Category: Nevin Manimala

Pediatrics. 2023 May 10:e2021056140. doi: 10.1542/peds.2021-056140. Online ahead of print.

ABSTRACT

OBJECTIVES: Describe characteristics of gastroenteritis, bacteremia, and meningitis caused by nontyphoidal Salmonella among US infants.

METHODS: We analyze national surveillance data during 1968-2015 and active, sentinel surveillance data during 1996-2015 for culture-confirmed Salmonella infections by syndrome, year, serotype, age, and race.

RESULTS: During 1968-2015, 190 627 culture-confirmed Salmonella infections among infants were reported, including 165 236 (86.7%) cases of gastroenteritis, 6767 (3.5%) bacteremia, 371 (0.2%) meningitis, and 18 253 (9.7%) with other or unknown specimen sources. Incidence increased during the late 1970s-1980s, declined during the 1990s-early 2000s, and has gradually increased since the mid-2000s. Infants’ median age was 4 months for gastroenteritis and bacteremia and 2 months for meningitis. The most frequently reported serotypes were Typhimurium (35 468; 22%) for gastroenteritis and Heidelberg for bacteremia (1954; 29%) and meningitis (65; 18%). During 1996-2015 in sentinel site surveillance, median annual incidence of gastroenteritis was 120, bacteremia 6.2, and meningitis 0.25 per 100 000 infants. Boys had a higher incidence of each syndrome than girls in both surveillance systems, but most differences were not statistically significant. Overall, hospitalization and fatality rates were 26% and 0.1% for gastroenteritis, 70% and 1.6% for bacteremia, and 96% and 4% for meningitis. During 2004-2015, invasive salmonellosis incidence was higher for Black (incident rate ratio, 2.7; 95% confidence interval, 2.6-2.8) and Asian (incident rate ratio, 1.8; 95% confidence interval, 1.7-1.8) than white infants.

CONCLUSIONS: Salmonellosis causes substantial infant morbidity and mortality; serotype heidelberg caused the most invasive infections. Infants with meningitis were younger than those with bacteremia or gastroenteritis. Research into risk factors for infection and invasive illness could inform prevention efforts.

PMID:37161700 | DOI:10.1542/peds.2021-056140

Turk J Pharm Sci. 2023 May 9;20(2):115-120. doi: 10.4274/tjps.galenos.2022.95994.

ABSTRACT

OBJECTIVES: Dexketoprofen is a non-steroidal analgesic/anti-inflammatory drug and its trometamol salt is extensively preferred in mild or moderate pain due to its rapid onset of relief. A new formulation of 36.9 mg of dexketoprofen trometamol (equivalent to 25 mg dexketoprofen) tablet has been developed and its bioequivalence to the reference product was proven.

MATERIALS AND METHODS: An open-label, single-dose, randomized, two-period, and cross-over bioequivalence study was conducted with healthy males under fasting conditions for two different tablet formulations of 25 mg dexketoprofen. To prove the bioequivalence of the test product with the reference product, a comparison study has been performed in compliance with regulations in force under Good Clinical Practice principles. A single-center clinical study was run and blood samples of the participants were withdrawn at specified time points, before and after dosing, to measure the plasma concentrations of dexketoprofen trometamol. A validated analytical method has been developed using an liquid chromatography with tandem mass spectrometry. Instrument to assess the plasma concentrations of the test and reference products.

RESULTS: Forty-seven volunteers completed clinical phase of the study. For the test and reference products, the mean ± standard deviations (SD) of C_max were found 2543.82 ± 655.42 ng/mL and 2539.11 ± 662.57 ng/mL, and the mean ± SD of area under the curve (AUC) from time 0 to the last measurable concentration (AUC_0-tlast) were found 3483.49 ± 574.42 h.ng/mL and 3560.75 ± 661.83 h.ng/mL, respectively. The primary target variables data demonstrate the bioequivalence of test and reference products with regard to 90% confidence interval for C_max of 92.45-108.53% and for AUC_0-tlast of 95.57-100.87%. The geometric mean ratios were found as 100.16% and 98.18% for C_max and AUC_0-tlast, respectively. There were no serious adverse events or adverse reactions reported throughout the study.

CONCLUSION: After statistical evaluation of the analytical results, the test and reference products were considered bioequivalent. Both products were well tolerated and considered as safe.

PMID:37161687 | DOI:10.4274/tjps.galenos.2022.95994

BJS Open. 2023 May 5;7(3):zrad010. doi: 10.1093/bjsopen/zrad010.

ABSTRACT

BACKGROUND: Electrolyte disturbances and dehydration are common after anterior resection for rectal cancer with a defunctioning loop ileostomy. High-quality population-based studies on the impact of a defunctioning loop ileostomy on renal failure are lacking.

METHODS: This was a nationwide observational study, based on the Swedish Colorectal Cancer Registry of patients undergoing anterior resection for rectal cancer between 2008 and 2016, with follow-up until 2017. Patients with severe co-morbidity, with age greater than 80 years, and with pre-existing renal failure were excluded. Loop ileostomy at index surgery constituted exposure, while a diagnosis of renal failure was the outcome. Acute and chronic events were analysed separately. Inverse probability weighting with adjustment for confounding derived from a causal diagram was employed. Hazards ratios (HRs) with 95 per cent c.i. are reported.

RESULTS: A total of 5355 patients were eligible for analysis. At 5-year follow-up, all renal failure events (acute and chronic) were 7.2 per cent and 3.3 per cent in the defunctioning stoma and no stoma groups respectively. In the weighted analysis, a HR of 11.59 (95 per cent c.i. 5.68 to 23.65) for renal failure in ostomates was detected at 1 year, with the largest effect from acute renal failure (HR 24.04 (95 per cent c.i. 8.38 to 68.93)). Later follow-up demonstrated a similar pattern, but with smaller effect sizes.

CONCLUSION: Patients having a loop ileostomy in combination with anterior resection for rectal cancer are more likely to have renal failure, especially early after surgery. Strategies are needed, such as careful fluid management protocols, and further research into alternative stoma types or reduction in stoma formation.

PMID:37161674 | DOI:10.1093/bjsopen/zrad010

BJS Open. 2023 May 5;7(3):zrad045. doi: 10.1093/bjsopen/zrad045.

ABSTRACT

BACKGROUND: The aim of this study was to compare the pathological and perioperative outcomes of extracorporeal versus intracorporeal anastomosis after laparoscopic transverse colon cancer resection.

METHODS: In this retrospective study, patients from seven institutions in China who underwent laparoscopic resection of transverse colon cancer between 2019 and 2021 were selected and included. Either extended right hemicolectomy or transverse colectomy/extended left hemicolectomy was performed. The clinical characteristics and the pathological and perioperative outcomes were compared between patients undergoing extracorporeal or intracorporeal anastomosis. Resection margin lengths were measured on formalin-fixed specimens and an inadequate margin was defined as less than 4.2 cm between the division and the tumour. The outcome of interest was the prevalence of specimens with an inadequate margin. Length of incision, bowel function recovery, hospital stay, early postoperative pain (first day after surgery), 30-day complications, and nodal harvest were investigated as secondary outcomes.

RESULTS: Of 411 patients treated during the study interval, 370 patients with transverse colon cancer were included (23.2 per cent treated with intracorporeal anastomosis and 76.8 per cent treated with extracorporeal anastomosis). The prevalence of specimens with inadequate margins was lower in the intracorporeal anastomosis group compared with the extracorporeal anastomosis group in patients undergoing extended right hemicolectomy (P = 0.045) and in patients undergoing transverse colectomy/extended left hemicolectomy (P = 0.030). In multivariate analysis, extracorporeal anastomosis (OR 2.94 (95 per cent c.i. 1.33 to 6.49), P = 0.008) and transverse colectomy/extended left hemicolectomy (OR 1.75 (95 per cent c.i. 1.03 to 2.96), P = 0.038) were independent risk factors for specimens with an inadequate margin. Intracorporeal anastomosis was associated with a shorter incision length (P < 0.001), an earlier recovery of bowel function (P = 0.035), a shorter postoperative hospital stay (P = 0.042), less early postoperative pain (P < 0.001), a longer specimen length (P = 0.042), a longer resection margin (P = 0.007), and a greater lymph node harvest (P = 0.036). There was no statistically significant difference in 30-day complications.

CONCLUSION: Patients with transverse colon cancer have better perioperative outcomes, fewer margins of less than 4.2 cm, and larger lymph node harvests when the anastomosis is performed intracorporeally. Further studies are needed to confirm these findings.

REGISTRATION NUMBER: NCT05061199 (www.clinicaltrials.gov).

PMID:37161672 | DOI:10.1093/bjsopen/zrad045

Gut Pathog. 2023 May 10;15(1):22. doi: 10.1186/s13099-023-00546-z.

ABSTRACT

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) is associated with systemic hyper-inflammation. An adaptive interaction between gut microbiota and host immune systems is important for intestinal homeostasis and systemic immune regulation. The association of gut microbial composition and functions with COVID-19 disease severity is sparse, especially in India. We analysed faecal microbial diversity and abundances in a cohort of Indian COVID-19 patients to identify key signatures in the gut microbial ecology in patients with severe COVID-19 disease as well as in response to different therapies. The composition of the gut microbiome was characterized using 16Sr RNA gene sequences of genomic DNA extracted from faecal samples of 52 COVID-19 patients. Metabolic pathways across the groups were predicted using PICRUSt2. All statistical analyses were done using Vegan in the R environment. Plasma cytokine abundance at recruitment was measured in a multiplex assay.

RESULTS: The gut microbiome composition of mild and severe patients was found to be significantly different. Immunomodulatory commensals, viz. Lachnospiraceae family members and Bifidobacteria producing butyrate and short-chain fatty acids (SCFAs), were under represented in patients with severe COVID-19, with an increased abundance of opportunistic pathogens like Eggerthella. The higher abundance of Lachnoclostridium in severe disease was reduced in response to convalescent plasma therapy. Specific microbial genera showed distinctive trends in enriched metabolic pathways, strong correlations with blood plasma cytokine levels, and associative link to disease outcomes.

CONCLUSION: Our study indicates that, along with SARS-CoV-2, a dysbiotic gut microbial community may also play an important role in COVID-19 severity through modulation of host immune responses.

PMID:37161621 | DOI:10.1186/s13099-023-00546-z

J Diabetes. 2023 May 9. doi: 10.1111/1753-0407.13399. Online ahead of print.

ABSTRACT

BACKGROUND: Evidence links gamma-glutamyl transferase (GGT) to mortality in the general population. However, the relationship of GGT with all-cause and cause-specific mortality risk has been little explored in type 2 diabetes mellitus (T2DM) patients.

METHODS: We recruited 20 340 community-dwelling T2DM patients between 2013 and 2014 in Jiangsu, China. Cox regression models were used to assess associations of GGT with all-cause and specific-cause mortality. Restricted cubic splines were used to analyze dose-response relationships between GGT and mortality. Stratified analysis was conducted to examine potential interaction effects by age, sex, smoking status, body mass index (BMI), diabetes duration, and dyslipidemia.

RESULTS: During a median follow-up period of 7.04 years (interquartile range: 6.98-7.08), 2728 deaths occurred, including 902 (33.09%) due to cardiovascular disease (CVD), and 754 (27.58%) due to cancer. GGT concentrations were positively associated with all-cause, CVD, and cancer mortality. Multivariable hazard ratios (HRs) for the highest (Q5) vs. the lowest quintile (Q1) were 1.63 (95% confidence intervals [CI]: 1.44-1.84) for all-cause mortality, 1.87 (95% CI: 1.49-2.35) for CVD mortality, and 1.43 (95% CI: 1.13-1.81) for cancer mortality. Effect modification by BMI and dyslipidemia was observed for all-cause mortality (both p for interaction <.05), and HRs were stronger in the BMI <25 kg/m² group and those without dyslipidemia.

CONCLUSIONS: Our findings suggest that, in Chinese T2DM patients, elevated serum GGT concentrations were associated with mortality for all-cause, CVD, and cancer, and further research is needed to elucidate the role of obesity, nonalcoholic fatty liver disease, and lipids in this association.

PMID:37161588 | DOI:10.1111/1753-0407.13399

BMC Cancer. 2023 May 9;23(1):422. doi: 10.1186/s12885-023-10863-w.

ABSTRACT

BACKGROUND: Postoperative adjuvant chemotherapy (AC) is now well-accepted as standard for high-risk stage II and stage III colorectal cancer (CRC) patients, however the optimal time to initiate AC remains elusive.

METHODS: A comprehensive literature search was performed using the PubMed and Embase databases. The Hazard ratio (HR) with the corresponding 95% confidence interval (CI) was used as an effect measure to evaluate primary endpoints. All analyses were conducted using Stata software version 12.0 with the Random-effects model.

RESULTS: A total of 30 studies were included in our study. Upon comparison on overall survival (OS), we identified that delaying the initiation of AC for > 8 weeks after operation was significantly associated with poor OS (HR: 1.37; 95% CI: 1.27-1.48; P < 0.01). The poor prognostic value of AC delay for > 8 weeks was not undermined by subgroup analysis based on region, tumor site, sample size and study quality. No obvious differences were observed in survival between AC within 5-8 weeks and ≤ 4 weeks (HR: 1.03; 95% CI: 0.96 -1.10; P = 0.46). Moreover, two studies both highlighted that the survival benefit of AC was still statistically significant when AC was applied 5-6 months after surgery compared with the non-chemotherapy group.

CONCLUSIONS: Delaying the initiation of AC for > 8 weeks after surgery was significantly associated with poor OS. AC started within 8 weeks after surgery brought more benefits to CRC patients. There were no obvious differences in survival benefits between AC within 5-8 weeks and ≤ 4 weeks. Compared to patients not receiving AC after surgery, a delay of approximately 5-6 months was still useful to improve prognosis.

PMID:37161562 | DOI:10.1186/s12885-023-10863-w

Ultrasound Obstet Gynecol. 2023 May 9. doi: 10.1002/uog.26245. Online ahead of print.

ABSTRACT

OBJECTIVES: Prediction models can support clinical decision-making and inform women and their partners regarding obstetric and neonatal management in complicated pregnancies. The first aim of this systematic review was to identify all prediction models on fetal and neonatal outcomes in pregnancies with preterm manifestations of placental insufficiency (i.e. gestational hypertension, pre-eclampsia, HELLP-syndrome or fetal growth restriction with its onset before 37 weeks of gestational age). The second aim was to appraise the quality of the models and their performance at external validation.

METHODS: A systematic literature search was performed in Pubmed, Web of Science and Embase. Studies describing prediction models on fetal or neonatal mortality, or significant neonatal morbidity in patients with preterm placental insufficiency disorders were included. Data extraction was performed using the CHARMS-checklist. Risk of bias was assessed using PROBAST. Literature selection and data extraction were performed by two researchers independently.

RESULTS: Our literature search yielded 22,491 unique publications. Fourteen were included after full text screening. These fourteen studies derived 41 prediction models, four models in the setting of pre-eclampsia, two models in fetal growth restriction and/or pre-eclampsia and 35 models in fetal growth restriction. None of the models were externally validated and internal validation was performed by only two studies. Final models contained mainly ultrasound (Doppler) markers as predictors of fetal and neonatal mortality and morbidity. Discriminative properties were reported for 27/41 models (c-statistics between 0.6-0.9). Only two studies presented a calibration plot. The risk of bias was assessed as unclear in one model and high for all other models, mainly due to inappropriate statistical methods.

CONCLUSIONS: We identified 41 prediction models for fetal and neonatal outcomes in pregnancies with preterm manifestations of placental insufficiency. All models were considered of low methodological quality, apart from one model (unclear quality). Higher quality models and external validation studies are needed to inform clinical decision-making based on prediction models. This article is protected by copyright. All rights reserved.

PMID:37161550 | DOI:10.1002/uog.26245

Evolution. 2023 May 10:qpad068. doi: 10.1093/evolut/qpad068. Online ahead of print.

ABSTRACT

We address the problem of defining selection and extracting the adaptive part of evolutionary change, originally formalized by Fisher and Price. Conventionally selection and adaptation are defined through fitness attributed to genes or genotypes chosen as units of selection. The construction through fitness is known to suffer ambiguities and omissions as a theory of change due to selection. We construct an alternative framing in which units of selection and fitness are replaced as the main abstractions by formal lifecycle models and reproduction rates through genetically distinct lifecycle realizations. Graphical representations of lifecycles express relations among reproductive stages that cannot be assigned to any one unit of selection. The lifecycle partition refines the statistics of overall reproductive success and resolves modes of selection that fitness either excludes or distorts through additive projections. We derive the Price equation in the basis of lifecycle realizations and compare it to the conventional Price equation for additive fitness of organisms. We show how the lifecycle approach recovers fitnesses acting concurrently at multiple levels, or contrasts forms of competition within and between levels that are invisible to additive fitness. Defining selection through lifecycles recasts population genetics from an object-focused to a construction- and process-focused representation.

PMID:37161529 | DOI:10.1093/evolut/qpad068

BMC Musculoskelet Disord. 2023 May 9;24(1):366. doi: 10.1186/s12891-023-06466-y.

ABSTRACT

PURPOSE: To systematically review the studies regarding to the safety, efficacy and application methods of PRP in promoting the talar cartilage repair.

METHODS: A systematic review was performed by searching PubMed, Web of Science, OVID and EMBASE to identify studies that compared the clinical efficacy of PRP for talar cartilage repair. Main outcome was the American Orthopedic Foot and Ankle Society (AOFAS) score for function and Visual Analog Scale (VAS) for pain was the second outcome.

RESULTS: A total of 10 studies were included in this systematic review, including 4 randomized controlled trials, 1 controlled trial, 3 case series and 2 cohort studies. Four RCTs were analyzed using meta-analysis. For all outcomes, statistical results favored PRP group (AOFAS: MD = 7.84; 95% CI= [-0.13, 15.80], I² = 83%, P < 0.01; VAS: MD = 1.86; 95% CI= [0.68, 3.04], I² = 85%, P < 0.01). There were almost no reports of adverse events related to PRP intervention. Subgroup analysis showed that whether PRP was used alone or combined with other treatments could result in high heterogeneity but no more specific factors were identified to contribute to this.

CONCLUSION: PRP is safe and effective for talar cartilage repair. In addition to the standardization of PRP preparation and application, it is necessary to distinguish the effects of PRP used alone or in combination with other treatments. In PRP studies, surgical treatment of talar cartilage repair remains the mainstream. The regulation of PRP in surgical applications are worth exploring. The most relative component is the mesenchymal stem cell because it is the only exposed chondrocyte precursor in the articular cavity whether it is microfracture or cell transplantation.

TRIAL REGISTRATION: The study was registered in the PROSPERO International prospective register of systematic reviews (CRD42022360183).

PMID:37161527 | DOI:10.1186/s12891-023-06466-y