Medical sciences (Basel, Switzerland)最新文献

Background/Objectives: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) or without NP (CRSsNP) are common upper airway diseases with major impact on healthcare utilization. Little is known about the overall national financial burden of CRS. We aimed to assess the excess financial burden of CRS from a countrywide perspective. Methods: Annual expenditure from healthcare, welfare transfers and foregone income was retrieved from national databases, annualized and compared to matched healthy comparators. Results: Of the 303,475 patients included with CRS (mean age 51, 55% female), 18,142 were subclassified as CRSsNP (24%) or CRSwNP (76%). For CRS patients, annual excess healthcare costs were €1315 (1296-1333) compared to comparators. Patients with CRS earned €1356 (1230-1479) less annually compared to comparators. Patients with CRS of working age (18-64 years) had excess welfare transfers (€816 (782-850) compared to comparators, driven by sick leave and disability. Increases in healthcare costs were seen for patients with CRSwNP (€5406 (4860-6012) annually) compared to CRSsNP (€4945 (4293-5696)) driven by increases in CRS-related costs. Total societal burden for the entire cohort was €686,052,898, of which systemic corticosteroid exposure-related conditions represented €20,332,825. Excess welfare transfers represented €174,394,048 annually. Conclusions: Chronic rhinosinusitis is associated with a significant financial burden, both in terms of societal healthcare and welfare expenditure and patients' personal finances due to lost income.

Background: Prostate-specific membrane antigen (PSMA) is markedly overexpressed in prostate cancer (PCa), and there is growing evidence to support its usefulness in initial diagnostic assessments. This study compares the diagnostic performance of PSMA positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (mpMRI) in evaluating seminal vesicle invasion (SVI), extraprostatic extension (EPE), and pelvic lymph node involvement before radical prostatectomy.

Methods: A retrospective, single-institution analysis was performed. From a cohort of 325 patients who underwent radical prostatectomy between June 2022 to November 2024, 85 had undergone preoperative PSMA PET/CT for intermediate- and high-risk disease at biopsy, forming our study group. Two blinded specialists, one in radiology and one in nuclear medicine, independently interpreted the scans, using histopathological results as the reference standard. The primary outcome was diagnostic accuracy for T- and N-stage classification, while the secondary outcomes included the correct identification of the index lesion and comparative performance for each modality.

Results: The study cohort comprised patients with intermediate-to-high-risk prostate cancer (median age: 66 years; median PSA level: 11.6 ng/mL; median PSA density: 0.3 ng/mL/cm³). Forty-eight patients presented with an ISUP grade of 3 or higher on biopsy. PSMA PET/CT was more sensitive than MRI for detecting EPE (72.2% vs. 46.9%) and nodal metastases (91.7% vs. 8.3%). Furthermore, PSMA PET/CT demonstrated significantly higher concordance with histopathological findings in index tumor localization (76.5% vs. 67.9%, p < 0.001). An exploratory analysis revealed a potential age-dependent pattern, but this requires confirmation in larger studies.

Conclusions: In this select cohort, PSMA PET/CT demonstrated greater accuracy than MRI for locoregional staging in patients with intermediate-to-high-risk prostate cancer (PCa). However, the generalizability of these findings is limited by the retrospective design and potential selection bias. These results suggest that PSMA PET/CT may have a valuable role in the initial staging workflow, but this needs to be confirmed in larger, prospective studies. An exploratory analysis suggested a potential age-dependent pattern, but this requires confirmation in larger studies.

Background/Objectives: Epidemiological and clinical studies have linked both hypothyroidism and hyperthyroidism to adverse cardiac outcomes, including heart failure and myocardial fibrosis. Triiodothyronine (T3), a biologically active thyroid hormone, is important for cardiovascular homeostasis. While the effects of physiological and non-physiological T3 levels on cardiomyocytes have been extensively investigated, the impact of hypothyroidism and hyperthyroidism on cardiac stromal cells (CSCs), which constitute the majority of the cells in the heart, remains understudied. Given CSCs' essential role in extracellular matrix (ECM) remodeling and paracrine signaling, understanding their response to altered T3 states is necessary to fully elucidate the thyroid hormone-induced cardiac responses. Methods: Cardiac stromal cells were isolated from human atrial appendages and cultured under hypothyroid (0 nM T3), euthyroid (2.5 nM T3), and hyperthyroid (25 nM T3) conditions for 24 (short term) and 120 h (long term). The cells were harvested after 24 h of treatment using trypsin and automatically counted, and their ECM-related gene and growth factor expression levels were assessed using quantitative RT-PCR. Cardiac glucose uptake in hypothyroid, euthyroid, and hyperthyroid mice was monitored using [18F]-FDG PET/CT at acute (7 days) and chronic (42 days) time points. Results: Both hypo- and hyperthyroidism significantly increased the number of CSCs harvested after 24 h. There were acute alterations in the expression of the ECM-related genes COL1A1, COL3A1, TIMP3 (p < 0.05), and TIMP1 (p < 0.01). Similarly, growth factors such as PDGF-A (p < 0.001), TGF-b, and IGF1 (p < 0.05) were transiently upregulated under non-physiological T3 conditions, especially hypothyroidism. Most of these alterations were attenuated or reversed at the 120 h time point. In vivo PET imaging revealed significant increases in cardiac glucose uptake under acute hypothyroidism (p < 0.05) and decreases under acute hyperthyroidism (p < 0.05). However, these metabolic shifts normalized with chronic exposure, paralleling the transient nature of the gene expression changes observed in vitro. Conclusions: Non-physiological T3 concentrations induce proliferation and changes in ECM-related and growth factor gene expression in CSCs. Most of these changes are acute and return to normal levels after chronic exposure. These transient cellular responses correlate closely with the cardiac metabolic response patterns to acute and chronic hypothyroidism and hyperthyroidism.

Background/Objectives: The incidence of inflammatory bowel disease (IBD) is rising worldwide, particularly in Asia, while the highest prevalence remains in North America and Europe. Evidence on the relationship between IBD and the development of autoimmune thyroiditis is limited. This study investigated the association between IBD and a subsequent autoimmune thyroiditis in a large German primary care cohort over a 10-year period. Methods: Patients with IBD were propensity score matched to non-IBD individuals in a 1:5 ratio based on age, sex, index year, and average annual number of physician visits during follow-up. A total of 20,084 IBD patients-including 8791 with Crohn's disease and 11,293 with ulcerative colitis-and 100,420 matched controls were included. The primary outcome was the cumulative incidence of autoimmune thyroiditis, including Hashimoto's thyroiditis and Graves' disease. The association between IBD and autoimmune thyroiditis was evaluated using univariable conditional Cox regression analysis. Results: In the overall cohort, no significant association was found between IBD (Crohn's disease or ulcerative colitis) and autoimmune thyroiditis (Hashimoto's or Graves' disease). However, among patients aged ≥ 65 years, IBD was associated with a significantly increased risk of Graves' disease (HR 2.83; 95% CI 1.56-5.15), an effect observed in both Crohn's disease (HR 3.23; 95% CI 1.20-8.69) and ulcerative colitis (HR 2.64; 95% CI 1.25-5.60). Conclusions: While IBD was not associated with autoimmune thyroiditis overall, a significant positive association with Graves' disease was observed among patients aged ≥ 65 years, highlighting the importance of age-specific risk assessment.

Background/Objectives: Intensive postoperative pain is a common challenge after knee surgeries such as total knee arthroplasty, arthroscopy, cruciate ligament or meniscus repair, and fixation of tibial plateau or distal femoral fractures. This scoping review mapped and summarized non-regional postoperative analgesia strategies to provide an overview of available approaches when regional blocks or neuraxial anesthesia are not feasible.

Methods: We followed established methodological guidance for scoping reviews and report the data in accordance with the PRISMA-ScR checklist. We searched PubMed/MEDLINE, EMBASE, Scopus, and ClinicalTrials.gov in January 2025. Eligible designs included randomized controlled trials, non-randomized trials, observational studies, case series, and pilot studies.

Results: We screened 3390 records and assessed 332 in full text. A total of 43 studies met the inclusion criteria, and the literature was grouped into: (1) arthroplasty, (2) arthroscopy, (3) cruciate ligament or meniscus repair, and (4) tibial plateau or distal femoral fractures. We identified substantial heterogeneity in interventions, comparators, and outcome measures across the first three sets of literature but found no focused articles for tibial plateau or distal femoral fractures. Most studies evaluated multimodal approaches combining systemic analgesics with local periarticular or intraarticular techniques. Evidence on functional recovery and mobilization was limited.

Conclusions: Current evidence on non-regional postoperative analgesia in knee surgery is fragmented and varies considerably in design, intervention, and reported outcomes. Multimodal regimens and pre-emptive NSAID use were frequently associated with reduced early postoperative pain and lower opioid requirements, although comparability across studies remains limited. As existing evidence largely focuses on outcomes during hospitalization, future research should prioritize standardized pain and functional outcome reporting and directly compare systemic and local multimodal strategies, while extending follow-up beyond discharge to better characterize sustained clinical relevance.

Background/Objectives: Cholangiocarcinoma (CCA) is a very aggressive biliary carcinoma characterised by significant molecular heterogeneity and restricted treatment alternatives. Despite genomic and proteomic investigations revealing recurrent changes, the signalling dynamics influencing tumour behaviour remain inadequately comprehended. Methods: We conducted high-resolution Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)-based phosphoproteomics on paired tumour and surrounding tissues from 13 CCA patients in Northeast Thailand, meticulously sampling four geographically unique tumour areas for each patient. Our analysis concentrated on phosphoproteins consistently identified across all regions, delineating strong tumour-specific and cohort-wide phosphorylation signatures. Results: Notwithstanding considerable inter-patient variability, two conserved signalling modules were identified: an adhesion/Wnt axis regulated by hyperphosphorylated CTNNB1 protein (β-catenin) and a metal-handling module facilitated by metallothionein-1G (MT1G) protein and metallothionein-2A (MT2A) protein. Pathway enrichment identified focal adhesion, ECM-receptor interaction, cytoskeletal modulation, and mineral absorption as critical activities. Conclusions: This study elucidates conserved oncogenic pathways by analysing phosphoproteomic signatures across regional and patient-level variability, emphasising phosphoproteomics as a robust framework for biomarker and therapeutic development in CCA.

Background/Objectives: Given the rising prevalence of autoimmune diseases and the need for new insights into the pathology of these disorders, it is important to summarize current knowledge, with an emphasis on Hashimoto's thyroiditis (HT), since it is especially on the rise. Hypoxia is part of various pathophysiological conditions, and hypoxia-inducible factor (HIF) is a key factor in these processes. Hypoxia is involved in the regulation of hormones and the development of endocrine disorders. With this in mind, this narrative review summarizes the current state of knowledge on the relationship between autoimmune diseases, focusing on HT and the effects of hypoxia through the role of HIF. Methods: Multiple databases such as PubMed, NIH, Scopus, Web of Science, ScienceDirect, and Google Scholar were thoroughly searched for relevant keyword. Results: In HT, thyrocyte-derived reactive oxygen species and chronic lymphocytic infiltration stabilize HIF-1α, tilting CD4+ T cell polarity towards Th17 and away from regulatory T cells. Increased levels of Mammalian target of rapamycin (mTOR)/HIF-1α and reduced Sirtuin 1 (SIRT1) in T cells from patients diagnosed with HT confirm this metabolic skew. Furthermore, the data position HIF-1α as a therapeutic target. Inhibitors of mTOR or agents that restore SIRT1 could complement levothyroxine and antioxidant strategies. Hypoxia and the HIF signaling pathway have a role in energy homeostasis through various ways, for example, via metabolic effects of thyroid hormones, which are associated with the clinical manifestations of HT. Conclusions: Elucidation of HIF-1α-centered gene networks and testing of HIF-targeted interventions may curb the growing clinical burden of HT.

Introduction: Alcohol consumption is a significant risk factor for hypertension (HTN), a prevalent condition that substantially affects cardiovascular health. In Peru, where various traditional alcoholic beverages exist, the relationship between alcohol consumption and HTN has not been fully explored. Objective: To determine the association between different patterns of alcohol consumption, types of beverages, and various types of HTN. Methods: This cross-sectional analytical study utilized data from the Peruvian Demographic and Family Health Survey (2018-2023), including 236,243 adults (55.95% male; mean age: 41.06 years). General HTN, isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic-diastolic hypertension (SDH) were evaluated. Alcohol consumption was assessed through self-reported questionnaires evaluating consumption pattern (non-excessive vs. excessive), intensity (light, moderate, heavy), consistency (intermittent vs. consistent), and primary beverage type, including both commercial and traditional Peruvian drinks. Results: Excessive alcohol consumption was significantly associated with an increased risk of HTN (aPR: 1.19, 95% CI: 1.07-1.31), IDH (aPR: 1.61, 95% CI: 1.20-2.16), and SDH (aPR: 1.45, 95% CI: 1.18-1.78). Excessive alcohol consumption was significantly associated with an increased risk of HTN (aPR: 1.19, 95% CI: 1.07-1.31), IDH (aPR: 1.61, 95% CI: 1.20-2.16), and SDH (aPR: 1.45, 95% CI: 1.18-1.78). Consumption of traditional beverages such as chicha and Masato was associated with an elevated risk of various types of HTN. In contrast, wine consumption demonstrated a protective association against general HTN and IDH. Conclusions: Alcohol consumption patterns and beverage types have differential effects on HTN risk in the Peruvian population. These findings underscore the need for culturally adapted prevention strategies and more nuanced public health recommendations regarding alcohol consumption in Peru.

Background: Osteoradionecrosis (ORN) following head and neck radiotherapy has been demonstrated to induce structural and functional alterations of the upper airway, with the potential to complicate the process of tracheal intubation. Despite its clinical relevance, there is a paucity of systematic evidence on airway characteristics in ORN and reliable predictors of difficult tracheal intubation. This study compares preoperative airway parameters and tracheal intubation outcomes in irradiated patients with and without ORN and introduces a novel preoperative ORN-Difficult-Airway Score for risk stratification.

Methods: In this retrospective cohort study, airway assessments, tracheal intubation methods, and perioperative visualization parameters were evaluated in 105 patients following head and neck radiotherapy. Group differences between non-ORN and ORN were analyzed using chi-square tests. A preoperative ORN-Difficult-Airway Score was constructed using exclusively bedside parameters, based on statistically and clinically relevant predictors.

Results: Patients with ORN showed significantly restricted mouth opening (p < 0.001), higher Mallampati classes, particularly Mallampati IV, and a greater need for fiberoptic tracheal intubation (p < 0.01). Direct laryngoscopy (DL) was significantly less feasible in ORN, while hyperangulated videolaryngoscopy (VL) yielded consistently positive visualization (first-pass success (FPS) 100% in both groups). Under DL, FPS was lower in ORN (54.2% vs. 79.5%), resulting in an odds ratio of 0.305. Based on observed predictors, ORN status, mouth opening <3 cm, Mallampati class, restricted neck reclination, and history of difficult intubation, a preoperative ORN-Difficult-Airway Score was developed.

Conclusions: ORN has been associated with distinct alterations in airway anatomy and visualization, resulting in increased tracheal intubation complexity after head and neck radiotherapy. The proposed ORN-Difficult-Airway Score presents a clinically practical, bedside-applicable approach to stratifying the risk of tracheal intubation in this population. Prior to clinical implementation, prospective validation in larger cohorts is warranted.

Background/Objectives: Drug-induced sleep endoscopy (DISE) is used in obstructive sleep apnea (OSA) to visualize dynamic upper airway collapse, but sedation protocols vary widely with no consensus on the optimal agent or technique. This narrative review aims to clarify current sedation strategies for DISE in OSA and their clinical implications. Methods: We systematically searched PubMed, Scopus, Web of Science, and Cochrane Library for English-language publications on DISE sedation (2000-2025). Relevant clinical studies, guidelines, and reviews were included. Data were qualitatively synthesized due to heterogeneity among studies. Results: Sedation approaches in DISE varied considerably. Propofol, dexmedetomidine, and midazolam were the primary agents identified. Propofol provided rapid, titratable sedation but increased airway collapsibility at higher doses; dexmedetomidine produced a more natural sleep-like state with minimal respiratory depression; midazolam was less favored due to prolonged effects. Use of target-controlled infusion (TCI) and pharmacokinetic-pharmacodynamic (PK-PD) models improved control of propofol sedation. Co-sedative adjuncts (e.g., opioids) reduced the required sedative dose but added risk of respiratory depression. Careful titration to the lowest effective dose-often guided by bispectral index (BIS) monitoring-was emphasized to achieve adequate sedation without artifactual airway collapse. No universal DISE sedation protocol was identified. Conclusions: Optimal DISE sedation balances adequate depth with patient safety to ensure reliable findings. Using the minimum effective dose, guided by objective monitoring (e.g., BIS), is recommended. There is a need for standardized sedation protocols and further research (e.g., in obese patients) to resolve current controversies and improve DISE's utility in OSA management.