Category: Statistics

Int J Clin Oncol. 2025 Aug 29. doi: 10.1007/s10147-025-02869-0. Online ahead of print.

ABSTRACT

BACKGROUND: Novel hormonal agents (NHAs), including enzalutamide, abiraterone acetate, apalutamide, and darolutamide, have improved survival in advanced prostate cancer (PCa). However, their potential neurological adverse effects (AEs)-notably cognitive impairment, seizures, and falls-raise safety concerns, particularly in older adults. This study aimed to compare the neurological safety profiles of NHAs in men with advanced PCa using a Bayesian network meta-analysis (NMA).

METHODS: We conducted a systematic review and Bayesian NMA following PRISMA-NMA guidelines. Comprehensive searches of PubMed, EMBASE, and Web of Science were completed through May 21, 2025. Eligible randomized controlled trials (RCTs) compared NHAs plus androgen deprivation therapy (ADT) with placebo, ADT, or other NHAs. Neurological AEs of interest included cognitive impairment, falls, and seizures. Bayesian random-effects models were used to calculate risk ratios (RRs) with 95% credible intervals (CrIs). Treatments were ranked using surface under the cumulative ranking curve (SUCRA) values.

RESULTS: Twenty-five RCTs with over 19,000 patients were included. No treatments showed a statistically significant increased risk of neurological AEs. Enzalutamide had the highest estimated risk for cognitive impairment (RR 3.88; 95% CrI, 0.697-22.1) and seizures (RR 13.8; 95% CrI, 0.983-1.07 × 10³), although not statistically significant. Darolutamide and nonsteroidal antiandrogens exhibited the most favorable neurological safety profiles across outcomes based on SUCRA rankings.

CONCLUSION: Although no NHA significantly increased neurological AEs, enzalutamide showed the highest estimated risk, while darolutamide and NSAAs ranked best for neurological safety. Darolutamide may be preferred in elderly patients, highlighting the need for further long-term safety data.

PMID:40880017 | DOI:10.1007/s10147-025-02869-0

Clin Transl Oncol. 2025 Aug 29. doi: 10.1007/s12094-025-04036-3. Online ahead of print.

ABSTRACT

BACKGROUND: History of malignant disease is a common exclusion criterion in clinical cancer trials, yet data on the impact of cancer survivorship on outcome in gastroesophageal cancer patients are scarce.

METHODS: Retrospective association analyses of self-reported prior or concurrent malignancies with patient characteristics, tumor characteristics, symptoms and overall survival (OS) were performed in 1491 gastroesophageal cancers patients treated between 01/01/2000 and 31/12/2021 at the Medical University of Vienna.

RESULTS: Of 1491 patients 255 (18%) had other primary cancer diagnoses, of which 185 (73%) occurred before, 52 (20%) at the same time as and 18 (7%) both before and at the same time as gastroesophageal cancer diagnosis. 205 (80%) patients had one, 43 (17%) had 2 and 7 (3%) had 3 other malignancies. History of other malignancies was associated with older age (p < 0.0001), squamous cell histology (p = 0.018), less aggressive localized tumor stages (p = 0.037) and fewer acid reflux (p = 0.011). There was neither an association between history of other primary malignancies nor the number of other cancer entities and OS (p = 0.47; p = 0.43).

CONCLUSION: Self-reported history of other malignant diseases is frequent in a real-life European gastroesophageal cancer cohort and was not statistically significantly associated with outcome, but rather with older age and squamous cell histology. Our data emphasize that cancer survivors should not be categorically excluded from clinical cancer trials due to fear of dismal prognosis. Prospective research is warranted to improve eligibility for this subgroup.

PMID:40880012 | DOI:10.1007/s12094-025-04036-3

Ir J Med Sci. 2025 Aug 29. doi: 10.1007/s11845-025-04073-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Oesophageal reconstruction is a complex operation that continues to present a surgical challenge associated with significant morbidity and its associated sequelae. The conventional gastric conduit remains the gold standard reconstructive technique when available. Alternative conduits for oesophageal replacement become necessary when the stomach is unavailable with common options for conduit creation being the jejunum and the colon. The aim of this systematic review and network meta-analysis was to interrogate outcomes in oesophageal reconstruction with gastric pull-up, colonic interposition and jejunal flap.

METHODS: A systematic review of three electronic databases (PubMed, EMBASE and SCOPUS) was undertaken. An NMA as per the PRISMA-NMA guidelines. Statistical analysis was carried out using R and Shiny.

RESULTS: In a total of 19 studies, 3927 patients were included; 79.5% (3123/3927) of patients underwent gastric pull-up; 13.5% (531/3927) of patients underwent colonic interposition; 7% (273/3927) of patients underwent jejunal flap as their reconstructive method. At NMA, there was no significant difference in anastomotic leak rates, mortality rates, stricture formation, necrosis and length of stay between the three reconstructive techniques. Trend results showed jejunal flap performed better than colonic interposition in length of stay and mortality rates.

CONCLUSION: At present, the gastric conduit is the conventional and first choice for oesophageal reconstruction ab initio after oesophagostomy. Colonic interposition and jejunal free flap represent viable options and are associated with non-inferior short-term surgical outcomes when gastric pull-up is not available or feasible.

PMID:40879993 | DOI:10.1007/s11845-025-04073-5

Wien Med Wochenschr. 2025 Aug 29. doi: 10.1007/s10354-025-01107-6. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD), characterized by hepatic inflammation and damage due to fat accumulation. Psoriasis patients show higher NASH incidence due to overlapping risk factors like obesity and insulin resistance. The study aimed to determine the incidence of non-alcoholic steatohepatitis in patients with psoriasis vulgaris.

METHODS: This cross-sectional observational study included 80 adult patients diagnosed with psoriasis vulgaris. Psoriasis severity was assessed using the Psoriasis Area and Severity Index (PASI) score. All participants underwent abdominal ultrasonography to assess liver steatosis. Those with significant findings suggestive of fatty liver were further evaluated with transient elastography (FibroScan, EchoSens, Paris, France) to determine liver stiffness and controlled attenuation parameter (CAP) values.

RESULTS: Among psoriatic patient diagnosed with NASH, the mean PASI score was 8.8 ± 3.6 which was higher than those diagnosed with NAFLD and non-NASH non-NAFLD patients (6.7 ± 4.5 and 7.1 ± 3.9, respectively); however, this difference was not statistically significant (P = 0.19). The percentage of moderate and severe psoriasis was higher in NASH patients (68.75%) compared to NAFLD and non-NASH non-NAFLD subjects (57.1% and 46.5%, respectively).

CONCLUSION: NASH and NAFLD are linked to psoriasis severity and systemic metabolic dysfunction. Future studies with larger cohorts and prospective designs are needed to validate these findings and explore underlying mechanisms.

PMID:40879966 | DOI:10.1007/s10354-025-01107-6

Metabolomics. 2025 Aug 29;21(5):127. doi: 10.1007/s11306-025-02327-y.

ABSTRACT

INTRODUCTION: Fatty acids (FAs) are essential for cellular structure, metabolism, and inflammatory regulation. This study investigated FA profiles in Crimean-Congo hemorrhagic fever (CCHF), a severe viral illness with high mortality rates, to explore their potential as disease progression and severity biomarkers.

METHODS: 190 participants were included in the study, comprising 115 CCHF-positive patients, 30 CCHF-negative patients, and 45 healthy controls. FA concentrations were analyzed via gas chromatography‒mass spectrometry (GC-MS).

RESULTS: Statistically significant differences in specific FA levels were observed between the study groups. Compared with mild and moderate cases, severe cases showed distinctive FA profiles. Notably, higher omega-6/omega-3 ratios and linoleic acid to dihomo-γ-linolenic acid (LA/DGLA) ratios are associated with severe disease outcomes and poor prognosis and are correlated with inflammatory markers such as IL-6 and D-dimer. Pathway analysis was performed to identify disruptions in fatty acid biosynthesis and metabolism. Additionally, Cox regression analyses were conducted to determine key fatty acids associated with prognosis. Regression analyses identified several key fatty acids influencing prognosis, including myristic acid, phytanic acid, linoleic acid, gamma-linolenic acid, alpha-linolenic acid, oleic acid, behenic acid, cerotic acid, linoleic acid DGLA, omega-6 fatty acids, omega-9 fatty acids, and the omega-6/omega-3 ratio. Pathway analysis revealed that the disruptions in the most affected pathways were the biosynthesis of unsaturated fatty acids, α-linolenic acid metabolism, elongation, degradation, arachidonic acid metabolism, and fatty acid biosynthesis in CCHF pathogenesis.

CONCLUSION: This study highlights significant alterations in fatty acid metabolism and laboratory markers in CCHF. These findings provide insights into the pathophysiology of this disease and may guide future research on targeted therapeutic strategies.

PMID:40879927 | DOI:10.1007/s11306-025-02327-y

Bull Exp Biol Med. 2025 Aug 29. doi: 10.1007/s10517-025-06471-2. Online ahead of print.

ABSTRACT

The morphofunctional characteristics of rabbit corneas were studied after terahertz (THz) irradiation at a frequency of 2.3 THz with varying durations (15 or 30 min) or intensities (0.012 mW/cm² (38°C), 0.018 mW/cm² (40°C), 0.024 mW/cm² (42°C)) over a period of 1 week after exposure. The intensity of irradiation did not affect the functional changes in the eyes after exposure. However, in groups with different exposure durations, statistically significant changes in corneal hydration and endothelial cell density were observed, the extent of which depended on the exposure time. Endothelial cell density negatively correlated with corneal thickness (r = -0.36; p = 0.042), indicating a depletion of the endothelial cell pool associated with an increase in corneal thickness. These changes were subclinical in nature and did not lead to significant pathological changes in the cornea (no signs of hyperreflectivity were observed on optical coherence tomography of the anterior segment). Thus, the safety of THz irradiation at a frequency of 2.3 THz within the range of used intensities and exposure durations was confirmed in vivo study.

PMID:40879925 | DOI:10.1007/s10517-025-06471-2

Arch Osteoporos. 2025 Aug 29;20(1):118. doi: 10.1007/s11657-025-01600-w.

ABSTRACT

In middle-aged adults, we evaluated the associations between multimorbidity count and patterns with fall- and fracture-related hospitalisations. Falls risk increased linearly with multimorbidity count, and certain multimorbidity patterns were associated with increased risks of falls and fractures. Multimorbidity count and pattern should therefore be considered when risk stratifying patients.

PURPOSE: Although multimorbidity is recognised as a risk factor for falls and fractures, most studies are retrospective, and few have explored these relationships through statistically derived multimorbidity patterns. Our prospective cohort study with 4991 participants of the Busselton Healthy Ageing Study aged 45-69 years evaluated the associations of multimorbidity count and classes with incident fall- and fracture-related hospitalisations.

METHODS: Twenty-one morbidities were assessed at baseline, and four multimorbidity classes were identified using latent class analysis. Fall- and fracture-related hospitalisations were captured through the Western Australian Data Linkage System over a median follow-up of 7.9 years. Associations were examined using Cox regression models adjusting for sex, baseline age, lifestyle factors, and prior falls/fractures.

RESULTS: During follow-up, incident fall- and fracture-related hospitalisations were recorded for 177 (3.5%) and 197 (3.9%) participants, respectively. Each one-unit increase in multimorbidity count was associated with a 16% (95% CI, 7.8-25%) increased risk of fall-related hospitalisations. Multimorbidity scores of 9 and above (HR 2.32 [1.22-4.42]) showed an increased risk of fractures. Compared with the relatively healthy class, the cardiometabolic or mental health and musculoskeletal classes were associated with an increased risk of fall-related hospitalisations (HR 2.84 [1.76-4.59] and 1.78 [1.23-2.59], respectively). The cardiometabolic class was associated with an increased risk of fracture-related hospitalisations (HR 1.79 [1.04-3.07]).

CONCLUSION: In middle-aged adults, we showed that multimorbidity count and certain multimorbidity patterns were associated with increased risk for fall- and fracture-related hospitalisations. Multimorbidity should therefore be considered when assessing a patient’s risk of falls and fractures.

PMID:40879888 | DOI:10.1007/s11657-025-01600-w

Metabolomics. 2025 Aug 29;21(5):129. doi: 10.1007/s11306-025-02326-z.

ABSTRACT

INTRODUCTION: Melatonin has been proposed to aid recovery following physical exercise; however, few studies have investigated its effects on tissue amino acid profile.

OBJECTIVE: This study aimed to evaluate the effects of post-exercise melatonin administration on tissue amino acid concentration and metabolic regulation.

METHODS: Thirty Wistar rats engaged in a 60-minute swimming session at 90% of their individual maximal aerobic capacity (iMAC), followed by the intraperitoneal administration of melatonin (EM; 10 mg·kg⁻¹) or a vehicle solution (Ex) of equivalent volume. The animals were euthanized at 1, 3, or 24 h post-treatment to facilitate the collection of liver and skeletal muscle samples. Tissue amino acid profiles were analyzed using flow-injection analysis (FIA) in conjunction with targeted mass spectrometry (MS). Statistical analyses were conducted using the Friedman test, two-way analysis of variance (ANOVA), Newman-Keuls post hoc test, and effect size (ES), with significance determined at p < 0.05.

RESULTS: No significant effects were observed in the liver tissue. However, in skeletal muscle, melatonin significantly increased the levels of several amino acids, including arginine, glutamic acid, glutamine, ornithine, proline, and serine. Additionally, glycine levels were elevated 3 h post-exercise (EM3 > Ex3; p < 0.05), whereas methionine levels were reduced 24 h post-exercise in the melatonin group compared to control groups (EM24 < Ex24; p < 0.01).

CONCLUSION: Melatonin modulated the post-exercise amino acid profile in skeletal muscle, enhancing the levels of key metabolites involved in recovery and metabolic regulation, with no effects observed in liver tissue. These findings suggest a muscle-specific role for melatonin in supporting metabolic recovery after exercising.

PMID:40879884 | DOI:10.1007/s11306-025-02326-z

Pharmacoepidemiol Drug Saf. 2025 Sep;34(9):e70205. doi: 10.1002/pds.70205.

ABSTRACT

PURPOSE: The potential of vancomycin to cause acute kidney injury (AKI) in adult intensive care patients is subject to debate due to suboptimal designs of past studies. Therefore, we aimed to estimate the effect of initiating vancomycin versus one of several minimally nephrotoxic alternative antibiotics on the 14-day risk of AKI using the target trial emulation framework.

METHODS: A hypothetical trial was emulated using routinely collected data from 15 Dutch intensive care units (ICUs) spanning 2010-2019. We used an active comparator control group with the following alternative antibiotics: clindamycin, linezolid, teicoplanin, meropenem, cefazolin, and daptomycin. AKI was diagnosed according to the KDIGO serum creatinine (SCr) criteria. Cumulative incidence curves were estimated using the Aalen-Johansen method and adjusted for confounding and selection bias through inverse probability of treatment and censoring weighting. Given the time lag of 24-48 h between changes in renal function and SCr, we summarized the estimates by calculating the absolute risks and risk differences at both 2 and 14 days after initiation.

RESULTS: We included 1809 ICU admissions. After adjustment, vancomycin was associated with a higher risk of AKI at 14 days of follow-up compared to the alternative antibiotics (0.28 [95% confidence interval (CI) 0.21-0.34] vs. 0.17 [95% CI 0.14-0.20]; risk difference 0.11 [95% CI 0.04-0.19]), but not at 2 days of follow-up (0.10 [95% CI 0.06-0.12] vs. 0.10 [95% CI 0.08-0.11]; risk difference 0.00 [95% CI -0.03-0.03]).

CONCLUSIONS: Our findings indicate that vancomycin causes a higher risk of AKI compared to the alternative antibiotics. We recommend clinicians to be compliant with vancomycin-induced AKI prevention strategies, such as therapeutic drug monitoring or the consideration of an alternative antibiotic if possible.

PMID:40878006 | DOI:10.1002/pds.70205

J Invest Surg. 2025 Dec;38(1):2540814. doi: 10.1080/08941939.2025.2540814. Epub 2025 Aug 28.

ABSTRACT

BACKGROUND: Total hip arthroplasty (THA) in elderly patients is often associated with significant perioperative pain. This study aimed to evaluate the analgesic efficacy of fascia iliaca compartment block (FICB) and pericapsular nerve group block (PENGB) in elderly patients undergoing THA.

METHODS: This retrospective study included two patient groups: the PENGB group (n = 62) and the FICB group (n = 64). The primary outcome was the analgesic efficacy, assessed using Visual Analog Scale (VAS) pain scores at multiple postoperative time points. Secondary outcomes included motor blockade, the time to first rescue analgesia, postoperative analgesia quality and systemic inflammatory responses.

RESULTS: PENGB provided significantly superior analgesia at 6 and 12 h postoperatively, as evidenced by lower VAS pain scores compared to the FICB group. Motor blockade was also less pronounced in the PENGB group at 3 and 6 h post-surgery. The time to first rescue analgesia was significantly longer in the PENGB group, indicating more sustained pain control. Additionally, PENGB was associated with reduced use of patient-controlled analgesia pumps and lower total sufentanil consumption. At 24 h postoperatively, interleukin-6 levels were significantly lower in the PENGB group, suggesting an attenuated inflammatory response.

CONCLUSIONS: Compared to FICB, PENGB provided superior analgesia in elderly patients undergoing THA.

PMID:40878001 | DOI:10.1080/08941939.2025.2540814