Category: Nevin Manimala

Obes Surg. 2022 Aug 16. doi: 10.1007/s11695-022-06240-4. Online ahead of print.

ABSTRACT

PURPOSE: The development of Laparoscopic Linear Endostaplers (LLES) is crucial in minimally invasive approaches in bariatric surgery, but there have been very few published studies comparing 6-row LLES in Laparoscopic Sleeve Gastrectomy (LSG). The objective of this study was to compare two 6-row LLES in LSG.

METHODS: A total of 60 patients were prospectively randomized to undergo LSG with either Medtronic Endo GIA™ Tri-Staple technology (MTS) or AEON ™ Endostapler(Lexington Medical) LLES. The measured parameters included patient demographics, comorbidity indices, LLES and specimen characteristics, postoperative symptoms, hospital stay, and total adverse events (AEs). Intraoperative bleeding was evaluated using five laparoscopic and corresponding endoscopic images of staple line before clip application, compared with a 1-5 Visual Analogue Scale (VAS), assessed by an independent bariatric surgeon who was blinded to the LLES used. Images of all cases were reviewed on the same day to increase test-retest reliability.

RESULTS: Both groups were similar in patient demographics. Compared to MTS, AEON LLES group had significantly lower bleeding VAS scores in 4/5 laparoscopic images (pre-pyloric: 1.7 ± 0.7 vs. 2.36 ± 0.76, p = 0.0007, mid-sleeve: 1.46 ± 0.62 vs. 1.86 ± 0.68, p = 0.019, proximal sleeve: 1.6 ± 0.77 vs. 2.0 ± 0.83, p = 0.038, gastro-esophageal junction: 1.43 ± 0.67 vs. 1.86 ± 0.77, p = 0.014) and 3/5 endoscopic images (pre-pyloric: 1.56 ± 0.56 vs. 2.36 ± 0.76, p = 0.006, incisura: 1.66 ± 0.54 vs. 2.0 ± 0.52, p = 0.021, mid-sleeve: 1.63 ± 0.49 vs. 2.0 ± 0.45, p = 0.005). There was no statistical difference in other parameters.

CONCLUSION: Both devices were equally safe and effective in terms of LLES and specimen characteristics, patient symptoms, hospital stay, and AEs. Bleeding VAS scores were significantly lower, favoring the AEON LLES.

PMID:35974292 | DOI:10.1007/s11695-022-06240-4

Eur J Drug Metab Pharmacokinet. 2022 Aug 16. doi: 10.1007/s13318-022-00787-4. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Alirocumab is a cholesterol-lowering monoclonal antibody targeting proprotein convertase subtilisin kexin type 9 (PCSK9) indicated in the prevention of cardiovascular risk and exhibiting target-mediated drug disposition (TMDD). The aim of this work was to develop an integrated pharmacokinetic-pharmacodynamic model to describe the interaction of alirocumab with PCSK9 and its impact on the evolution of low-density lipoprotein cholesterol (LDL-C) levels and explore labeling specification for subpopulations.

METHODS: Using data collected from nine phase I/II/III clinical studies (n = 527, subcutaneous or intravenous administration), a TMDD model considering the quasi-steady-state approximation was developed to characterize the interaction dynamics of alirocumab and PCSK9, combined with an indirect pharmacodynamic model describing the inhibition of LDL-C by PCSK9 in a one-step approach using nonlinear-mixed effects modeling. A “full fixed effects modeling” strategy was implemented to quantify parameter-covariate relationships.

RESULTS: The model captures the interaction between alirocumab and its target PCSK9 and how this mechanism drives LDL-C depletion, with an estimation of the associated between-subject variability of model parameters and the quantification of clinically relevant parameter-covariate relationships. Co-administration of statins was found to increase the central volume of distribution of alirocumab by 1.75-fold (5.6 L versus 3.2 L) and allow for a 14% greater maximum lipid-lowering effect (88% versus 74%), highlighting the synergy of action between anti-PCSK9 therapeutic antibodies and statins toward lowering LDL-C plasma levels. Baseline levels of PCSK9 were found to be related to the amplitude of LDL-C variations by increasing the concentration of free PCSK9 necessary to reach half its capacity of inhibition of LDL-C degradation.

CONCLUSION: The maximum effect of alirocumab is achieved when free PCSK9 concentration is close to zero, as seen mostly after 150 mg every 2 weeks (Q2W) or 300 mg every 4 weeks (Q4W), indicating that there would be no additional clinical benefit of increasing the dose higher than these recommended dosing regimens.

PMID:35974290 | DOI:10.1007/s13318-022-00787-4

Environ Sci Pollut Res Int. 2022 Aug 16. doi: 10.1007/s11356-022-22528-5. Online ahead of print.

ABSTRACT

The accurate division of three zones of coal spontaneous combustion in the goaf plays a vital role for coal fire prevention. Based on the O₂ and CO volume fraction acquired from in situ test, this paper first fits the linear equation (characteristic equation) of O₂ volume fraction with the length of the goaf. Then a cloud map of the kernel density distribution of O₂ and CO volume fraction and the length of the goaf was drawn. According to the cloud map of CO, the distribution interval of CO volume fraction can be obtained, in which 0-100 ppm is the acceptable range, and greater than 100 ppm is the dangerous range, which can be used as a critical indicator for early warning of coal spontaneous combustion. According to the kernel density distribution cloud map of O₂ volume fraction, there are 3 peaks of the kernel density of O₂ volume fraction. According to the difference test, the 3 goaf lengths (characteristic lengths) corresponding to the 3 kernel density peaks are determined to be 12 m, 34 m, and 59 m, respectively. The characteristic O₂ volume fractions are obtained by substituting characteristic lengths into the characteristic equation, which are 17.9%, 13.6%, and 8.9%. Different from the traditional dividing method, the characteristic O₂ volume fractions and characteristic lengths divide the goaf into four areas: the heat dissipation zone, the first oxidation zone, the second oxidation zone, and the asphyxiation zone. The results of this study could refine the division of coal spontaneous combustion dangerous areas, reflect the dynamic change process of coal spontaneous combustion dangerous areas, and improve the efficiency of coal spontaneous combustion prevention.

PMID:35974273 | DOI:10.1007/s11356-022-22528-5

Environ Sci Pollut Res Int. 2022 Aug 16. doi: 10.1007/s11356-022-22515-w. Online ahead of print.

ABSTRACT

Geographical information system data has been used in forest fire risk zone mapping studies commonly. However, forest fires are caused by many factors, which cannot be explained only by geographical and meteorological reasons. Human-induced factors also play an important role in occurrence of forest fires, and these factors depend on various social and economic conditions. This article aims to prepare a fire risk zone map by using a data set consisting of 11 human-induced factors, a natural factor, and temperature, which is one of the risk factors that determine the conditions for the occurrence of forest fires. Moreover, k-means clustering algorithm, which is an artificial intelligence method, was employed in preparation of the fire risk zone map. Turkey was selected as the study area because there are social and economic variations among its regions. Thus, the regional forest directorates in Turkey were separated into four clusters as extreme-risk zone, high-risk zone, moderate-risk zone, and low-risk zone. Also, a map presenting these risk zones were provided. The map reveals that, in general, the western and southwestern coastal areas of Turkey are at high risk of forest fires. On the other hand, the fire risk is relatively low in the northern, central, and eastern areas.

PMID:35974271 | DOI:10.1007/s11356-022-22515-w

Environ Sci Pollut Res Int. 2022 Aug 16. doi: 10.1007/s11356-022-22098-6. Online ahead of print.

ABSTRACT

Lipases are important biocatalysts having the third largest global demand after amylases and proteases. In the present study, we have screened 56 potential lipolytic Pseudomonas strains for their lipolytic activity. Pseudomonas plecoglossicida S7 showed highest lipase production with specific activity of 70 U/mg. Statistical optimizations using Plackett Burman design and response surface methodology evaluated fourteen different media supplements including various oilcakes, carbon sources, nitrogen sources, and metal ions which led to a 2.23-fold (156.23 U/mg) increase in lipase activity. Further, inoculum size optimization increased the overall lipase activity by 2.81-folds. The lipase was active over a range of 30-50° C with a pH range (7-10). The enzyme was tolerant to various solvents like chloroform, methanol, 1-butanol, acetonitrile, and dichloromethane and retained 60% of its activity in the presence of sodium dodecyl sulfate (0.5% w/v). The enzyme was immobilized onto Ca-alginate beads which increased thermal (20-60 °C) and pH stability (5-10). The purified enzyme could successfully remove sesame oil stains and degraded upto 25.2% of diesel contaminated soil. These properties of the lipase will help in its applicability in detergent formulations, wastewater treatments, and biodegradation of oil in the environment.

PMID:35974269 | DOI:10.1007/s11356-022-22098-6

Inflammopharmacology. 2022 Aug 16. doi: 10.1007/s10787-022-01049-0. Online ahead of print.

ABSTRACT

BACKGROUND: Inflammation is a prominent clinical manifestation in type 2 diabetes mellitus (T₂DM) patients, often associated with insulin resistance, metabolic dysregulation, and other complications.

AIM OF THE STUDY: The present study has been designed to check the serum levels of PAR-1 and correlate with various clinical manifestations and inflammatory cytokines levels in type 2 diabetic subjects.

MATERIAL AND METHODS: The study population was divided into two groups, healthy volunteers (n = 15): normal glycated hemoglobin (HbA1c) (4.26 ± 0.55) and type 2 diabetic subjects (n = 30): HbA1c levels (7.80 ± 2.41). The serum levels of PAR-1 (ELISA method) were studied in both groups and correlated with demographic parameters age, weight, body mass index (BMI), and conventional inflammation biomarkers like C-reactive protein (CRP), interleukin 6 (IL-6), interleukin 8 (IL-8), and tumour necrosis factor-alpha (TNF-α).

RESULTS: The demographic variables including the body weight (77.38 ± 10.00 vs. controls 55.26 ± 6.99), BMI (29.39 ± 3.61 vs. controls 25.25 ± 4.01), glycemic index HbA1c (7.80 ± 2.41 vs. controls 4.26 ± 0.55) were found to be statistically increased in T₂DM subjects than the healthy control group. The levels of various inflammatory biomarkers and PAR-1 were significantly elevated in T₂DM groups in comparison to healthy volunteers. The univariate and multivariate regression analysis revealed that elevated PAR-1 levels positively correlated with increased body weight, BMI, HbA1c, and inflammatory cytokines.

CONCLUSION: Our findings indicate that the elevated serum PAR-1 levels serve as an independent predictor of inflammation in T₂DM subjects and might have prognostic value for determining T₂DM progression.

PMID:35974263 | DOI:10.1007/s10787-022-01049-0

Am J Gastroenterol. 2022 Jun 17. doi: 10.14309/ajg.0000000000001884. Online ahead of print.

ABSTRACT

INTRODUCTION: The incidence of early-onset colorectal cancer (eoCRC) has been increasing in North America. Debate remains as to whether the trends by topography, histology, stage, or mortality in this population are amenable to intervention from screening.

METHODS: CRC incidence (2000-2017) and mortality (2000-2018) data were obtained from the Canadian Cancer Registry and Vital Statistics. Annual percent changes (APC) in the incidence (topography and histology) and mortality of eoCRC were estimated using Joinpoint Regression. Incidence of late stage CRC (III or IV) versus early stage (I or II) was compared between eoCRC (age 20-49) and eligible screening (age 50-74) groups with Poisson regression.

RESULTS: Among females aged 20-49, the incidence of CRC significantly increased from 2000-2017 in both the distal colon (APC=1.40) and rectum (APC=3.00), while for males aged 20-49, CRC incidence increased in the proximal colon (APC=1.10), distal colon (APC=3.00), and rectum (APC=3.70). Among both males and females aged 20-49, incidence of non-mucinous adenocarcinomas significantly increased (APCs: 1.90 and 2.30, respectively), while mucinous adenocarcinomas decreased for females (APC=-1.60) and remained stable for males. Adults 30 to 49, when diagnosed with CRC, had a significantly higher risk of being diagnosed with a late stage CRC compared to the 50-74 age group. Rectal-cancer mortality increased from 2000-2018 in the eoCRC group (APCs for females and males 3.80 and 3.40, respectively).

DISCUSSION: Emerging data support future modifications to guidelines on screening for eoCRC in Canada. Further research is required on impact, cost-effectiveness, and risk prediction for targeted screening within this group.

PMID:35973186 | DOI:10.14309/ajg.0000000000001884

Am J Gastroenterol. 2022 Jun 17. doi: 10.14309/ajg.0000000000001883. Online ahead of print.

ABSTRACT

BACKGROUND AIMS: Frailty and sarcopenia are common complications of advanced liver disease. Due to associated morbidity/mortality, there have been targeted efforts to prevent and/or improve both by enrolling these patients in focused exercise programs. This review systematically analyzes the data of randomized clinical trials (RCT) on anthropometric, physical fitness, quality of life, and safety outcomes of exercise interventions in patients with advanced liver disease.

METHODS: Two authors independently searched trials on PubMed and EMBASE from inception up to 11/18/2021. A third independent arbitrator adjudicated all disagreements. We qualitatively summarized these outcomes: 1) muscular fitness (maximal inspiratory/expiratory pressures, muscle size, muscle strength, and bioimpedance testing); 2) cardiorespiratory fitness (cardiopulmonary exercise testing, 6-minute walk distance), 3) quality of life, and 4) others (safety or frailty indices).

RESULTS: There were eleven RCTs (4 home-based interventions) with 358 participants. Interventions ranged from 8-14 weeks and included cycling, walking, resistance exercises, balance and coordination training, and respiratory exercises. All described outcomes compared pre- to post-intervention measurements. Nine studies showed statistically significant improvements in at least one physical fitness variable. Ten studies showed statistically significant improvements in at least one muscular fitness variable. Six studies showed statistically significant improvements in at least one quality of life variable. Attrition rates ranged from 5-36% and adherence rates ranged very widely from 14-100%. Only one study reported frailty indices. Notably, no complications of portal hypertension were seen in intervention groups in the nine studies that reported this data.

CONCLUSIONS: A review of eleven randomized clinical trials with 358 participants with advanced liver disease demonstrates that exercise interventions can have favorable outcomes on muscular/cardiorespiratory fitness, and quality of life. While attrition and adherence varied, these interventions appear to be safe in patients with cirrhosis and are well tolerated.

PMID:35973182 | DOI:10.14309/ajg.0000000000001883

Am J Gastroenterol. 2022 Jun 17. doi: 10.14309/ajg.0000000000001878. Online ahead of print.

ABSTRACT

OBJECTIVES: Non-invasive criteria to predict progression of low-risk esophageal varices (EV) in patients with compensated HCV cirrhosis after sustained virological response (SVR) by direct-acting antivirals (DAAs) are lacking. Our aim was to assess the diagnostic performance of RESIST-HCV criteria for EV progression compared to elastography-based criteria (Baveno VI, Expanded Baveno VI and Baveno VII-HCV criteria).

METHODS: All consecutive patients observed at three referral centers with compensated HCV cirrhosis with or without F1 EV who achieved SVR by DAAs were classified at last esophagogastroduodenoscopy (EGDS) as RESIST-HCV Low Risk (LR – i.e. low probability of high-risk varices-HRV) if platelets were >120 x 109/L and serum albumin >3.6 g/dL or RESIST-HCV High Risk (HR-i.e. high probability of HRV) if platelets were <120 x 109/L or serum albumin <3.6 g/dL. Primary outcome was the progression to HRV. Area under the receiver operating characteristic (AUROC) curve and decision curve analysis (DCA) of non-invasive criteria were calculated.

RESULTS: The cohort consisted of 353 patients in Child-Pugh A class (mean age 67.2 years, 53.8% males). During a mean follow-up of 44.2 months, 34 patients (9.6%, 95%CI 6.7%-13.5%) developed HRV. At the last EGDS, 178 patients(50.4%) were RESIST-LR and 175(49.6%) were RESIST-HR. RESIST-HCV criteria showed the highest AUROC (0.70, 95%CI 0.65-0.75), correctly sparing the highest number of EGDS (54.3%), with the lowest false positive rate (45.7%), compared to elastography-based criteria. DCA showed that RESIST-HCV had higher clinical utility than elastography-based criteria.

CONCLUSIONS: Biochemical-based RESIST-HCV criteria are useful to easily predict HRV development after HCV eradication by DAAs in patients with compensated cirrhosis and low-risk EV.

PMID:35973181 | DOI:10.14309/ajg.0000000000001878

J Glob Health. 2022 Aug 17;12:11010. doi: 10.7189/jogh.12.11010.

ABSTRACT

BACKGROUND: The effects of meteorological factors and air pollutants on respiratory diseases (RDs) were various in different populations according to the demographic characteristics, and children were considered a vulnerable population. Previous studies were mainly based in cities with serious air pollution. This study aimed to qualify the lag effects of meteorological factors and air pollution on respiratory diseases among children under 18 years old in Fuzhou.

METHODS: Meteorological data, air pollutants concentrations and hospital admission data of Fujian Maternity and Child Health Hospital between 2015 and 2019 were collected. A Distributed Lag Nonlinear Model (DLNM) was used to evaluate the nonlinear and lagged effect of meteorological factors and air pollutants on daily RDs number. A subgroup analysis was also conducted to evaluate the effect on different sex groups and age groups.

RESULTS: A total number of 796 125 RDs visits was included during the study period. For meteorological factors, lower mean temperature and relative humidity were significantly associated with daily RDs number (peak relative risk (RR) = 1.032 (95% confidence interval (CI) = 1.011-1.053) and 1.021 (95% CI = 1.013-1.029)), while lower wind speed showed a significant association at low range (peak RR = 0.995 (95% CI = 0.992-0.999)). Temperature warming was a significant protective factor for RDs (peak RR = 0.989 (95% CI = 0.986-0.993)). For air pollutants, SO₂, NO₂, PM₁₀ and PM_2.5 were all significantly associated with RDs (peak RR = 1.028 (95% CI = 1.022-1.035), 1.024 (95% CI = 1.013-1.034), 1.036 (95% CI = 1.025-1.047), 1.028 (95% CI = 1.019-1.037)), and the relationship had no threshold. The estimated RR and peak lag day did not change extremely between subgroups.

CONCLUSIONS: The findings provide statistical evidence for the prevention of child RDs. In addition, our findings suggested that even at low concentrations, air pollutants still have negative effects on the respiratory system.

PMID:35973040 | DOI:10.7189/jogh.12.11010