Category: Nevin Manimala

Microsurgery. 2021 Jul 2. doi: 10.1002/micr.30783. Online ahead of print.

ABSTRACT

INTRODUCTION: In flap transfer with perforator to perforator anastomosis (FTPPA), encountering poor pulsation and blood flow in a recipient perforator intraoperatively often makes FTPPA impossible. This study sought to identify color and spectral Doppler ultrasonography (CSDUS) parameters that can aid reliable preoperative selection of a recipient perforator artery.

PATIENTS AND METHODS: The study enrolled 38 patients with lower extremity lymphedema who underwent vascularized lymphatic tissue transfer with perforator to perforator anastomosis for physiological lymphatic flow reconstruction. In all cases, three candidate recipient perforators were searched in each lower extremities, and vessel diameter and peak systolic flow velocity (PSFV) were measured. The inclusion criteria for candidates were a vessel diameter of >0.5 mm and a PSFV of >10 cm/s. These measures were compared with intraoperative findings, diameters and if there was pulsation and visible spurting evident.

RESULTS: A total of 114 candidates were selected, and 52 of the candidates were dissected until suitable perforators were found. PSFV (cm/s) on CSDUS was ≥20.0 in 32 perforators (84.2%) and was 15.0-19.9 in 6 perforators (15.8%) in the group with pulsation and visible spurting evident, and 15.0-19.9 in one perforator (7.1%) and ≤ 14.9 in 13 perforators (92.9%) in the group without pulsation and visible spurting evident. There was a statistically significant correlation between preoperative PSFV and intraoperative pulsation and visible spurting evident after dissection (P = 0.021 × 10^-3 ). The flap survival rate was 92.1%.

CONCLUSION: PSFV is an important preoperative determinant of the suitability of a recipient perforator artery for FTPPA.

PMID:34213025 | DOI:10.1002/micr.30783

Biometrics. 2021 Jul 2. doi: 10.1111/biom.13526. Online ahead of print.

ABSTRACT

Multiple types of molecular (genetic, genomic, epigenetic, etc.) measurements, environmental risk factors, and their interactions have been found to contribute to the outcomes and phenotypes of complex diseases. In each of the previous studies, only the interactions between one type of molecular measurement and environmental risk factors have been analyzed. In recent biomedical studies, multidimensional profiling, in which data from multiple types of molecular measurements are collected from the same subjects, is becoming popular. A myriad of recent studies have shown that collectively analyzing multiple types of molecular measurements is not only biologically sensible but also leads to improved estimation and prediction. In this study, we conduct an M-E interaction analysis, with M standing for multidimensional molecular measurements and E standing for environmental risk factors. This can accommodate multiple types of molecular measurements and sufficiently account for their overlapping as well as independent information. Extensive simulation shows that it outperforms several closely related alternatives. In the analysis of TCGA (The Cancer Genome Atlas) data on lung adenocarcinoma and cutaneous melanoma, we make some stable biological findings and achieve stable prediction. This article is protected by copyright. All rights reserved.

PMID:34213006 | DOI:10.1111/biom.13526

Biometrics. 2021 Jul 2. doi: 10.1111/biom.13524. Online ahead of print.

ABSTRACT

Mendelian randomization (MR) has been a popular method in genetic epidemiology to estimate the effect of an exposure on an outcome using genetic variants as instrumental variables (IV), with two-sample summary-data MR being the most popular. Unfortunately, instruments in MR studies are often weakly associated with the exposure, which can bias effect estimates and inflate Type I errors. In this work, we propose test statistics that are robust under weak instrument asymptotics by extending the Anderson-Rubin, Kleibergen, and the conditional likelihood ratio test in econometrics to two-sample summary-data MR. We also use the proposed Anderson-Rubin test to develop a point estimator and to detect invalid instruments. We conclude with a simulation and an empirical study and show that the proposed tests control size and have better power than existing methods with weak instruments. This article is protected by copyright. All rights reserved.

PMID:34213007 | DOI:10.1111/biom.13524

Ulus Travma Acil Cerrahi Derg. 2021 Jul;27(4):449-456. doi: 10.14744/tjtes.2020.49196.

ABSTRACT

BACKGROUND: The optimal timing of intervention for aneurysmatic subarachnoid hemorrhage is one of the historically controversial issues in neurosurgery. Although numerous studies investigated the subject, they had many limitations due to the nature of the disease. Early and ultra-early interventions have gained more and more supporters in recent decades. Nevertheless, the effects of the early and ultra-early intervention on the outcome of the disease are far from clarity.

METHODS: A single-center retrospective cohort study was carried out at Trakya University Medical Faculty Training and Practice Hospital. The study includes data on all patients admitted with an aneurysmal subarachnoid hemorrhage between January 1, 2001, and December 31, 2005. Patients were divided into two groups according to their WFNS grade status: Good (I-III) or poor (IV-V) grades. Patients are also classified according to their Glasgow Outcome Scale score: Unfavorable (1-2) or favorable (3-5) outcomes. Data were analyzed statistically, and the effects of the early and ultra-early intervention on the outcome were assessed.

RESULTS: A total of 580 patients were admitted in the study period. Among them, 494 were eligible for the study. The median age (interquartile range) was 55 (18) years. While 244 (49.4%) patients were women, 250 (50.6%) patients were men. Three hundred and fourteen (63.6%) patients were operated, and 25 patients (5.1%) were undergone endovascular treatment. The ultra-early intervention was achieved in 60 (12.1%) patients and 142 patients (28.7%, including the previous ultra-early intervention group) early intervention was achieved. A meaningful outcome difference was present between the poor-grade ultra-early treatment group and the rest (p=0.007). Analogously, a meaningful outcome difference was present between the poor-grade early treatment group and the rest (p<0.001).

CONCLUSION: This study supports the growing trend toward early or ultra-early intervention in aneurysmatic subarachnoid hemorrhage. Our findings showed that both early and ultra-early interventions have positive effects on the outcome in poor-grade aneurysmatic subarachnoid hemorrhage patients. Future studies with more homogenized and larger samples should be realized to clarify the optimal timing of intervention for aneurysmatic subarachnoid hemorrhage.

PMID:34212997 | DOI:10.14744/tjtes.2020.49196

Ulus Travma Acil Cerrahi Derg. 2021 Jul;27(4):402-409. doi: 10.14744/tjtes.2020.76767.

ABSTRACT

BACKGROUND: The increase in free oxygen radicals and proinflammatory cytokines in the ischemia-reperfusion injury caused by acute mesenteric ischemia are the key responsibilities of intestinal histopathological alterations. It has been reported that Ficus carica and its various parts contain antioxidant and anti-inflammatory compounds recently. Thus, in the present study, we aimed to investigate how Ficus carica seed oil affects intestinal ischemia-reperfusion injury in a rat model.

METHODS: In this study, 50 male Wistar albino rats were randomly divided into five equal groups. Negative control (NC), sham-operated (Sham), ischemia and reperfusion (IR), 3 ml/kg/day Ficus carica seed oil (FC3), 6 ml/kg/day Ficus carica seed oil (FC6). IR, FC3 and FC6 groups underwent ischemia and reperfusion procedure for 45+120 min. Only abdominal midline laparotomy was performed in the Sham group for 165 minutes.

RESULTS: Tissue levels of TNFα and IL-1β, which were proinflammatory cytokines, were significantly reduced in the FC6 group than the IR group (p<0.05). In FC3 and FC6 groups, the tissue MPO and MDA enzyme levels were significantly lower than the IR group, but there was a significantly greater decrease in the FC6 group than the FC3 group (p<0.05). SOD and CAT enzymes and reduced glutathione levels of FC3 and FC6 groups were significantly lower than IR group (p<0.05); however, there was no statistically significant difference between the FC3 and FC6 groups. FC3 and FC6 groups were histopathologically graded statistically lower than the IR group, and the FC6 group showed a significant decrease than the FC3 group (p<0.05).

CONCLUSION: Oral administration of fig seed oil may reverse biochemical and histopathological findings resulting from ischemia-reperfusion injury in an experimental model of acute mesenteric ischemia in rats, probably because of its antioxidant and anti-inflammatory compounds.

PMID:34213002 | DOI:10.14744/tjtes.2020.76767

Ulus Travma Acil Cerrahi Derg. 2021 Jul;27(4):381-388. doi: 10.14744/tjtes.2020.81782.

ABSTRACT

BACKGROUND: Ischemia-reperfusion injury (IRI) is cellular damage that emerges from re-oxygenation of a hypoxic organ. In the present study, we aimed to examine the effects of a combination of levosimendan, an inotropic agent, and N-Acetylcysteine, the precursor of antioxidants and glutathione, in an experimental liver IRI model.

METHODS: In this study, 38 rats were randomly divided into five groups. Before the ischemia, study arms were given physiological saline solution, N-Acetylcysteine (NAS), levosimendan or a combination of NAS+levosimendan in a predetermined amount and duration, and the infusion was continued until the end of this study. The hepatic pedicle was occluded using an atraumatic vein clamp, and 60 minutes of ischemia was achieved. The clamp was then opened and 60 minutes of reperfusion was ensured. Liver tissue samples were obtained after sacrifice, and tissue malondialdehyde (MDA) and myeloperoxidase (MPO) levels were determined. Serum Tumor Necrosis Factor (TNF)-α, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and MPO levels of blood samples were also measured.

RESULTS: Among the histopathological changes in the liver tissue after IRI, differences between groups were statistically significant in the injury scoring system based on congestion, vacuolization and necrosis levels. Histopathological injury score, plasma MPO, AST, ALT, tissue MPO and tissue MDA values were statistically significantly lower in the treatment groups, prominently in the levosimendan and NAS combination group concerning liver histopathological damage.

CONCLUSION: The use of a levosimendan plus NAS combination in liver IRI markedly suppressed inflammation and oxidative stress and significantly reduced liver ischemia-reperfusion injury and can be recommended for decreasing IRI instead of single agent use of levosimendan or NAS.

PMID:34213003 | DOI:10.14744/tjtes.2020.81782

Ulus Travma Acil Cerrahi Derg. 2021 Jul;27(4):427-433. doi: 10.14744/tjtes.2020.04788.

ABSTRACT

BACKGROUND: In this study, we aimed to evaluate the outcomes of patients transported by Helicopter Emergency Medical Services in East Azerbaijan Province.

METHODS: This retrospective cross-sectional study was conducted on patients transported by the HEMS centre of Tabriz from August 2014 to March 2017. Records of the centre were used to collect data. Statistical analysis was performed by SPSS software version 20; the statistical significance level was considered below 0.05.

RESULTS: In this study, 268 patients were transferred to Tabriz hospitals by 167 missions performed. The mean age of patients was 34.26±19.43, and 173 (65%) patients were male. The most common reason for call-out was the need for professional care (91.4%). The target of the majority of missions was on countryside routes. The mean distance of destinations was about 99.13±35.9 Kms, with a mean transference time of 54.68±14.17 minutes, while the mean estimated ground route time was 86.38±26.26 minutes. The most prevalent diagnosis was trauma; The Glasgow Coma Scale (GCS) and vital signs of the majority of patients were above 13 and stable, respectively. About 98 percent of patients received fluid therapy, and 71 percent were immobilized, and only 6 percent needed intubation. Also, 28 percent of patients needed Intensive Care Unit (ICU), 56 percent of whom passed away later.

CONCLUSION: Our results suggest that Tabriz HEMS missions have reduced the patient transport time and also made the mortality rate closer to international standards.

PMID:34212990 | DOI:10.14744/tjtes.2020.04788

Ulus Travma Acil Cerrahi Derg. 2021 Jul;27(4):410-420. doi: 10.14744/tjtes.2020.18552.

ABSTRACT

BACKGROUND: Organ failures that develop due to acute pancreatitis (AP), some laboratory values and the anthropometric characteristics of the patients have been shown to play a role in the prognosis AP and have been increasingly used to investigate the prognosis of the disease although classification systems, such as Ranson’s criteria, are still used habitually. In this stud, we aimed to investigate the relationship of the organ failures observed during the course of AP, the biochemical parameters and the anthropometric characteristics of the patients and compare using Ranson’s and Atlanta Classifica-tion (AC) systems.

METHODS: Laboratory values, anthropometric data, including the waist circumference and body mass index, Systemic inflammatory response syndrome (SIRS) and organ failures developed during the course of the disease, were investigated prospectively in 153 AP patients and the Ranson and Modified Atlanta Classifications (MAC) were made.

RESULTS: A relationship was observed between the organ failures that were established in the course of the disease (lung, liver, kidney, heart and MOF (multiple organ failure)) and higher Ranson’s and MAC scores (p<0.05). Among the patients included in this study, 13 (8.4%) had multiple organ failure and 17 (11.1%) had SIRS. Exitus occurred in 10 patients (6.5%). A statistically significant relationship was found with organ failure, multiple organ failure and SIRS; and ensuing exitus (p<0.05). While no relationship was observed between the waist circumference, body mass index, Ranson’s score, there was a significant relationship between the MAC and the waist circumference (p<0.01). Among the laboratory values, high urea and ALT values showed a relationship with the Ranson and MAC (p<0.001), while between the CRP values tested at the 0 time point and the 48th hour, only the CRP value at the 48th hour had a relationship with Ranson’s score (p<0.05). Organ failure, MOF, and SIRS showed a correlation with both the severity scores and the mortality rate. In addition, a significant corre-lation was observed between the cholesterol, triglycerides and the CRP level at the time of hospitalisa-tion and mortality. On the contrary, no significant relationship was observed with the other laboratory results, including calcium, lipase and hematocrit.

CONCLUSION: In conclusion, to determine the severity and prognosis of acute pancreatitis, and ex-pect the organ failures that may occur in severe pancreatitis, the body mass index, waist circumference and laboratory values, including cholesterol, triglycerides, ALT, and CRP may supply important prog-nostic data besides the conventional disease severity scoring methods.

PMID:34212994 | DOI:10.14744/tjtes.2020.18552

Chem Soc Rev. 2021 Jul 2. doi: 10.1039/d0cs01065k. Online ahead of print.

ABSTRACT

COVID-19 has resulted in huge numbers of infections and deaths worldwide and brought the most severe disruptions to societies and economies since the Great Depression. Massive experimental and computational research effort to understand and characterize the disease and rapidly develop diagnostics, vaccines, and drugs has emerged in response to this devastating pandemic and more than 130 000 COVID-19-related research papers have been published in peer-reviewed journals or deposited in preprint servers. Much of the research effort has focused on the discovery of novel drug candidates or repurposing of existing drugs against COVID-19, and many such projects have been either exclusively computational or computer-aided experimental studies. Herein, we provide an expert overview of the key computational methods and their applications for the discovery of COVID-19 small-molecule therapeutics that have been reported in the research literature. We further outline that, after the first year the COVID-19 pandemic, it appears that drug repurposing has not produced rapid and global solutions. However, several known drugs have been used in the clinic to cure COVID-19 patients, and a few repurposed drugs continue to be considered in clinical trials, along with several novel clinical candidates. We posit that truly impactful computational tools must deliver actionable, experimentally testable hypotheses enabling the discovery of novel drugs and drug combinations, and that open science and rapid sharing of research results are critical to accelerate the development of novel, much needed therapeutics for COVID-19.

PMID:34212944 | DOI:10.1039/d0cs01065k

Sci Rep. 2021 Jul 1;11(1):13654. doi: 10.1038/s41598-021-93096-w.

ABSTRACT

Prediction models for population-based screening need, for global usage, to be resource-driven, involving predictors that are affordably resourced. Here, we report the development and validation of three resource-driven risk models to identify people with type 2 diabetes (T2DM) at risk of stage 3 CKD defined by a decline in estimated glomerular filtration rate (eGFR) to below 60 mL/min/1.73m². The observational study cohort used for model development consisted of data from a primary care dataset of 20,510 multi-ethnic individuals with T2DM from London, UK (2007-2018). Discrimination and calibration of the resulting prediction models developed using cox regression were assessed using the c-statistic and calibration slope, respectively. Models were internally validated using tenfold cross-validation and externally validated on 13,346 primary care individuals from Wales, UK. The simplest model was simplified into a risk score to enable implementation in community-based medicine. The derived full model included demographic, laboratory parameters, medication-use, cardiovascular disease history (CVD) and sight threatening retinopathy status (STDR). Two less resource-intense models were developed by excluding CVD and STDR in the second model and HbA1c and HDL in the third model. All three 5-year risk models had good internal discrimination and calibration (optimism adjusted C-statistics were each 0.85 and calibration slopes 0.999-1.002). In Wales, models achieved excellent discrimination(c-statistics ranged 0.82-0.83). Calibration slopes at 5-years suggested models over-predicted risks, however were successfully updated to accommodate reduced incidence of stage 3 CKD in Wales, which improved their alignment with the observed rates in Wales (E/O ratios near to 1). The risk score demonstrated similar model performance compared to direct evaluation of the cox model. These resource-driven risk prediction models may enable universal screening for Stage 3 CKD to enable targeted early optimisation of risk factors for CKD.

PMID:34211028 | DOI:10.1038/s41598-021-93096-w