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Nevin Manimala Statistics

Interleukin-1 activity regulators in acute decompensated heart failure: dependence on obesity degree

Ter Arkh. 2026 May 2;98(4):226-230. doi: 10.26442/00403660.2026.04.203576.

ABSTRACT

AIM: To assess the circulating levels of IL-1 and its activity regulators, IL-1Ra and IL-1R2, in patients with acute decompensated heart failure (ADHF) depending on body mass index (BMI).

MATERIALS AND METHODS: The study included 159 patients hospitalized for ADHF. Depending on the BMI, the patients were assigned to 5 groups. The first group included 30 patients with healthy weight (BMI<25 kg/m2), the second – 50 overweight patients (25≤BMI<30 kg/m2), the third – 38 patients with class I obesity (30≤BMI<35 kg/m2), the fourth – 28 patients with class II obesity (35≤BMI<40 kg/m2), the fifth group – 13 patients with class III obesity (BMI≥40 kg/m2).

RESULTS: With increasing BMI, IL-1 levels increased, while IL-1R2 levels, on the contrary, decreased, but no statistically significant differences were found. IL-1Ra concentrations changed ambiguously and had U-shaped dependence. IL-1Ra levels were lower in overweight patients than in normal weight and obese groups. At the same time, the increase in obesity was accompanied by higher IL-1Ra levels. The highest IL-1Ra value was observed at a BMI≥40 kg/m2.

CONCLUSION: In ADHF an increase in obesity is accompanied by an increase in the inhibition of IL-1 activity, which may be one of the mechanisms by which adipose tissue exerts a protective effect.

PMID:42107125 | DOI:10.26442/00403660.2026.04.203576

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Features of disorders of the gut microbiota in patients with urolithiasis, depending on the severity of symptoms of intestinal indigestion and indicators obtained in laboratory and instrumental assessment

Ter Arkh. 2026 May 2;98(4):217-225. doi: 10.26442/00403660.2026.04.203575.

ABSTRACT

AIM: The study examined the composition of the gut microbiota (GM) in patients with urolithiasis compared to healthy volunteers, based on laboratory, instrumental, and gastroenterological quality of life questionnaire (Gastrointestinal Symptom Rating Scale – GSRS) results.

MATERIALS AND METHODS: The composition of GM was studied using fecal samples obtained from 35 patients with urolithiasis and 31 healthy volunteers using gas chromatography-mass spectrometry. The GSRS questionnaire was used to assess gastrointestinal symptoms. In the group of patients with urolithiasis, the body mass index, serum creatinine concentration (with calculation of glomerular filtration rate), and serum uric acid concentration were analyzed, as well as the density of urinary stones using multispiral computed tomography (MSCT) in Hounsfield units (HU).

RESULTS: Statistical analysis of the data revealed violations of the composition of the GM against the background of urolithiasis in comparison with healthy volunteers (control group): patients with urolithiasis had a statistically significant increase in the content of bacteria Corynebacterium spp., Peptostreptococcus anaerobius 18623, a decrease in the number of Clostridium propionicum (Anaerotignum propionicum), on average, 7 times, compared to the control group. When comparing the composition of the GM depending on the type of urinary stones, in the subgroup of patients with oxalate stones (n=18), an increase in the number of Clostridium perfringens was detected in the fecal samples, and in the subgroup of patients with uric acid stones (n=17), a decrease in the number of Prevotella bacteria was observed. In patients with urolithiasis, there was a negative correlation between the total GSRS score and the severity of dyspepsia syndrome, as well as the number of Propionibacterium spp. in the GM.

CONCLUSION: The composition of the GM in patients with urolithiasis was significantly different from that of the GM in healthy volunteers. Statistically significant differences in the composition of the GM were found in patients with uric acid and oxalate stones.

PMID:42107124 | DOI:10.26442/00403660.2026.04.203575

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Forced oscillation technique in the diagnosis of fibrotic phenotype interstitial lung diseases

Ter Arkh. 2026 May 2;98(4):209-216. doi: 10.26442/00403660.2026.04.203574.

ABSTRACT

AIM: To identify functional features in patients with interstitial lung diseases (ILD), depending on disease phenotypes, using the forced oscillation technique.

MATERIALS AND METHODS: A single-center cross-sectional observational study was conducted on 68 patients with ILD (mean age 64 years, 70.6% women). The diagnoses were distributed as follows: idiopathic pulmonary fibrosis 17.7%, chronic hypersensitivity pneumonitis 44.1%, non-specific interstitial pneumonia 14.7%, unclassified ILD 23.5%. According to Tomographia Computata data, fibrotic changes were detected in 74.1% of patients. All patients underwent comprehensive pulmonary function testing, including spirometry, body plethysmography, measurement of diffusing capacity of the lungs, and oscillometry (forced oscillation technique).

RESULTS: The ΔX5 parameter was statistically significantly higher in patients with a fibrotic phenotype than in those without fibrosis [0.92 (0.06- 1.63) hPa×s/L vs 0.19 (-0.05-0.43) hPa×s/L; p=0.016]. Patients with fibrosis also had significantly lower for diffusing capacity of the lungs (45.5% vs 52% predicted; p=0.027) and CO diffusion capacity – Kco (73% vs 81.5% predicted; p=0.037) values. Independent predictors of the fibrotic phenotype were ΔX5 (odds ratio 6.386, 95% confidence interval 1.479-27.564; p=0.013) and Kco (odds ratio 0.929, 95% confidence interval 0.867-0.997; p=0.040). ROC analysis showed that the combination of ΔX5 and Kco parameters has high diagnostic value for detecting fibrosis (AUC 0.817; p<0.001).

CONCLUSION: The oscillometry parameter ΔX5 and the Kco index from diffusing capacity measurement are independent predictors of a fibrotic phenotype in patients with ILD. The combination of these functional parameters improves diagnostic capabilities for detecting fibrotic changes. The FOT method provides clinically important information in patients with ILD and restrictive impairment.

PMID:42107123 | DOI:10.26442/00403660.2026.04.203574

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Assessment of DNA Variations From Two In Vivo Skeletal Muscle Disorder Mouse Models Using Complementary Square-Wave Voltammetry and LC-MS/MS Analysis

Chembiochem. 2026 May 14;27(9):e70368. doi: 10.1002/cbic.70368.

ABSTRACT

Duchenne Muscular Dystrophy (DMD) and Ehlers-Danlos Syndrome (EDS) are characterized by genetic instability due to DNA damage leading to loss of muscular function. Genetic impacts of these diseases were probed by extracting DNA from selected muscle tissues of either a mouse model of X chromosome-linked muscular dystrophy (mdx, DMD model) or a heterozygous col5a1 (+/-) mouse (EDS model). Complementary square wave voltammetry (SWV) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) approaches were used to assess extracted DNA. SWV analysis was performed by immobilizing DNA layer-by-layer (LbL) on pyrolytic graphite (PG) electrodes before oxidation in the presence of Ru(bpy)3 2+. Changes in SWV peak currents (Ip) at ∼+1.05 V vs. SCE indicated significant DNA alterations in the genetically altered mouse tissues compared to wild type (WT) controls. Both mdx and heterozygous col5a1(+/-) samples exhibited statistically significant decreased Ip levels (p < 0.05) compared to WT DNA suggesting guanine content varied due to the genetic alterations, which was statistically more significant in leg muscle DNA. MS/MS validated and expanded on the SWV results. DNA base analysis showed increased oxidative damage alongside changes in undamaged base content in mdx mice. DNA from col5a1(+/-) leg muscles exhibited significant changes to undamaged base content, showcasing similar trends.

PMID:42107099 | DOI:10.1002/cbic.70368

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Feasibility and acceptability of a group-based intervention to support LGBTQ+ cancer survivors: QT cancer StoryListening

J Psychosoc Oncol. 2026 May 10:1-10. doi: 10.1080/07347332.2026.2668705. Online ahead of print.

ABSTRACT

BACKGROUND: We adapted a previously-successful intervention, StoryListening, to a group setting for LGBTQ+ cancer survivors.

OBJECTIVE: Our goal was to assess the feasibility and acceptability of the QT (Queer/Trans) Cancer StoryListening Workshop.

METHODS: We conducted a single-arm pilot feasibility trial of QT Cancer StoryListening for LGBTQ+ cancer survivors in September, 2025. Feasibility was assessed by enrollment and questionnaire completion data. Acceptability was evaluated using self-report questionnaires with both closed-ended and open-ended items. We used a mixed methods analytic approach, including both descriptive statistics and deductive thematic content analysis.

RESULTS: Twelve individuals responded with interest in 5 wk of community outreach; 10 (83%) attended the workshop and 8 completed follow-up questionnaires (80%). Participants identified no emotional or logistical difficulty in participating and all identified value, particularly around the community aspect of the workshop. LGBTQ+ cancer survivors lack specifically-tailored support.

CONCLUSION: StoryListening is a brief, scalable intervention that is both feasible and acceptable to LGBTQ+ cancer survivors.

PMID:42107087 | DOI:10.1080/07347332.2026.2668705

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Reply to: Personalized reference intervals based on biological variation: a critical evaluation of strengths and limitations

Clin Chem Lab Med. 2026 May 11. doi: 10.1515/cclm-2026-0554. Online ahead of print.

NO ABSTRACT

PMID:42107068 | DOI:10.1515/cclm-2026-0554

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Nevin Manimala Statistics

Sponsor Initiated Requests to Delay Pediatric Postmarketing Studies

Pharmaceut Med. 2026 May 10. doi: 10.1007/s40290-026-00610-4. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Lagging pediatric safety and effectiveness data increase the risks to children associated with off-label drug use. The objective of this study was to delineate the frequency of, and reasons behind, delays in the completion of mandated pediatric postmarketing requirement (PMR) studies.

METHODS: Publicly accessible and internal US Food and Drug Administration (FDA) data were aggregated to characterize pediatric PMRs issued from 2012 to 2024, including relevant dates, durations, and deferral extension (DE) requests. Sponsor size, and clinical trial enrollment status were also examined.

RESULTS: There were 1160 pediatric PMRs identified, 459 of which were associated with 1176 DE requests. Despite a significant decline in the annual number of PMRs issued (slope [95% confidence interval]: – 3.64 [- 6.50, – 0.79] year-1, p = 0.02), an increase in the annual number of DE requests (5.24 [2.16, 8.31] year-1, p < 0.01) was observed. Declines in negotiated timelines for PMR completion and durations of time granted per request were also seen. Issues related to clinical trial conduct predominated DE rationale in every year and accounted for 48% of all requests. One in 10 delayed trials failed to initiate enrollment before the PMR due date and 1 in 5 cited problems with clinical trial conduct before enrollment began. Smaller companies (< 500 employees) exhibited higher DE request rates, lower PMR success rates, and accounted for an increasing proportion of PMRs over the review period (from 17% in 2012 to 72% in 2024).

CONCLUSIONS: Year-on-year increases in DE requests reinforce ongoing challenges to timely and successful pediatric trial completion. Difficulties with clinical trial conduct appear to be the primary driver for these delays although the underlying root causes have yet to be elucidated. Regulators, sponsors, and stakeholder partners should work cooperatively to remediate delayed pediatric drug development timelines and reduce the duration of off-label drug use in children.

PMID:42107033 | DOI:10.1007/s40290-026-00610-4

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Enhanced detection of bladder cancer using combined circulating tumor cells, urine-derived epithelial cells, and molecular biomarkers

J Cancer Res Clin Oncol. 2026 May 10. doi: 10.1007/s00432-026-06469-x. Online ahead of print.

ABSTRACT

PURPOSE: The sensitivity of bladder cancer detection using a single biomarker from single sample type is limited. This study aimed to investigate whether a combined approach utilizing multiple biomarkers from different clinical samples could improve detection sensitivity.

METHODS: A total of 85 patients with bladder cancer and 30 healthy individuals were enrolled in this study. Urine and blood samples were collected for the isolation of urine-derived epithelial cells (UDECs) and circulating tumor cells (CTCs). These cells were then analyzed via PD-L1 assay and fluorescence in situ hybridization (FISH) targeting chromosomes 7 and 8. In parallel, matched urine samples from patients underwent conventional urine exfoliation cytology testing (UEC). All data were analyzed in conjunction with pathological information using specialized statistical software.

RESULTS: Analysis of CTCs demonstrated a significantly higher bladder cancer detection rate (78.6%) compared to UEC (36.7%). The combination of UDEC-FISH and CTC analysis utilizing urine and blood samples achieved a higher detection rate (94.1%) than the combination of UDEC-FISH with UEC performed on the same urine sample (79.8%). Furthermore, combined analysis of three markers of CTC, UEC, and UDEC-FISH (96.5%) or CTC, UEC, and UDEC-PD-L1 (90.6%) yielded significantly higher detection rates than any single biomarker analysis alone.

CONCLUSION: Integrating multiple biomarkers from distinct sample types significantly enhances the detection sensitivity for bladder cancer.

PMID:42107019 | DOI:10.1007/s00432-026-06469-x

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Efficacy and Safety of Digitalis Glycosides in Heart Failure: A Meta-Analysis

JAMA. 2026 May 10. doi: 10.1001/jama.2026.7886. Online ahead of print.

ABSTRACT

IMPORTANCE: Digitalis glycosides may be used as additional therapy in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or HF with reduced EF (HFrEF).

OBJECTIVE: To assess the effect of digitalis glycosides on clinical outcomes in patients with HFmrEF or HFrEF.

DATA SOURCES AND STUDY SELECTION: PubMed was searched from inception to March 1, 2026, using medical subject headings and keywords related to digitalis glycosides and HF. The review was restricted to placebo-controlled randomized clinical trials including more than 1000 patients and articles published in the English language.

DATA EXTRACTION AND SYNTHESIS: Data were extracted by 2 reviewers who followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline. Risk of bias was assessed with the Cochrane Risk of Bias tool (version 2). A fixed-effects model was used to estimate the hazard ratios (HRs) with 95% CIs.

MAIN OUTCOMES AND MEASURES: The primary end point was the composite of time to cardiovascular death or first worsening HF event. Secondary outcomes included individual components of the composite outcome and time to all-cause death.

RESULTS: A total of 3 studies met the inclusion criteria and included 9013 patients with HFmrEF or HFrEF (weighted mean age, 64.5 [weighted SD, 11.2] years; 22% female and 78% male). The composite outcome of cardiovascular death or first worsening HF event occurred in 1852 of 4510 patients (41%) in the digitalis glycoside group vs 2037 of 4503 patients (45%) in the placebo group (HR, 0.85 [95% CI, 0.80-0.90]; P < .001). First worsening HF event occurred in 1183 (26%) patients in the digitalis glycoside group vs 1474 (33%) patients in the placebo group (HR, 0.75 [95% CI, 0.69-0.81]; P < .001). There were 1224 cardiovascular events in the digitalis glycoside group vs 1224 in the placebo group (27% of participants in each group; HR, 0.99 [95% CI, 0.92-1.07]; P = .81) and there were 1466 vs 1497, respectively, all-cause deaths (32% of participants vs 33%; HR, 0.97 [95% CI, 0.90-1.04]; P = .41). There was no statistically significant heterogeneity by trial, type of digitalis glycoside treatment, or extent of background HF therapy.

CONCLUSIONS AND RELEVANCE: Treatment with digitalis glycosides was associated with a lower risk of the composite of cardiovascular death or first worsening HF event in patients with HFmrEF or HFrEF, mainly through a lower risk of worsening HF events. There was no statistically significant interaction with important study characteristics, including the extent of HF background therapy or type of digitalis glycosides treatment. These results suggest digitalis glycosides may be used as additional medical therapy to reduce worsening HF events in patients with HFmrEF or HFrEF.

PMID:42106991 | DOI:10.1001/jama.2026.7886

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Impulsivity, Self-Esteem, Meaning in Life, and Internet Addiction Among University Students: A Moderated Mediation Analysis

Psychol Rep. 2026 May 10:332941261450508. doi: 10.1177/00332941261450508. Online ahead of print.

ABSTRACT

This study examined whether the relationship between impulsivity and Internet addiction (IA) levels among university students varies depending on the indirect pathway mediated by the meaning-seeking in life and whether this indirect pathway is dependent on self-esteem levels. The study was conducted using data collected from 500 university students in Türkiye via valid self-report measures, employing a cross-sectional, correlational design. Controlling for daily internet usage time, the assumed direct, indirect, and conditional associations were tested using Hayes’ PROCESS macro (Model 14). Correlation analyses found that impulsivity was negatively related to meaning-seeking in life (r = -.120, p < .01) and positively related to IA (r = .261, p < .001). In the conditional process analysis, impulsivity was negatively associated with meaning-seeking in life (B = -0.180, p = .003) and positively associated with IA (B = 0.592, p < .001). The interaction between meaning-seeking in life and self-esteem was significantly associated IA (B = 0.180, p = .009) and contributed additional explanatory power to the model (ΔR2 = 0.0125, p < .01; total R2 = .117). The direct association between meaning-seeking in life and IA in the regression model was statistically significant (B = 0.214, p = .004); however, the indirect pathway through meaning-seeking in life was moderated by self-esteem. The moderated mediation index was significant (Index = -0.032, 95% CI [-0.076, -0.007]), and the findings indicate that the indirect component of the relationship between impulsivity and IA level, mediated by meaning-seeking in life, varies according to self-esteem level; the indirect association is more pronounced at lower self-esteem scores. These findings were interpreted within a cross-sectional design framework and suggest that impulsivity is related to IA levels and that the conditional indirect mechanism is present, although its magnitude appears modest.

PMID:42106983 | DOI:10.1177/00332941261450508