Tag: pubmed

Blood Press. 2026 Aug 14:1-17. doi: 10.1080/08037051.2026.2719281. Online ahead of print.

ABSTRACT

BACKGROUND: Vasovagal syncope (VVS) without aura is characterized by a high fall risk and misdiagnosis rate. However, its hemodynamic characteristics remain unclear. In this study, we aimed to analyze the cardio-cerebral hemodynamic changes in patients with non-prodromal VVS, to generate a scientific basis for its management.

METHODS: A total of 221 participants were prospectively and consecutively enrolled, including 34 patients with non-prodromal VVS, 118 patients with prodromal VVS, and 69 non-syncope controls. All participants completed the head-up tilt test (HUTT) combined with transcranial Doppler (TCD). Blood pressure, heart rate, and cerebral hemodynamic parameters were monitored dynamically during the test. Data were statistically analyzed.

RESULTS: The non-prodromal VVS group consisted predominantly of males (70.59% vs. 37.29%), had a higher body mass index (median 24.14 vs. 21.26 kg/m²), and was older (median 47 vs. 37 years) (all P < 0.05). The baseline cerebral blood flow velocity (CBFV) in the non-prodromal VVS group was significantly lower than that in the prodromal VVS group (55 vs. 60 cm/s, P = 0.009), and the decrease of CBFV during the tilt test preceded the change of blood pressure. During the return to the supine position after HUTT, systolic blood pressure was significantly higher in the non-prodromal VVS group than in the prodromal VVS group (117.19 vs. 111.95 mmHg, P = 0.019), and the heart rate increment was greater during the drug-induced phase (11.35 vs. 8.38 beats per minute).

CONCLUSIONS: Non-prodromal VVS, with its unique hemodynamic profile involving early cerebral hypoperfusion and impaired central compensatory mechanisms, represents a high-risk subtype associated with higher fall risk. The identified hemodynamic differences may serve as objective biomarkers for its diagnosis. This study highlights the need for tailored management strategies, including comprehensive fall prevention measures and targeted interventions.

PMID:42599143 | DOI:10.1080/08037051.2026.2719281

Stat Med. 2026 Aug;45(18-19):e70705. doi: 10.1002/sim.70705.

ABSTRACT

The increasing prevalence of high-dimensional covariates presents a significant challenge to precision medicine. To overcome this, we propose a novel multi-stage optimal dynamic treatment regime method specifically designed for high-dimensional accelerated failure time models. Our approach, which aims to maximize individual survival time, employs backward induction with counterfactual survival times as the optimization objective at each stage. Parameter estimation leverages weighted counterfactual survival times to account for censoring, followed by the slope determination by analysis of residuals (SDAR) algorithm. Theoretical analysis guarantees exponential convergence with non-asymptotic error bounds under mild conditions. Simulation studies demonstrate a substantial improvement in survival time estimation, particularly under high censoring rates, compared to existing methods. We illustrate the practical utility of our method by applying it to a sepsis dataset, revealing clinically meaningful treatment recommendations.

PMID:42599126 | DOI:10.1002/sim.70705

Pharm Stat. 2026 Sep-Oct;25(5):e70111. doi: 10.1002/pst.70111.

ABSTRACT

In multiregional clinical trials (MRCTs), regional consistency probabilities (RCPs) must be evaluated at the trial design stage in addition to the power for the entire trial population. The Japanese Ministry of Health, Labour and Welfare guidance proposes two widely used criteria for this purpose, referred to as Method 1 and Method 2. While multiplicity adjustment for familywise error rate control is standard practice when multiple primary endpoints are employed, its implications for regional consistency evaluation in MRCTs have not been addressed in the existing literature. In this article, we demonstrate that applying unadjusted consistency thresholds under the Bonferroni procedure leads to monotone inflation of the null RCP with increasing number of endpoints for both Method 1 and Method 2, because the Bonferroni-adjusted critical value progressively selects more extreme overall treatment effect estimates, which in turn inflates the probability of satisfying the regional consistency criterion even when the true treatment effect is absent. To correct for this inflation, we propose adjusted consistency thresholds that restore the null RCP to its single-endpoint reference level, and show that these thresholds can be efficiently obtained via a standard root-finding algorithm. Through numerical studies, we demonstrate that the proposed adjusted thresholds result in only a modest reduction in RCP under the alternative hypothesis, and that thresholds derived under the Bonferroni procedure also prevent null RCP inflation when step-down procedures such as Holm, Hochberg, and Hommel are applied. The methodology is illustrated using a hypothetical MRCT with multiple primary endpoints, and an R package “rcpmcp” implementing all proposed methods is publicly available on GitHub.

PMID:42599125 | DOI:10.1002/pst.70111

Cancer Rep (Hoboken). 2026 Aug;9(8):e70649. doi: 10.1002/cnr2.70649.

ABSTRACT

BACKGROUND: Cholangiocarcinoma (CCA) is a highly heterogeneous malignancy with a poor prognosis. However, the molecular mechanisms underlying CCA and its treatment options remain unclear and limited.

AIMS: This study aims to identify novel prognostic biomarkers and potential therapeutic targets for CCA through transcriptomics and whole-exome sequencing analysis.

METHODS AND RESULTS: We analyzed the relationship between overall survival and various risk factors in 255 CCA samples from a published dataset and 36 samples from The Cancer Genome Atlas (TCGA) database. Transcriptomics analysis was used to identify genes whose expression plays a crucial role in CCA development and progression. Targeted drug databases were used to examine which gene expression signatures represent potential therapeutic targets for CCA. Mutated genes were analyzed to explore potential mechanisms. Standard statistical methods were applied to analyze associations between clinical data and candidate targets. A nomogram was constructed to predict the prognostic impact of the optimal candidate. Cell experiments were used to demonstrate the role of PKLR in CCA growth and metastasis. We identified FOLH1, PKLR, PTH1R, GPR114, KCNH2, LCN2, MMP10, PORCN, RIPK3, and SRPK3 as potential therapeutic targets for CCA, with PKLR being the most promising candidate based on the computational analyses. PKLR was lowly expressed in CCA tissues. PKLR expression was closely associated with ARID1A and KRAS mutations. PKLR mRNA levels were significantly correlated with tumor size (p = 0.024) and metastasis (p = 0.014). Low PKLR expression in CCA was positively associated with poor survival. A nomogram accurately predicted the prognosis of CCA patients based on PKLR expression levels. Silencing PKLR expression promotes growth and metastasis of CCA in vitro.

CONCLUSION: Our findings indicate that PKLR, an independent protective factor in CCA, is a potential prognostic biomarker and a candidate for further investigation as a therapeutic target. PKLR expression is significantly associated with ARID1A and KRAS mutations.

PMID:42599115 | DOI:10.1002/cnr2.70649

Microbiol Spectr. 2026 Aug 14:e0035426. doi: 10.1128/spectrum.00354-26. Online ahead of print.

ABSTRACT

Mycoplasma pneumoniae pneumonia (MPP) is the most common form of community-acquired pneumonia, which shows an epidemic interval of 3-7 years. This study was conducted to understand the changing trends in MPP in children hospitalized before and during the coronavirus disease 2019 pandemic and determine adverse outcomes and their influencing factors. This was a retrospective cohort study of children aged 28 days to 14 years hospitalized for MPP at our institution between January 2018 and December 2023. Clinical characteristics, adverse outcomes, and associated factors were analyzed using the chi-square test and multivariable logistic regression. A P < 0.05 was considered statistically significant. A total of 17,505 MPP cases were included, with the highest case number (4,619) in 2023. In 2023, the proportion of severe pneumonia was 44.1%, and bronchoscopy usage was 33.5%, both significantly higher than in 2018-2022. Older age, admission during July-December, co-infection with Epstein-Barr virus, chlamydia, or other bacteria, and complications, including pleural effusion, abnormal liver enzymes, acute respiratory distress syndrome, or atelectasis, were associated with bronchoscopy. Older age, admission during October-December, co-infection with respiratory syncytial virus, adenovirus, Epstein-Barr virus, chlamydia, or other bacteria, and complications, including cardiac failure, abnormal liver enzymes, myocardial damage, or anemia, were associated with severe pneumonia. Cases of MPP, severe pneumonia, and those requiring bronchoscopy increased in 2023 compared with the five previous years. Children with MPP were more susceptible to adverse clinical outcomes, which were associated with age, month of admission, co-infection, and complications.IMPORTANCEMycoplasma pneumoniae pneumonia (MPP) is a leading cause of community-acquired pneumonia in children. This study analyzed 17,505 hospitalized children in Northeast China from 2018 to 2023 to explore MPP trends before, during, and after the coronavirus disease 2019 pandemic. We found a sharp resurgence of MPP in 2023 with higher rates of severe pneumonia, complications, and bronchoscopy use. Key risk factors for adverse outcomes included older age, admission in October-December, viral/bacterial co-infection, and pulmonary or extrapulmonary complications. These findings improve understanding of post-pandemic MPP epidemiology, support early risk stratification, and help optimize clinical management and public health interventions for childhood MPP.

PMID:42599103 | DOI:10.1128/spectrum.00354-26

J Nephrol. 2026 Aug 14:aajag146. doi: 10.1093/joneph/aajag146. Online ahead of print.

ABSTRACT

BACKGROUND: Novel myosteatosis indices that measure intra- and inter-muscular fat content in abdominal muscles using computed tomography (CT) have been recently introduced. Therefore, we evaluated their usefulness in diagnosing low muscle strength in patients undergoing hemodialysis.

METHODS: This study included 114 patients on maintenance hemodialysis who underwent CT and handgrip strength assessments. Skeletal muscle density , total abdominal muscle area, normal-attenuation muscle area , low-attenuation muscle area, and intermuscular adipose tissue area at the third lumbar vertebral level were measured. Additionally, novel myosteatosis indices (normal-attenuation muscle area/total abdominal muscle area, low-attenuation muscle area/height2, and intermuscular adipose tissue area/total abdominal muscle area) were calculated. The relationship between myosteatosis indices and handgrip strength was examined.

RESULTS: Skeletal muscle density, normal-attenuation muscle area/total abdominal muscle area index, low-attenuation muscle area/height2, and intermuscular adipose tissue area/total abdominal muscle area index were 34.4 ± 9.0 Hounsfield Unit (HU), 58.2 ± 17.0%, 14.3 ± 5.7 cm2/m2, and 7.2 (3.9-12.8)%, respectively. The normal-attenuation muscle area/total abdominal muscle area index (r = 0.987), low-attenuation muscle area/height2 (r = 0.853), and log-transformed intermuscular adipose tissue area/total abdominal muscle area index (r = 0.843) were significantly correlated with skeletal muscle density (all P < .0001). Additionally, skeletal muscle density (β = 0.305), normal-attenuation muscle area/total abdominal muscle area index (β = 0.297), low-attenuation muscle area/height2 (β = -310), and intermuscular adipose tissue area/total abdominal muscle area index (β = -0.321) were independently linked to handgrip strength. The diagnostic value of the new myosteatosis index was similar to that of skeletal muscle density: age-sex-adjusted C-statistics (0.810): normal-attenuation muscle area/total abdominal muscle area index (0.809, P = .84), low-attenuation muscle area/height2 (0.810, P = .98), and intermuscular adipose tissue area/total abdominal muscle area index (0.810, P = .97). Increase in normal-attenuation muscle area/total abdominal muscle area index, but not in skeletal muscle density, was independently associated with reduced risk of low handgrip strength. Increase in intermuscular adipose tissue area/total abdominal muscle area index, but not low-attenuation muscle area/height2, was independently associated with greater risk of low handgrip strength.

CONCLUSIONS: Novel myosteatosis indices were independently associated with handgrip strength in patients undergoing hemodialysis and demonstrated diagnostic usefulness, were clinically acceptable, and comparable to that of skeletal muscle density.

PMID:42599101 | DOI:10.1093/joneph/aajag146

Microbiol Spectr. 2026 Aug 14:e0135726. doi: 10.1128/spectrum.01357-26. Online ahead of print.

ABSTRACT

Fluorescence microscopy and fungal culture are the primary diagnostic methods for superficial fungal infections, but they are limited by low sensitivity and long turnaround time, respectively. We determined the optimal cycle threshold (Ct) cutoff for a novel multiplex PCR assay (iFIND) using receiver operating characteristic analysis and evaluated whether a “microscopy + iFIND” combined strategy improves diagnostic performance. This prospective study enrolled 113 patients with suspected superficial mycoses. Specimens underwent fluorescence microscopy, fungal culture, and automated iFIND. Using a composite reference standard, we calculated positive percent agreement (PPA), negative percent agreement, and overall percent agreement. Cohen’s kappa and McNemar’s test assessed inter-method agreement. To mitigate verification bias, we performed a sensitivity analysis excluding cases diagnosed solely by clinical response. Internal bootstrap validation (1,000 resamples) was used to assess overfitting of the Ct cutoff. The optimal Ct cutoff for any fungal infection was 32.66 (area under the curve [AUC] = 0.746). Bootstrap validation confirmed robustness (optimism-corrected AUC = 0.7431, optimism = 0.00275, bias-corrected and accelerated 95% confidence interval for cutoff: 32.5-33.7). iFIND showed excellent discrimination for Epidermophyton (AUC = 0.824) and Trichophyton (AUC = 0.834). The combined approach achieved a PPA of 65.6%, superior to microscopy alone (50.0%, P < 0.001) and comparable to culture (75.0%, P = 0.701), while reducing turnaround time from weeks to <3 h. Sensitivity analysis excluding 15 clinically diagnosed cases yielded consistent results: iFIND alone PPA = 46.9% (23/49), combined strategy PPA = 69.4% (34/49). iFIND detected an additional 17.2% of infections missed by conventional methods. The iFIND assay is a rapid, accurate tool for superficial mycoses. The microscopy + iFIND strategy combines speed and sensitivity, offering culture-comparable utility with substantially faster results. However, positive results should be interpreted in a clinical context to avoid overtreatment.

IMPORTANCE: Fungal skin infections affect one in four people worldwide, but current diagnostic methods are either insensitive (microscopy) or painfully slow (culture, taking 2-4 weeks). This study validates a rapid PCR test that delivers results in under 3 h and, when combined with microscopy, matches the accuracy of culture. By establishing a data-driven cutoff value for test positivity and using rigorous statistical methods to confirm its reliability, we provide a practical framework that clinics can adopt immediately. The combined strategy reduces diagnostic delay, enabling same-day treatment decisions and reducing unnecessary antibiotic use. This is especially critical, given the global spread of antifungal-resistant strains, where rapid genus-level identification can guide appropriate therapy and curb resistance. Our approach offers an actionable, culture-comparable solution for routine clinical practice, directly addressing the urgent need for faster, more accurate fungal diagnostics worldwide.

PMID:42599092 | DOI:10.1128/spectrum.01357-26

Gerodontology. 2026 Aug 14. doi: 10.1111/ger.70117. Online ahead of print.

ABSTRACT

BACKGROUND: Denture stomatitis is a common oral mucosal lesion among older adults wearing removable prostheses. Its prevalence and associated risk factors, however, vary across populations.

OBJECTIVE: To describe denture stomatitis and its associations with patient- and prosthesis-related factors among older adults wearing removable dentures in the United Arab Emirates.

METHODS: 280 patients wearing 492 removable dentures were examined in a specialty dental facility in Ras Al-Khaimah, United Arab Emirates. Clinical assessment of patients and dentures was performed by three prosthodontists. Patient-related variables included years of denture wear, vertical dimension of occlusion, salivary flow, diabetes and hypertension. Prosthetic-related variables included denture integrity, plaque and calculus deposits, use of reline materials or denture adhesives, denture tooth wear, and denture stability and retention. Statistical analysis used SPSS (version 29).

RESULTS: Denture stomatitis was diagnosed in 42 participants (15%). Years of denture wear, reduced vertical dimension of occlusion, low salivary flow and all prosthesis-related variables were associated with denture stomatitis. Multivariate Poisson regression showed that longer years of denture wear were associated with a higher risk of denture stomatitis (PR = 1.09; 95% CI: 1.03-1.16), while adequate denture retention was associated with a lower risk (PR = 0.50; 95% CI: 0.25-0.99).

CONCLUSION: Denture stomatitis was associated with longer denture wear duration and inadequate denture retention. Regular denture assessment and maintenance may help support oral mucosal health in older adults.

PMID:42596855 | DOI:10.1111/ger.70117

Pediatr Allergy Immunol. 2026 Aug;37(8):e70424. doi: 10.1111/pai.70424.

ABSTRACT

BACKGROUND: Prenatal exposure to ambient air pollution has been associated with early-life allergic outcomes; however, underlying biological mechanisms remain incompletely understood.

METHODS: A total of 101 mother-infant pairs were ultimately included in this prospective birth cohort study. Maternal exposure to ambient air pollutants was assigned to geocoded residential addresses using spatiotemporal models. Allergic symptoms were defined as cumulative caregiver-reported symptoms occurring from birth to 6 months and assessed at the 6-month follow-up. DNA methylation in naïve CD4⁺ T cells was analyzed in a subset of 30 cord blood samples using targeted bisulfite sequencing. Associations were evaluated using regression models, and statistical mediation analysis was performed under a counterfactual-based approach.

RESULTS: Higher first-trimester exposure to PM₁₀ (adjusted odds ratio [AOR], 2.27; 95% confidence interval [CI], 1.09-4.98) and NO₂ (AOR, 2.11; 95% CI, 1.02-4.53) was associated with an increased likelihood of allergic symptoms within the first 6 months of life. In addition, third-trimester exposure to PM_2.5 components, including sulfate (SO₄ ^2-), nitrate (NO₃ ^–), and ammonium (NH₄ ⁺), was positively associated with these outcomes. DNA methylation at a CpG site within the PRKACB promoter showed statistical evidence consistent with a potential mediating role in the association between third-trimester sulfate exposure and allergic symptoms. Functional assays supported the regulatory relevance of this locus.

CONCLUSIONS: Prenatal ambient air pollution exposure was associated with early-life allergic symptoms, and cord blood DNA methylation at the PRKACB locus may represent a potential molecular mechanism underlying these associations. These findings are exploratory and require confirmation in larger studies.

PMID:42596852 | DOI:10.1111/pai.70424

Emerg Med Australas. 2026 Aug;38(4):e70308. doi: 10.1111/1742-6723.70308.

ABSTRACT

OBJECTIVE: To inform in-event health service (IEHS) delivery and harm minimisation strategies for the planned youth mass gathering event (MGE) known as ‘Leavers’ in the Southwest region of Western Australia. This study aimed to describe patient emergency department (ED) presentation characteristics and outcomes for Leavers WA.

METHODS: A retrospective observational study of patient presentations by Leavers to the Busselton ED at the 2022 MGE. This included 4 days with IEHS operation (7 pm to 1 am), 2 days prior to and 3 days post the MGE. Data analysis included descriptive and inferential statistics.

RESULTS: Of 9621 Leavers, 121 (1.26%, PPR 12.6/1000) presented to ED: 12 prior to, 85 during and 24 post the MGE. The majority of presentations were from the community (n = 103, 85.1%). Of 557 Leavers who presented to the IEHS, 18 were transported to hospital (TTHR 1.87/1000). The majority of presentations were ATS 3 and ATS 4 (43.8%, 42.1%). Medical illness was the most common presentation category (n = 59, 48.8%). 51.2% of presentations were related to alcohol/illicit substance use. 85.6% of Leavers were seen and allocated a discharge disposition within 4 h.

CONCLUSIONS: Leavers WA celebrations introduced a significant burden on the regional ED with over half the presentations drug and alcohol related and the majority of patients requiring urgent or semi-urgent assessment. The IEHS likely reduced this burden during operational hours. Future research should focus on standardisation of data collection, comparing IEHS and ED presentations, and measuring effectiveness of harm minimisation strategies.

PMID:42596843 | DOI:10.1111/1742-6723.70308