Nevin Manimala

Liver Transpl. 2021 Oct 7. doi: 10.1002/lt.26326. Online ahead of print.

ABSTRACT

Normothermic machine perfusion (NMP) allows objective assessment of donor liver transplantability. Several viability evaluation protocols have been established, consisting of parameters such as perfusate lactate clearance, pH, transaminase levels, and the production and composition of bile. The aims of this study were to assess three such protocols, namely those introduced by the teams from Birmingham (BP), Cambridge (CP) and Groningen (GP), using a cohort of high-risk marginal livers that had initially been deemed unsuitable for transplantation, and to introduce the concept of the viability assessment sensitivity and specificity. To demonstrate and quantify the diagnostic accuracy of these protocols, we used a composite outcome of organ utilisation and 24-month graft survival as a surrogate endpoint. The effects of assessment modifications, including the removal of the most stringent components of the protocols, were also assessed. Of the 31 organs, 22 were transplanted after a period of NMP, of which 18 achieved the outcome of 24-month graft survival. The BP yielded 94% sensitivity and 50% specificity when predicting this outcome. The GP and CP both seemed overly conservative, with one and zero organs, respectively, meeting these protocols. Modification of the GP and CP to exclude their most stringent components increased this to 11 and 8 organs, respectively, and resulted in moderate sensitivity (56% and 44%) but high specificity (92% and 100%, respectively) with respect to the composite outcome. This study shows that the normothermic assessment protocols can be useful in identifying potentially viable organs, but that the balance of risk of under- and overutilization varies by protocol.

PMID:34619014 | DOI:10.1002/lt.26326

Scand J Med Sci Sports. 2021 Oct 7. doi: 10.1111/sms.14073. Online ahead of print.

ABSTRACT

This study aimed to determine the specific adaptations provoked by power-oriented resistance training using light (LL-PT, 40% 1-RM) vs. heavy (HL-PT, 80% 1-RM) loads in older adults. Using a randomized within-subject study design, 45 older adults (>65 years) completed an 8-week control period (CTR) followed by 12 weeks of unilateral LL-PT vs. HL-PT on a leg press. The 1-RM, theoretical force at zero velocity (F₀ ), maximal unloaded velocity (V₀ ), and maximal muscle power (P_max ) were determined through a force-velocity relationship test. Isometrically, the rate of force development (RFD) and the corresponding muscle excitation of the knee extensor muscles were assessed. In addition, muscle cross-sectional area (CSA) and architecture of two quadriceps muscles were determined. Changes after CTR, LL-PT and HL-PT were compared using linear mixed models. HL-PT provoked greater improvements in 1-RM and F₀ (effect size (ES)=0.55-0.68; p<0.001) than those observed after LL-PT (ES=0.27-0.47; p≤0.001) (post-hoc treatment effect, p≤0.057). By contrast, ES of changes in V₀ were greater in LL-PT compared to HL-PT (ES=0.71, p<0.001 vs. ES=0.39, p<0.001), but this difference was not statistically significant. Both power training interventions elicited a moderate increase in P_max (ES=0.65-0.69, p<0.001). Only LL-PT improved early RFD (i.e., ≤100 ms) and muscle excitation (ES=0.36-0.60, p<0.05). Increased CSA were noted after both power training programs (ES=0.13-0.35, p<0.035), whereas pennation angle increased only after HL-PT (ES=0.37, p=0.004). In conclusion, HL-PT seems to be more effective in improving the capability to generate large forces, whereas LL-PT appears to trigger greater gains in movement velocity in older adults. However, both interventions promoted similar increases in muscle power as well as muscle hypertrophy.

PMID:34618979 | DOI:10.1111/sms.14073

Hepatology. 2021 Oct 7. doi: 10.1002/hep.32185. Online ahead of print.

ABSTRACT

BACKGROUND: Most patients with hepatocellular carcinoma (HCC) are diagnosed at a late stage, highlighting the need for more accurate surveillance tests. Although biomarkers for HCC early detection have promising data in phase II case-control studies, evaluation in cohort studies is critical prior to adoption in practice.

METHODS: We leveraged a prospective cohort of patients with Child Pugh A or B cirrhosis who were followed until incident HCC, liver transplantation, death, or lost to follow-up. We used a prospective specimen-collection, retrospective-blinded-evaluation (PRoBE) design for biomarker evaluation of GALAD, longitudinal GALAD and the HES algorithm -compared to alpha fetoprotein (AFP) – using patient-level sensitivity and screening-level specificity.

RESULTS: Of 397 patients with cirrhosis, 42 patients developed HCC (57.1% early-stage) over a median of 2.0 years. Longitudinal GALAD had the highest c-statistic for HCC detection (0.85, 95%CI 0.77 – 0.92), compared to single-timepoint GALAD (0.79, 95%CI 0.71 – 0.87), AFP (0.77, 95%CI 0.69 – 0.85), and HES (0.76, 95%CI 0.67 – 0.83). When specificity was fixed at 90%, the sensitivity for HCC of single-timepoint and longitudinal GALAD was 54.8% and 66.7%, respectively, compared to 40.5% for AFP. Sensitivity for HCC detection was higher when restricted to patients with biomarker assessment within 6 months prior to HCC diagnosis, with the highest sensitivities observed for single-timepoint (72.0%) and longitudinal GALAD (64.0%), respectively. Sensitivity of single-timepoint and longitudinal GALAD for early-stage HCC was 53.8% and 69.2%, respectively.

CONCLUSION: GALAD demonstrated high sensitivity for HCC detection in a cohort of patients with cirrhosis. Validation of these results are warranted in large phase III datasets.

PMID:34618932 | DOI:10.1002/hep.32185

Aesthet Surg J. 2021 Oct 7:sjab355. doi: 10.1093/asj/sjab355. Online ahead of print.

ABSTRACT

BACKGROUND: Capsular Contracture (CC) is the most common long-term complication of breast surgery with prosthesis. Leukotriene Receptor Antagonists (LRAs) have been tested as a potential treatment; however, mixed results have been observed.

OBJECTIVES: This study presents a meta-analysis to clarify the treatment and prophylactic capabilities of LRAs in the management of CC.

METHODS: A systematic literature search in the most popular English databases was performed to identify relevant primary publications. We included all studies that evaluated the treatment and preventive capabilities of LRAs using the Baker scale assessment.

RESULTS: Six eligible studies were included based on predefined inclusion and exclusion criteria, totalling 2276 breasts, out of which 775 did not receive LRAs and 1501 did. Final pooled results showed that LRAs could help manage CC with a Risk Difference (RD) of -0.38 with the corresponding 95% Confidence Interval (CI) between -0.69 and -0.08, showing statistical significance at a Z value of 2.48, p=0.01. Subgroup analysis based on the type of drug used showed that only montelukast yielded statistical significance (RD=-0.27, 95% CI between -0.51 and -0.03, Z=2.20, p=0.03). Zafirlukast did not seem to influence CC. Further subgroup analysis based on treatment timing showed that prophylaxis was ineffective and only treatment for ongoing CC yielded statistical significance.

CONCLUSIONS: The current meta-analysis proved that LRAs could be used in the management of CC. Only treatment for the ongoing CC showed statistical significance. Montelukast seemed to be more efficient with a safer profile for adverse effects, while zafirlukast yielded no statistical significance.

PMID:34618886 | DOI:10.1093/asj/sjab355

PLoS One. 2021 Oct 7;16(10):e0258169. doi: 10.1371/journal.pone.0258169. eCollection 2021.

ABSTRACT

INTRODUCTION: Congestion in emergency departments [ED] is a significant challenge worldwide. Any delay in the timely and immediate medical care provided in the ED can affect patient morbidity and mortality. Our research analyzed the use of an innovative platform to improve patient navigation in the ED, as well as provide updated information about their care. Our hope is that this can improve ED efficiency and improve overall patient care.

OBJECTIVE: The primary objective of our study was to determine whether the use of an automatic push notification system can shorten ‘length of stay’ (LOS) in the ED, improve patient flow, and decrease ED patient load.

METHODS: This was a prospective cohort study utilizing data extrapolated from the electronic medical records of 2972 patients who visited the walk-in ED of a large-scale central hospital in Israel from January 17, 2021 to March 15, 2021. During this period, the automatic push text notification system was activated on a week-on week-off basis. We compared data from our experimental group with the control group.

RESULTS: The results of this study indicate that the use of an automatic push notification system had a minimal impact on specific parameters of ED patient flow. Apart from a few significant reductions of specific timed-intervals during patients’ ED visit, the majority of results were not statistically significant.

CONCLUSION: This study concluded that the anticipated benefits of a push text notification system in the ED do not, at this stage, justify the system’s additional cost. We recommend a follow-up study to further investigate other possible benefits.

PMID:34618849 | DOI:10.1371/journal.pone.0258169

PLoS One. 2021 Oct 7;16(10):e0258267. doi: 10.1371/journal.pone.0258267. eCollection 2021.

ABSTRACT

INTRODUCTION: In 2009 and 2010, Athens, Greece experienced a hepatitis C virus (HCV) and a Human Immunodeficiency Virus (HIV) outbreak among People Who Inject Drugs (PWID), respectively. The HCV outbreak was not detected, while that of HIV was identified in 2011. The integrated HIV-interventions, launched in early 2012, managed to reduce directly the HIV incidence and indirectly the HCV incidence. This study aims to assess what would have been the course of the HIV outbreak and its associated economic consequences if the 2009 HCV outbreak had been detected and integrated interventions had been initiated 1- or 2-years earlier.

METHODS: The model was calibrated to reproduce the observed HIV epidemiological and clinical parameters among PWID of Athens, Greece. We examined the effect of the 1- or 2-years earlier detection scenarios, the 1-year later detection, the non-detection scenario, and compared them to the status quo scenario.

RESULTS: Cumulative HIV cases, under the status-quo scenario during 2009-2019, were 1360 (90% Credible intervals: 290, 2470). If the HCV outbreak had been detected 1- or 2- years earlier, with immediate initiation of integrated interventions, 740 and 1110 HIV cases could be averted by 2019, respectively. Regarding the costs, if there was an efficient notification system to detect the HCV outbreak 1 or 2 years earlier, 35.2-53.2 million euros could be saved compared to the status quo by 2019.

CONCLUSIONS: If the HCV outbreak had been detected and promptly addressed, the HIV outbreak would have been prevented and 35.2-53.2 million euros could have been saved.

PMID:34618836 | DOI:10.1371/journal.pone.0258267

PLoS One. 2021 Oct 7;16(10):e0257441. doi: 10.1371/journal.pone.0257441. eCollection 2021.

ABSTRACT

OBJECTIVE: Patients who undergo Fontan surgery for complex cardiac anomalies are prone to developing liver and gastrointestinal complications. In particular, gastroesophageal varices (GEVs) can occur, but their prevalence is unknown. We aimed to elucidate the occurrence of GEVs and the predicting parameters of GEVs in these patients.

MATERIALS AND METHODS: Twenty-seven patients (median age, 14.8 years; median time since surgery, 12.9 years) who had undergone the Fontan surgery and were examined by abdominal dynamic computed tomography (CT) for the routine follow-up were included in the study. Radiological findings including GEVs and extraintestinal complications were retrospectively evaluated by experienced radiologists in a blinded manner. Relationships between blood-biochemical and demographic parameters and the presence of GEVs were statistically analyzed.

RESULTS: Dynamic CT revealed gastric varices (n = 3, 11.1%), esophageal varices (n = 1, 3.7%), and gastrorenal shunts (n = 5, 18.5%). All patients with gastric varices had gastrorenal shunts. All gastric varices were endoscopically confirmed as being isolated and enlarged, with indications for preventive interventional therapy. A platelet count lower than 119 × 109 /L was identified as a predictor of GEV (area under the receiver operating curve, 0.946; sensitivity, 100%; and specificity, 87%).

CONCLUSIONS: GEVs are important complications that should not be ignored in patients who have undergone a Fontan procedure. Platelet counts lower than 119 × 109 /L may help to prompt patient screening by using abdominal dynamic CT to identify GEVs and their draining collateral veins in these patients.

PMID:34618830 | DOI:10.1371/journal.pone.0257441

PLoS One. 2021 Oct 7;16(10):e0257306. doi: 10.1371/journal.pone.0257306. eCollection 2021.

ABSTRACT

BACKGROUND: Metabolic syndrome (MetS) is becoming a major public health problem globally; it is clear that the burden of MetS is rapidly increasing the rates of non-communicable diseases (NCD). In Ethiopia studies done so far have shown a large disparity in magnitude of the prevalence of MetS and were mainly institution-based studies. Therefore, this study assess the prevalence of MetS among adults who are residing in Gondar city using Adult Treatment Panel III (ATP III) and the International Diabetes Federation (IDF) assessment tool. The findings are imperative to developing and strengthening national NCD prevention and control programs.

METHODS: This study was conducted in Gondar city Northwest Ethiopia in 2018. It employs a community-based cross-sectional study design among 3,227 individuals 18 years of age or older. Data was collected using the WHO stepwise tool, lipid profile, blood pressure (BP), waist circumference (WC) body mass index (BMI), fasting blood glucose levels (FG), and anthropometric measurements. The prevalence estimation was made along with a 95% confidence interval (CI). The Kappa statistic was used to analyze the statistical agreement between ATP III and IDF definitions of the MetS. Stratified analysis was also performed for description and analysis components using ATP III and IDF as an outcome.

RESULT: Of the total study participants (3227), 3059 (94.8%) were included in the final analysis and 52.5% were female. The mean (±SD) age of the study participant was 40.8 years (16.2 ±SD). The overall prevalence of MetS using ATP III was 11.2% [95%CI: 10.1, 12.3] and using IDF was 11.9% [95%CI: 10.8, 13.2]. The sex-specific proportion was high in females rather than males irrespective of the criteria. The overall level of agreement between ATP III and IDF prevalence was 91.7% and the Kappa statistics was 0.594. Older age, low-density lipoprotein cholesterol, body mass index, being female, born in an urban area, consumption of an alcoholic drink in the preceding 30 days, and non-fasting practice was significantly associated with MetS.

CONCLUSION AND RECOMMENDATION: There was a higher prevalence of metabolic syndrome among females than males irrespective of metabolic syndrome diagnostic criteria. This also shows good agreement between ATP III and IDF. Being female, urban birthplace, frequent alcohol consumption in the last 30 days, and non-fasting practice are factors associated with higher rates of metabolic syndrome. Hence, awareness campaigns, physical exercise, and nutrition education intervention should be undertaken to promote health behavioral practice.

PMID:34618823 | DOI:10.1371/journal.pone.0257306

PLoS One. 2021 Oct 7;16(10):e0256984. doi: 10.1371/journal.pone.0256984. eCollection 2021.

ABSTRACT

Wheat is an important global staple food crop; however, its productivity is severely hampered by changing climate. Erratic rain patterns cause terminal drought stress, which affect reproductive development and crop yield. This study investigates the potential and zinc (Zn) and silicon (Si) to ameliorate terminal drought stress in wheat and associated mechanisms. Two different drought stress levels, i.e., control [80% water holding capacity (WHC) was maintained] and terminal drought stress (40% WHC maintained from BBCH growth stage 49 to 83) combined with five foliar-applied Zn-Si combinations (i.e., control, water spray, 4 mM Zn, 40 mM Si, 4 mM Zn + 40 mM Si applied 7 days after the initiation of drought stress). Results revealed that application of Zn and Si improved chlorophyll and relative water contents under well-watered conditions and terminal drought stress. Foliar application of Si and Zn had significant effect on antioxidant defense mechanism, proline and soluble protein, which showed that application of Si and Zn ameliorated the effects of terminal drought stress mainly by regulating antioxidant defense mechanism, and production of proline and soluble proteins. Combined application of Zn and Si resulted in the highest improvement in growth and antioxidant defense. The application of Zn and Si improved yield and related traits, both under well-watered conditions and terminal drought stress. The highest yield and related traits were recorded for combined application of Zn and Si. For grain and biological yield differences among sole and combined Zn-Si application were statistically non-significant (p>0.05). In conclusion, combined application of Zn-Si ameliorated the adverse effects of terminal drought stress by improving yield through regulating antioxidant mechanism and production of proline and soluble proteins. Results provide valuable insights for further cross talk between Zn-Si regulatory pathways to enhance grain biofortification.

PMID:34618822 | DOI:10.1371/journal.pone.0256984

PLoS Biol. 2021 Oct 7;19(10):e3001419. doi: 10.1371/journal.pbio.3001419. Online ahead of print.

ABSTRACT

Evolving in sync with the computation revolution over the past 30 years, computational biology has emerged as a mature scientific field. While the field has made major contributions toward improving scientific knowledge and human health, individual computational biology practitioners at various institutions often languish in career development. As optimistic biologists passionate about the future of our field, we propose solutions for both eager and reluctant individual scientists, institutions, publishers, funding agencies, and educators to fully embrace computational biology. We believe that in order to pave the way for the next generation of discoveries, we need to improve recognition for computational biologists and better align pathways of career success with pathways of scientific progress. With 10 outlined steps, we call on all adjacent fields to move away from the traditional individual, single-discipline investigator research model and embrace multidisciplinary, data-driven, team science.

PMID:34618807 | DOI:10.1371/journal.pbio.3001419