Background/Objectives: Advanced gastric cancer usually has an unfavorable prognosis. Stroma AReactive Invasion Front Area (SARIFA) is a newly recognized biomarker of aggressiveness, easily recognized as five tumor cells in direct contact with adipocytes in perigastric, submucosal, and perivascular adipose tissue. We investigated this phenomenon and correlated it with other pathohistological variables. Material and Methods: The sample includes 102 Croatian patients with locally advanced gastric cancer, who underwent total gastrectomy/lymphadenectomy between 2012–2018 and in 2023 at University Hospital Split, Croatia, and had pathological stage pT3 or pT4. Representative histological specimens were analyzed for SARIFA, and results were compared with other variables and overall survival. External validation and gene expression analysis of CD36 and FABP4 were performed using the TCGA-STAD cohort. Results: SARIFA was significantly associated with positive pN status (p = 0.009) and perineural invasion (p = 0.043). Patients with SARIFA had a more than fivefold increased risk of nodal involvement (OR = 6.35; 95% CI: 1.35–29.84; p = 0.019). Lymphovascular invasion (LVI) was associated with nodal disease (OR = 4.39; 95% CI: 1.194–16.143; p = 0.026), and SARIFA was marginally associated (OR = 4.886; 95% CI: 0.985–24.241; p = 0.052). Patients who had both LVI and SARIFA had a higher proportion of affected lymph nodes (p = 0.009). SARIFA status did not significantly affect overall survival. Gene expression analysis showed a significant increase in CD36 expression, while FABP4 expression was elevated but not statistically significant, in SARIFA-positive cases. Conclusions: SARIFA could be used as a marker for invasiveness and further investigated due to its predictive potential.

Background/Objectives: Clear cell renal cell carcinoma (ccRCC) is characterized by dysregulated apoptotic and inflammatory signaling, yet the tissue-level behavior of several candidate regulators remains poorly defined. Materials and Methods: We quantified ectodysplasin A2 receptor (EDA2R), TNF-receptor-associated factor 7 (TRAF7) and the apoptotic fragments cleaved-PARP1 and cleaved-CASP3 by immunofluorescence in 49 ccRCC and 27 matched non-tumoral cortex samples and analyzed the corresponding transcripts in TCGA-KIRC and GTEx. Results: TRAF7 protein was higher in tumor than in control tissue (median 0.81% vs. 0.63% positive area, p = 0.015), an increase concentrated in grade 2–3 tumors, whereas EDA2R and the apoptotic fragments did not differ (all p > 0.59). The positive EDA2R–cleaved-PARP1 correlation in low-grade tumors (ρ = +0.54, p = 0.002) was attenuated in high-grade tumors (ρ = +0.06, p = 0.84). In TCGA-KIRC, EDA2R mRNA was overexpressed in tumors, and higher expression was associated with better overall survival (HR = 0.60, p = 0.0011), including after mutual adjustment for the four transcripts (HR = 0.66, p = 5.3 × 10⁻⁵) and after adjustment for age, sex, stage and grade (HR per standard deviation = 0.83, p = 0.008). TRAF7 mRNA did not differ between tumor and normal tissue, but higher levels were associated with worse overall survival after the same adjustment (HR = 1.38, p < 0.001). Conclusions: TRAF7 and EDA2R show opposite, marker-specific discordance between protein- and transcript-level data across cohorts, consistent with, but not demonstrating, regulation beyond transcription. EDA2R is a candidate transcript-level prognostic marker requiring validation, and TRAF7 is a protein-level feature of ccRCC; paired RNA–protein and functional studies are needed.

Background/Objectives: Hip fractures are associated with high short-term mortality in older adults. This study aimed to determine 30-day mortality after hip fracture surgery and evaluate factors associated with short-term mortality, with particular attention to baseline comorbidity indices and in-hospital adverse events. Methods: This retrospective cohort study included 785 patients who underwent surgery for hip fracture at University Hospital of Split, Croatia, between January 2021 and December 2022. Clinical data were extracted from medical records. The primary outcome was 30-day mortality, including in-hospital and post-discharge deaths. Associations with mortality were examined using univariable and multivariable logistic regression. Baseline-only comorbidity models were constructed using the American Society of Anesthesiologists Physical Status Classification System (ASA PS Classification), the Charlson Comorbidity Index (CCI), and the Elixhauser Comorbidity Index (ECI). Exploratory hospital-course models additionally included in-hospital adverse events, which were interpreted as time-dependent hospital-course events rather than baseline predictors. Results: 30-day mortality was 11.0% (86/785). Older age, male sex, higher comorbidity burden, and in-hospital adverse events were associated with mortality. Mortality was 5.7% without documented adverse events, 24.2% with one adverse event, and 42.4% with two or more adverse events. Baseline-only comorbidity models showed acceptable and broadly comparable discrimination, with AUCs of 0.73–0.77. Exploratory hospital-course models showed higher discrimination, with AUCs of 0.80–0.82. Conclusions: 30-day mortality after hip fracture surgery was associated with baseline patient vulnerability and in-hospital adverse events. Baseline-only models based on the ASA PS Classification, the CCI, and the ECI provided broadly comparable short-term risk stratification. In-hospital adverse events should be viewed as markers of an adverse clinical trajectory, not evidence of causality.

Background and Objectives: FOXP3+ (Forkhead box P3) regulatory T cells contribute to immune tolerance after kidney transplantation, but their role in T cell-mediated rejection (TCMR) remains controversial. This study investigated the association between intragraft FOXP3+ cells and the recently introduced Banff-derived activity (AI) and chronicity index (CI) in biopsy-proven TCMR. Materials and Methods: This retrospective cross-sectional study included 119 kidney allograft biopsies diagnosed as acute or chronic active TCMR according to the Banff classification. FOXP3+ cells were assessed by immunohistochemistry and expressed as cortical cell density (cells/mm²). Associations between FOXP3+ cell density, Banff-derived indices, inflammatory cell densities, and clinical parameters were analyzed using non-parametric statistical methods. Results: FOXP3+ cells were detected in 17.6% of biopsies. FOXP3+ cell density was univariately associated with higher CI values (ρ = 0.228, p = 0.013) and chronic lesions interstitial fibrosis (ci) (ρ = 0.284, p = 0.002) and tubular atrophy (ct) (ρ = 0.246, p = 0.008). No association was observed with AI or activity lesions, except for a weak negative correlation with interstitial inflammation (i) (ρ = −0.209, p = 0.025). In multivariable analysis, FOXP3 positivity was not significantly associated with CI after adjustment for transplantation–biopsy interval (B = 0.568, 95% CI −0.741–1.876, p = 0.391). FOXP3+ cell density positively correlated with cluster of diferentiation (CD)4+ (ρ = 0.350, p < 0.001), CD8+ (ρ = 0.229, p = 0.018), and CD163+ (ρ = 0.207, p = 0.047) cell densities. No association with short-term graft outcome was observed. Conclusions: FOXP3+ cell infiltration was associated with chronic histological changes in unadjusted analyses, but this association did not remain statistically significant after adjustment for transplantation-to-biopsy interval. These preliminary findings suggest that FOXP3+ cell accumulation and chronic histological changes may represent parallel time-dependent phenomena and require confirmation in larger cohorts.

Background/Objectives: Patients with local/locally advanced gastric cancer (GC) undergo gastrectomy/lymphadenectomy, but recurrences are common and the disease usually progresses to death. Tertiary lymphoid structures (TLS) of varying maturity can be observed in the immune microenvironment of the primary tumor. The aim of the study was to analyze the association of TLSs and their immune cellular composition with clinicopathological variables and overall survival (OS). Methods: In a cohort of 92 GC patients who underwent gastrectomy, the characteristics of tumor core TLSs were assessed and the density of cytotoxic CD8⁺ T cells and regulatory FOXP3⁺ T cells was analyzed. Results: Patients with TLS had a better OS than patients without TLS, 19.4 months vs. 9.2 months (p = 0.001). Immature TLSs were more frequently associated with lymphovascular invasion and regional lymph node metastasis (p = 0.014 and p = 0.034). Mature TLSs had a higher FOXP3⁺ T lymphocyte density and lower CD8⁺/FOXP3⁺ ratio than immature TLSs (p = 0.029 and p = 0.013), and patients had a longer OS than patients with immature TLSs, 34.55 months vs. 15.2 months (p = 0.033). In patients with TLS-positive GC, cases with FOXP3⁺ T cells had a shorter OS, 12.7 months vs. 47.5 months (p < 0.001). Conclusions: The presence of FOXP3⁺ cells in TLS is associated with significantly shorter OS of patients with local/locally advanced GC.

Background/Objectives: Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal cancer, characterized by frequent metastasis and poor prognosis. Epithelial–mesenchymal transition (EMT) plays a pivotal role in tumor progression. Protocadherin 9 (PCDH9) has emerged as a potential tumor suppressor, but its relationship with EMT markers in ccRCC remains unclear. This study aimed to investigate the expression patterns and prognostic significance of PCDH9, β-catenin (CTNNB1), Snail (SNAI1), and Vimentin (VIM) in ccRCC. Methods: Immunofluorescence analysis was performed on formalin-fixed paraffin-embedded tissue sections from 48 ccRCC patients (31 low-grade, 17 high-grade) and adjacent normal renal cortex. Findings were validated using The Cancer Genome Atlas (TCGA-KIRC) dataset via GEPIA2/GEPIA3 platforms, including differential expression, correlation, and survival analyses. Results:PCDH9 mRNA was significantly downregulated in ccRCC tumors (TCGA-KIRC), while VIM was upregulated at the transcriptomic level. Tissue-level immunofluorescence quantification revealed discordant patterns, highlighting the influence of cellular heterogeneity on bulk protein assessment. The strong positive correlation between PCDH9 and CDH1 observed in normal kidney was completely lost in tumor tissue. Unexpectedly, PCDH9 showed positive correlations with EMT transcription factors (ZEB1, SNAI1) in tumors. In univariate survival analysis, high PCDH9 and CTNNB1 expression were associated with improved overall survival. Multivariate Cox regression revealed endpoint-specific prognostic signatures: VIM independently predicted disease progression, while SNAI1 predicted overall mortality. CTNNB1 was consistently protective across both endpoints. Conclusions: Our findings support a tumor-suppressive role for PCDH9 in ccRCC and reveal disruption of epithelial adhesion molecule co-regulation during tumorigenesis. The identification of endpoint-specific prognostic signatures has implications for patient stratification and suggests that ccRCC exhibits a partial EMT phenotype rather than classical EMT.