Search Results (14,144)

Background: Psychosocial assessment is a core component of lung transplant candidate evaluation, but total scores and broad candidate categories do not necessarily show how individual psychosocial concerns co-occur or which modifiable domains require further clinical attention. This study describes the development and internal evaluation of a clinical decision-support application that reorganizes Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) data into structured multidomain profiles. Methods: The application was developed using a retrospective single-center dataset of 496 adult lung transplant candidates. It integrates the SIPAT total score and candidate category with seven SIPAT-derived domain indicators, domain burden scores, cohort-referenced z-scores, graphical displays, and a ranked summary of domains for clinical review. All seven indicator targets were prespecified deterministic functions of SIPAT items or domain scores obtained during the same assessment. Random forest algorithms with sigmoid calibration were used to transform these targets into percentage-scaled display values; they were not trained using independently assessed clinical outcomes. Analyses included descriptive statistics, Spearman correlations, exploratory clustering, resampling-based cluster stability assessment, threshold sensitivity analyses, and subgroup analyses by age, sex, and primary pulmonary diagnosis. Results: Upper display-band classifications were identified for depression-related concerns in 32 candidates (6.5%), anxiety-related concerns in 11 (2.2%), nicotine-related concerns in 56 (11.3%), alcohol-related concerns in 22 (4.4%), illicit drug-use concerns in 11 (2.2%), social-support deficits in 40 (8.1%), and non-adherence-related concerns in 7 (1.4%). Exploratory clustering yielded a low-burden majority group (n = 432), a nicotine-dominant group (n = 53), and a small multidomain-elevation group (n = 11). The generated percentage-scaled indicators were positively associated with their conceptually corresponding SIPAT domains (Spearman’s ρ = 0.321–0.774) and with the total SIPAT score (ρ = 0.406–0.802; all p < 0.001). Sensitivity analyses showed that the smaller clusters were less stable under bootstrap resampling. These findings demonstrate internal alignment with the source instrument but do not constitute validation against independent clinical outcomes. Conclusions: The application provides an early-stage framework for organizing and visualizing SIPAT information and identifying domains that may warrant additional clinical assessment. Its outputs should be interpreted as SIPAT-derived decision-support indicators, not as independently validated probabilities of future clinical events. Prospective studies are required to evaluate usability, clinical impact, and associations with longitudinal outcomes. Full article

Soil microbiomes are essential for nutrient cycling, plant health, stress resilience, and sustainable agriculture. Recent advances in high-throughput sequencing, multi-omics technologies, systems biology, and artificial intelligence (AI) have transformed our understanding of plant–microbiome interactions and enabled the development of innovative microbiome engineering strategies. This review provides a comprehensive overview of the mechanisms governing plant-associated soil microbiome assembly, microbial community functions, plant–microbe communication, and microbiome-mediated stress resistance in agricultural ecosystems. Current approaches to plant-associated soil microbiome manipulation and engineering, including microbial inoculants, synthetic microbial communities (SynComs), microbiome transplantation, rhizosphere steering, and synthetic biology-based interventions, are critically examined. The review further discusses the growing role of metagenomics, metabolomics, metatranscriptomics, machine learning (ML), and precision agriculture technologies in improving microbiome characterization, prediction, and management. Particular attention is given to the application of microbiome-based solutions for sustainable crop production, nutrient management, biological control, climate-smart agriculture, and ecosystem restoration. Despite significant progress, challenges related to field-scale variability, colonization stability, biosafety, regulatory frameworks, and data integration continue to limit large-scale implementation. Future advances in precision microbiome engineering are expected to combine ecological principles, multi-omics technologies, AI, and synthetic biology to develop predictive and resilient microbiome-based solutions for sustainable and climate-resilient agriculture. Full article

This study aimed to clarify whether interleukin-1 receptor antagonist (IL-1RA) mediates the age-dependent immunomodulatory capacity of adipose-derived stem cells (ASCs) via regulating macrophage polarization. ASCs from young (Y-ASCs) and aged (O-ASCs) C57BL/6 mice were isolated. IL-1RA, which was identified as an age-sensitive candidate through integrated transcriptomic and proteomic screening in our prior publication, was validated by qPCR, immunofluorescence, and ELISA. RAW264.7 macrophages were polarized and co-cultured with ASCs or treated with recombinant IL-1RA; IL-1RA in Y-ASCs was silenced by siRNA (82.3 ± 5.1% knockdown efficiency). The results showed Y-ASCs had 2.1-fold higher IL-1RA mRNA and significantly higher protein secretion than O-ASCs (p < 0.001). Y-ASC transplantation enhanced M2 polarization (CD206⁺ cells increased from 9.36% to 21.4% in vivo; p < 0.01) in aged mouse adipose tissue and reduced inflammation (serum IL-1β lowered by 42.3 ± 5.1%; p < 0.001), while O-ASCs had no effect. Recombinant IL-1RA recapitulated Y-ASC effects (M2 macrophages increased from 0.92% to 61.8%; p < 0.001), and IL-1RA silencing abrogated Y-ASC function. The data indicate IL-1RA is a key age-sensitive mediator of ASC immunomodulation. Declined IL-1RA may contribute to impaired aged ASC efficacy, highlighting donor age’s importance. This provides mechanistic insights and guides IL-1RA-targeted optimization for ASC therapies in age-related inflammatory disorders. Full article

Background/Objectives: Nonselective beta-blockers (NSBBs) are foundational for variceal bleeding prophylaxis in cirrhosis. After transjugular intrahepatic portosystemic shunt (TIPS) placement, portal pressure is mechanically decompressed, and practice guidance generally supports discontinuing NSBBs when shunt function is adequate and no other indication exists; however, real-world adoption and outcomes associated with post-TIPS NSBB strategies remain incompletely characterized in large, multicenter populations. Methods: We performed a real-world, target-trial emulation in the TriNetX U.S. Collaborative Network using a prespecified 90-day landmark. Adults (≥18 years) with cirrhosis undergoing first TIPS who had NSBB prescribed in the prior year and who survived to post-TIPS day 90 were included. Strategy was classified during days 0–90 (continuation: ≥1 NSBB prescription; discontinuation: none). Propensity score matching (1:1) balanced demographics, comorbidities, portal hypertension complications, and laboratory values (including the components of the Freiburg Index of Post-TIPS Survival [FIPS], Model for End-stage Liver Disease–Sodium [MELD-Na], and Child–Pugh scores). Follow-up began at day 90 and continued through day 365. Primary outcomes were overall survival and transplant-free survival; secondary outcomes were hepatic encephalopathy (HE), esophageal variceal bleeding (EVB), and ICU admission. Results: Among 5111 patients (continuation: n = 2558; discontinuation: n = 2553), 2180 matched pairs were analyzed. One-year survival was similar (89.3% vs. 89.6%; HR: 1.03; 95% CI: 0.84–1.27), as was transplant-free survival (78.8% vs. 77.9%; HR: 0.95; 95% CI: 0.82–1.10). The cause-specific hazard of HE was higher with continuation (HR; 1.29; 95% CI: 1.14–1.46), while those of EVB (HR: 1.08; 95% CI: 0.90–1.29) and ICU admission (HR: 1.02; 95% CI: 0.86–1.22) were similar. Results were consistent in both strict discontinuation and adherence-based sensitivity analyses. Conclusions: In stabilized post-TIPS patients with prior NSBB use, continuation was not associated with improved 1-year survival or transplant-free survival and was associated with a higher cause-specific hazard of HE. Full article

Human cytomegalovirus (CMV) remains a significant infectious complication after kidney transplantation, reflecting gaps in the understanding of the molecular and immunological mechanisms regulating the transition from latency to productive infection. Following primary infection, CMV establishes lifelong latency in hematopoietic and myeloid lineage cells, maintained by viral chromatin repression and robust CMV-specific immune surveillance. CMV reactivation is associated with graft dysfunction, increased risk of rejection, opportunistic infections, and reduced patient survival. In kidney transplantation, CMV reactivation is driven by the interplay between tissue injury, inflammation, and immunosuppression. Ischemia–reperfusion injury and peri-operative stress produce reactive oxygen species, DNA damage, and pro-inflammatory cytokines (e.g., TNF-α, IL-6), which activate transcription factors such as NF-κB and AP-1. These factors regulate the CMV major immediate-early promoter (MIEP), thereby triggering lytic viral gene expression. At the same time, immunosuppressive therapies impair antiviral immune surveillance and, in some cases, induce cytokine release, potentially contributing to the pro-inflammatory environment that favors viral reactivation. In this review, we summarize current molecular and immunologic mechanisms governing CMV latency and reactivation with a focus on how immunosuppressive strategies and injury-associated pathways converge to promote CMV reactivation. We also discuss implications of risk stratification and the development of targeted therapeutic strategies to prevent CMV reactivation in kidney transplant recipients (KTRs). Full article

Background: Hematologic malignancies (HMs) represent a growing global health burden, and HSCT remains a cornerstone of treatment for many HMs. Despite improvements in survival, transplantation-related physical deconditioning is a persistent clinical challenge, and evidence supporting structured inpatient exercise interventions is scarce. Objectives: To evaluate the effects of a self-directed aerobic exercise program on a cycle ergometer in inpatients under isolation precautions related to HSCT. Methods: In this single-center prospective, non-randomized controlled interventional study, 73 patients were enrolled in an intervention group (n = 43) performing daily aerobic exercise on a cycle ergometer, or a control group (n = 30) receiving standard care. Physical performance was assessed at baseline and at discharge using the 6-min walk test (6 MWT), Timed Up and Go test (TUG), and 30-s chair stand test (30 s-CST). Results: Significant group-by-time interactions were observed for the TUG (F(1,71) = 10.35; p = 0.001; ηp² = 0.13) and the 30 s-CST (F(1,71) = 21.61; p < 0.0001; ηp² = 0.23). No significant interaction was detected for the 6 MWT (F(1,71) = 2.01; p = 0.16; ηp² = 0.03), although the decline in walking distance was smaller in the intervention group than in the control group (−4.1% vs. −10.5%). Post hoc analyses demonstrated significant within-group deterioration only in the control group. Conclusions: Self-directed aerobic exercise during inpatient isolation may mitigate physical deconditioning in HSCT recipients, supporting its integration into routine care. Full article

Background: High-dose melphalan 140–200 mg/m² (HDM) with autologous stem cell transplant (ASCT) is standard first-line treatment in multiple myeloma (MM), yet standard BSA-based dosing results in wide variation in systemic exposure (AUC). We developed a pharmacokinetic (PK)-guided dosing strategy using a 100 mg/m² first dose, enabling real-time PK assessment and individualized adjustment for the second dose. We report final results of Phase A of our multi-center Phase 1 trial (NCT04483206, MyMel) evaluating feasibility and accuracy of this personalized approach. Methods: Patients received melphalan 100 mg/m² on Day −3, and seven PK samples were collected and shipped overnight for LC-MS/MS analysis. Real-time AUC estimation using noncompartmental analysis (NCA) guided Day −1 dosing to achieve pre-specified AUC targets (13.5 or 14.5 mg × h/L). For comparison, post hoc Bayesian estimation using a nonlinear mixed effects (NLME) model was performed. Sparse sampling designs were evaluated using NONMEM. Results: All 20 patients successfully received PK-guided dosing, with Day −1 doses determined within 48 h. PK-guided dosing reduced AUC variability (CV 4.20–5.62%), with 19 of 20 achieving AUCs within ±10% of the target, compared to what would have been achieved by BSA dosing (CV 9.74–15.34%). NLME improved accuracy, particularly in patients with missing samples, and maintained performance using only four PK time points. Conclusions: This study demonstrates that PK-guided dosing is accurate and feasible with HDM-ASCT. NLME enhances accuracy and enables simplified sampling. Phase B will identify maximum tolerated systemic exposure of seven additional AUC cohorts using the NLME model and a four-sample design. Full article

Introduction: Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers, with a subset progressing to locally advanced (laSCC) or metastatic (mSCC) stages. The introduction of anti-PD1 immunotherapy has transformed treatment, but real-world data remain limited, particularly in immunosuppressed patients. Methods: This single-centre, retrospective study included 189 patients with advanced cSCC treated between 2012 and 2022. Demographic, clinical, and treatment data were analyzed to assess clinical management and outcomes before and after the introduction of anti-PD1. Results: Among the 189 patients, 72.5% were male, with a median age of 79 years. Overall, 86 patients presented with laSCC and 103 with mSCC. In 100 patients, a preceding primary cSCC was documented, and its complete resection (R0) was associated with significantly better overall survival (OS) after diagnosis of advanced disease (p < 0.001). Immunosuppressed patients, including organ transplant recipients and those with chronic lymphocytic leukemia (CLL), had significantly reduced OS (p = 0.017 and p = 0.0059, respectively). First-line treatment prior to 2018 predominantly involved surgery and radiotherapy. Following the introduction of anti-PD1 therapy, its use increased rapidly in both first- and second-line settings. From 2018 onward, the number of advanced cSCC cases discussed at the multidisciplinary tumorboard increased approximately threefold. Median OS was significantly longer for mSCC patients treated in the post-2018 era (p = 0.025), while the survival disadvantage of CLL patients compared to non-CLL patients widened, suggesting limited benefit from advances in systemic therapy in this subgroup. Best overall response to first-line anti-PD1 correlated significantly with OS, with complete responders achieving a 1-year progression-free survival of 83.3%. Conclusions: The introduction of anti-PD1 has demonstrated improved survival outcomes in advanced cSCC, though significant challenges remain for immunosuppressed patients, particularly those with CLL and solid organ transplant recipients. Future research should focus on optimizing treatment for these high-risk groups, therapeutic sequencing, and the role of perioperative (neoadjuvant and adjuvant) immunotherapy strategies. Full article

Myocarditis is a clinically challenging form of inflammatory heart disease with heterogeneous etiologies, limited diagnostic tools, no targeted therapies, and a substantial risk of progression to heart failure or sudden cardiac death, particularly in young adults. Emerging evidence has increasingly associated myocarditis with gut microbiota dysbiosis. This review explores the gut–myocarditis axis, highlighting key mechanisms and therapeutic strategies. Significant alterations in gut microbial composition are observed in myocarditis patients and animal models. Gut microbiota influences disease development through multiple pathways: compromised intestinal barrier integrity leading to bacterial translocation and systemic inflammation via MAMP/PRR signaling (e.g., TLRs, NLRs); production of metabolites—including pro-inflammatory trimethylamine N-oxide (TMAO), anti-inflammatory short-chain fatty acids (SCFAs), and immunomodulatory bile acids—that regulate host inflammatory responses, immune cell differentiation, oxidative stress, and fibrotic remodeling; and molecular mimicry, where microbial peptides (e.g., from Bacteroides thetaiotaomicron) trigger cross-reactive autoimmune responses against cardiac proteins. Regarding therapeutic strategies, this review discusses fecal microbiota transplantation (FMT), probiotics, prebiotics, dietary modulation, and emerging approaches including engineered bacteria and oral nanomedicines. Although these strategies hold promise, their efficacy and safety remain to be validated in large-scale clinical trials, and further investigation is warranted. Full article

Background/Objectives: Selecting the optimal biliary reconstruction technique for liver transplantation (LT) in primary sclerosing cholangitis (PSC) remains challenging. Many centers have historically favored Roux-en-Y hepaticojejunostomy (RYHJ) to bypass potentially diseased recipient ducts, whereas duct-to-duct (D-D) anastomosis preserves endoscopic access and decreases cholangitis rates. We evaluated outcomes during an institutional, anatomy-driven transition toward D-D reconstruction. Methods: We retrospectively analyzed primary LTs for PSC performed at Münster University Hospital between January 2008 and February 2021. Patients were stratified by biliary reconstruction technique into a RYHJ and D-D group. The reconstruction strategy was based on the recipient’s bile duct anatomy (D-D when distal extrahepatic duct pathology was absent and duct quality was deemed suitable; RYHJ otherwise). Postoperative complications within 12 months, biliary complications, and long-term patient and graft survival were assessed. Results: Forty-six patients were included (RYHJ n = 24; D-D n = 22). Overall biliary complication rates and patient and graft survival were comparable between the groups. Anastomotic strictures occurred more frequently after D-D reconstruction, whereas the rates of bile leakage, cholangitis, and revision surgery were similar between the two groups. In exploratory multivariable analyses, reconstruction type was not associated with mortality or overall biliary complications, whereas recipient age and male donor sex were associated with biliary complications. Conclusions: In selected patients with PSC undergoing LT with an anatomy-driven reconstruction strategy, D-D anastomosis achieved outcomes comparable to those of RYHJ, with a higher rate of anastomotic strictures but preserved potential for endoscopic management. Full article

Background/Objectives: Tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, is increasingly used for glycemic control and weight reduction and has a generally favorable hepatic safety profile. However, rare cases of clinically significant drug-induced liver injury have been reported. We report a case of severe hepatocellular injury during tirzepatide therapy and compare it with previously reported cases. Case Presentation: A 36-year-old man developed gastrointestinal symptoms, dark urine, and severe hepatocellular injury approximately 5 weeks after starting tirzepatide for weight reduction, shortly after dose escalation from 2.5 mg to 5 mg weekly and amid rapid weight loss of approximately 10 kg. Extensive evaluation excluded viral, autoimmune, metabolic, biliary, and structural causes, with no competing medication or supplement exposure identified. Tirzepatide was discontinued, and clinical and biochemical status improved rapidly. The Roussel Uclaf Causality Assessment Method (RUCAM) score was 7, indicating probable drug-induced liver injury. Discussion: Previously reported cases demonstrate heterogeneous biochemical patterns and severity, ranging from mild hepatocellular injury to mixed or cholestatic presentations and acute liver failure requiring transplantation. The mechanism remains uncertain. An idiosyncratic drug reaction is the most plausible explanation, while rapid weight loss, dose escalation, and hepatic steatosis may represent susceptibility modifiers rather than established causes. Conclusions: Tirzepatide-associated liver injury appears rare but can be clinically severe. Clinicians should remain alert to the possibility of drug-induced liver injury when unexplained hepatic symptoms or liver biochemical abnormalities arise during treatment. Full article

Glycyrrhizic acid (GL), a natural triterpenoid glycoside extracted from the “medicine food homology” herb Glycyrrhiza glabra L., exhibits potent anti-atherosclerotic effects; yet its underlying mechanisms remain unclear due to its poor oral bioavailability. The gut microbiota plays a pivotal role in the development of atherosclerosis (AS). In this study, the microbiota-dependent anti-AS effects of GL were evaluated in high-fat diet (HFD)-fed ApoE^−/− mice using antibiotic depletion and fecal microbiota transplantation (FMT). Integrated metagenomic and metabolomic analyses were performed to identify the key bioactive microbial metabolite. Further in vivo and in vitro experiments, including co-immunoprecipitation and dual-luciferase reporter assays, were utilized to elucidate the underlying molecular mechanisms. It was demonstrated that oral administration of GL alleviated AS in a microbiota-dependent manner by reversing gut dysbiosis, improving intestinal barrier function, and reducing pro-inflammatory lipopolysaccharide (LPS) levels. GL shifted intestinal tryptophan metabolism toward bacterial-derived indole-3-lactic acid (ILA) production, suppressing LPS-induced vascular endothelial adhesion dysfunction by activating the aryl hydrocarbon receptor (AhR). Mechanistically, ILA-activated AhR interacted with the NF-κB subunit p65 in the cytoplasm, effectively preventing the nuclear translocation of p65 and suppressing the promoter activities of adhesion molecules (VCAM1 and ICAM1), resulting in the amelioration of HFD-induced AS. These findings elucidate the microbiota-dependent mechanism of orally administered GL against AS, and highlight the therapeutic potential of targeting the ILA-AhR-p65 axis in the vascular endothelium as a strategy for AS. Full article

Background: Native nephrectomy is frequently required in autosomal-dominant polycystic kidney disease (ADPKD) before or during transplantation, but the optimal minimally invasive approach is unsettled, and it is unclear whether the pattern of post-operative complications tracks with operative technique. We report a retrospective single-centre experience of hand-assisted laparoscopic (HAL) native nephrectomy and, alongside it, a technique-stratified scoping review of complications. Methods: We retrospectively reviewed all consecutive adults undergoing HAL native nephrectomy—with an infra-umbilical midline hand-port and free intraperitoneal cyst rupture—in preparation for transplantation in the period between December 2019 and December 2025. In parallel, we performed a PRISMA-ScR-compliant scoping review (MEDLINE, Embase, Scopus) of minimally invasive ADPKD nephrectomy, with duplicate independent screening and extraction, stratifying complications by operative approach and cyst-decompression method. No quantitative pooling was undertaken. Results: Twenty-three patients (mean age 52.8 ± 9.9 years; 87% dialysis-dependent; 78% for transplant preparation) were included. Median operative time was 102 min (IQR 90–122) with minimal blood loss, one transfusion (4%), and no open conversion. Complications occurred in 8/23 (35%) and were bowel-predominant: one small-bowel perforation, two obstructions, and one ileus—three of Clavien–Dindo grade IIIb, all in right-sided nephrectomies and independent of specimen weight. Peri-operative mortality was 1/23 (4%), from a non-technique-related mycotic aortic dissection. Of 481 records screened, 19 studies met inclusion; the cyst-decompression method was reported in only 7 (37%). Bowel events clustered in series using free intraperitoneal cyst rupture or puncture and were largely absent where decompression was contained, a pattern crossing platform boundaries and that is mechanistically consistent with intraperitoneal spillage of cyst contents. Conclusions: HAL native nephrectomy is a rapid and feasible means of removing massively enlarged polycystic kidneys before transplantation but, in our experience, carries a bowel-predominant morbidity that clustered in right-sided procedures and was independent of specimen weight. The sparse literature is consistent with—but cannot confirm—a relationship to intraperitoneal cyst spillage rather than to the hand-assisted approach itself. Whether contained cyst decompression can preserve operative efficiency while reducing bowel morbidity is a hypothesis warranting prospective study. Full article

Acute myeloid leukemia (AML) develops within a bone marrow environment that influences leukemic stem cell behavior, residual disease, and response to therapy. This review examines evidence that the marrow microenvironment is not only a site of leukemic growth, but can actively shape AML initiation, maintenance, and treatment resistance. Clinical observations such as donor cell leukemia after allogeneic transplantation, together with experimental models in which stromal or osteolineage abnormalities induce myeloid disease, suggest that altered niches may contribute to leukemogenesis in selected settings. In established AML, vascular and endosteal compartments provide adhesive, chemokine, inflammatory, and metabolic signals that promote leukemic-cell retention, quiescence, survival, and chemotherapy tolerance. AML cells also remodel the surrounding marrow, suppressing normal hematopoiesis and generating stromal, endothelial, osteoblastic, adipocytic, and immune-cell programs that favor leukemic persistence. These interactions are especially relevant to drug resistance, including resistance to venetoclax-based therapy, where cytokine-mediated changes in apoptotic dependence, fatty-acid metabolism, mitochondrial adaptation, and stromal support may all contribute. Several therapeutic approaches have attempted to disrupt niche-mediated protection, including targeting CXCL12/CXCR4 signaling, adhesion pathways, inflammatory circuits, Hedgehog signaling, and metabolic dependencies. Although early-phase studies have shown activity in some AML subsets, randomized evidence remains limited and results have been inconsistent. We discuss how a better understanding of microenvironmental biology may help define when niche-directed therapy is most likely to complement conventional and molecularly targeted AML treatment. Full article

Background: Psychosocial assessment is an important component of lung transplant evaluation. Substance-related concerns may coexist with broader psychosocial vulnerabilities, but this relationship is difficult to evaluate when substance-use indicators and psychosocial scores contain overlapping information. We aimed to characterize psychosocial risk in lung transplant candidates and examine whether alcohol-, nicotine-, and illicit drug-related concerns were associated with psychosocial burden outside the SIPAT substance-use domain. Methods: We retrospectively analyzed 491 adult lung transplant candidates admitted for their first inpatient evaluation at the University Clinical Center in Gdańsk, Poland, between December 2021 and November 2025. All patients underwent routine psychosocial consultation, including the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT), completed using a locally developed Polish translation. To avoid conceptual and statistical overlap with substance-related indicators derived from Domain D, we calculated a non-substance psychosocial score as the sum of Domains A, B, and C. Three logistic regression models adjusted for age and sex examined associations with alcohol-, nicotine-, and illicit drug-related concerns. Holm correction was applied across the three primary tests. Results: The mean age was 57.2 years (SD = 10.7), and 40.5% of participants were women. Most candidates were classified as excellent or good (89.4%). Alcohol-, nicotine-, and illicit drug-related concerns were documented in 39.5%, 43.8%, and 13.4% of candidates, respectively. In complete-case models (N = 489), each five-point increase in the non-substance psychosocial score was associated with higher odds of alcohol-related concerns (OR = 1.26, 95% CI 1.07–1.48, p = 0.006; Holm-adjusted p = 0.017) and nicotine-related concerns (OR = 1.22, 95% CI 1.04–1.43, p = 0.014; Holm-adjusted p = 0.028). No significant association was observed for illicit drug-related concerns (OR = 0.81, 95% CI 0.62–1.02, p = 0.090). Male sex was associated with alcohol-related concerns (OR = 2.16, 95% CI 1.47–3.19, p < 0.001). Conclusions: Alcohol- and nicotine-related concerns were associated with broader psychosocial burden extending beyond the SIPAT substance-use domain. These findings suggest that substance-related concerns may coexist with difficulties in readiness, social support, or psychological functioning rather than representing isolated behavioral findings. Because this study was cross-sectional and used a non-validated local translation, the results should not be interpreted as evidence of psychometric or predictive validity. Full article