Diseases (Basel, Switzerland)最新文献

Bacterial vaginosis (BV) is a leading cause of genital discomfort among women globally, and it arises from dysbiosis of the vaginal ecosystem characterized by the overgrowth of pathogenic bacteria. Current therapeutic strategies primarily rely on antibiotics and/or probiotics, which demonstrate clinical efficacy but are frequently associated with limitations such as antimicrobial resistance, high recurrence rates, and incomplete restoration of a healthy vaginal microbiota. Inspired by the success of fecal microbiota transplantation in gastrointestinal disorders, vaginal microbiome transplantation (VMT) from healthy donors has emerged as a potential alternative therapeutic approach for BV. However, experimental and early clinical studies indicate that VMT efficacy is not uniform across individuals, with considerable inter-individual variability in treatment outcomes. Host genetic factors, baseline vaginal microbial composition, immune status, and environmental influences are likely to modulate therapeutic success, underscoring the need for personalized interventions. This article critically evaluates the shortcomings of existing standardized treatments, highlights the potential advantages and challenges of VMT, and discusses emerging, precision-based therapeutic strategies for BV in light of recent research advances and ongoing clinical trials worldwide.

Background: Sleep deprivation may contribute to increased abdominal adiposity. Although weekend catch-up sleep is associated with various health outcomes, its role in abdominal adiposity remains unclear, particularly among female fixed-shift workers. Therefore, this study aimed to explore the association of workday sleep deprivation and weekend catch-up sleep with abdominal adiposity indicators in Brazilian female fixed-shift workers.

Methods: A cross-sectional study was conducted on 450 female fixed-shift workers aged ≥ 18 years from a large industrial group in Southern Brazil. Abdominal adiposity indicators linked to cardiovascular risk were assessed: waist circumference (WC ≥ 88 cm), waist-to-height ratio (WHtR > 0.5), weight-to-waist index (WWI ≥ 11), conicity index (C-Index ≥ 1.27), and WC & Body Mass Index (combined WC ≥ 88 cm and BMI ≥ 30 kg/m²). Workday sleep deprivation was defined as <6 h (h) of sleep on workdays, and weekend catch-up sleep (absolute difference between weekend and workday sleep duration) was defined as >2 h longer sleep on weekends vs. workdays. Associations were estimated using a Poisson regression with robust variance adjusted for demographic, socioeconomic, behavioral, reproductive, and occupational confounders.

Results: The mean age was 34.9 ± 9.9 years. The prevalence rates of abdominal adiposity were 45.3% for WC, 47.6% for WHtR, 26.2% for WWI and C-Index, and 28.7% for WC&BMI. Workday sleep deprivation and weekend catch-up sleep were reported by 27.1% and 43.3% of the participants, respectively. After adjustment for confounders, workday sleep deprivation was consistently associated with higher abdominal adiposity: Prevalence Ratio (PR) = 1.37 (95% CI: 1.10-1.69) for WC; 1.25 (95% CI: 1.02-1.53) for WHtR; 1.48 (95% CI: 1.07-2.04) for WWI; 1.43 (95% CI: 1.03-1.99) for C-Index, and 1.59 (95% CI: 1.17-2.16) for WC&BMI. Longer weekend catch-up sleep was positively associated with WHtR (PR = 1.24; 95% CI: 1.03-1.49) and WC&BMI (PR = 1.39; 95% CI: 1.04-1.85).

Conclusions: Workday sleep deprivation was consistently linked to increased abdominal adiposity, whereas associations with longer weekend catch-up sleep were less consistent. These findings underscore the potential metabolic risk of insufficient sleep among female shift workers.

Background: Low-density lipoprotein cholesterol (LDL-C) is a major cardiovascular risk factor and an indicator of hypolipidemic therapy effectiveness. However, direct and calculated methods for determining "LDL-C" present the sum of the cholesterol in all apoB-containing lipoproteins, including lipoprotein(a) [Lp(a)]. There has been an ongoing debate about the correctness of LDL-C in patients with elevated Lp(a) concentrations up to now. The aim of this study was to evaluate the effect of Lp(a) concentration on the LDL-C calculated by different equations.

Methods: The study included the results of fasting lipids and Lp(a) concentration of 566 measurements from 283 patients (before and after lipid-lowering therapy prescribing, after exclusion of 17 patients with incomplete data). LDL-C and LDL-C corrected for Lp(a)-cholesterol (LDL-C_corr) were calculated by Friedewald, Martin-Hopkins, and Sampson equations.

Results: We assessed 566 measurements of lipids and Lp(a). The number of values reclassified to a higher risk category was 10% and 13% with Martin-Hopkins and Sampson equations compared to the Friedewald formula. The percentage of Lp(a)-cholesterol (Lp(a)-C) in the LDL-C calculated by three formulas was up to 90% or more depending on the concentration of LDL-C and Lp(a). When stratified by clinically significant LDL-C thresholds, the proportion of values LDL-C_corr reclassified to a lower risk category ranged from 30 to 59%.

Conclusion: Comparison of LDL-C concentrations calculated by Friedewald, Martin-Hopkins, and Sampson equations showed high consistency in patients without elevated triglycerides. The LDLcorr is reasonable to use in patients with Lp(a) concentration ≥ 30 and ≥41 mg/dL when using the Martin-Hopkins and Sampson equations, respectively. These data may help clinicians interpret LDL-C goal attainment in patients with elevated Lp(a) and avoid misclassification driven by the Lp(a)-cholesterol component.

Background: Cancer-related fatigue (CRF) is one of the most common and burdensome symptoms faced by patients with cancer, yet effective drug-based treatments remain limited. In recent years, phytotherapeutic agents have drawn attention as complementary options, supported by plausible anti-inflammatory, antioxidant, and immunomodulatory mechanisms.

Methods: We performed a systematic review and meta-analysis to quantitatively synthesize randomized controlled trial evidence on the efficacy of phytotherapeutic interventions for cancer-related fatigue and to assess the certainty of evidence. Databases were searched from inception, with the final search update completed in October 2025. Eligible studies included adults with CRF and compared herbal interventions with placebo controls. Standardized mean differences (SMDs) were pooled using a DerSimonian-Laird random-effects model. We also evaluated risk of bias (RoB 2), publication bias, and certainty of evidence using GRADE. This systematic review and meta-analysis was conducted in accordance with the PRISMA 2020 guidelines.

Results: Fourteen trials were included, studying agents such as Paullinia cupana, Panax ginseng, multi-herbal Traditional Chinese Medicine formulations, and other botanical extracts. Overall, phytotherapy provided a modest improvement in CRF (SMD = 0.31; 95% CI, 0.08-0.53; p = 0.022), though heterogeneity was substantial (I² = 56.7%). In subgroup analyses, only the group of "other formulations" demonstrated significant benefit; ginseng and guaraná did not demonstrate statistically significant effects. Most trials had high or unclear risk of bias, and the certainty of evidence was rated very low.

Conclusions: Current evidence does not firmly support phytotherapeutic agents as effective treatments for CRF, hindered largely by methodological weaknesses, heterogeneous interventions, and imprecise effect estimates. Even so, the biological rationale and the variability in clinical responses point toward an opportunity for the emerging field of precision herbal oncology. Well-designed, multicenter trials are essential to determine whether phytotherapy can meaningfully contribute to CRF management.

Background/objectives: Colorectal cancer (CRC) is a major public health challenge in Brazil, characterized by marked regional disparities. Although national legislation mandates that treatment begin within 60 days after diagnosis, compliance remains inconsistent, particularly within the Unified Health System (SUS). This study aimed to analyze the time to treatment initiation for colon (C18) and rectal (C20) cancer in Brazil from 2013 to 2024, assessing regional inequalities, temporal trends, and factors associated with treatment delays.

Methods: We conducted an ecological study using secondary data from the Ministry of Health's PAINEL-Oncologia platform, which integrates information from SIA/SUS, SIH/SUS, and SISCAN. Records of patients diagnosed with colon and rectal cancer (ICD-10 C18-C20) were evaluated. Temporal trends were analyzed using Joinpoint regression, and factors associated with delayed treatment initiation (>60 days) were identified through multiple logistic regression models.

Results: Persistent discrepancies were observed between diagnostic and treatment trends from 2013 to 2024, with the Annual Percent Change (APC) for diagnosis exceeding that for treatment, particularly among adults aged 55-69 years. The Southeast and South regions accounted for over 70% of all diagnosed cases, starkly contrasting with the less than 25% in the North and Northeast. More than 50% of patients across all clinical stages initiated treatment after the legally mandated 60-day period. Women with rectal cancer had a 28% higher risk (RR = 1.28) of being diagnosed at stage IV. Chemotherapy was the predominant initial therapeutic modality, while the need for combined chemo-radiotherapy was associated with markedly elevated risk ratios for delay (e.g., RR = 26.53 for stage IV rectal cancer). Treatment initiation delays (>60 days) were significantly associated with residence in the North/Northeast regions, female sex (for rectal cancer), advanced-stage disease, and complex therapeutic regimens.

Conclusions: The study demonstrates persistent regional inequalities and highlights a substantial mismatch between diagnostic capacity and therapeutic availability in Brazil. These gaps contribute to treatment delays and reinforce the need to strengthen and expand oncological care networks to ensure equitable access and improve outcomes, particularly in underserved regions.

Background/objectives: The aim of this study was to evaluate the tolerability and effectiveness of subcutaneous immunotherapy (SCIT) in allergic adults and children treated with a polymerized-glutaraldehyde undiluted mixture of house dust mites (HDMs) under routine clinical practice.

Methods: This was an observational, ambispective, controlled, real-world, multicenter study including patients ≥ 5 years with allergic rhinitis (AR), due to Dermatophagoides sensitization. Patients who started AIT with a D. pteronyssinus/D. farinae extract and those who continued symptomatic treatment were included in the treatment (DP&DF) and untreated (UT) groups, respectively. We evaluated adverse reactions (ARs) and changes in effectiveness variables through changes in symptoms, disease control, medication use, and patient- and investigator-reported outcomes.

Results: We included 130 patients in the DP&DF group, and 90 (69.2%) adults, 23 adolescents (17.7%), 17 (13.1%) children, and 94 patients in the UT group. Patients received treatment for a mean (SD) of 9.01 (3.1) months at the time of evaluation. Seven (5.4%) patients, all adults, reported eight ARs, five local and three systemic (mean rate of 0.62 ARs per 100 injections); all recovered, and epinephrine was not required. The proportion of patients reporting no rhinitis symptoms at follow-up significantly increased (+13.6%; p < 0.001). Rhinitis frequency, intensity, and control significantly improved overall and in specific age groups. Similarly, the proportion of patients reporting no asthma symptoms at follow-up significantly increased (+29.0%; p < 0.001). The use of all symptomatic medications significantly decreased, while the UT group showed no significant changes, except for worsened asthma classification and control in specific age groups. Both investigators and patients perceived a marked improvement in symptoms and medication use, with high satisfaction scores reported on the visual analogue scale.

Conclusions: A subcutaneous allergen extract with a mixture of HDMs is safe and effective for allergic rhinitis and asthma in adults and children in the real-world setting.

Background: Type 2 diabetes mellitus (T2DM) and periodontitis are highly prevalent immune-inflammatory diseases that interact bidirectionally. However, how early-onset T2DM, periodontitis, and adverse lifestyle behaviors collectively remodel the gingival plaque microbiome at the ecological network level remains poorly understood in Indian populations.

Methods: A cross-sectional 16S rRNA gene (V3-V4) sequencing study was conducted on supragingival and subgingival plaque from 60 adults (30-40 years) recruited in Mumbai. Participants were categorized as healthy (H, n = 10), periodontitis (P, n = 10), T2DM (n = 20), and T2DM with periodontitis (T2DM_P, n = 20). Comprehensive demographic, anthropometric, metabolic, periodontal, dietary, lifestyle, and oral hygiene data were collected. Sequence data were processed using QIIME2-DADA2, followed by diversity, differential abundance, and genus-level co-occurrence network analyses (Spearman |r| ≥ 0.6, FDR < 0.05; core prevalence ≥ 70%).

Results: α-diversity showed no marked depletion across groups, whereas Bray-Curtis β-diversity revealed significant global separation, with maximal dissimilarity between H and T2DM_P. Healthy individuals with favorable lifestyle behaviors harbored scaffold-forming taxa such as Corynebacterium matruchotii, Lautropia mirabilis, and Capnocytophaga spp. In contrast, P and T2DM_P groups showed enrichment of proteolytic, inflammation-adapted genera including Porphyromonas, Tannerella, Treponema, Fretibacterium, Peptostreptococcus, and Selenomonas. Network analysis revealed a shift from commensal-rich modular networks to densely connected, keystone-centered disease modules.

Conclusion: Early-onset T2DM and periodontitis, particularly under adverse lifestyle behaviors, reorganize plaque microbial composition and interaction architecture rather than depleting diversity, highlighting plaque-based keystone taxa and networks as targets for microbiome-informed risk stratification and integrated medical-dental-lifestyle interventions.

Background: Early recognition of renal allograft dysfunction requires biochemical markers capable of detecting molecular injury before functional decline becomes apparent. Serum creatinine, a late and nonspecific indicator of renal function, has limited value for early diagnosis. Protein biomarkers implicated in tubular injury, inflammation, and immune activation-including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), β2-microglobulin, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α)-have emerged as promising alternatives. This study evaluated early post-transplant serum profiles of these biomarkers and their prognostic relevance for long-term graft outcomes.

Methods: Nineteen adult recipients undergoing primary kidney transplantation were prospectively enrolled. Serum creatinine and protein biomarkers were measured 24 h post-transplant using validated immunochemical assays. Biomarker concentrations were compared with values from healthy controls, and correlations with renal function at 12 months were assessed. Receiver operating characteristic (ROC) analysis was used to evaluate predictive performance.

Results: Significant biochemical alterations were observed at 24 h post-transplant. KIM-1 levels were markedly elevated compared with controls (74.50 ± 98.45 vs. 10.54 ± 17.19 ng/mL; p = 0.01), consistent with early tubular injury. IL-1β and NGAL showed upward trends without reaching statistical significance. β2-microglobulin and TNF-α levels did not differ substantially from control values. Serum KIM-1 correlated with serum creatinine both at 24 h (r = 0.35) and at 12 months (r = 0.40). ROC analysis identified a KIM-1 threshold of 24.5 ng/mL (AUC = 0.68) as a potential indicator of future graft dysfunction, outperforming serum creatinine (AUC = 0.64). Six patients experienced graft dysfunction at 12 months post-transplant, five of whom had serum creatinine values > 5 mg/dL at 24 h. Based on early creatinine levels, patients were stratified into low-risk (creatinine < 5 mg/dL; n = 10) and high-risk groups (creatinine > 5 mg/dL; n = 9). Mean KIM-1 concentrations were significantly higher in the high-risk group (110.68 ± 115.29 vs. 26.67 ± 18.05 ng/mL; p = 0.05), consistent with more severe early tubular injury.

Conclusions: Among the evaluated biomarkers, KIM-1 demonstrated the strongest potential as an early biochemical indicator of renal allograft dysfunction. Its rapid post-transplant elevation underscores its sensitivity to early tubular injury. Further prospective validation in larger, multicenter cohorts is warranted.

Objective: The aim of this study was to evaluate the impact of chronic kidney disease (CKD) on clinical presentation, laboratory parameters, ECG, and echocardiographic features of patients with chronic heart failure (CHF).

Methods: This retrospective cross-sectional study included 2227 patients hospitalized in a tertiary care center due to CHF. Patients were divided into two groups based on the presence of CKD, defined as eGFR < 60 mL/min/1.73 m². Demographic, clinical, laboratory, and echocardiographic data were collected for all patients. Comparative analyses were performed to assess differences in cardiovascular risk factors, comorbidities, laboratory parameters, and echocardiographic findings between the two groups.

Results: The proportion of men was significantly higher in the non-CKD group, whereas women predominated in the CKD group (p < 0.001). Dyspnea, orthopnea, leg swelling, claudication, and expectoration were significantly more frequent in patients with CKD, while chest pain and palpitations were more common in the non-CKD group (all p < 0.05). A significant difference in the distribution of NYHA functional classes was observed between the groups (p < 0.001), with NYHA class IV being more prevalent in the CKD group and classes II and III more frequent in the non-CKD group. Levels of CRP and NT-proBNP were significantly higher in the CKD group (p < 0.001). In-hospital mortality was 2.5-fold higher in patients with CKD (28.6% vs. 11.1%; p < 0.001).

Conclusions: Coexistence of CKD was associated with a more severe clinical presentation, advanced functional limitation, and a distinct laboratory and echocardiographic profile in CHF patients.

Background: Postpartum haemorrhage (PPH) remains the leading cause of maternal mortality globally. Women with inherited or unexplained bleeding disorders such as von Willebrand disease (VWD), factor XI deficiency (FXI), platelet function disorders, or bleeding disorder of unknown cause (BDUC) face a higher risk. While tranexamic acid (TXA) is routinely used in obstetric care, its specific efficacy and safety in these populations remain unclear. Methods: A systematic review and meta-analysis followed PRISMA 2020 guidelines (PROSPERO: CRD420251082349). Databases searched included PubMed, Scopus, Web of Science, and Dimensions. Studies evaluating TXA for PPH prevention or treatment in women with bleeding disorders were included. Six cohort studies (2016-2024) involving 213 deliveries met the criteria. Three contributed to a meta-analysis on primary PPH; the other three were synthesised narratively. Results: TXA use was associated with a 56% reduction in primary PPH risk (risk ratio 0.44; 95% CI: 0.27-0.70; p = 0.0007), with no observed heterogeneity (I² = 0%). Because contributing cohorts were phenotypically heterogeneous (BDUC, FXI, mixed), the pooled effect reflects an average across disorders rather than disorder-specific efficacy. TXA also appeared to reduce secondary and severe PPH in some cohorts. However, bleeding occurred in 26-36% of high-risk deliveries despite prophylaxis. No maternal deaths or thromboembolic events were reported in 136 TXA-exposed cases. Attribution was complicated by concurrent use of desmopressin and platelet transfusions. Most studies had moderate to severe bias. Conclusions: TXA significantly lowers the risk of primary PPH in women with bleeding disorders and appears safe. Despite this, residual bleeding underscores the need for trials to optimise TXA use alongside disease-specific strategies. However, this conclusion is derived from only six observational studies with heterogeneous patient populations and co-interventions. The evidence remains preliminary and should be interpreted cautiously. TXA should be considered as part of a multimodal postpartum haemorrhage management algorithm rather than a stand-alone therapy.