Nevin Manimala

Leg Med (Tokyo). 2024 Aug 8;71:102508. doi: 10.1016/j.legalmed.2024.102508. Online ahead of print.

ABSTRACT

INTRODUCTION: The postmortem diagnosis of acute myocardial ischemia (AMI) represents a challenging issue in forensic practice. Immunohistochemical studies and gene expression studies are becoming a promising field of research in forensic pathology. The present study aims to evaluate HIF-1α expression through immunohistochemistry (IHC), and mRNA-210 level using real-time polymerase chain reaction (RT-PCR), in order to define if HIF-1α and mRNA-210 in post-mortem myocardium could be adopted in the diagnosis of AMI.

MATERIALS AND METHODS: Thirty-five deceased individuals, who underwent forensic autopsy at the Legal Medicine Service of the University of Parma, between 2010 and 2018, were investigated. The cohort was divided into two groups according to the cause of death (sudden deaths caused by AMI vs control cases). Cardiac specimens were collected during autopsy, then samples were processed for morphological evaluation using haematoxylin-eosin staining, for IHC, and for RT-PCR. HIF-1α expression and mRNA-210 levels were investigated.

RESULTS: Statistical evaluation demonstrated statistically significant differences in terms of number of IHC positive vessels, leukocytes, and cardiomyocytes between the two groups. Moreover, in the majority of cases, immunostaining positivity was observed only in myocardial and subendocardial samples. With reference to mRNA-210, the difference between the two groups proved to be statistically significant.

CONCLUSIONS: The present study indicates that HIF-1α and mRNA-210 in post-mortem cardiac specimens could represent appropriate biomarkers in the diagnosis of AMI. The current study was primarily limited by the scarcity of the cohort, so further research is required to confirm these preliminary observations.

PMID:39137459 | DOI:10.1016/j.legalmed.2024.102508

Appl Physiol Nutr Metab. 2024 Aug 13. doi: 10.1139/apnm-2024-0126. Online ahead of print.

ABSTRACT

Foot immersion and neck cooling are recommended cooling strategies for protecting heat-vulnerable persons during heat waves. While we recently showed that these strategies do not limit core temperature increases in older adults during prolonged heat exposure, we did observe small reductions in heart rate. Expanding on these findings, we examined the effects of foot immersion with and without neck cooling on cardiac autonomic function. Seventeen adults (9 females; 65-81 years) underwent 3 randomized, 6-hour exposures to 38°C and 35% relative humidity with: no cooling (control), foot immersion (20°C water), or foot immersion with a wet towel (20°C) around the neck. Cardiac autonomic responses were measured at baseline and end-exposure. These included heart rate variability, cardiac and systolic blood pressure responses to standing, indexed via the 30:15 ratio and supine-to-standing systolic pressure change, respectively, and baroreflex sensitivity during repeated sit-to-stand maneuvers. The 30:15 ratio was 0.04 [95% CI: 0.01, 0.07] greater with foot immersion and neck cooling (1.08 (0.04)) relative to control (1.04 (0.06); P=0.018). Similarly, standing systolic pressure was elevated 9 [0, 17] mm Hg with foot immersion and neck cooling (P=0.043). That said, neither difference remained statistically significant after adjusting for multiplicity (Padjusted≥0.054). No differences in 30:15 ratio or standing systolic pressure were observed with foot immersion alone, while heart rate variability and baroreflex sensitivity were unaffected by either cooling intervention. While foot immersion with neck cooling potentially improved cardiac autonomic responses in older adults exposed to simulated indoor overheating, these effects were small and of questionable clinical importance.

PMID:39137443 | DOI:10.1139/apnm-2024-0126

Plast Reconstr Surg. 2024 Aug 12. doi: 10.1097/PRS.0000000000011675. Online ahead of print.

ABSTRACT

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a common complication lacking medical treatment. Lymfactin® is an adenovirus type 5-based gene therapy and prolymphangiogenic growth factor vector that induces vascular endothelial growth factor C (VEGF-C) expression. Our aim was to evaluate the therapeutic effect of Lymfactin® with vascularized lymph node transfer (VLNT).

METHODS: This Phase II, double-blind, placebo-controlled, randomized multicenter study evaluated the efficacy and safety of Lymfactin® in combination with VLNT. The primary endpoints were edema volume, quality of life (LyQoLI), and lymphoscintigraphy. All adverse events were recorded. A mixed model of repeated measures analysis of covariance was performed. This study was a continuation of a previous Phase I Lymfactin® study.

RESULTS: Thirty-nine patients with BCRL were recruited between June 2018 and December 2019 and randomized to receive either Lymfactin® (n = 20) or placebo (n = 19). The primary endpoints showed a positive effect of VLNT in both groups compared to the baseline, but without statistical differences between groups at 12 months. Additionally, greater improvements were observed in the tissue dielectric constant ratios measuring skin interstitial fluid levels in the Lymfactin® group compared to the placebo group (p = 0.020). No differences in adverse events were detected between the groups.

CONCLUSIONS: This study was one of the few studies to objectively show a positive effect of VLNT in a prospective clinical multicenter setting. It was also the first-ever randomized prospective clinical study showing a quantitatively positive effect of a medical therapy on the edema of lymphedema although failing to show differences between groups in primary outcome measures.

PMID:39137430 | DOI:10.1097/PRS.0000000000011675

JMIR AI. 2024 Aug 13;3:e54371. doi: 10.2196/54371.

ABSTRACT

BACKGROUND: Although uncertainties exist regarding implementation, artificial intelligence-driven generative language models (GLMs) have enormous potential in medicine. Deployment of GLMs could improve patient comprehension of clinical texts and improve low health literacy.

OBJECTIVE: The goal of this study is to evaluate the potential of ChatGPT-3.5 and GPT-4 to tailor the complexity of medical information to patient-specific input education level, which is crucial if it is to serve as a tool in addressing low health literacy.

METHODS: Input templates related to 2 prevalent chronic diseases-type II diabetes and hypertension-were designed. Each clinical vignette was adjusted for hypothetical patient education levels to evaluate output personalization. To assess the success of a GLM (GPT-3.5 and GPT-4) in tailoring output writing, the readability of pre- and posttransformation outputs were quantified using the Flesch reading ease score (FKRE) and the Flesch-Kincaid grade level (FKGL).

RESULTS: Responses (n=80) were generated using GPT-3.5 and GPT-4 across 2 clinical vignettes. For GPT-3.5, FKRE means were 57.75 (SD 4.75), 51.28 (SD 5.14), 32.28 (SD 4.52), and 28.31 (SD 5.22) for 6th grade, 8th grade, high school, and bachelor’s, respectively; FKGL mean scores were 9.08 (SD 0.90), 10.27 (SD 1.06), 13.4 (SD 0.80), and 13.74 (SD 1.18). GPT-3.5 only aligned with the prespecified education levels at the bachelor’s degree. Conversely, GPT-4’s FKRE mean scores were 74.54 (SD 2.6), 71.25 (SD 4.96), 47.61 (SD 6.13), and 13.71 (SD 5.77), with FKGL mean scores of 6.3 (SD 0.73), 6.7 (SD 1.11), 11.09 (SD 1.26), and 17.03 (SD 1.11) for the same respective education levels. GPT-4 met the target readability for all groups except the 6th-grade FKRE average. Both GLMs produced outputs with statistically significant differences (P<.001; 8th grade P<.001; high school P<.001; bachelors P=.003; FKGL: 6th grade P=.001; 8th grade P<.001; high school P<.001; bachelors P<.001) between mean FKRE and FKGL across input education levels.

CONCLUSIONS: GLMs can change the structure and readability of medical text outputs according to input-specified education. However, GLMs categorize input education designation into 3 broad tiers of output readability: easy (6th and 8th grade), medium (high school), and difficult (bachelor’s degree). This is the first result to suggest that there are broader boundaries in the success of GLMs in output text simplification. Future research must establish how GLMs can reliably personalize medical texts to prespecified education levels to enable a broader impact on health care literacy.

PMID:39137416 | DOI:10.2196/54371

Am J Sports Med. 2024 Aug 13:3635465241265721. doi: 10.1177/03635465241265721. Online ahead of print.

ABSTRACT

BACKGROUND: Arthroscopic treatment of femoroacetabular impingement has increased in popularity since the early 2000s when it was first described, although only a few midterm follow-up studies have been published.

PURPOSE: To describe the outcomes of patients undergoing hip arthroscopy for femoroacetabular impingement at a mean 12-year follow-up and to determine the risk factors for failure.

STUDY DESIGN: Case-control study; Level of evidence, 3.

METHODS: The Non-Arthritic Hip Score (NAHS) and a radiographic evaluation were completed preoperatively and at midterm follow-up. Participants were divided into 2 groups according to their clinical evolution. The success group consisted of patients whose NAHS at the final follow-up was above the established Patient Acceptable Symptom State (PASS) threshold of 81.9, whereas patients who underwent a second surgical intervention or did not reach the PASS threshold at final follow-up were assigned to the failure group. These groups were compared to identify preoperative differences in demographic, pathological, and surgical factors.

RESULTS: A total of 95 hips were included, after 23 were lost to follow-up (80.5% follow-up). At a mean follow-up of 12.1 years (range, 9.2-16.0 years), 9 hips required total hip arthroplasty (9.5%), 5 required revision hip arthroscopy (5.3%), 29 did not achieve the NAHS PASS threshold (30.5%), and 52 achieved the NAHS PASS threshold (54.7%). The mean NAHS was 82.4 at final follow-up compared with 66.9 preoperatively (mean difference = 15.5; P < .001). Higher mean body mass index (24.9 vs 23.0; P = .030), older age (30.0 vs 27.2; P = .035), and inferior preoperative lateral joint space width (3.9 vs 4.4; P = .019) were associated with inferior prognosis in the failure group versus success group. Osteoarthritis progression was observed in 69.2% of the failure group and in 34.8% of the success group (P = .082). Labral ossification was observed in 78.3% of all patients, and its lateral projection length was statistically associated with failure (P = .015).

CONCLUSION: At a mean 12-year follow-up, hip arthroscopy for femoroacetabular impingement led to significant clinical improvement, with 55% PASS achievement. In total, 31% of patients were below the PASS threshold, 5% had revision arthroscopy, and only 9% had conversion to total hip arthroplasty for a 45% global failure rate. Increased body mass index, older age, and smaller preoperative lateral joint space width were significant negative prognostic factors. Postoperative degenerative changes were highly prevalent and demonstrated association with failure.

PMID:39137412 | DOI:10.1177/03635465241265721

JMIR Mhealth Uhealth. 2024 Aug 13;12:e51932. doi: 10.2196/51932.

ABSTRACT

BACKGROUND: Delivery of preventative interventions via mobile phone apps offers an effective and accessible way to address the global priority of improving the mental health of adolescents and young adults. A proven risk factor for anxiety and depression is elevated worry and rumination, also known as repetitive negative thinking (RNT).

OBJECTIVE: This was a prevention mechanism trial that aimed to investigate whether an RNT-targeting self-help mobile phone app (MyMoodCoach) reduces worry and rumination in young adults residing in the United Kingdom. A secondary objective was to test whether the app reduces symptoms of anxiety and depression and improves well-being.

METHODS: A web-based, single-blind, 2-arm parallel-group randomized controlled trial was conducted with 236 people aged between 16 and 24 years, who self-reported high levels of worry or rumination. Eligible participants were randomized to an active intervention group (usual practice, plus up to 6 weeks of using the RNT-targeting mobile app, n=119) or a waitlist control group (usual practice with no access to the app until after 6 weeks, n=117). The primary outcome was changes in worry and rumination 6 weeks after randomization. Secondary outcomes included changes in well-being and symptoms of anxiety and depression after 6 weeks and changes in all measures after 12 weeks.

RESULTS: Participants randomly allocated to use the RNT-targeting self-help app showed significantly lower levels of rumination (mean difference -2.92, 95% CI -5.57 to -0.28; P=.03; η_p²=0.02) and worry (mean difference -3.97, 95% CI -6.21 to -1.73; P<.001; η_p²=0.06) at 6-week follow-up, relative to the waitlist control. Similar differences were observed for well-being (P<.001), anxiety (P=.03), and depression (P=.04). The waitlist control group also showed improvement when given access to the app after 6 weeks. Improvements observed in the intervention group after 6 weeks of using the app were maintained at the 12-week follow-up point.

CONCLUSIONS: The MyMoodCoach app had a significant positive effect on worry and rumination, well-being, anxiety, and depression in young adults, relative to waitlist controls, providing proof-of-principle that an unguided self-help app can effectively reduce RNT. This app, therefore, has potential for the prevention of anxiety and depression although longer-term effects on incidence need to be directly evaluated.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04950257; https://www.clinicaltrials.gov/ct2/show/NCT04950257.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12888-021-03536-0.

PMID:39137411 | DOI:10.2196/51932

J Am Acad Orthop Surg Glob Res Rev. 2024 Aug 9;8(8). doi: 10.5435/JAAOSGlobal-D-24-00206. eCollection 2024 Aug 1.

ABSTRACT

BACKGROUND: Acute hip fractures are a public health problem affecting primarily older adults. Chat Generative Pretrained Transformer may be useful in providing appropriate clinical recommendations for beneficial treatment.

OBJECTIVE: To evaluate the accuracy of Chat Generative Pretrained Transformer (ChatGPT)-4.0 by comparing its appropriateness scores for acute hip fractures with the American Academy of Orthopaedic Surgeons (AAOS) Appropriate Use Criteria given 30 patient scenarios. “Appropriateness” indicates the unexpected health benefits of treatment exceed the expected negative consequences by a wide margin.

METHODS: Using the AAOS Appropriate Use Criteria as the benchmark, numerical scores from 1 to 9 assessed appropriateness. For each patient scenario, ChatGPT-4.0 was asked to assign an appropriate score for six treatments to manage acute hip fractures.

RESULTS: Thirty patient scenarios were evaluated for 180 paired scores. Comparing ChatGPT-4.0 with AAOS scores, there was a positive correlation for multiple cannulated screw fixation, total hip arthroplasty, hemiarthroplasty, and long cephalomedullary nails. Statistically significant differences were observed only between scores for long cephalomedullary nails.

CONCLUSION: ChatGPT-4.0 scores were not concordant with AAOS scores, overestimating the appropriateness of total hip arthroplasty, hemiarthroplasty, and long cephalomedullary nails, and underestimating the other three. ChatGPT-4.0 was inadequate in selecting an appropriate treatment deemed acceptable, most reasonable, and most likely to improve patient outcomes.

PMID:39137403 | DOI:10.5435/JAAOSGlobal-D-24-00206

Dis Esophagus. 2024 Aug 14:doae063. doi: 10.1093/dote/doae063. Online ahead of print.

ABSTRACT

The impact of sex on the prognosis of patients with esophageal cancer remains unclear. Evidence supports that sex- based disparities in esophageal cancer survival could be attributed to sex- specific risk exposures, such as age at diagnosis, race, socioeconomic status, smoking, drinking, and histological type. The aim of our study is to investigate the role of sex disparities in survival of patients who underwent surgery for esophageal cancer. A systematic review and meta-analysis of the existing literature in PubMed, EMBASE, and CENTRAL from December 1966 to February 2023, was held. Studies that reported sex-related differences in survival outcomes of patients who underwent esophagectomy for esophageal cancer were identified. A total of 314 studies were included in the quantitative analysis. Statistically significant results derived from 1-year and 2-year overall survival pooled analysis with Relative Risk (RR) 0.93 (95% Confidence Interval (CI): 0.90-0.97, I2 = 52.00) and 0.90 (95% CI: 0.85-0.95, I2 = 0.00), respectively (RR < 1 = favorable for men). In the postoperative complications analysis, statistically significant results concerned anastomotic leak and heart complications, RR: 1.08 (95% CI: 1.01-1.16) and 0.62 (95% CI: 0.52-0.75), respectively. Subgroup analysis was performed among studies with <200 and > 200 patients, histology types, study continent and publication year. Overall, sex tends to be an independent prognostic factor for esophageal carcinoma. However, unanimous results seem rather obscure when multivariable analysis and subgroup analysis occurred. More prospective studies and gender-specific protocols should be conducted to better understand the modifying role of sex in esophageal cancer prognosis.

PMID:39137391 | DOI:10.1093/dote/doae063

Swiss Med Wkly. 2024 Jul 16;154:3861. doi: 10.57187/s.3861.

ABSTRACT

AIM OF THIS STUDY: General internal medicine is a crucial element in healthcare systems. Understanding how many people are and will be working in this field is important to maintain and improve quality for patients in healthcare systems. This can provide a basis for political decisions.

METHODS: We conducted a cross-sectional study to analyse the current and future workforce of generalists (general practitioners and internists in hospitals) in Switzerland. The Swiss Society of General Internal Medicine (SSGIM) distributed a survey to all members. Respondents were asked about their current average workload in 2023 and planned workload in 2033. The responses were used to calculate full-time equivalent (FTE) for the current and future workforce of generalists and to extrapolate FTE for all active SSGIM members. To model the demand by 2033, we derived different scenarios.

RESULTS: Of all 6,232 active SSGIM members, 2,030 (33%) participated: 46% female, 25% (largest age group) 56-65 years old, 19% still in postgraduate training. The average workload in 2023 was 78% for female and 87% for male generalists; the FTE extrapolated to all active SSGIM members in 2023 was 5,246. By 2033, 1,935 FTEs (36%) will retire, 502 FTEs (10%) will reduce their workload, 116 FTEs (2%) will increase their workload and 2,800 FTEs (53%) will remain in the workforce with the same workload as in 2023. To maintain the same workforce as in 2023, 2,321 new FTEs (44%) will be needed by 2033. To fill this gap of 232 FTE new generalists per year, we modelled different scenarios with assumptions of interest, workload, migration and dropouts.

CONCLUSIONS: Within only one decade, 44% of the current workforce of generalists will disappear, mainly due to retirement and decreased workload. To fill this gap, various scenarios need to be incorporated. Politicians are called upon to create the political framework to create attractive training and working conditions for generalists to address the future demand for healthcare services.

PMID:39137384 | DOI:10.57187/s.3861

Swiss Med Wkly. 2024 Jul 16;154:3751. doi: 10.57187/s.3751.

ABSTRACT

AIMS OF THE STUDY: Limited knowledge exists regarding exposures to non-therapeutic chemicals by women planning to conceive, or during pregnancy or breastfeeding. The Swiss Teratogen Information Service (STIS) provides information to healthcare professionals about medications and other exposures during pregnancy or breastfeeding. This study aimed to describe the queries on non-therapeutic chemicals addressed to the STIS over the past two decades.

METHODS: Using data from the STIS for the years 2000 to 2019, we conducted a descriptive analysis of all queries related to women’s exposures to non-therapeutic chemicals during pregnancy planning, pregnancy or breastfeeding.

RESULTS: Over two decades, the STIS database recorded 320 exposures to chemicals. Workplace settings accounted for over 60% of queries, followed by exposures at home (20%). In almost half (48%) of the queries, more than one chemical was mentioned, totalling 885 chemicals across these 320 queries. Commonly mentioned chemicals included isopropanol, acetone and lead. Solvents were the leading category of products (16%), followed by cleaning products (10%), paints (8%) and insecticides (5%). The follow-up data showed five diverse cases of congenital malformations, accounting for 4.0% (5 out of 125) of the sample, a figure in line with the background risk of malformations in the general population.

CONCLUSIONS: This study emphasises the importance of conducting research that comprehensively captures the highly heterogeneous exposures to non-therapeutic chemicals during pregnancy and suggests that attention should be given not only to professional settings, but also to domestic contexts.

PMID:39137375 | DOI:10.57187/s.3751