Medical sciences (Basel, Switzerland)最新文献

Background: Intestinal angioedema is an important drug-induced adverse effect that is often misdiagnosed due to vague and nonspecific symptoms. This study aimed to identify drugs with potential to cause intestinal angioedema by performing a disproportionality analysis, supplemented with literature review.

Methods: Using OpenVigil, we extracted relevant individual case safety reports from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. Drugs with signal of disproportionate reporting (SDR) of intestinal angioedema were identified. A literature review was performed using PubMed and Embase databases to identify potential suspect drugs.

Results: During 2004-2024, 303 cases of intestinal angioedema were reported to FAERS. Fourteen suspect medications showed SDR; of these, seven drugs were also reported in the literature to have caused intestinal angioedema, including angiotensin-converting enzyme inhibitors, losartan, and acetylsalicyclic acid. A literature search identified 89 relevant articles, providing details of 121 cases. Some drugs linked to intestinal angioedema in the literature did not show SDR.

Conclusions: Disproportionality analysis as well as a literature review showed that most patients were middle-aged females on antihypertensive therapy. The results will assist health professionals in determining the temporal association of acute abdomen with the suspected drug, potentially avoiding unnecessary interventions and their attendant complications.

Background: Interleukin-6 (IL-6) is a key inflammatory cytokine implicated in atherosclerotic plaque progression and carotid vulnerability. Although elevated IL-6 levels have been linked to cerebrovascular risk, its prognostic value in patients undergoing carotid endarterectomy (CEA) remains undefined. This systematic review aimed to investigate the available evidence on the relationship between IL-6 levels, surgical outcomes and mechanistic evidence in CEA patients. Materials and Methods: The review followed the PRISMA statement and AMSTAR-2 critical appraisal guidelines, with the protocol registered on PROSPERO (CRD420251120023). PubMed/MEDLINE, Scopus, and Web of Science were systematically searched up to July 2025 using the terms "interleukin-6" and "carotid endarterectomy". Original studies in humans assessing IL-6 in relation to clinical outcomes after CEA or mechanistic evidence were included without language or date restrictions. Study quality was evaluated using the Cochrane Risk of Bias 2 and NHLBI tools, and evidence certainty was appraised using the GRADE framework. Given the heterogeneity of studies, only a qualitative synthesis was performed. Results: From 1232 records identified, 13 studies encompassing 1396 patients met the inclusion criteria. Most were prospective observational cohorts, with a mean participant age of 68.52 years and 81.16% male predominance. Perioperative stroke and mortality rates were uniformly low (≤2%), consistent with contemporary registry data. Across studies, elevated IL-6 levels-whether systemic or plaque-derived-were consistently associated with symptomatic carotid disease, plaque vulnerability, and adverse long-term outcomes. However, not all studies presented quantitative data on IL-6 levels, limiting the ability to draw definitive prognostic conclusions. Conclusions: Current evidence supports a mechanistic link between IL-6-mediated inflammation and carotid plaque instability, yet robust clinical validation in surgical populations is lacking. Future large-scale, prospective studies incorporating IL-6 measurement are warranted to establish its prognostic utility, guide anti-inflammatory therapeutic strategies, and refine postoperative risk stratification in patients undergoing CEA.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) commonly coexists with type 2 diabetes (T2D), but their independent contributions to redox imbalance, inflammation and immune signaling remain uncertain.

Objectives: This study aimed to evaluate whether the presence of MASLD alone, and the presence of T2D within MASLD, are independently associated with high-risk profiles of oxidative/antioxidant markers, peripheral blood mononuclear cell (PBMC) gene expression and adipocytokines.

Methods: A total of 190 participants were categorized via abdominal ultrasound as controls (n = 46), MASLD (n = 83) or MASLD with T2D (n = 61). Measurements included advanced oxidation protein products (AOPP) and paraoxonase-1 (PON1) activity in serum; messenger ribonucleic acids expression of cluster of differentiation 36 (CD36), Toll-like receptor 9 (TLR9), and glutathione peroxidase-1 in PBMC; and adiponectin, leptin, and resistin in plasma. Biomarker values were adjusted and statistical comparisons among groups were performed using the Quade test. Subsequently, biomarkers were stratified into tertiles to examine associations between high-risk biomarker levels and the presence of MASLD or T2D in patients with MASLD using multivariate binary logistic regression.

Results: Multivariate analysis showed that MASLD presence was independently associated with both increased AOPP and decreased resistin levels in the circulation. Furthermore, T2D presence in patients with MASLD was independently associated with increased CD36 and decreased TLR9 gene expression in PBMCs, as well as elevated circulating leptin levels.

Conclusions: Collectively, these findings underscore the complex interplay between oxidative stress, insulin resistance, inflammation, and immune signaling in the pathogenesis of MASLD, which are fundamental factors contributing to this condition.

Background/objectives: Serum calcium concentrations have been associated with bone mineral density (BMD), but results seem to depend on sex. Genetic variants in the Ryanodine Receptor1 (RYR1) gene have been previously associated with low BMD in postmenopausal women. Serum RYR1 concentration was found to be higher in osteopenia and osteoporosis groups. The function and biological relevance of RYR1 in bone remodeling remains unknown. This cross-sectional study explored the relationship between serum calcium concentrations, BMD, and genetic variants in RYR1 in a Mexican-mestizo population.

Methods: Serum samples from 966 participants were obtained from the third measurement of the Health Workers Cohort Study (HWCS) 2017-2019, conducted by the Mexican Social Security Institute (IMSS). All participants included in this study were of Mexican Mestizo origin and had data on BMD. We measured ionized calcium and genotyped the genetic variants rs2288888 (g.38455542G>A) and rs11083462 (g.38469040C>T) of the RYR1 gene. BMD of the total hip, lumbar spine, and femoral neck was measured using a Lunar DPX NT DEXA device.

Results: Our results show that elevated serum calcium concentrations in females are associated with lower BMD at the hip and femoral neck. In contrast, higher calcium concentrations in males were associated with greater total hip BMD. In our study, the variants rs2288888 and rs11083462 were associated with higher serum calcium concentrations (under-adjusted and unadjusted data) in males but not females.

Conclusions: Serum calcium levels are associated with BMD, depending on sex. The RYR1 gene variants rs2288888 and rs11083462 may have a protective effect in men.

Background/objectives: Hypertension is a major modifiable risk factor for cardiovascular disease and may negatively affect muscle strength through vascular and metabolic mechanisms. Nevertheless, reference values for respiratory muscle strength (RMS) in hypertensive adults remain unavailable. This study aimed to establish sex- and age-specific reference values for maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) in Brazilian adults with hypertension and to investigate clinical factors associated with these measures.

Methods: This cross-sectional study included 234 hypertensive adults (109 women and 125 men; 30-80 years) enrolled in a cardiovascular rehabilitation program. Anthropometric, hemodynamic, and clinical data were collected. RMS was assessed using standardized procedures for MIP and MEP with an analog manovacuometer (-300 to +300 cmH₂O). Participants were stratified by age and sex. Statistical analyses included the Mann-Whitney U and Kruskal-Wallis tests and multivariate linear regression (p < 0.05).

Results: Men exhibited significantly higher MIP and MEP values than women across most age groups. RMS declined progressively with age, with a more marked reduction after 60 years. MIP was identified as the primary predictor of MEP in both sexes, with higher coefficients of determination in men. The reference values obtained were largely comparable to those reported for healthy individuals.

Conclusions: This study provides clinically relevant reference values for RMS Brazilian individuals with hypertension, offering useful parameters for respiratory assessment and individualized rehabilitation strategies.

Background: Periprostatic adipose tissue (PPAT) has been shown to play a significant role in prostate cancer (PCa) development and progression. This relationship is further exacerbated by obesity, as PPAT-secreted factors increase PCa aggressiveness and have also been implicated in chemotherapy resistance. Therefore, identifying the molecular mediators of PPAT-prostate interorgan communication and the factors that disrupt this crosstalk is pivotal for better disease management. Obesogens, i.e., endocrine-disrupting chemicals that dysregulate adipose tissue towards an "obese" phenotype, have recently been implicated in disrupting this crosstalk, with an impact on prostate cell fate.

Objectives: This study aimed to investigate whether obesogenic dysregulation of human PPAT secretory activity affects PCa cell viability and their response to docetaxel and cabazitaxel.

Methods/results: Through ex vivo culture of human PPAT and conditioned medium assays, we demonstrated that exposure to the model obesogen tributyltin (TBT) induced an "obese" phenotype in human PPAT, characterised by adipocyte enlargement and increased secretion of leptin and C-C motif chemokine ligand 7. The TBT-treated PPAT secretome enhanced cell viability and decreased the sensitivity of PCa cells to taxanes.

Conclusions: This study provides preliminary evidence that lays the groundwork for future investigations, dissecting the molecular pathways underpinning prostate carcinogenesis and resistance to chemotherapy induced by obesogen-dysregulated PPAT.

Background: Chronic pain is a prevalent and disabling condition, affecting 20-30% of the global population, which requires multidisciplinary approaches integrating non-pharmacological therapies and promoting patient engagement in self-management.

Objective: To describe the structure, content, outcomes, and lessons learned from multicomponent workshops for chronic non-cancer pain using non-pharmacological therapies.

Methods: A quasi-experimental before-after study was conducted in patients attending a chronic pain workshop at San Juan de Dios Hospital (Bormujos, Seville, Spain) between November 2021 and May 2024, with a 3-month follow-up, Validated scales and an ad hoc patient survey were administered at baseline, immediately post-workshop, and at 3-month follow-up. Furthermore, comparative analysis was conducted 4 months before and after the intervention for emergency visits and consultations, medication consumption, and employment status. Analyses employed Chi-square or Fisher's exact tests (categorical variables); student's t-tests or Mann-Whitney U (between-group); paired t-tests or Wilcoxon (within-group pre-post); and effect sizes (Cohen's d, Rosenthal's r). Significance was set at p < 0.05.

Results: 197 patients completed the workshop; 178 (90.4%) were women, mean age: 55.0; 114 (57.9%) had fibromyalgia. Reductions were observed in: pain (scale 0-10) (baseline: 7.0; end of workshop: 5.0; 3 months: 5.0; p < 0.001); anxiety (13.0; 9.0; 11.0; p < 0.001); and depression (11.4; 7.2; 6.8; p < 0.001) (scales 0-21). Increases were noted in: well-being (scale 0-10) (4.0; 6.0; 5.0; p < 0.001); quality of life (scale 0-1) (0.399; 0.581; 0.556; p < 0.001); health status (scale 0-100) (40.0; 60.0; 60.0; p < 0.001); self-esteem (scale 9-36) (23.5; 27.1; 26.6; p < 0.001); and resilience (scale 6-30) (17.0; 18.0; 18.0; p = 0.002, p < 0.001). PROMs were completed by 189 patients at the end of the workshop and 110 at 3 months: pain decreased (end of workshop: 76.7%; 3 months: 80.7%); medication decreased (80.5%; 78.1%); and habits improved (87.2%; 87.6%). 40 patients (37.4%) reduced emergency visits and scheduled consultations. Overall satisfaction: 9.7.

Conclusions: The workshop enhanced patients' self-management and produced improvements in pain, quality of life, emotional well-being, and self-esteem, with effects maintained at 3 months.

Children with Hutchinson-Gilford progeria syndrome (HGPS) are born without height and weight abnormalities, and postnatal development is delayed from two months of age. The pathophysiological manifestations of HGPS can be categorized into the three tissue systems that are primarily affected: bone and cartilage, the smooth muscular layer of the vasculature, and the dermis layer. To understand the biology of the syndrome's complications resulting from the inherited dominant mutation of the LMNA gene, HGPS has to be considered in embryogenesis. Since the development of the primarily affected HGPS tissues involves a simultaneous contribution of mesodermal and neural crest cells, we hypothesized that the stochastic and heterogeneous coexistence of mesoderm and neural crest cells might be crucial for the onset and manifestation of HGPS. In addition, the expression of Lamin A and/or progerin during embryonic development tends to accumulate in the cell nucleus, causing the syndrome manifestation. Then, how and why are infants with the LMNA gene mutation born without severe deviations? Migration is a distinguishing property of mesoderm and neural crest cells, so that they are continuously subjected to mechanical stimuli throughout development and require normal lamina function. However, the viscoelastic property and the mechanosensor capability to respond to mechanical stress of the HGPS cell nucleus are disturbed. Despite the presence of progerin in development, we assume that high levels of Lamin B1 in cells determine the delayed onset of HGPS after birth. We also hypothesized that progerin toxicity could be managed and prevented, potentially allowing for rescue by the presence of Lamin B1.

Background: Guidelines suggest that a single lifetime measurement of lipoproteina(a) [Lp(a)] is sufficient for most patients as its levels are largely genetically determined and do not significantly change over time. The aim of the study was to assess the midterm variability in Lp(a) levels and its determinants. Methods: The analysis included 1263 patients (68.7% women, median age 69.0 [59.0-75.0] years) who underwent two measurements of Lp(a) levels at an interval of at least one year and up to a maximum of three years. Results: The median Lp(a) level in the first measurement was 9.0 ± 19.0 mg/dl, compared to 8.8 ± 19.1 mg/dL in the second measurement (p < 0.001). The mean increase in Lp(a) level (N = 692) was 4.1 ± 6.9 mg/dL, while the mean decrease (N = 483) was 5.6 ± 11.4 mg/dL. A total of 64.7% of patients exhibited a change in Lp(a) level ≥ 10%, 44.3% ≥ 20%; 28.2% ≥ 30% and 14.0% ≥ 50% of the baseline values. We found no significant differences in the Lp(a) level change related to sex, age, or comorbidities. Conclusions: A significant change in Lp(a) levels was observed in the midterm follow-up. These findings potentially have a profound clinical importance. The current expert recommendation to measure Lp(a) at least once in a lifetime appears to be inaccurate and should be revised.

Artificial intelligence (AI) is reshaping robotic rehabilitation and shifting practice beyond pre-programmed repetitive movement patterns toward data-driven and personalised therapeutic interventions for people with neurological and musculoskeletal impairments [...].