Tag: pubmed

Pathologica. 2024 Feb;116(1):32-45. doi: 10.32074/1591-951X-926.

ABSTRACT

INTRODUCTION: Endometrial carcinoma (EC) is the commonest gynecological cancer affecting women in Western populations. To predict patient risk, the 2020 edition of the World Health Organization (WHO) Classification of Tumors of the Female Genital Tract stressed the importance of integrated histo-molecular classification of the disease. This survey analysis poses attention on the most frequently used immunohistochemical and molecular markers adopted in daily categorization of ECs in European laboratories.

METHODS: We analyzed data collected through questionnaires administered to 40 Italian, 20 Spanish, 3 Swiss and 6 United Kingdom (UK) laboratories. We collected information regarding daily practice in EC evaluation, specifically concerning mismatch repair status (MMR) and microsatellite instability (MSI). Summary and descriptive statistical analyses were carried out to evaluate the current practice of each laboratory.

RESULTS: The results show that MMR status is mainly evaluated by using immunohistochemistry (IHC) on most EC samples. The most frequent approach for the analysis of MMR status is IHC of four proteins (PMS2, MSH6, MSH2, MLH1). MSI analysis by molecular methods is uncommon but useful as a supplemental tool in specific conditions. MLH1 promoter hypermethylation and BRAF V600 mutations analysis are performed in case of negative expression of MLH1/PMS2. Other markers (mainly p53 followed by POLE and PTEN) are investigated in particular in Spain and Switzerland in a consistent number of cases.

CONCLUSION: Guidelines consultation and standardization of laboratory procedures are efficient means for EC prognostic risk stratification and improving the quality of care.

PMID:38482673 | DOI:10.32074/1591-951X-926

Ann Surg. 2024 Mar 14. doi: 10.1097/SLA.0000000000006267. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study was to compare the perioperative outcomes of robotic liver surgery (RLS) and laparoscopic liver surgery (LLS) in various settings.

SUMMARY BACKGROUND DATA: Clear advantages of RLS over LLS have rarely been demonstrated, and the associated costs of robotic surgery are generally higher than those of laparoscopic surgery. Therefore, the exact role of the robotic approach in minimally invasive liver surgery remains to be defined.

METHODS: In this international retrospective cohort study, the outcomes of patients who underwent RLS and LLS for all indications between 2009 and 2021 in 34 hepatobiliary referral centers were compared. Subgroup analyses were performed to compare both approaches across several types of procedures: minor resections in the anterolateral (2, 3, 4b, 5, and 6) or posterosuperior segments (1, 4a, 7, 8), and major resections (≥3 contiguous segments). Propensity score matching (PSM) was used to mitigate the influence of selection bias. The primary outcome was textbook outcome in liver surgery (TOLS), previously defined as the absence of intraoperative incidents ≥grade 2, postoperative bile leak ≥grade B, severe morbidity, readmission, and 90-day or in-hospital mortality with the presence of an R0 resection margin in case of malignancy. The absence of a prolonged length of stay was added to define TOLS+.

RESULTS: Among the 10.075 included patients, 1.507 underwent RLS and 8.568 LLS. After PSM, both groups constituted 1.505 patients. RLS was associated with higher rates of TOLS (78.3% vs. 71.8%, P<0.001) and TOLS+ (55% vs. 50.4%, P=0.026), less Pringle usage (39.1% vs. 47.1%, P<0.001), blood loss (100 vs. 200 milliliters, P<0.001), transfusions (4.9% vs. 7.9%, P=0.003), conversions (2.7% vs 8.8%, P<0.001), overall morbidity (19.3% vs. 25.7%, P<0.001) and R0 resection margins (89.8% vs. 86%, P=0.015), but longer operative times (190 vs. 210 min, P=0.015). In the subgroups, RLS tended to have higher TOLS rates, compared to LLS, for minor resections in the posterosuperior segments (n=431 per group, 75.9% vs. 71.2%, P=0.184) and major resections (n=321 per group, 72.9% vs. 67.5%, P=0.086), although these differences did not reach statistical significance.

CONCLUSIONS: While both producing excellent outcomes, RLS might facilitate slightly higher TOLS rates than LLS.

PMID:38482665 | DOI:10.1097/SLA.0000000000006267

Epigenomics. 2024 Mar 14. doi: 10.2217/epi-2023-0343. Online ahead of print.

ABSTRACT

Aim: To elucidate the epigenetic consequences of DNA methylation in healthspan termination (HST), considering the current limited understanding. Materials & methods: Genetically predicted DNA methylation models were established (n = 2478). These models were applied to genome-wide association study data on HST. Then, a poly-methylation risk score (PMRS) was established in 241,008 individuals from the UK Biobank. Results: Of the 63,046 CpGs from the prediction models, 13 novel CpGs were associated with HST. Furthermore, people with high PMRSs showed higher HST risk (hazard ratio: 1.18; 95% CI: 1.13-1.25). Conclusion: The study indicates that DNA methylation may influence HST by regulating the expression of genes (e.g., PRMT6, CTSK). PMRSs have a promising application in discriminating subpopulations to facilitate early prevention.

PMID:38482663 | DOI:10.2217/epi-2023-0343

Epigenomics. 2024 Mar 14. doi: 10.2217/epi-2023-0424. Online ahead of print.

ABSTRACT

Aim: The current work was designed to demonstrate the application of the exposome framework in examining associations between exposures and children’s long-term neurodevelopmental and behavioral outcomes. Methods: Longitudinal data were collected from birth through age 6 from 402 preterm infants. Three statistical methods were utilized to demonstrate the exposome framework: exposome-wide association study, cumulative exposure and machine learning models, with and without epigenetic data. Results: Each statistical approach answered a distinct research question regarding the impact of exposures on longitudinal child outcomes. Findings highlight associations between exposures, epigenetics and executive function. Conclusion: Findings demonstrate how an exposome-based approach can be utilized to understand relationships between internal (e.g., DNA methylation) and external (e.g., prenatal risk) exposures and long-term developmental outcomes in preterm children.

PMID:38482639 | DOI:10.2217/epi-2023-0424

JBI Evid Synth. 2024 Mar 14. doi: 10.11124/JBIES-23-00029. Online ahead of print.

ABSTRACT

OBJECTIVE: The purpose of this scoping review was to examine the depiction of conversational agents as health professionals. We identified the professional characteristics that are used with these depictions and determined the prevalence of these characteristics among conversational agents that are used for health care.

INTRODUCTION: The depiction of conversational agents as health professionals has implications for both the users and the developers of these programs. For this reason, it is important to know more about these depictions and how they are implemented in practical settings.

INCLUSION CRITERIA: This review included scholarly literature on conversational agents that are used for health care. It focused on conversational agents designed for patients and health seekers, not health professionals or trainees. Conversational agents that address physical and/or mental health care were considered, as were programs that promote healthy behaviors.

METHODS: This review was conducted in accordance with JBI methodology for scoping reviews. The databases searched included MEDLINE (PubMed), Embase (Elsevier), CINAHL with Full Text (EBSCOhost), Scopus, Web of Science, ACM Guide to Computing Literature (ACM Digital Library), and IEEE Xplore (IEEE). The main database search was conducted in June 2021, and an updated search was conducted in January 2022. Extracted data included characteristics of the report, basic characteristics of the conversational agent, and professional characteristics of the conversational agent. Extracted data were summarized using descriptive statistics. Results are presented in a narrative summary and accompanying tables.

RESULTS: A total of 38 health-related conversational agents were identified across 41 reports. Six of these conversational agents (15.8%) had professional characteristics. Four conversational agents (10.5%) had a professional appearance in which they displayed the clothing and accessories of health professionals and appeared in professional settings. One conversational agent (2.6%) had a professional title (Dr), and 4 conversational agents (10.5%) were described as having professional roles. Professional characteristics were more common among embodied versus disembodied conversational agents.

CONCLUSIONS: The results of this review show that the depiction of conversational agents as health professionals is not particularly common, although it does occur. More discussion is needed on the potential ethical and legal issues surrounding the depiction of conversational agents as health professionals. Future research should examine the impact of these depictions, as well as people’s attitudes toward them, to better inform recommendations for practice.

PMID:38482610 | DOI:10.11124/JBIES-23-00029

JBI Evid Synth. 2024 Mar 14. doi: 10.11124/JBIES-23-00439. Online ahead of print.

ABSTRACT

OBJECTIVE: The proposed systematic review will evaluate the evidence on the effectiveness and safety of enhanced post-operative care (EPC) units on patient and health service outcomes in adult patients following non-cardiac, non-neurological surgery.

INTRODUCTION: The increase in surgical procedures globally has placed a significant economic and societal burden on health care systems. Recognizing this challenge, EPC units have emerged as a model of care, bridging the gap between traditional, ward-level care and intensive care. EPC offers benefits such as higher staff-to-patient ratios, close patient monitoring (eg, invasive monitoring), and access to critical interventions (eg, vasopressor support). However, there is a lack of well-established guidelines and empirical evidence regarding the safety and effectiveness of EPC units for adult patients following surgery.

INCLUSION CRITERIA: This review will include studies involving adult patients (≥ 18 years) undergoing any elective or emergency non-cardiac, non-neurological surgery, who have been admitted to an EPC unit. Experimental, quasi-experimental, and observational study designs will be eligible.

METHODS: This review will follow the JBI methodology for systematic reviews of effectiveness. The search strategy will identify published and unpublished studies from the Cochrane Library, MEDLINE (Ovid), Embase (Ovid), and Scopus, as well as gray literature sources, from 2010 to the present. Two independent reviewers will screen studies, extract data, and critically appraise selected studies using standardized JBI assessment tools. Where feasible, a statistical meta-analysis will be performed to combine study findings. The certainty of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology.

REVIEW REGISTRATION NUMBER: PROSPERO CRD42023455269.

PMID:38482608 | DOI:10.11124/JBIES-23-00439

Acta Oncol. 2024 Mar 14;63:70-75. doi: 10.2340/1651-226X.2024.34139.

ABSTRACT

BACKGROUND: Assessment of homologous recombinant deficient (HRD) phenotypes is key for managing Poly (ADP-ribose) polymerase inhibitor (PARPi) treatment. To accommodate the need for a validated HRD platform and enhance targeted treatment of ovarian cancer patients, a Nordic core facility for the myChoice® CDx platform was established in Denmark.

MATERIALS AND METHODS: Comparative calculations and statistics are based on information from test requisitions and results (Genome Instability Score [GIS], BRCA status and combined HRD status) obtained from ovarian and breast cancer samples submitted for HRD-testing by myChoice® CDx through the Nordic core facility in the 2-year period.

RESULTS: Copenhagen University Hospital received 1,948 requisitions during the 2-year period. Conclusive results were obtained in 89% of the tests, while 7% were inconclusive due to the lack of GIS and 4% were not able to be analysed. Comparing the conclusive HRD status results across countries, Sweden had the highest percentage of HRD positives (38%) compared to Denmark, Norway, and Finland (28-32%).

INTERPRETATION: The myChoice® CDx Nordic core facility has been well received among the Nordic countries and provides new insights on the influence of national guidelines on HRD testing. Overall, we experienced an efficient turnaround time and a high fraction of conclusive results. Interestingly, prior somatic BRCA testing is redundant when assessing HRD status through myChoice® CDx test since somatic BRCA screening is already a significant component of the myChoice® CDx test. Thus, it should be considered to omit prior somatic BRCA testing to ensure a rationalised HRD diagnostic flow optimised for clinical use.

PMID:38482597 | DOI:10.2340/1651-226X.2024.34139

J Clin Endocrinol Metab. 2024 Mar 14:dgae169. doi: 10.1210/clinem/dgae169. Online ahead of print.

ABSTRACT

BACKGROUND: Previous observational studies have indicated a bidirectional association between metabolic syndrome (MetS) and osteoarthritis (OA). However, it remains unclear whether these bidirectional associations reflect causal relationships or shared genetic factors, and the underlying biological mechanisms of this association are not fully understood.

METHODS: Leveraging summary statistics from genome-wide association studies (GWASs) conducted by the UK Biobank and the Glucose and Insulin-related Traits Consortium (MAGIC), we performed global genetic correlation analyses, genome-wide cross-trait meta-analyses, and a bidirectional two-sample Mendelian randomization analyses using summary statistics from GWASs to comprehensively assess the relationship of MetS and OA.

RESULTS: We first detected an extensive genetic correlation between MetS and OA (rg=0.393, P=1.52×10-18), which was consistent in four MetS components, including waist circumference, triglycerides, hypertension and high-density lipoprotein cholesterol and OA with rg ranging from -0.229 to 0.490. We then discovered 32 variants jointly associated with MetS and OA through multi-trait Analysis of GWAS. Co-localization analysis founded 12 genes shared between MetS and OA, with functional implications in several biological pathways. Finally, MR analysis suggested genetic liability to MetS significantly increased the risk of OA, but no reverse causality was found.

CONCLUSION: Our results illustrate a common genetic architecture, pleiotropic loci, as well as causality between MetS and OA, potentially enhancing our knowledge of high comorbidity and genetic processes that overlap between the two disorders.

PMID:38482593 | DOI:10.1210/clinem/dgae169

Cardiol Young. 2024 Mar 14:1-9. doi: 10.1017/S1047951124000167. Online ahead of print.

ABSTRACT

OBJECTIVES: Children with CHD are at heightened risk of neurodevelopmental problems; however, the contribution of acute neurological events specifically linked to the perioperative period is unclear.

AIMS: This secondary analysis aimed to quantify the incidence of acute neurological events in a UK paediatric cardiac surgery population, identify risk factors, and assess how acute neurological events impacted the early post-operative pathway.

METHODS: Post-operative data were collected prospectively on 3090 consecutive cardiac surgeries between October 2015 and June 2017 in 5 centres. The primary outcome of analysis was acute neurological event, with secondary outcomes of 6-month survival and post-operative length of stay. Patient and procedure-related variables were described, and risk factors were statistically explored with logistic regression.

RESULTS: Incidence of acute neurological events after paediatric cardiac surgery in our population occurred in 66 of 3090 (2.1%) consecutive cardiac operations. 52 events occurred with other morbidities including renal failure (21), re-operation (20), cardiac arrest (20), and extracorporeal life support (18). Independent risk factors for occurrence of acute neurological events were CHD complexity 1.9 (1.1-3.2), p = 0.025, longer operation times 2.7 (1.6-4.8), p < 0.0001, and urgent surgery 3.4 (1.8-6.3), p < 0.0001. Unadjusted comparison found that acute neurological event was linked to prolonged post-operative hospital stay (median 35 versus 9 days) and poorer 6-month survival (OR 13.0, 95% CI 7.2-23.8).

CONCLUSION: Ascertainment of acute neurological events relates to local measurement policies and was rare in our population. The occurrence of acute neurological events remains a suitable post-operative metric to follow for quality assurance purposes.

PMID:38482588 | DOI:10.1017/S1047951124000167

Ren Fail. 2024 Dec;46(1):2320834. doi: 10.1080/0886022X.2024.2320834. Epub 2024 Mar 14.

ABSTRACT

BACKGROUND: This study aims to undertake a comprehensive assessment of the effectiveness and safety profile of Mahuang Fuzi and Shenzhuo Decoction (MFSD) in the management of primary membranous nephropathy (PMN), within the context of a prospective clinical investigation.

METHODS: A multicenter, open-label clinical trial was executed on patients diagnosed with PMN. These individuals were subjected to MFSD therapy for a duration of at least 24 months, with primary outcome of clinical remission rates. The Cox regression analysis was employed to discern the pertinent risk factors exerting influence on the efficacy of MFSD treatment, with scrupulous monitoring of any adverse events.

RESULTS: The study comprised 198 participants in total. Following 24 months of treatment, the remission rate was 58.6% (116/198). Among the subgroup of 130 participants subjected to a 36-month follow-up, the remission rate reached 70% (91/130). Subgroup analysis revealed that neither a history of immunosuppressive therapy (HIST) nor an age threshold of ≥60 years exhibited a statistically significant impact on the remission rate at the 24-month mark (p > .05). Multivariate Cox regression analyses elucidated HIST, nephrotic syndrome, or mass proteinuria, and a high-risk classification as noteworthy risk factors in the context of MFSD treatment. Remarkably, no fatalities resulting from side effects were documented throughout the study’s duration.

CONCLUSIONS: This trial establishes the efficacy of MFSD as a treatment modality for membranous nephropathy. MFSD demonstrates a favorable side effect profile, and remission rates are consistent across patients, irrespective of HIST and age categories.

PMID:38482580 | DOI:10.1080/0886022X.2024.2320834