Pathophysiology

Background and aims: This study aimed to determine whether neuromuscular electrical stimulation (NMES) combined with nutritional counseling promotes an increase in thigh muscle thickness (MT), as well as to assess changes in the relationship between MT and intracellular water (ICW). Body composition methods such as ultrasound may overestimate muscle mass, depending on the context, because they cannot distinguish the contractile protein component from body fluids, including intra- and extracellular water. Methods: A pilot randomized parallel trial was conducted with 25 hospitalized patients with unselected cancer, who were divided into two groups: NMES + Diet and Diet. Both groups received nutritional counseling, but only one group received NMES. NMES was applied bilaterally to the origin and insertion points of the quadriceps twice daily, with a 3 h interval between sessions, for 7 consecutive days. MT and ICW were measured before and after the intervention. Food consumption was assessed using a 24 h dietary recall at baseline and at the end of the study to quantify and adjust macronutrient intake during the intervention. Results: Both treatment groups (Diet × NMES + Diet) showed similar dropout rates which means participants in the more intensive treatment did not quit more frequently, once intervention with NMES was feasible and well tolerated. In addition, both groups showed a reduction in carbohydrate intake (p = 0.012) and an increase in leucine intake (p < 0.001) post-intervention. The increase in leucine intake was significantly greater in the NMES + Diet group (p < 0.001), and the reduction in carbohydrate intake was also greater in this group (p = 0.012). In the delta analysis, the NMES + Diet group showed an increase in thigh MT, whereas the Diet group experienced a decrease (Diet group: ∆ = −2.53 ± 3.73 mm vs. NMES + Diet group: ∆ = 2.09 ± 2.27 mm, p = 0.001). Moreover, the MT/ICW ratio was higher in the NMES + Diet group post-intervention (Diet group: ∆ = −0.15 ± 0.19 mm/L vs. NMES + Diet group: ∆ = 0.11 ± 0.09 mm/L, p < 0.001), while no significant difference in ICW was observed between groups. Conclusions: short-term intervention combining nutritional counseling with NMES increased thigh MT and the MT/ICW ratio, possibly due to NMES-induced extracellular water expansion. Full article

Objectives: This study investigates the effects of resveratrol on systemic inflammatory, oxidative, and metabolic responses in a rat model that combines surgical trauma with prior exposure to Single Prolonged Stress (SPS), an established experimental protocol for modeling post-traumatic stress disorder (PTSD). Methods: Male Wistar rats (n = 21) were randomly assigned to three groups: (I) control (polyvinylpyrrolidone, PVP), (II) SPS + laparotomy + PVP), and (III) SPS + laparotomy + resveratrol. Resveratrol (5 mg/kg of body weight/day) or vehicle was administered intragastrically for seven days. Serum concentrations of cortisol, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), glucose, insulin, lipid fractions, and thiobarbituric acid–reactive substances (TBA-RS) were determined by enzyme-linked immunosorbent assay and spectrophotometric methods. Insulin resistance was assessed using the homeostatic model assessment of insulin resistance (HOMA-IR) index. Results: Combined SPS and surgical trauma induced a pronounced systemic inflammatory response characterized by elevated cortisol (+138%), TNF-α (+83%), IL-6 (+465%), and ceruloplasmin (+71%), as well as hyperglycemia, hyperinsulinemia, increased HOMA-IR, and atherogenic dyslipidemia with reduced high-density lipoprotein cholesterol (HDL-CH; −64%), elevated triglycerides (TGs; +216%), and very low-density lipoprotein cholesterol (VLDL-CH; +218%). Marked activation of lipid peroxidation was observed, as indicated by increased TBA-RS levels before and after incubation. Resveratrol administration significantly decreased cortisol (−45%), TNF-α (−47%), and IL-6 (−85%), normalized the IL-10/IL-6 ratio, and reduced ceruloplasmin levels (−13%). The compound improved insulin sensitivity (HOMA-IR −50%), elevated HDL-CH (+115%), and lowered TGs and VLDL-CH (−44%). It also attenuated both basal and inducible lipid peroxidation (TBA-RS −11% and −13%), indicating restoration of antioxidant capacity. Conclusions: Thus, resveratrol effectively counteracts the neuroendocrine, inflammatory, and metabolic disturbances induced by combined PTSD-like stress and surgical trauma. Full article

Background: Vascular calcification is a strong predictor of cardiovascular morbidity and mortality. Oxidative stress plays a key role in promoting vascular calcification. Glutathione (GSH), as a major cellular antioxidant, is produced in response to oxidative stress and is regulated by the enzyme glutamate-cysteine ligase (GCL). In this study, we examined the role of the GCL modifier subunit (GCLm) in regulating vascular smooth muscle cell (VSMC) calcification. Methods: Human coronary artery VSMCs were exposed to phosphate-rich media to induce calcification. Results: Calcification led to a decrease in the GSH:GSSG ratio (reduced glutathione to oxidized glutathione), and elevated GCLm expression, coincident with mobilization of osteogenic genes and loss of contractile phenotype. KEGG pathway analysis of human unstable atherosclerotic plaques similarly showed increased GCLm expression and activation of reactive oxygen species (ROS)-related pathways. Notably, forced overexpression of GCLm in murine VSMCs (MOVAS cells) significantly accelerated calcification. These findings implicate GCLm upregulation in promoting VSMC calcification, potentially by disrupting redox homeostasis and driving phenotypic switching. Further mechanistic studies are warranted to evaluate GCLm as a potential therapeutic target in vascular calcification. Full article

Introduction: The prognosis for patients admitted to emergency departments (ED) after drowning or diving accidents is often uncertain. In this study, we evaluated a range of clinical and laboratory parameters as potential indicators of survival. Many of these markers have previously been investigated in the context of survival prediction in both trauma-related and non-trauma-related clinical scenarios. Methods: We conducted a retrospective analysis of 25 patients aged >17 years who were admitted to the ED of the University Hospital Leipzig after drowning or diving accidents between 2012 and 2024. Clinical and laboratory parameters were compared between survivors and non-survivors, with survival defined as discharge from the hospital. Results: Of all cases analyzed—comprising 19 drowning and six diving incidents—10 patients (40%) survived, while 15 (60%) did not. Age, sex, or etiology of the accident were not statistically associated with survival. Compared to survivors, non-survivors were significantly more likely to have received prehospital cardiopulmonary resuscitation (CPR; 20% vs. 86.7%) and to have exhibited lower Glasgow Coma Scale scores and lower pH values (7.4 vs. 6.7). They were also more likely to have shown increased levels of lactate (4.3 mmol/L vs. 14.8 mmol/L), CK-MB quotient (9.7% vs. 51.8%), myoglobin (188.9 µg/L vs. 1930.9 µg/L), and blood glucose (6.6 mmol/L vs. 14.3 mmol/L). Conclusions: The need for CPR appears to be the most significant risk factor for not surviving a drowning or diving accident. Furthermore, certain laboratory parameters, such as pH and lactate, may provide supportive information regarding the severity of hypoxia and could be cautiously considered as indicators of survival likelihood in these patients. Our findings offer a rationale for future prospective studies, aiming to incorporate additional clinical and biochemical markers and potentially develop new prognostic scoring systems for patients following drowning or diving accidents. This study examines the association between clinical and laboratory parameters and survival in patients following drowning and diving accidents. A total of 25 cases from 2012 to 2024 were retrospectively analyzed. The results showed that patients who required CPR had significantly poorer outcomes. Certain laboratory markers; such as pH and lactate levels; were closely related to survival status in this patient group. Full article

Objectives: Serum ferritin (SF) reflects iron homeostasis, in addition to being an acute phase reactant protein. Since its levels are altered in the obesity state, we compared body composition, metabolic profile, liver alterations, and dietary patterns in adults stratified by SF levels (normal vs. high). Methods: A cross-sectional study was conducted using secondary data from 113 adults (≥18 years) of both sexes, attended at an outpatient nutrition clinic in southern Brazil and categorized for normal or high SF. Socioeconomic, anthropometric, blood pressure, dietary, biochemical, and liver parameters were assessed and statistical analyses performed. Results: Participants with high SF were more frequently male (p < 0.0001), married or in a civil union (p = 0.012), and had lower educational levels (p = 0.009). Moreover, higher rates of obesity (p = 0.003), cardiovascular risk (p = 0.004), increased body fat percentage (BF%; p = 0.002) and metabolic disturbances such as elevated glucose (p = 0.023), triglycerides (p = 0.003), insulin resistance (p = 0.027), hypertension (p = 0.001), and metabolic syndrome (MS) (p = 0.001) were noted in this group. Liver-related findings comprised increased ALT (p = 0.008), uric acid (p = 0.016), and indicators of steatosis (p = 0.022). Logistic regression demonstrated a higher likelihood of elevated SF among men (OR = 16.82) and individuals with increased BF% (OR = 7.5), without significant influence of diet. Conclusions: Adults with elevated SF were predominantly obese men with excess adiposity, insulin resistance, and metabolic and hepatic dysfunctions, conditions that increase the risk of MS and liver injury. These findings suggest that SF and other iron biomarkers may serve as valuable tools for diagnosing metabolic dysfunctions and obesity-related liver diseases, particularly Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Full article

Objectives: Breast cancer survivors often experience long-term neurological complications, including balance impairments, following treatment. This study aimed to investigate microstructural changes in white matter tracts in breast cancer survivors with balance impairment using diffusion tensor tractography. Methods: An open, single-center, prospective study was conducted including two groups—healthy age-matched volunteers (n = 28) and breast cancer survivors (n = 35) with balance impairment. All participants underwent diffusion tensor tractography at baseline and at the end of the follow-up period of six months. Quantitative anisotropy was analyzed using DSI Studio to assess white matter integrity. Results: At baseline, patients with balance impairment exhibited significantly reduced quantitative anisotropy values in the middle cerebellar peduncles (p = 0.046) and cerebellar hemispheres (p = 0.024, 0.055) compared to healthy controls. At the end of the follow-up, quantitative anisotropy values were increased across most tracts, though some differences persisted between groups (p < 0.001). Conclusions: Breast cancer survivors with balance impairment demonstrate sustained microstructural white matter changes, particularly in cerebellar and vestibular pathways. These findings suggest that diffusion tensor tractography can provide valuable insights into central nervous system alterations contributing to post-treatment balance dysfunction and may serve as a potential tool for early diagnosis and rehabilitation planning. Full article

Background: Spontaneous bacterial peritonitis (SBP) is a serious complication in patients with decompensated cirrhosis and ascites. Diagnosis typically relies on an ascitic polymorphonuclear (A-PMN) cell count ≥ 250 cells/high-power field (HPF). Methods: In this retrospective cohort study, 117 hospitalized patients with acute decompensation of chronic liver disease and a diagnostic paracentesis were evaluated. Clinical, laboratory, and imaging data were collected. Patients were stratified by A-PMN counts of ≤50, 51–249, or ≥250 cells/HPF. Additional analysis was performed with patients stratified by ascitic white blood cell (WBC) count and albumin. Mortality risk was assessed at 28, 90, and 365 days. Results: Patients with A-PMN ≤ 50 cells/HPF had the lowest 28-day mortality (8%). At 90 and 365 days, mortality risk was significantly higher for the A-PMN 51–249 cells/HPF group (90-day hazard ratio (HR) 3.55, p = 0.01; 365-day HR 2.43, p = 0.02), but not A-PMN ≥ 250 cells/HPF group (90-day HR 2.95, p = 0.1; 365-day HR 2.95, p = 0.2). Ascitic WBC count did not significantly predict mortality, though higher counts were associated with extraperitoneal infections. Ascitic fluid albumin ≤ 1.0 g/dL was independently associated with increased 365-day mortality (HR 3.53, p = 0.03). Conclusions: Binary SBP A-PMN thresholds may not adequately capture mortality risk in cirrhotic patients with ascites. Low ascitic albumin and intermediate A-PMN counts are associated with increased long-term mortality, suggesting the need for more nuanced diagnostic and prognostic criteria in SBP evaluation. Full article

Systemic lupus erythematosus is a multifactorial autoimmune disease characterized by the dysregulation of both innate and adaptive immunity, resulting in chronic inflammation, autoantibody production, and multi-organ damage. Innate immune dysfunction involves macrophages, neutrophils, plasmacytoid dendritic cells, natural killer cells, and the complement system, which collectively amplify autoimmunity through defective clearance of apoptotic cells, overproduction of pro-inflammatory cytokines, and abnormal type I interferon signaling. Adaptive immune abnormalities, including skewed T-cell subsets, impaired regulatory T and B cells, and autoreactive B-cell hyperactivity, further perpetuate pathogenic autoantibody generation. Gut microbiota dysbiosis contributes to SLE pathogenesis via Th17 activation, loss of mucosal tolerance, and molecular mimicry mechanisms. This review synthesizes current knowledge on the immunopathogenesis of SLE, emphasizing the interplay between innate and adaptive immunity and integrating evidence from both human and experimental murine models to provide a comprehensive understanding of disease mechanisms. Full article

Background: Thromboembolic events, though infrequent, remain a significant complication of atrial fibrillation (AF) ablation, largely related to endothelial damage. Cryoballoon (CB) and radiofrequency ablation can induce pro-coagulant responses, whereas pulsed-field ablation (PFA), a novel non-thermal electroporation-based technique, has shown tissue selectivity with potential endothelial-sparing effects. Methods: We aimed to compare PFA and second-generation CB ablation regarding endothelial injury in patients with paroxysmal AF. In this single-center prospective observational study, 25 patients with paroxysmal drug-refractory AF underwent pulmonary vein isolation using either a pentaspline PFA catheter (n = 14) or a second-generation CB catheter (n = 11). Circulating von Willebrand factor antigen (vWF) levels were assessed before and after ablation as a biomarker of endothelial damage, alongside routine laboratory and echocardiographic parameters. Procedural characteristics were also analyzed. Results: Baseline demographic, clinical, and echocardiographic data were comparable between groups. PFA was associated with significantly shorter skin-to-skin procedure time (59 vs. 94 min, p = 0.005) and left atrial dwell time (44 vs. 79 min, p < 0.001) compared with CB ablation. Importantly, vWF levels decreased significantly after PFA (−7.6%, p = 0.007), while CB ablation showed a non-significant increase (+9.5%, p = 0.155). The between-group difference in percent change of vWF was statistically significant (−5.6% vs. +8.3%, p = 0.006). Conclusions: PFA was associated with reduced endothelial injury and shorter procedural times compared with CB ablation, suggesting a potential advantage in lowering thromboembolic risk. These findings support the concept of PFA as an “endothelial sparing” ablation modality. However, the PFA procedure was associated with a significantly greater extent of myocardial injury, as reflected in circulating high-sensitivity cardiac troponin T values, compared to CB ablation (p = 0.007). Larger, randomized studies are warranted to confirm these results and evaluate long-term clinical outcomes. Full article

Background/Objectives: Extremity trauma represents a significant proportion of battlefield injuries and is prevalent in polytraumatized patients from accidents. Delayed antibiotic treatment and surgical intervention can lead to wound infections, contributing to preventable mortality. This preliminary study aimed to develop a conscious swine model of complex extremity trauma that induces systemic inflammatory response syndrome (SIRS). Methods: All surgical procedures were conducted under anesthesia with sufficient analgesia. All swine were instrumented with a telemetry device and catheters at least 3 days prior to any injury. In phase 1 of model development, a complex extremity injury was performed that consisted of skin and muscle loss, bone defect, severe hemorrhage, and 2 h tourniquet application. In phase 2, multi-drug resistant Gram-positive and Gram-negative bacteria were inoculated topically at the injury site to exacerbate pathophysiological changes towards SIRS. Post-injury, conscious animals were assessed a minimum of twice daily, including pain assessment, neurological response, and vital signs. Blood samples were collected for microbiological testing, complete blood cell counts, and biochemical analysis. Results: After establishing SIRS criteria for Sinclair swine, we developed a model of severe extremity trauma leading to SIRS. During phase 1, resuscitative fluids were reduced and discontinued, with animals surviving 24 h and maintaining SIRS for up to 4 h post-recovery. Phase 2 showed that Gram-negative and Gram-positive pathogens can exacerbate and prolong SIRS. After 72 h, localized infection at the injury site was observed in all animals. Conclusions: We established a new swine model of complex extremity trauma with SIRS. Our model is consistent, reproducible, and relevant to prolonged care scenarios, providing a platform for future research into the evaluation of preventative and therapeutic strategies. Full article

Background: To address limitations in static cold storage (SCS) of donor hearts, we developed the High-Pressure Gaseous Perfusion without Fluidic Preservation Media (HIPPER) method, along with the necessary equipment for its application. Methods: 33 Wistar rat hearts were split into five groups: (Control) static cold storage (SCS) in HTK solution, (Exp) HIPPER using oxygen–xenon gas mixtures of varying ratios (“Gas-A”: 1/9, “Gas-B”: 9/1, and “Gas-C”: 1/1), and (Air) HIPPER using air. Hearts were preserved for six hours, followed by a one-hour Langendorff assessment. Results: Beating was restored in 4/10 Control hearts, 15/15 Exp hearts across all gas mixtures (p = 0.001 Control vs. Exp), and 6/8 Air hearts. Among resuscitated hearts, the mean heart rates (in bpm) were 131 ± 10 (Control), 164 ± 21 (Air), and 226 ± 13 (Exp) (p = 0.001 Control vs. Exp; p = 0.015 Exp vs. Air). The mean left ventricular pressures (in mmHg) were 31 ± 5 (Control), 45 ± 9 (Air), and 73 ± 7 (Exp) (p = 0.002 Control vs. Exp; p = 0.014 Exp vs. Air), with dP/dT max/min showing consistent trends (p < 0.006 Control vs. Exp and Air vs. Exp). Infarct size in Exp group was also significantly reduced, averaging 39.6 ± 6.6% (Control), 12.6 ± 3.3% (Air), and 6.3 ± 0.7% (Exp) of total myocardium area (p < 0.014 for Control vs. all). Conclusions: as evidenced by both quantitative and qualitative data, HIPPER consistently outperformed SCS following six hours of storage of rat heart regardless of the gas mixture, highlighting its potential as a more robust preservation method. Full article

Background/Objectives: Systemic sclerosis (SSc) is a heterogeneous connective tissue disease characterized by immune dysregulation, vasculopathy, and fibrosis. Objectives: To evaluate the genetic architecture and autoantibody profile in a Kazakh cohort of patients with SSc. Methods: A total of 26 Kazakh patients with diffuse SSc were examined for disease activity and organ impairment using EScSG and the modified Rodnan skin score (mRSS). Eighteen healthy volunteers were enrolled in the control group. Antinuclear factor (ANF) was estimated on HEp-2 cells, while antibodies to Scl-70, CENP-B, U1-snRNP, SS-A/Ro52, SS-A/Ro60, Sm/RNP, Sm, SS-B, Rib-P0, and nucleosomes were determined by immunoblotting. The level of IL-6 cytokine was detected using ELISA. To investigate the genetic basis of SSc in Kazakh patients, a custom AmpliSeq panel including targeting immune/fibrosis pathways and 120 genes was used on the Ion Proton sequencer. The statistical analysis of categorical variables was conducted using Fisher’s exact test and Chi-square (χ²) test. Results: The examination of SSc patients (mRSS 16 ± 7.2; EScSG 3.54 ± 2.18) revealed a broad range of antibodies to Scl-70, CENP-B, SS-A/Ro60, SS-A/Ro52, U1-snRNP, and RNP/Sm, which were undetectable in the control group. Genetic analysis identified multiple variants across immune regulatory genes, including likely pathogenic changes in SAMD9L, REL, IL6ST, TNFAIP3, ITGA2, ABCC2, AIRE, IL6R, AFF3, and TREX1. Variants of uncertain clinical significance were detected in LY96, IRAK1, RBPJ, IL6ST, ITGA2, AIRE, IL6R, JAZF1, IKZF3, IL18, IL12B, PRKCQ, PXK, and DNASE1L3. Novel variants at the following genomic coordinates were identified and have not been previously reported in association with SSc: LY96 (chr8:74922341 CT/C), PTPN22 (chr1:114381166 CT/C), IRAK1 (indels at chrX:153278833), and SAMD9L (chr7:92761606 GT/G; chr7:92764981 T/TT). Conclusions: The first immunogenetic investigation of SSc in Kazakhstan revealed a polygenic architecture involving immune signalling pathways that partially overlap with international cohorts while exhibiting region-specific variation. Although the limited sample size and lack of functional validation constrain the interpretability of the findings, the results provide a framework for larger research to confirm the pathogenic mechanisms and establish clinical relevance. Full article

Medullary thyroid carcinoma (MTC) is a thyroid tumor with neuroendocrine properties purportedly derived from C-cells. The biochemical activity of medullary thyroid carcinoma includes the production of calcitonin and carcinoembryonic antigen, which are sensitive tumor markers, facilitating diagnosis, follow-up, and prognostication. Calcitonin-negative medullary thyroid carcinoma is a rare, poorly understood primary neuroendocrine carcinoma of the thyroid characterized by classic medullary thyroid carcinoma morphology without raised serum calcitonin and with or without the expression of calcitonin detected by immunohistochemistry. Previous studies reported that C-cells were derived from the neural crest; however, more recently, C-cells have been indisputably shown to be derived from the pharyngeal endoderm and ultimobranchial bodies. Ultimobranchial body (UBB) remnants can persist in the thyroid and express p63, but their function is poorly understood. Some have postulated that ultimobranchial bodies may be the “stem” cell of the thyroid and may be precursors for thyroid tumors, particularly mixed tumors with follicular and medullary components. We present a unique case of calcitonin-negative MTC in a 58-year-old male arising in an inflamed and fibrotic thyroid with numerous scattered ultimobranchial body remnants and concomitant C-cell hyperplasia/medullary microcarcinoma (CCH/MMC). The ultimobranchial body remnants, C-cell hyperplasia, and medullary thyroid carcinoma were MTC classifier positive according to ThyroSeq^®. The areas representing CCH/MMC expressed calcitonin by IHC while the main MTC tumor was negative. An additional unique feature was an area demonstrating a “mixed” C-cell/thyroid follicular epithelial phenotype. In this review we review the possible etiologies of calcitonin-negative MTC, the possibility of a neoplastic sequential progression from ultimobranchial bodies to CCH/MMC to medullary thyroid carcinoma with the individual elements (UBB, CCH/MMC, MTC) demonstrated in this thyroid, and previous postulations that ultimobranchial bodies may be the source of some follicular thyroid cancers, medullary thyroid cancers, and mixed tumors of medullary and follicular epithelial types. Full article

Objectives: To evaluate the diagnostic and prognostic value of histophenotyping of the extracellular matrix of the cervical stroma at cervical intraepithelial neoplasia (CIN). Methods: Retrospective analysis of 160 biopsies and surgical preparations of the cervix in women of reproductive age included cases of CIN 1–3 and the group with confirmed persistence or lesion progression (CIN P) at repeated biopsy. The control group (n = 40) consisted of morphologically intact cervical tissue. Histophenotypes were evaluated by staining with hematoxylin, eosin, and Masson trichrome, and classified as follows: normal (dense parallel bundles of type I collagen), intermediate (disorganized and fragmented type I collagen fibers), and myxoid (amorphous weakly fibrillar matrix). The clinical, viral, and inflammatory characteristics between histophenotypes were statistically compared. Results: The distribution of histophenotypes of the extracellular matrix of the cervix varied significantly depending on the CIN degree (p < 0.001). In the control group, the normal pattern was detected in 97.5% of cases; its frequency decreased from CIN 1 (27.5%) to CIN 2 (12.5%) and was absent at CIN 3. The frequency of the myxoid pattern increased significantly in severe and persistent forms: 55% at CIN 3 and 62.5% at CIN P. Human papillomavirus 16/18 was most frequently detected in groups with intermediate (69.1%) and myxoid (27.2%) patterns. Inflammatory changes were more often accompanied by disorganized extracellular matrix; however, intermediate and myxoid types also occurred in the absence of inflammation. Conclusions: The myxoid histophenotype of the extracellular matrix is significantly associated with the high degree of dysplasia and CIN persistence. It can reflect the morphological equivalent of tumor-associated stroma remodeling. Histophenotyping of the extracellular matrix of the cervix appears to be a promising method of risk stratification and may complement existing diagnostic algorithms for CIN. Full article

Background/Objectives: Testicular germ cell tumours (GCT) have high cure rates, especially in early stages. MicroRNA-371a-3p (M371) has recently emerged as a highly sensitive biomarker for malignant GCTs, except teratoma. This study aimed to evaluate the diagnostic performance of M371-test in a real-life clinical setting, compared to conventional markers alpha-fetoprotein (AFP), lactate-dehydrogenase (LDH), and beta-human chorionic gonadotropin (β-HCG) in patients with suspected GCT. Methods: The study, approved by the Ethic-Committee of the Provincial Hospital of Bolzano (N.97-2021), included 91 M371-tests, performed from March 2021 to May 2025. A total of 75 patients had suspected GCT; 19 healthy males served as control. Serum levels of M371, AFP, LDH, and β-HCG were compared with final histopathological diagnosis. M371 was also assessed in controls to evaluate test performance. Secondary analyses investigated correlations between preoperative M371 levels and tumour size in non-metastatic patients, and between M371-levels and clinical stage in the entire GCT cohort. A cut-off of RQ > 5 (relative quantification) was used to calculate sensitivity, specificity, and predictive values. Results: M371 showed a sensitivity of 90.9% and specificity of 89.3%, outperforming in terms of sensitivity AFP (20.4%/96.4%), LDH (40.9%/96.4%), and β-HCG (43.1%/100%). Positive predictive value (PPV) and negative predictive value (NPV) were 93.0% and 86.2%, respectively. Sensitivity was 95% for non-seminomas and 87.5% for seminomas. In non-metastatic patients, M371 levels correlated with tumour size and were significantly higher in advanced stages (median RQ 1128.35 vs. 98.36; p = 0.015). Conclusions: M371 showed excellent diagnostic performance, even for small tumours, supporting its clinical use. Further studies are needed to define its role in treatment planning and follow-up. Full article

Current standard treatments for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), a urological disorder with anxiety as a major comorbidity, are limited in success rates. Recent findings revealed the anti-inflammatory and neuroprotective effects of CO-releasing molecules (CO-RMs), but there is a gap in the knowledge on its effects in CP/CPPS. Therefore, the objective of our study was to investigate the potential therapeutic effects of CORM-A1 on the scrotal pain threshold and anxiety-related behaviors in experimental model of CP/CPPS. Adult Wistar albino male rats were randomized to Sham (intraprostatic saline) or CP/CPPS (intraprostatic λ-carrageenan) groups (n = 12). Half received CORM-A1 (2 mg/kg/day, i.p., days 1–7), others PBS, forming four subgroups (n = 6). The pain threshold (by an electronic von Frey esthesiometer) and anxiety-like behavior (by an open field, elevated plus maze and light/dark test) were assessed; prostates were histologically examined. Carrageenan-induced CP/CPPS caused significant mechanical pain hypersensitivity (p < 0.001), anxiety-like behaviors (p < 0.001–0.05), and histological prostate damage when compared to corresponding Sham groups. CORM-A1 treatment increased pain thresholds (p < 0.001) and improved behavioral outcomes (p < 0.001–0.01) in all ethological tests. These findings indicate that CORM-A1 exerts analgesic and anxiolytic effects in an experimental model of CP/CPPS in rats. Full article

The morphogenesis of the primordial gut relies on signaling pathways such as Wnt, FGF, Notch, Hedgehog, and Hippo. Reciprocal crosstalk between the endoderm and mesoderm is integrated into the signaling pathways, resulting in craniocaudal patterning. These pathways are also involved in adult intestinal homeostasis including cell proliferation and specification of cell fate. Perturbations in this process can cause growth disturbances manifesting as adenomas, serrated lesions, and cancer. Significant differences have been observed between right and left colon cancers in the hindgut, and between the jejunoileum, appendix, and right colon in the midgut. The question is to what extent the embryology of the mid- and hindgut contributes to differences in the underlying tumor biology. This review examines the precursor lesions and consensus molecular subtypes (CMS) of colorectal cancer (CRC) to highlight the significance of embryology and tumor microenvironment (TME) in CRC. The three main precursor lesions, i.e., adenomas, serrated lesions, and inflammatory bowel disease-associated dysplasia, are linked to the CMS classification, which is based on transcriptomic profiling and clinical features. Both embryologic and micro-environmental underpinnings of the mid- and hindgut contribute to the differences in the tumors arising from them, and they may do so by recapitulating embryonic signaling cascades. This manifests in the range of CRC CMS and histologic cancer subtypes and in tumors that show multidirectional differentiation, the so-called stem cell carcinomas. Emerging evidence shows the limitations of CMS particularly in patients on systemic therapy who develop drug resistance. The focus is thus transitioning from CMS to specific components of the TME. Full article

Background/Objectives: Lichen Planus Pemphigoides (LPP) represents a rare variant of Oral Lichen Planus in which the typical pemphigoid-associated antibodies, BP180 and BP230, are present. The objectives of this Systematic Review are to analyze the data currently available in the literature on this rare condition, with the aim of laying the groundwork for future investigations and research. Methods: This Systematic Review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD420251133018. Subsequently, a search was conducted on PubMed/Medline, Scopus, and Ovid using specific keywords combined with Boolean operators. Articles published up to 2025 were included. The following types of studies were considered eligible: case reports, clinical conferences, clinical studies, clinical trials, controlled clinical trials, letters, multicenter studies, observational studies, randomized controlled trials, and human-based studies. Book chapters, systematic reviews, narrative reviews, in vitro studies, and animal models were excluded. Results: A total of 67 articles were initially identified; following thorough review and exclusion, 20 articles were retained. The patient data extracted from these selected studies were used to construct a table in which patients were categorized according to both qualitative and quantitative variables. The results highlight that LPP is a condition requiring a complex diagnostic process involving both histological examination and serological testing (Immunofluorescence and Enzyme-Linked Immunosorbent Assay—ELISA). Conclusions: Furthermore, with the advent of immunotherapy, an increasingly well-documented new category of drug-induced LPP has emerged, associated with PD-1 and PD-L1 inhibitors. Full article

Background: Obstructive Sleep Apnea Syndrome (OSAS) is a prevalent and underdiagnosed condition with significant systemic and quality-of-life impacts. While polysomnography remains the gold standard for diagnosis, cone-beam computed tomography (CBCT) presents a potential adjunctive imaging tool for anatomical airway evaluation. Objective: We aimed to assess the effectiveness of three-dimensional airway evaluation via CBCT as a complementary diagnostic tool for OSAS. Methods: A diagnostic test study (experimental pilot study) was conducted using CBCT scans of 30 patients, divided into two groups: 15 scans from patients with a confirmed OSAS diagnosis through polysomnography and 15 scans from healthy controls. Five tomographic variables were analyzed: anteroposterior distance, lateral distance, minimum cross-sectional area, airway volume, and airway shape. Statistical analysis was performed comparing both groups. Results: The minimum cross-sectional area and airway volume showed statistically significant differences between the OSAS and control groups (p = 0.038 and p = 0.0055, respectively). Anteroposterior and lateral distances showed trends toward significance but were not statistically significant. Conclusions: CBCT-based airway analysis, particularly focusing on volumetric and cross-sectional area parameters, demonstrates strong potential as a complementary tool in the diagnosis of peripheral-type OSAS. However, it cannot replace polysomnography, especially for central OSAS diagnosis. Full article