM5 regional climate model (RCM) driven by the CanESM2 global climate model (GCM) under two representative concentration pathways (RCP4.5, RCP8.5), for a baseline (1976–2005) and two future periods (2041–2070, 2071–2100). A hybrid mechanistic model (ForestGALES) that considers species resistance to uprooting and wind speed distribution was used to calculate windthrow risk. An increased risk of windthrow (3 to 30%) was predicted for the future mainly due to an increased duration of unfrozen soil conditions (by up to 2 to 3 months by the end of the twenty-first century under RCP8.5). In contrast, wind speed did not vary markedly with a changing climate. Strong regional variations in wind speeds translated into regional differences in windthrow risk, with the easternmost region (Atlantic provinces) having the strongest winds and the highest windthrow risk. Because of the inherent uncertainties associated with climate change projections, especially regarding wind climate, further research is required to assess windthrow risk from the optimum combination of RCM/GCM ensemble simulations.



http://ift.tt/2rRRrLa

The prevalence of REM-related obstructive sleep apnoea is reduced by the AASM 2012 hypopnoea criteria

Abstract

Purpose

The variations in reported prevalence of rapid eye movement-related obstructive sleep apnoea (REM-OSA) have been attributed to different definitions, although the effect of hypopnoea criteria has not been previously investigated.

Methods

Within this retrospective study, 134 of 382 consecutive patients undertaking polysomnography (PSG) for the suspicion of OSA met the inclusion criteria. PSGs were scored using both the 2007 AASM recommended hypopnoea criteria (AASM2007Rec) and the 2012 AASM recommended hypopnoea criteria (AASM2012Rec). For each hypopnoea criteria, REM-OSA patients were grouped as REM-related [either as REM-predominant OSA (rpOSA) or REM-isolated OSA (riOSA)] or non-stage-specific OSA (nssOSA). Outcome measures (SF-36, FOSQ and DASS-21) were also compared between groups.

Results

Incorporation of the AASM2012Rec criteria compared to the AASM2007Rec criteria increased the apnoea-hypopnoea index (AHI) for NREM and REM sleep but decreased the AHIREM/AHINREM ratio from 1.9 to 1.3 (p < 0.001). It also decreased the prevalence of riOSA [15.7 vs 2.2% (p < 0.001) for AASM2007Rec and AASM2012Rec, respectively]. The prevalence of rpOSA remained the same for each hypopnoea criteria although the prevalence of nssOSA increased with the AASM2012Rec hypopnoea criteria [53.0 vs 66.4% (p < 0.006) for AASM2007Rec and AASM2012Rec, respectively]. There were no differences in clinical symptoms between the groups, irrespective of hypopnoea criteria used.

Conclusions

This study demonstrates that in comparison with AASM2007Rec, the AASM2012Rec hypopnoea criteria reduce the prevalence of riOSA but not rpOSA by reducing the ratio of REM respiratory events and NREM respiratory events.



http://ift.tt/2rRw50o

Biocontrol of the toxigenic plant pathogen Fusarium culmorum by soil fauna in an agroecosystem

Abstract

In 2011 and 2013, a field experiment was conducted in a winter wheat field at Adenstedt (northern Germany) to investigate biocontrol and interaction effects of important members of the soil food web (Lumbricus terrestris, Annelida; Folsomia candida, Collembola and Aphelenchoides saprophilus, Nematoda) on the phytopathogenic fungus Fusarium culmorum in wheat straw. Therefore, soil fauna was introduced in mesocosms in defined numbers and combinations and exposed to either Fusarium-infected or non-infected wheat straw. L. terrestris was introduced in all faunal treatments and combined either with F. candida or A. saprophilus or both. Mesocosms filled with a Luvisol soil, a cover of different types of wheat straw and respective combinations of faunal species were established outdoors in the topsoil of a winter wheat field after harvest of the crop. After a time span of 4 and 8 weeks, the degree of wheat straw coverage of mesocosms was quantified to assess its attractiveness for the soil fauna. The content of Fusarium biomass in residual wheat straw and soil was determined using a double-antibody sandwich (DAS)-ELISA method. In both experimental years, the infected wheat straw was incorporated more efficiently into the soil than the non-infected control straw due to the presence of L. terrestris in all faunal treatments than the non-infected control straw. In addition, Fusarium biomass was reduced significantly in all treatments after 4 weeks (2011: 95–99%; 2013:15–54%), whereupon the decline of fungal biomass was higher in faunal treatments than in non-faunal treatments and differed significantly from them. In 2011, Fusarium biomass of the faunal treatments was below the quantification limit after 8 weeks. In 2013, a decline of Fusarium biomass was observed, but the highest content of Fusarium biomass was still found in the non-faunal treatments after 8 weeks. In the soil of all treatments, Fusarium biomass was below the quantification limit. The earthworm species L. terrestris revealed a considerable potential as an effective biocontrol agent contributing to a sustainable control of a Fusarium plant pathogen in wheat straw, thus reducing the infection risk for specific plant diseases in arable fields.



http://ift.tt/2s97eZ1

Characterization and use of Equine Bone Marrow Mesenchymal Stem Cells in Equine Cartilage Engineering. Study of their Hyaline Cartilage Forming Potential when Cultured under Hypoxia within a Biomaterial in the Presence of BMP-2 and TGF-ß1

Abstract

Articular cartilage presents a poor capacity for self-repair. Its structure-function are frequently disrupted or damaged upon physical trauma or osteoarthritis in humans. Similar musculoskeletal disorders also affect horses and are the leading cause of poor performance or early retirement of sport- and racehorses. To develop a therapeutic solution for horses, we tested the autologous chondrocyte implantation technique developed on human bone marrow (BM) mesenchymal stem cells (MSCs) on horse BM-MSCs. This technique involves BM-MSC chondrogenesis using a combinatory approach based on the association of 3D–culture in collagen sponges, under hypoxia in the presence of chondrogenic factors (BMP-2 + TGF-β1) and siRNA to knockdown collagen I and HtrA1. Horse BM-MSCs were characterized before being cultured in chondrogenic conditions to find the best combination to enhance, stabilize, the chondrocyte phenotype. Our results show a very high proliferation of MSCs and these cells satisfy the criteria defining stem cells (pluripotency-surface markers expression). The combination of BMP-2 + TGF-β1 strongly induces the chondrogenic differentiation of MSCs and prevents HtrA1 expression. siRNAs targeting Col1a1 and Htra1 were functionally validated. Ultimately, the combined use of specific culture conditions defined here with specific growth factors and a Col1a1 siRNAs (50 nM) association leads to the in vitro synthesis of a hyaline-type neocartilage whose chondrocytes present an optimal phenotypic index similar to that of healthy, differentiated chondrocytes. Our results lead the way to setting up pre-clinical trials in horses to better understand the reaction of neocartilage substitute and to carry out a proof-of-concept of this therapeutic strategy on a large animal model.



http://ift.tt/2rRmI0Q

Sustained attention to a predictable, unengaging Go/No-Go task shows ongoing development between 6 and 11 years

Abstract

Response time variability (RTV) is a useful measure of sustained attention; however, little is known about developmental changes in RTV at different temporal frequencies. Thirty-five 6-year-olds, 31 8-year-olds, and 37 10-year-olds completed the fixed-sequence Sustained Attention to Response Task on three occasions, six months apart. Fast Fourier Transform and ex-Gaussian analyses of response time (RT) data assessed momentary fluctuations in RT, gradual changes in RT, and very long responses, thought to reflect attentional control fluctuations, slow-shifting arousal, and infrequent lapses in attention, respectively. A half-by-half analysis measured within-occasion time-on-task effects. The 10-to 11-year-olds performed with less momentary fluctuations in RT, fewer long responses, and fewer commission and omission errors than the younger groups. This group performed well in the first half of the task but showed time-on-task effects on measures of momentary fluctuations in RT, very long responses, target sensitivity (d'), and commission errors. The 6- to 7-year-olds performed less well than the older groups, and showed time-on-task effects, on almost all measures. The 8- to- 9-year-olds mostly performed at an intermediate level compared with the other groups; however, this group performed with a similar level of momentary fluctuations in RT and very long responses as the 6- to 7-year-olds. These findings indicate that there is ongoing maturation of various aspects of sustained attention on a predictable task, with a period of relative stability in performance between 8 and 9 years of age.



http://ift.tt/2rGsiVg

Transmural Migration of Gossypiboma: a Rare Cause of Acute Abdomen

Abstract

Gossypiboma is the retained foreign body which is generally a cotton sponge/gauze after surgery. Incidence of gossypiboma is around one in 3000 to 5000 surgeries. This low incidence is mainly attributed to a low case reporting due to an associated medicolegal aspect. We are reporting a case of a 38 years old male, who presented with signs and symptoms of peritonitis. The patient had a history of open cholecystectomy 2 years back. A working diagnosis of perforation peritonitis was made, and the patient underwent exploratory laparotomy. Intraoperatively, a surgical sponge was present inside the ileal lumen causing intestinal obstruction with dense adhesion of bowel loops proximal to the site of obstruction with multiple ileal perforations. Even though the incidence of gossypiboma is very low, it should always be kept in mind as a cause of chronic abdominal pain and abdominal discomfort in a patient with previous abdominal surgery.



http://ift.tt/2raSPqq

Old Drugs May Be Good Friends but Always Under Prerequisites



http://ift.tt/2raLJlS

Comparison of endoscopic sphincterotomy techniques after Billroth II gastrectomy using a novel mechanical simulator

Abstract

Background and aims

A postsurgical anatomy renders endoscopic sphincterotomy (EST) more challenging. Although different EST techniques for such a situation exist, comparative studies are lacking. The aim of the study was to compare the efficacy of different EST techniques using a novel mechanical simulator.

Methods

Ten expert endoscopists performed 6 different EST techniques on a novel mechanical Billroth II (BII) simulator in a random sequence. The EST techniques were (1) standard sphincterotome used with a side-viewing endoscope, (2) BII sphincterotome used with a side-viewing endoscope, (3) needle-knife EST guided by biliary endoprosthesis used with a side-viewing endoscope, (4) standard sphincterotome used with a forward-viewing endoscope, (5) BII sphincterotome used with a forward-viewing endoscope, and (6) needle-knife EST guided by biliary endoprosthesis used with a forward-viewing endoscope. The results of videotaped ESTs were evaluated by a blinded expert and duration for each EST modality was calculated.

Results

Needle-knife EST guided by endoprosthesis was rated superior to EST using a BII sphincterotome (p = 0.017) or a standard sphincterotome (p < 0.001). EST using the BII sphincterotome was significantly faster than EST with the needle knife (p = 0.004) and the standard sphincterotome (p = 0.005). There were no differences between the use of a forward-viewing endoscope and a side-viewing endoscope.

Conclusion

In an ex vivo model for EST in B II gastrectomy needle-knife EST guided by endoprosthesis achieved superior ratings in comparison to the use of a BII sphincterotome, although it was more time-consuming. A standard sphincterotome should not be used for such a procedure.



http://ift.tt/2sZoXyG

Safety and efficacy of endoscopic submucosal dissection of large (≥3 cm) subepithelial tumors located in the cardia

Abstract

Background

Upper gastrointestinal subepithelial tumors (SETs) may harbor potential malignancy. Although it is well recognized that large SETs should be resected, the treatment strategy remains controversial. Compared to surgical resection, endoscopic resection has many advantages such as less invasive, shorter hospital stay, lower costs, and better quality of life. However, Endoscopic resection of large SETs in the cardia is challenging. The purpose of this study was to evaluate the safety and efficacy of endoscopic submucosal dissection (ESD) in the treatment of such SETs.

Methods

A total of 41 patients with large SETs (≥3 cm in diameter) located in the cardia were involved in the study. All patients underwent ESD. Data on therapeutic outcomes and follow-up were collected, for analysis of risk factors of complication rates.

Results

The average tumor size was 4.7 ± 1.7 cm. The average procedure time was 69.3 ± 32.7 min and the average postoperative hospital stay was 3.5 ± 1.1 days. A total of 41 tumors were removed successfully, in which 35 were leiomyomas, three were gastrointestinal stromal tumors, two were lipomas, and one was gastritis cystica profunda. The en bloc resection rate was 90.2%, and was significantly higher for tumors with a round or oval shape (100%) than for those with an irregular shape (75.0%) (P < 0.05). Five patients experienced complications (12.2%), all of which were managed conservatively. The complication rates were significantly higher in patients with a tumor originating from the deep muscularis propria layer and demonstrating a trans-cardia growth pattern. No residual or tumor recurrence was observed and no stricture occurred during the follow-up period (average, 26.7 ± 18.4 months).

Conclusions

ESD is safe and effective to curatively remove most large SETs in the cardia, and may serve as an accurate histopathology measurement to direct future therapy.



http://ift.tt/2s1F9Ss

Design features of offshore oil production platforms influence their susceptibility to biocorrosion

Abstract

Offshore oil-producing platforms are designed for efficient and cost-effective separation of oil from water. However, design features and operating practices may create conditions that promote the proliferation and spread of biocorrosive microorganisms. The microbial communities and their potential for metal corrosion were characterized for three oil production platforms that varied in their oil-water separation processes, fluid recycling practices, and history of microbially influenced corrosion (MIC). Microbial diversity was evaluated by 16S rRNA gene sequencing, and numbers of total bacteria, archaea, and sulfate-reducing bacteria (SRB) were estimated by qPCR. The rates of 35S sulfate reduction assay (SRA) were measured as a proxy for metal biocorrosion potential. A variety of microorganisms common to oil production facilities were found, but distinct communities were associated with the design of the platform and varied with different locations in the processing stream. Stagnant, lower temperature (<37 °C) sites in all platforms had more SRB and higher SRA compared to samples from sites with higher temperatures and flow rates. However, high (5 mmol L−1) levels of hydrogen sulfide and high numbers (107 mL−1) of SRB were found in only one platform. This platform alone contained large separation tanks with long retention times and recycled fluids from stagnant sites to the beginning of the oil separation train, thus promoting distribution of biocorrosive microorganisms. These findings tell us that tracking microbial sulfate-reducing activity and community composition on off-shore oil production platforms can be used to identify operational practices that inadvertently promote the proliferation, distribution, and activity of biocorrosive microorganisms.



http://ift.tt/2rGunAx

Inhibition Efficiency in Highly Proficient Bilinguals and Simultaneous Interpreters: Evidence from Language Switching and Stroop Tasks

Abstract

The present behavioral study aimed to examine the impact of language control expertise on two domain-general control processes, i.e. active inhibition of competing representations and overcoming of inhibition. We compared how Simultaneous Interpreters (SI) and Highly Proficient Bilinguals—two groups assumed to differ in language control capacity—performed executive tasks involving specific inhibition processes. In Experiment 1 (language decision task), both active and overcoming of inhibition processes are involved, while in Experiment 2 (bilingual Stroop task) only interference suppression is supposed to be required. The results of Experiment 1 showed a language switching effect only for the highly proficient bilinguals, potentially because overcoming of inhibition requires more cognitive resources than in SI. Nevertheless, both groups performed similarly on the Stroop task in Experiment 2, which suggests that active inhibition may work similarly in both groups. These contrasting results suggest that overcoming of inhibition may be harder to master than active inhibition. Taken together, these data indicate that some executive control processes may be less sensitive to the degree of expertise in bilingual language control than others. Our findings lend support to psycholinguistic models of bilingualism postulating a higher-order mechanism regulating language activation.



http://ift.tt/2rbjdQW

Diagnostic Laparoscopy Prior to Neoadjuvant Therapy in Pancreatic Cancer Is High Yield: an Analysis of Outcomes and Costs

Abstract

Background

There is currently no standardized regimen for management of borderline resectable pancreatic cancer (BRPC), and treatment includes varying sequences of surgery, chemotherapy, and/or radiation. This study examines the diagnostic yield and cost of performing staging diagnostic laparoscopy (SDL) prior to neoadjuvant therapy (NAT) in BRPC.

Methods

Sequential patients treated for BRPC between January 2010 and October 2013 were included. SDL was adopted in a staged fashion due to surgeon preference, and included biopsy of visible lesions and washings for cytology. Cost ratios (CRs) were calculated to compare the direct cost of the SDL versus no-SDL groups and to compare patients with positive versus negative SDL.

Results

Of 116 patients evaluated for BRPC, 75 patients underwent SDL and 19 (25%) revealed occult metastatic disease. Sixteen patients had a positive biopsy and three had positive cytology alone. There was no difference in overall treatment cost (CR 0.95, 95% CI 0.62–1.37), oncologic treatment (CR 0.66, 95% CI 0.32–1.23), or remaining surgical treatment (CR 1.14, 95% CI 0.77–1.71) for patients who underwent SDL compared to those who did not. Patients with a positive SDL incurred lower overall cost compared to those with a negative SDL (CR 0.23, 95% CI 0.16–0.32) due to lack of further surgery or radiation, and less intensive chemotherapy regimens.

Conclusions

SDL prior to NAT is a useful adjunct to CT to diagnose occult metastatic disease in BRPC.



http://ift.tt/2r70BGC

Erratum to: Biliary Intraductal Papillary Mucinous Neoplasm: the “Thread Sign”



http://ift.tt/2rQNWon

Phosphate Removal from Agricultural Drainage Water Using an Iron Oxyhydroxide Filter Material

Abstract

Phosphate discharged in agricultural drainage causes water quality degradation on local, regional, and national scales. Iron oxyhydroxide filter materials can potentially remove the soluble phosphate present in drainage waters. Laboratory saturated column experiments and preliminary small-scale field tests were carried out to evaluate the effectiveness and efficiency of a synthetic goethite iron oxyhydroxide (α-FeOOH) filter material for phosphate treatment. Original iron oxyhydroxide filter material (SG-IOH-O) and the same filter material regenerated with sodium hydroxide (SG-IOH-R) were assessed. Results of replicated laboratory experiments showed that columns packed with SG-IOH-O or SG-IOH-R almost totally removed phosphate (>98%) from drainage waters spiked with an additional 1 or 10 ppm phosphate-P (PO4-P). The column experiments with SG-IOH-O or SG-IOH-R additionally indicated that contact times of only 10 to 15 s were sufficient for near complete removal of phosphate from drainage water spiked with 1 ppm PO4-P. In an initial small-scale filter treatment system field test with SG-IOH-O, percent phosphate removal averaged 89% in the first 200 days, which then decreased to an average 40% phosphate removal in the last 80 days. Following this initial field test, two field tests, one with SG-IOH-O and the other with SG-IOH-R, were conducted concurrently over a period of 193 days, with the SG-IOH-O system phosphate removal averaging 75%, while the SG-IOH-R system phosphate removal averaged 34%. This study's findings support possible goethite iron oxyhydroxide filter material use for drainage water phosphate treatment; however, larger-scale field investigations are needed, particularly with modified regeneration procedures.



http://ift.tt/2sYKfw7

Effects of Fat Grafting Containing Stem Cells in Microstomia and Microcheilia Derived from Systemic Sclerosis

Abstract

Background

Systemic sclerosis (SSc) is an autoimmune disease with multisystem involvement, dominated by a general fibrosis. The early stage of the disease is associated with progressive damage to microcirculation, particularly in the respiratory tract, the gastrointestinal tract and skin. The face assumes a typical appearance characterized by microstomia (reduction of mouth opening) and microcheilia (thinning of the lips). These conditions cause a considerable reduction in performance status of patients. We treated them by fat grafting, rich in adipose stem cells, and we evaluated through time clinical, functional and aesthetic evaluation of oral pathology associated with SSc.

Materials and Method

From September 2014 to May 2016, we enrolled and treated seven patients in the plastic, reconstructive and aesthetic surgery clinic. Through time, we evaluated the following parameters: evaluation of mouth opening (maximum opening in superior–inferior and lateral directions) and lip thicknesses, both measured by doctors of the aforementioned operating unit; variation in the quality of life as perceived by patients according to the MHISS scale (Mouth Handicap Systemic Sclerosis); variation in severity of labial fibrosis assessed by microscopic analysis of pre- and post-fat transfer samples in the pathology clinic; safety of the protocol, according to the management of side effects resulting from the procedure; aesthetic evaluation, made by external observers and non-experts in the field, on pre- and post-operative photographs.

Results and Conclusions

We reported satisfying results, both functionally and aesthetically, for all parameters except one, for which the sample size might have proven critical. These data should be a starting point for further experimental research and clinical trials.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.



http://ift.tt/2rQO8nD

Technologische Entwicklungen in der Schlafmedizin



http://ift.tt/2s89kZ2

Mitteilungen der DGSM



http://ift.tt/2sHw4w9

Impaired laparoscopic performance of novice surgeons due to phone call distraction: a single-centre, prospective study

Abstract

Background

Distractions such as phone calls during laparoscopic surgery play an important role in many operating rooms. The aim of this single-centre, prospective study was to assess if laparoscopic performance is impaired by intraoperative phone calls in novice surgeons.

Methods

From October 2015 to June 2016, 30 novice surgeons (medical students) underwent a laparoscopic surgery training curriculum including two validated tasks (peg transfer, precision cutting) until achieving a defined level of proficiency. For testing, participants were required to perform these tasks under three conditions: no distraction (control) and two standardised distractions in terms of phone calls requiring response (mild and strong distraction). Task performance was evaluated by analysing time and accuracy of the tasks and response of the phone call.

Results

In peg transfer (easy task), mild distraction did not worsen the performance significantly, while strong distraction was linked to error and inefficiency with significantly deteriorated performance (P < 0.05). Precision cutting (difficult task) was not slowed down by mild distraction, but surgical and cognitive errors were significantly increased when participants were distracted (P < 0.05). Compared to mild distraction, participants reported a more severe subjective disturbance when they were diverted by strong distraction (P < 0.05).

Conclusion

Our data reveals that phone call distractions result in impaired laparoscopic performance under certain circumstances. To ensure patient safety, phone calls should be avoided as far as possible in operating rooms.



http://ift.tt/2r0oQ51

Comparison of single-incision laparoscopic percutaneous extraperitoneal closure (SILPEC) and open repair for pediatric inguinal hernia: a single-center retrospective cohort study of 2028 cases

Abstract

Backgroud

Recently, laparoscopic percutaneous extraperitoneal closure (LPEC) has gained increased popularity for pediatric inguinal hernia repair. To improve cosmesis, we developed single incision LPEC (SILPEC). The aim of this study was to assess the safety and feasibility of SILPEC compared with traditional open repair (OR).

Methods

This was a single-center retrospective cohort study of 2028 children who underwent inguinal hernia repair between April 2005 and August 2014. Nine hundred and ninety-five patients underwent OR and 1033 patients underwent SILPEC. Medical records were reviewed with respect to operative time, recurrence, incidence of contralateral metachronous inguinal hernia (CMIH), and complications. Patient satisfaction with cosmetic result was also investigated using questionnaires sent by mail.

Results

All SILPEC procedures were completed without conversion. Operative time was longer in the SILPEC group than in the OR group for both unilateral and bilateral surgery regardless of sex (unilateral male: p = 0.0006, unilateral female: p < 0.0001, bilateral male: p < 0.0001, bilateral female: p < 0.0001). There was no statistically significant difference in recurrence rate (p = 0.43). The incidence of CMIH was significantly higher in the OR than in the SILPEC group (p < 0.0001). No postoperative testicular atrophy was found in either group. There was no statistically significant difference in ascending testis (p = 0.09), but the frequency of surgical site infection was higher in the SILPEC than in the OR group (p = 0.0013). According to the questionnaire, operative scar was more invisible in the SILPEC than in the OR group (p < 0.0001), but both procedures had equally high levels of satisfaction for cosmetic results (p = 0.58).

Conclusion

SILPEC proved to be a safe and feasible procedure compared with OR with an equally low recurrence rate, more effectiveness for preventing CMIH, and more invisible scar.



http://ift.tt/2sk85FT

What are the differences in the outcome of laparoscopic axial (I) versus paraesophageal (II–IV) hiatal hernia repair?

Abstract

Introduction

Comparison of elective laparoscopic repair of axial vs paraesophageal hiatal hernias reveals relevant differences in both the patient collectives and the complexity of the procedures.

Materials and methods

The present uni- and multivariable analysis of data from the Herniamed Registry compares the outcome for 2047 (67.3%) (type I) axial with 996 (32.7%) (types II–IV) paraesophageal primary hiatal hernias following laparoscopic repair.

Results

Compared with the patients with axial hiatal hernias, patients with paraesophageal hiatal hernia were nine years older, had a higher ASA score (ASA III/IV: 34.8 vs 13.7%; p < 0.001), and more often at least one risk factor (38.8 vs 21.4%; p < 0.001). This led in the univariable analysis to significantly more general postoperative complications (6.0 vs 3.0%; p < 0.001). Reflecting the greater complexity of the procedures used for laparoscopic repair of paraesophageal hiatal hernias, significantly higher intraoperative organ injury rates (3.7 vs 2.3%; p = 0.033) and higher postoperative complication-related reoperation rates (2.1 vs 1.1%; p = 0.032) were identified. Univariable analysis did not reveal any significant differences in the recurrence and pain rates on one-year follow-up. Multivariable analysis did not find any evidence that the use of a mesh had a significant influence on the recurrence rate.

Conclusion

Surgical repair of paraesophageal hiatal hernia calls for an experienced surgeon as well as for corresponding intensive medicine competence because of the higher risks of general and surgical postoperative complications.



http://ift.tt/2r0nl7f

Transumbilical laparoscopic-assisted appendectomy in children: is it worth it?

Abstract

Introduction

Transumbilical laparoscopic-assisted appendectomy (TULAA) is the technique of choice for all types of appendicitis in our Department. It combines the advantages of laparoscopy (global vision and minimally invasion) and open surgery (lower cost). The objective was to assess the results of our TULAA series and compare them to the results of standard laparoscopic appendectomies (SLA) performed during the same period.

Methods

Retrospective review of total appendectomies performed since TULAA introduction (September 2003 to December 2015) with statistic analysis of the results.

Results

A total of 1309 patients underwent TULAA approach, but 126 (9.6%) needed reconversion to open appendectomy, 1 (0.08%) to SLA, and 9 (0.7%) introduction of a second port. Mean age and weight of patients was 121.5 ± 36 months and 37.6 ± 14 kg, respectively. Mean operative time was 40.9 ± 15.5 min, ranging from 11 to 110. All types of appendicitis were present, with 394 being complicated (29.9%). Postoperative complications were seen in 168 patients (14.3%), 37 being readmitted (3.2%), and only five needing reintervention (Two intestinal occlusions and three abscess debridement). When comparing TULAA and SLA, there were no significant differences in the length of hospitalization, time to tolerate soft diet, analgesic requirements, and complications depending on the type of appendicitis, but TULAA was significantly faster and cheaper (average 900€).

Conclusions

In our hands, TULAA has shown to be effective, easy to learn, and fast to perform. Low surgical cost is probably its principal advantage, which might be encouraging in times of crisis.



http://ift.tt/2sjXIBS

Development of an In Vitro PIV Setup for Preliminary Investigation of the Effects of Aortic Compliance on Flow Patterns and Hemodynamics

Abstract

The aorta with its compliance plays a major role in hemodynamics as it saves a portion of ejected blood during systole which is then released in diastole. The aortic compliance decreases with increasing age, which is related to several cardiovascular imparities and diseases. Changes in flow patterns and pressure curves, due to varying aortic compliance, are difficult to investigate in vivo. As a result, the aim of the present work was to develop an in vitro setup enabling standardized investigations on the effect of compliance changes on flow patterns and pressure curves. Therefore an experimental setup with an anatomically correct silicone phantom of the aortic arch was developed, suitable for optical flow measurements under pulsatile inflow conditions. The setup was developed for precise adjustments of different compliances and optical flow measurements. Particle image velocimetry measurements were carried out downstream of the aortic valve in the center plane perpendicular to the valve with compliance adjusted between 0.62 × 10−3 to 1.82 × 10−3 mmHg−1. Preliminary results of the in vitro investigations showed that decreases in compliance results in significant increases in pressure changes with respect to time (dp/dt) and altered pressure curves in the aortic arch. In terms of flow, an increased aortic stiffness lead to higher mean velocities and decreased vortex development in the aortic sinuses. As in vivo validation and translation remains difficult, the results have to be considered as preliminary in vitro insights into the mechanisms of (age-related) compliance changes.



http://ift.tt/2sHQGEt

The effects of strength training versus ski-ergometer training on double-poling capacity of elite junior cross-country skiers

Abstract

Purpose

To compare the effects of strength training versus ski-ergometer training on double-poling gross efficiency (GE), maximal speed (V max), peak oxygen uptake ( \(\dot{V}{\text{O}}_2}}\) ) for elite male and female junior cross-country skiers.

Methods

Thirty-three elite junior cross-country skiers completed a 6-week training-intervention period with two additional 40-min training sessions per week. The participants were matched in pairs and within each pair randomly assigned to either a strength-training group (STR) or a ski-ergometer-training group (ERG). Before and after the intervention, the participants completed three treadmill roller-skiing tests to determine GE, V max, and \(\dot{V}{\text{O}}_2}}\) . Mixed between-within subjects analysis of variance (ANOVA) was conducted to evaluate differences between and within groups. Paired samples t tests were used as post hoc tests to investigate within-group differences.

Results

Both groups improved their V max and \(\dot{V}{\text{O}}_2}}\) expressed absolutely (all P < 0.01). For the gender-specific sub-groups, it was found that the female skiers in both groups improved both V max and \(\dot{V}{\text{O}}_2}}\) expressed absolutely (all P < 0.05), whereas the only within-group differences found for the men were improvements of V max in the STR group. No between-group differences were found for any of the investigated variables.

Conclusions

Physiological and performance-related variables of importance for skiers were improved for both training regimes. The results demonstrate that the female skiers' physiological adaptations to training, in general, were greater than those of the men. The magnitude of the physiological adaptations was similar for both training regimes.



http://ift.tt/2raewqx

Digital tomosynthesis as a new diagnostic tool for assessing of chronic gout arthritic feet and ankles: comparison of plain radiography and computed tomography

Abstract

This aimed to compare the three radiographic methods of digital tomosynthesis (DT), plain radiography, and computed tomography (CT) for evaluating changes in feet of patients with chronic gouty arthritis. Two independent radiologists read the plain radiography, DT, and CT images of 30 male patients with gout. The degrees of erosion and joint space narrowing were scored using the Sharp–van der Heijde scoring method in 18 foot joints, which consisted of four proximal interphalangeal and one interphalangeal joint of the first toe, five metatarsophalangeal, five tarsometatarsal, and three naviculo-cuneiform joints of the foot. DT showed high reproducibility [0.929 for intraobserver intraclass correlation coefficient (ICC) and 0.838 for interobserver ICC]. DT showed similar results to those of CT and superior results to those of plain radiography for evaluating radiographic damage [mean total score, 8.5 ± 14.6 (±standard deviation) for plain radiography, 12.9 ± 12.4 for DT, and 12.6 ± 11.2 for CT]. This study showed that DT is a good method for evaluating radiographic changes in patients with gout. Further research is needed to apply DT to actual clinical settings.



http://ift.tt/2sjQFcJ

Real-life 10-year retention rate of first-line anti-TNF drugs for inflammatory arthritides in adult- and juvenile-onset populations: similarities and differences

Abstract

The aim of this study is to retrospectively analyze 10-year drug survival of first-line TNF inhibitor (TNFi) in rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), and juvenile idiopathic arthritis (JIA) patients, comparing withdrawal rates and discontinuation pattern between adult- and juvenile-onset populations. RA, AS, PsA, and JIA patients treated with infliximab, etanercept, or adalimumab as first TNFi between 1999 and 2015 were extracted from a local registry. Drug survival up to 10-year follow-up was evaluated by the Kaplan-Meier method and compared according to age (adult vs juvenile onset), TNFi agent, and discontinuation reason by a stratified log-rank test. Three hundred sixty JIA (205 etanercept, 66 adalimumab, and 89 infliximab) and 951 (607 RA, 188 AS, and 156 PsA) adult patients (464 infliximab, 262 adalimumab, and 225 etanercept) were included. After exclusion of systemic-onset JIA (18.5%), overall 10-year retention rate was 31.8%, with no difference between adult- and juvenile-onset patients (32.1 and 30.2%, respectively; HR 0.938 [95% CI 0.782–1.125]). Etanercept showed the highest drug survival in adult-onset population (p < 0.0001 vs both monoclonal antibodies) and infliximab the lowest in juvenile-onset population (p = 0.005 vs adalimumab and p < 0.0001 vs etanercept). Inefficacy was the most frequent reason for TNFi withdrawal in adult population (29.75%) with a significantly higher risk of discontinuation than in juvenile-onset subgroup (HR 1.390 [95% CI 1.060–1.824]). Serious infections and malignancies caused TNFi withdrawal only in adult whereas gastrointestinal, neuropsychiatric, and ocular complications quite only in juvenile patients. Despite a similar 10-year drug survival, adult- and juvenile-onset subpopulations showed a significantly different pattern of TNFi reasons for discontinuation.



http://ift.tt/2qZXmg4

Apremilast: A Novel Oral Treatment for Psoriasis and Psoriatic Arthritis

Abstract

Psoriasis is a chronic immune-mediated disease associated with several co-morbidities and negative impacts on a patient's quality of life. Despite the advances in biologic therapy, there are still unmet needs in the treatment of psoriasis, as current treatments are limited in terms of long-term efficacy, tolerability, safety, route of administration, and cost. Apremilast is an oral, small-molecule phosphodiesterase 4 inhibitor that works intracellularly by blocking the degradation of cyclic adenosine 3′,5′-monophosphate, resulting in increased intracellular cyclic adenosine 3′,5′-monophosphate levels in phosphodiesterase 4-expressing cells. This inhibition results in the reduced expression of proinflammatory mediators, and an increased expression of anti-inflammatory mediators, providing apremilast with an anti-inflammatory rather than immunosuppressive mode of action. Apremilast offers a novel therapeutic option for patients with psoriasis and psoriatic arthritis and may fulfill some of the unmet needs in patients with psoriasis. Potential advantages of apremilast include moderate activity for both psoriasis and psoriatic arthritis and efficacy in difficult-to-treat forms of psoriasis, a good safety profile, no need of laboratory prescreening or ongoing monitoring for laboratory parameters, owing to the absence of organ toxicity, a potentially advantageous weight loss effect, and a convenient oral administration and dosing. Cost effectiveness and health economics considerations will be decisive in determining the ultimate place of apremilast in the therapeutic armamentarium for psoriasis.



http://ift.tt/2s0oSNM

Vaginal drug delivery for the localised treatment of cervical cancer

Abstract

Cervical cancer is usually treated by surgery, with the more advanced cancers requiring adjuvant chemotherapy or radiotherapy. The location of the cervix makes it easily accessible through the vagina for the localised delivery of chemotherapeutic drugs. Localised delivery has the advantage of direct delivery to the site of action resulting in a lower dose having to be required and a reduction in systemic side effects. This approach would be advantageous for fertility sparing surgery, whereby localised delivery could be used to reduce tumour size allowing for a much smaller tumour to be removed, reducing the risk of preterm birth. Furthermore, localised delivery could be used after surgery to reduce the risk of recurrence, which is significantly higher in fertility sparing surgery compared to standard surgery. In this paper, we discuss the number of vaginal dosage forms that have investigated for this purpose, including tablets, rings, bioadhesive and cervical caps. APIs under investigation have ranged from well-established chemotherapeutic drugs to more experimental compounds.



http://ift.tt/2sI52F8

Tetramethylpyrazine attenuates periorbital allodynia and neuroinflammation in a model of traumatic brain injury

Abstract

Background

Traumatic brain injury (TBI) is a public health issue. As the major complaint in 51% of TBI patients, chronic pain is an important aspect in TBI treatment. Tetramethylpyrazine (TMP) is an important compound in Ligustrazine, an analgesic drug in traditional Chinese medicine, but its potential in relieving pain symptom in TBI has not been tested. We established a TBI mouse model with controlled cortical impact (CCI), and measured periorbital hypersensitivity with von Frey monofilaments. We examined activated microglia and astrocytes and the levels of substance P (SP) and inducible isoform of nitric oxide synthase (iNOS) with immunohistochemistry, measured mRNA and protein levels of proinflammatory cytokines with qPCR and enzyme-linked immunosorbent assay, respectively. Western blot was employed to detect molecules in NF-κB signaling pathway.

Results

TMP significantly attenuated periorbital hypersensitivity in TBI mice. Within 3 days after CCI, TMP attenuated activation of microglia and astrocytes, levels of SP, iNOS, and CGRP in trigeminal pathway, and levels of proinflammatory cytokines (including IL-6, TNF-α, IL-12). In isolated microglia, TMP attenuated the effects of lipopolysaccharide on the phosphorylation of cytoplasmic IKKα/β and IKB-α, and levels of nucleic p65.

Conclusion

TMP reversed periorbital hypersensitivity by limiting neuroinflammation at the primary stage of TBI, and could be a promising drug for pain treatment in TBI.



http://ift.tt/2sHtXsf

Fiber-type distribution in insect leg muscles parallels similarities and differences in the functional role of insect walking legs

Abstract

Previous studies have demonstrated that myofibrillar ATPase (mATPase) enzyme activity in muscle fibers determines their contraction properties. We analyzed mATPase activities in muscles of the front, middle and hind legs of the orthopteran stick insect (Carausius morosus) to test the hypothesis that differences in muscle fiber types and distributions reflected differences in their behavioral functions. Our data show that all muscles are composed of at least three fiber types, fast, intermediate and slow, and demonstrate that: (1) in the femoral muscles (extensor and flexor tibiae) of all legs, the number of fast fibers decreases from proximal to distal, with a concomitant increase in the number of slow fibers. (2) The swing phase muscles protractor coxae and levator trochanteris, have smaller percentages of slow fibers compared to the antagonist stance muscles retractor coxae and depressor trochanteris. (3) The percentage of slow fibers in the retractor coxae and depressor trochanteris increases significantly from front to hind legs. These results suggest that fiber-type distribution in leg muscles of insects is not identical across leg muscles but tuned towards the specific function of a given muscle in the locomotor system.



http://ift.tt/2s88ifQ

Digital tomosynthesis as a new diagnostic tool for assessing of chronic gout arthritic feet and ankles: comparison of plain radiography and computed tomography

Abstract

This aimed to compare the three radiographic methods of digital tomosynthesis (DT), plain radiography, and computed tomography (CT) for evaluating changes in feet of patients with chronic gouty arthritis. Two independent radiologists read the plain radiography, DT, and CT images of 30 male patients with gout. The degrees of erosion and joint space narrowing were scored using the Sharp–van der Heijde scoring method in 18 foot joints, which consisted of four proximal interphalangeal and one interphalangeal joint of the first toe, five metatarsophalangeal, five tarsometatarsal, and three naviculo-cuneiform joints of the foot. DT showed high reproducibility [0.929 for intraobserver intraclass correlation coefficient (ICC) and 0.838 for interobserver ICC]. DT showed similar results to those of CT and superior results to those of plain radiography for evaluating radiographic damage [mean total score, 8.5 ± 14.6 (±standard deviation) for plain radiography, 12.9 ± 12.4 for DT, and 12.6 ± 11.2 for CT]. This study showed that DT is a good method for evaluating radiographic changes in patients with gout. Further research is needed to apply DT to actual clinical settings.



http://ift.tt/2sjQFcJ

Real-life 10-year retention rate of first-line anti-TNF drugs for inflammatory arthritides in adult- and juvenile-onset populations: similarities and differences

Abstract

The aim of this study is to retrospectively analyze 10-year drug survival of first-line TNF inhibitor (TNFi) in rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), and juvenile idiopathic arthritis (JIA) patients, comparing withdrawal rates and discontinuation pattern between adult- and juvenile-onset populations. RA, AS, PsA, and JIA patients treated with infliximab, etanercept, or adalimumab as first TNFi between 1999 and 2015 were extracted from a local registry. Drug survival up to 10-year follow-up was evaluated by the Kaplan-Meier method and compared according to age (adult vs juvenile onset), TNFi agent, and discontinuation reason by a stratified log-rank test. Three hundred sixty JIA (205 etanercept, 66 adalimumab, and 89 infliximab) and 951 (607 RA, 188 AS, and 156 PsA) adult patients (464 infliximab, 262 adalimumab, and 225 etanercept) were included. After exclusion of systemic-onset JIA (18.5%), overall 10-year retention rate was 31.8%, with no difference between adult- and juvenile-onset patients (32.1 and 30.2%, respectively; HR 0.938 [95% CI 0.782–1.125]). Etanercept showed the highest drug survival in adult-onset population (p < 0.0001 vs both monoclonal antibodies) and infliximab the lowest in juvenile-onset population (p = 0.005 vs adalimumab and p < 0.0001 vs etanercept). Inefficacy was the most frequent reason for TNFi withdrawal in adult population (29.75%) with a significantly higher risk of discontinuation than in juvenile-onset subgroup (HR 1.390 [95% CI 1.060–1.824]). Serious infections and malignancies caused TNFi withdrawal only in adult whereas gastrointestinal, neuropsychiatric, and ocular complications quite only in juvenile patients. Despite a similar 10-year drug survival, adult- and juvenile-onset subpopulations showed a significantly different pattern of TNFi reasons for discontinuation.



http://ift.tt/2qZXmg4

Comprehensive Model for Remediation of Sandy Soils Contaminated with Volatile Organic Compounds Using Thermal Enhancement of Soil Vapor Extraction Method

Abstract

In today's world, remediation of the environmental pollutants including soil contaminations is among the main issues and concerns considered by environmental scientists. Vapor extraction method is an in situ method to clean up volatile and semi-volatile contaminants of soil especially in unsaturated areas. Thermal enhancement to extract vapors includes different technologies. Its purpose is to transfer heat to the subsurface of the soil to increase the vapor pressure of volatile organic compounds and, consequently, to increase the amount of extracted VOCs. In this study, modeling was done by using laboratory data after screening. Validation was also done with the help of an artificial neural network using the response surface methodology. After training and evaluating the model, it was found that this model determines the amount of contaminant removal rate according to available data and different temperatures by good measures. The correlation coefficient square was equal to 0.95 in the validation section by the neural network. This coefficient was equal to 0.99 in the original model. At the end, a contaminant removal formula for sandy soils has been presented. As a result, due to the proximity of the correlation coefficient to 1, this model can be used to predict the removal rate of thermal enhancement in the relevant circumstances with a slight error.



http://ift.tt/2sYsZax

Headache in children and dynamic thiol/disulfide balance evaluation with a new method

Abstract

Headache is one of the most common causes of presentation to the physician in children. We aimed to evaluate the dynamic thiol/disulfide homeostasis with a new method in children with headache and also to investigate the relationship between the headache type, pain severity and duration in our study. We included 40 patients diagnosed with migraine, 40 patients diagnosed with tension-type headache (TTH) and 40 healthy children in the study. No significant difference was found between the total thiol, native thiol, and disulfide levels of the patient and control groups. However, the disulfide/native thiol and disulfide/total thiol ratios were higher in the migraine group than in the TTH and control groups. No correlation was found between the Pediatric Migraine Disability Assessment (PedMIDAS) score and the headache duration and any of the thiol/disulfide parameters. A negative correlation was found between the total thiol and native thiol levels and the PedMIDAS score in the TTH group. Migraine and TTH patients have different effect to thiol/disulfide homeostasis.



http://ift.tt/2rQabLi

Pharmacodynamics of Insulin Preparations Administered in Different Subcutaneous Injection Sites: Are There Differences Between Healthy Subjects Versus Diabetic Patients?



http://ift.tt/2rQlXoR

Pharmacokinetic Properties of Fast-acting Insulin Aspart Administered in Different Subcutaneous Injection Regions: Response to the commentary by Nuggehally R. Srinivas



http://ift.tt/2r5AHmN

Effects of progressive resistance training and weight loss versus weight loss alone on inflammatory and endothelial biomarkers in older adults with type 2 diabetes

Abstract

Purpose

Type 2 diabetes has been associated with an increase in inflammatory and endothelial biomarkers, which are associated with an increased risk of cardiovascular disease and diabetes-related complications. This study examined the effects of high-intensity progressive resistance training (PRT) with moderate weight loss (WL) versus WL alone on inflammatory and endothelial biomarkers in older overweight adults with type 2 diabetes.

Methods

This was a 12-month randomized controlled trial in which 36 inactive, overweight adults aged 60–80 years with poorly controlled type 2 diabetes were randomized to 6 months of supervised PRT + WL or stretching (sham) exercise plus WL followed by 6 months of home-training without dietary modification. Fasted blood samples were collected at baseline and subsequent 3-month intervals with the following inflammatory [interleukin (IL)-10, IL-6, tumor necrosis factor (TNF)-α, adiponectin] and endothelial markers [resistin and intercellular adhesion molecule (ICAM)-1)] assessed.

Results

No significant within-group changes or between-group differences were detected for any inflammatory or endothelial biomarker following the 6-month supervised exercise and WL phase. There was a greater reduction in IL-10 at 9 months in the PRT + WL relative to WL group (P = 0.033). There was also a greater reduction in TNF-α at 9 and 12 months in the PRT + WL relative to WL group (P = 0.026 and P = 0.024, respectively). Serum adiponectin increased in the PRT + WL relative to WL group after 12 months (P = 0.036). All results were adjusted for baseline values, age, weight, sex, diabetes duration, medication use and any change in medication.

Conclusions

Long-term participation in PRT, independent of change in weight, can result in some improvements in certain inflammatory markers in older overweight adults with type 2 diabetes.



http://ift.tt/2sHCCuK

Gangrenous cholecystitis: innovative laparoscopic techniques to facilitate subtotal fenestrating cholecystectomy when a critical view of safety cannot be achieved

Abstract

Background

Gangrenous cholecystitis is associated with a higher conversion rate of conversion from laparoscopic to open than acute non-gangrenous cholecystitis. New strategies and techniques are needed to decrease conversion rates and improve outcomes.

Methods

In this article, we provide a richly detailed, illustrated description of a modified fundus-first technique that we have developed over the last 15 years and now use routinely with rare conversions. We also compared outcomes of laparoscopic (LC) and open (OC) approaches for pathologically confirmed gangrenous cholecystitis in 146 patients during 1995–2005, the first 10 years during which these two approaches were performed contemporaneously at our institution on comparable patients.

Results

Among the 142 patients that met the inclusion criteria, laparoscopic procedures were started in 112 (79%) of these patients, with successful completion in 72 resulting in an overall conversion rate of 36%. During the last 5 years, however, in cases where the described laparoscopic technique was used, no patient has required conversion. The laparoscopic LC group had shorter average ICU stay (p < 0.05) and overall length of stay (2 vs 6 days, p < 0.001). Intraoperative cholangiography was completed in 37 of 72 LC patients (52%) versus 6 of 30 OC (20%). In five of the LC patients, a filling defect was seen on the cholangiogram and laparoscopic transcystic common bile duct stones, thereby avoiding a second anesthetic and endoscopic procedure.

Conclusions

In the setting of severe inflammation, a number of procedural modifications can be incorporated to allow the surgeon to approach dissection of the gangrenous gallbladder using a flexible operative plan designed to optimize safe completion of this challenging procedure, with the expected improvement in surgical outcomes.



http://ift.tt/2s82pPU

The general surgeon’s perspective of rectus diastasis. A systematic review of treatment options

Abstract

Background

Diastasis of the rectus abdominis muscles (DRAM) is characterised by thinning and widening of the linea alba, combined with laxity of the ventral abdominal musculature. This causes the midline to "bulge" when intra-abdominal pressure is increased. Plastic surgery treatment for DRAM has been thoroughly evaluated, though general surgical treatments and the efficacy of physiotherapy remain elusive. The aim of this systematic literature review is to evaluate both general surgical and physiotherapeutic treatment options for restoring DRAM in terms of postoperative complications, patient satisfaction, and recurrence rates.

Method

MEDLINE®, Embase, PubMed, PubMed Central®, The cochrane central registry of controlled trials (CENTRAL), Google Scholar, and the Physiotherapy Evidence Database (PEDro) were searched using the following terms: 'rectus diastasis', 'diastasis recti', 'midline', and 'abdominal wall'. All clinical studies concerning general surgical or physiotherapeutic treatment of DRAM were eligible for inclusion.

Result

Twenty articles describing 1.691 patients (1.591 surgery/100 physiotherapy) were included. Surgical interventions were classified as plication techniques (313 patients; 254 open/59 laparoscopic), modified hernia repair techniques (68 patients, all open), and combined hernia & DRAM techniques (1.210 patients; 1.149 open/40 hybrid). The overall methodological quality was low. Plication techniques with interrupted sutures and mesh reinforcement were applied most frequently for DRAM repair. Open repairs were performed in 85% of patients. There was no difference in postoperative complications or recurrence rate after laparoscopic or open procedures, or between plication and modified hernia repair techniques. Physiotherapy programmes were unable to reduce IRD in a relaxed state. Though reduction of IRD during muscle contraction was described.

Conclusion

Both plication-based methods and hernia repair methods are used for DRAM repair. Based on the current literature, no clear distinction in recurrence rate, postoperative complications, or patient reported outcomes can be made. Complete resolution of DRAM, measured in a relaxed state, following a physiotherapy training programme is not described in current literature. Physiotherapy can achieve a limited reduction in IRD during muscle contraction, though the impact of this finding on patient satisfaction, cosmesis, or function outcome is unclear.



http://ift.tt/2sHS75S

Tetramethylpyrazine attenuates periorbital allodynia and neuroinflammation in a model of traumatic brain injury

Abstract

Background

Traumatic brain injury (TBI) is a public health issue. As the major complaint in 51% of TBI patients, chronic pain is an important aspect in TBI treatment. Tetramethylpyrazine (TMP) is an important compound in Ligustrazine, an analgesic drug in traditional Chinese medicine, but its potential in relieving pain symptom in TBI has not been tested. We established a TBI mouse model with controlled cortical impact (CCI), and measured periorbital hypersensitivity with von Frey monofilaments. We examined activated microglia and astrocytes and the levels of substance P (SP) and inducible isoform of nitric oxide synthase (iNOS) with immunohistochemistry, measured mRNA and protein levels of proinflammatory cytokines with qPCR and enzyme-linked immunosorbent assay, respectively. Western blot was employed to detect molecules in NF-κB signaling pathway.

Results

TMP significantly attenuated periorbital hypersensitivity in TBI mice. Within 3 days after CCI, TMP attenuated activation of microglia and astrocytes, levels of SP, iNOS, and CGRP in trigeminal pathway, and levels of proinflammatory cytokines (including IL-6, TNF-α, IL-12). In isolated microglia, TMP attenuated the effects of lipopolysaccharide on the phosphorylation of cytoplasmic IKKα/β and IKB-α, and levels of nucleic p65.

Conclusion

TMP reversed periorbital hypersensitivity by limiting neuroinflammation at the primary stage of TBI, and could be a promising drug for pain treatment in TBI.



http://ift.tt/2sHtXsf

Clinical Signs, Pathophysiology and Management of Cutaneous Side Effects of Anti-Tumor Necrosis Factor Agents

Abstract

Approximately one in four patients treated with anti-TNF agents (infliximab, etanercept, adalimumab, certolizumab, and golimumab) develops cutaneous adverse events, typically months to years after the initiation of treatment, with xerosis cutis, eczema (often psoriasiform), psoriasis, palmoplantar pustulosis, cutaneous infections, alopecia, and skin cancer being the most frequently encountered. The typical skin lesion of anti-tumor necrosis factor (TNF)-treated patients is orange–red psoriasiform eczema affecting the flexures, genitalia, scalp, or face, with high susceptibility to bacterial superinfection with Staphylococcus aureus. When adequate dermatological treatment is administered to patients with skin lesions receiving anti-TNF treatment, the discontinuation of anti-TNF agents is only rarely required. Smoking, female sex, and Crohn's disease are most frequently observed as risk factors for anti-TNF-induced cutaneous adverse events. The underlying pathophysiology is still poorly understood, but epidermal permeability barrier dysfunction, increased susceptibility to bacterial superinfection, and cytokines derived from T helper (Th) 1 (interferon-γ), Th17 cells (interleukin [IL]-17A and IL-22), plasmocytic dendritic cells (interferon-α), and keratinocytes (IL-36γ and IL-17C) appear to play a role. In this review, we describe the clinical characteristics, risk factors, pathophysiology, and management of cutaneous adverse events of patients treated with anti-TNF agents. In addition, we try to give some practical guidance on how to prevent and manage the skin changes in anti-TNF-treated patients, based on our own experience with dermatological care in a large cohort of inflammatory bowel disease patients receiving anti-TNF therapy.



http://ift.tt/2s82oLQ

Erratum to: High incidence of periprosthetic joint infection with propionibacterium acnes after the use of a stemless shoulder prosthesis with metaphyseal screw fixation - a retrospective cohort study of 241 patients propionibacter infections after eclipse TSA



http://ift.tt/2rZLi1F

Leishmaniasis

Zusammenfassung

Das zeitlich verzögerte Auftreten einer Papel nach einem Auslandsaufenthalt kann auf das Vorliegen einer kutanen Leishmaniasis hinweisen. Histologisch zeigt sich eine granulomatöse Entzündungsreaktion, in den Histiozyten findet man in der Giemsa-Färbung intrazelluläre Parasiten. Mittels Polymerasekettenreaktion aus dem Gewebe oder der Kultur lassen sich potenzielle Differenzialdiagnosen ausschließen, aber auch die Leishmania-Subspezies identifizieren. Letzteres ist wichtig für die Wahl des optimalen Therapieregimes.



http://ift.tt/2sHx0Rd

Deltamethrin as inductor agent of precocious ovarian degeneration in Rhipicephalus sanguineus s.l. (Acari: Ixodidae) ticks

Abstract

The cosmopolitan species Rhipicephalus sanguineus s.l. is one of the most widely distributed ticks all over the world. These ectoparasites are vectors of several pathogens and cause significant direct damage to their hosts. The biological success of these ectoparasites has been attributed to their ovaries and salivary glands, organs that ensure their survival in various environmental conditions. The importance of the ovaries in ticks is that, after mating, the individuals are able to lay approximately three thousand eggs. The present study had the objective to demonstrate the effects of deltamethrin obtained from the product Butox P CE 25® (MSD Saúde Animal, São Paulo, Brazil) on the ovarian development of R. sanguineus s.l. females. The chemical was tested in the concentrations of 25, 50, 100 and 200 ppm (respectively 80, 40, 20 and 10 times lower than the recommended by the manufacturer). Through the application of histological techniques and HE staining, the results showed that the deltamethrin was potentially able to modify the morphophysiology of the oocytes in all developmental stages, interfering in the vitellogenesis, causing intense vacuolation, cytoplasmic disorganization, and alterations in the chorion secretion. In addition, the chemical affected the germ vesicle of some oocytes, causing damages and hypertrophy, fragmenting the chromatin and forming bodies strongly stained by hematoxylin. Therefore, this study confirmed that the deltamethrin had an important action on the reproductive system of the R. sanguineus s.l. females, causing the precocious structural disorganization of the germ cells, consequently preventing the generation of new individuals.



http://ift.tt/2s86KCs

Nanoparticle-in-gel system for delivery of vitamin C for topical application

Abstract

Hyperpigmentation is a dermal condition of melanocyte proliferation, induced by various factors like ultraviolet radiation producing reactive oxygen species, DNA damage, and apoptosis. The application of topical antioxidants through the different type of formulations can help to prevent oxidative damage to the skin. L-ascorbic acid (vitamin C) is a water-soluble compound and the most abundant antioxidant in human skin, but this vitamin is unstable and loses its potency with poor formulation strategies. Nanotechnology has been effectively used to promote stability and therapeutic activity of various drug molecules. With this context, the objective of the work was set to formulate a topical delivery system of vitamin C nanoparticles incorporated into the polymeric gel. Vitamin C (50 mg) was loaded into ethyl cellulose nanoparticles, of varying concentrations (50–250 mg), by the solvent evaporation method and subsequently incorporated into hydroxypropyl methyl cellulose gels (3, 5, and 7%). The formulations were characterized for various physico-chemical properties such as particle size, drug content, entrapment efficiency, and drug-polymer interactions. In vitro, drug release studies were conducted by using dialysis bag method and Franz diffusion cell for the nanoparticles and gel formulations, respectively. The optimized formulation exhibited sustained release over 8 h. The ex vivo skin permeation studies were performed and the amount of drug retained and released through the skin were determined. The results obtained from the study proved the potentiality and suitability of this novel system to treat hyperpigmentation.



http://ift.tt/2r5KSru