Background/Objectives: To evaluate the tolerability and effectiveness of subcutaneous immunotherapy (SCIT) with a glutaraldehyde-polymerized undiluted mixture of grass and olive pollen in adults and children with allergic respiratory disease in routine clinical practice. Methods: Observational, ambispective, controlled multicenter study including patients ≥ 5 years with allergic rhinitis/rhinoconjunctivitis +/− asthma due to olive and grass pollen. Patients initiating SCIT with Olea europaea/grass pollens undiluted mixtures were included in the O&G group, and those continuing symptomatic treatment in the untreated (UT) group. Safety (primary objective) was assessed as the incidence of adverse reactions. Effectiveness variables (symptoms, control, and medication use) were compared during the pollen season before and after AIT; patients and investigators reported perceived satisfaction. Results: We included 218 patients in the O&G group (children, 23.4%; adolescents, 13.8%; adults, 62.8%) with a mean (SD) age of 26.5 (15.6) years, and 94 in the UT group. At the time of evaluation, patients had received treatment for a mean (SD) of 10.6 (2.5) months. Seventeen patients (7.8%) experienced 18 adverse reactions in total, all local (12 in adults, 6 in children; mean overall rate: 0.8%). Rhinitis frequency shifted from predominantly persistent to intermittent (−64.6% in persistent) (p < 0.0001), with significantly improved intensity and control overall and across age groups in the O&G group but not in the UT group. Patients with asthma symptoms decreased by −46.6% (p < 0.0001), along with improved asthma classification, treatment steps, and control overall (O&G group), and across most age groups. Changes in conjunctivitis symptoms followed a similar trend. Symptomatic medication use significantly decreased overall (O&G group) and across specific age groups. Patients and investigators perceived decreased symptoms and medication use after AIT. Conclusions: SCIT with a glutaraldehyde-polymerized undiluted allergen mixture of olive/grass pollen extract demonstrated safety and effectiveness to treat allergic rhinitis and asthma in adults and children in a real-world setting.
Background/Objectives: Functional constipation is common in older adults and impairs quality of life. Evidence for multi-strain orally disintegrating (OD) probiotic formulations in this population remains limited. Methods: In this single-center, open-label, single-arm pre–post study, adults aged 65–90 years meeting the Rome IV criteria for functional constipation were administered an OD tablet containing Bacillus subtilis TO-A, Enterococcus faecium T-110, and Clostridium butyricum TO-A for 8 weeks. The primary endpoint was change in the defecation score based on a modified Bristol Stool Form Scale. Secondary endpoints included stool frequency, straining, JPAC-QOL, the modified Constipation Scoring System, Izumo Scale, Dietary Variety Score (DVS), selected metabolic/nutritional variables, and exploratory gut microbiota analyses. Results: Fifty participants provided consent, and 49 were included in the full analysis set; 45 participants completed the 8-week intervention and were included in the paired primary endpoint analysis. The defecation score showed a nominally significant change toward normalization of stool form at week 8 (IQR: −1.0, 7.0; 95%CI: −9.6, −4.2). Stool frequency did not change significantly, whereas constipation-related quality of life and symptom burden significantly changed. DVS increased modestly, and HbA1c decreased slightly; however, these secondary findings should be interpreted as exploratory because no adjustment for multiplicity was performed. Four patients withdrew from this study: one was due to death, but a causal relationship with the study drug was not confirmed. Two gastrointestinal adverse events could have been related to the study product. Exploratory subgroup analyses suggested a larger change in participants not receiving acid-suppressive therapy. Conclusions: The three-strain OD probiotic tablet was associated with changes in stool form and constipation-related symptom burden in older adults with functional constipation. Because this was a single-arm, open-label study without multiplicity adjustment for secondary endpoints, the findings should be regarded as exploratory and hypothesis-generating. Given the absence of a control group, causal efficacy cannot be inferred, and placebo effects, natural symptom fluctuation, or other time-varying confounders cannot be excluded; therefore, the most robust conclusion is that the preparation appeared safe and well tolerated for over 8 weeks in this population.
Background/Objectives: Leptin is a pleiotropic adipokine linking energy metabolism with innate and adaptive immunity. Its relationship with clinical severity across distinct airway disease phenotypes remains insufficiently characterized. This study examined serum leptin concentrations in adults with allergic rhinitis, non-allergic asthma, and allergic asthma associated with allergic rhinitis. Methods: This single-center retrospective observational study analyzed fully anonymized clinical and laboratory data from 88 adults: patients with allergic rhinitis (n = 31), non-allergic asthma (n = 15), or allergic asthma with allergic rhinitis (n = 22) and healthy controls (n = 20). Serum leptin was measured using a quantitative sandwich enzyme-linked immunosorbent assay. Disease severity was classified using the Allergic Rhinitis and its Impact on Asthma and Global Initiative for Asthma frameworks applicable during the study period. Statistical analyses were performed using IBM SPSS Statistics, version 26.0 (IBM Corp., Armonk, NY, USA), and available original statistical outputs were summarized using retained t statistics and two-sided p values. Results: Stage-specific mean serum leptin concentrations were heterogeneous and non-monotonic. Statistically significant relationships between leptin concentration and disease stage were reported for allergic rhinitis (t = 2.844; p = 0.008), non-allergic asthma (t = 4.240; p = 0.001), and allergic asthma with allergic rhinitis (t = 2.700; p = 0.013). In the allergic rhinitis subgroup, 64.5% of participants had normal weight, 32.3% were overweight, and 3.2% had grade II obesity; weight category was not significantly related to rhinitis stage. Conclusions: The retained analyses indicate statistically significant relationships between serum leptin concentration and clinical disease stage across the investigated airway phenotypes. However, the stage-specific descriptive means were heterogeneous and non-monotonic and therefore do not support a uniform progressive increase in leptin with increasing disease severity. Because complete model outputs and covariate-adjusted estimates were unavailable, these findings should be regarded as exploratory and require prospective validation with appropriate adjustment for adiposity and other relevant metabolic confounders.
Background: Psoriatic arthritis (PsA) is a chronic inflammatory disease frequently associated with obesity and metabolic comorbidities. Increasing evidence suggests that obesity is associated with systemic inflammation, insulin resistance, and adverse clinical outcomes; however, the immunometabolic profile associated with obesity in PsA has not been fully characterized. Objective: To investigate the relationship between obesity, inflammatory biomarkers, cytokine profiles, metabolic parameters, insulin resistance, and disease-related characteristics in patients with PsA. Methods: In this monocentric cross-sectional study, 224 consecutive patients fulfilling the Classification Criteria for Psoriatic Arthritis (CASPAR) for PsA were evaluated. Clinical, inflammatory, metabolic, and cytokine-related variables were analyzed within an integrated immunometabolic framework. Patients were stratified according to obesity status based on body mass index (BMI ≥ 30 kg/m2). Correlation analyses, multivariable regression analyses, and exploratory machine-learning approaches were applied to identify multidimensional patterns associated with obesity. Adjusted multivariable regression analyses were performed to account for available demographic, clinical, comorbidity-related, and therapeutic covariates. Results: Ninety-four patients (42.0%) were classified as obese and 130 (58.0%) as non-obese. Compared with non-obese patients, obese individuals exhibited significantly higher levels of C-reactive protein (CRP; 0.31 vs. 0.13 mg/dL, p < 0.001), erythrocyte sedimentation rate (ESR; 15.0 vs. 10.0 mm/h, p = 0.006), serum amyloid A (SAA; 7.7 vs. 6.4 mg/L, p = 0.008), insulin (8.0 vs. 6.1 μU/mL, p < 0.001), glycated hemoglobin (HbA1c; 38.0 vs. 37.0 mmol/mol, p = 0.003), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR; 1.29 vs. 1.21, p = 0.007), triglycerides (106.0 vs. 85.0 mg/dL, p = 0.019), and Health Assessment Questionnaire (HAQ) scores (p < 0.001). Obese patients also showed a higher prevalence of hypertension (18.1% vs. 6.9%, p = 0.018). BMI was positively correlated with several inflammatory, metabolic, and disease-related variables, including CRP (ρ = 0.383), interleukin-6 (IL-6; ρ = 0.295), insulin (ρ = 0.289), ESR (ρ = 0.245), SAA (ρ = 0.228), HbA1c (ρ = 0.199), HAQ score (ρ = 0.351), and Disease Activity Index for Psoriatic Arthritis (DAPSA) score (ρ = 0.183), while showing an inverse correlation with high-density lipoprotein cholesterol (HDL-C) (ρ = −0.189). After adjustment for age, sex, disease duration, DAPSA, hypertension, type 2 diabetes mellitus, and current therapy class, obesity remained associated with higher CRP and fasting insulin levels and with greater odds of belonging to a higher HAQ category. Machine-learning analyses identified inflammatory biomarkers, insulin resistance indices, and lipid-related parameters as the most informative features associated with obesity-related phenotypes. Conclusions: Obesity in PsA was associated with a broader immunometabolic phenotype characterized by increased inflammatory burden, metabolic dysfunction, and worse functional outcomes. These findings support the integration of metabolic and cardiovascular assessment into routine rheumatology practice and highlight obesity as an important marker of increased immunometabolic and clinical burden in PsA. Although the cross-sectional design precludes causal inference, the observed associations may help identify patients requiring closer metabolic and cardiovascular assessment.
Inflammation can either encourage or suppress tumor growth, thus having a two-sided effect on cancer development. This depends on the balance between pro-tumor and anti-tumor immune responses within the tumor microenvironment (TME). Pro-tumor inflammation, driven by specific immune cells, enhances blood flow and nutrient supply to tumors, promoting the activation of dormant cancer cells (DCCs). Conversely, antitumor inflammation hinders blood flow and can force active cancer cells into a state of dormancy. Tumors actively shift this balance towards pro-tumor inflammation to create a favorable environment for growth. Therefore, anti-inflammatory therapy may be an integral part of comprehensive cancer immunotherapy. This review explores how different anti-inflammatory medications, such as glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), antihistamines, anti-leukotrienes, statins, drugs that block pro-inflammatory cytokines, agents that inhibit oxidative phosphorylation, antioxidant vitamins, anti-angiogenic drugs, and low-dose chemotherapy, can be used to combat cancer. Granulocyte counts and erythrocyte sedimentation rate (ESR) can be used to assess inflammation levels and the effectiveness of anti-inflammatory treatments. We advocate for a paradigm shift in cancer treatment, moving away from aggressive tumor destruction, which triggers uncontrolled tumor regeneration, toward long-term immunological control of tumor growth while preserving the patient’s overall health.
Background: Obesity is a chronic, multifactorial disease that demands personalized and sustainable management approaches. Digital health technologies, such as artificial intelligence, wearable devices, mobile health apps, and virtual reality (VR), may support obesity care by providing enhanced behavioral monitoring, personalized feedback, and patient engagement. Objective: This critical narrative review discusses the current evidence on artificial intelligence, wearable technologies, and VR in the context of precision nutrition and obesity management and their possible clinical applications and limitations. Method: A critical narrative review was conducted using peer-reviewed literature published between 2019 and 2026 and identified through PubMed and Google Scholar. Search terms included combinations of “precision nutrition,” “personalized nutrition,” “obesity,” “weight management,” “metabolic health,” “digital health,” “artificial intelligence,” “machine learning,” “mobile health,” “wearable devices,” and “omics” using Boolean operators. Evidence from randomized controlled trials, systematic reviews, meta-analyses, and key conceptual studies was critically synthesized due to substantial heterogeneity in interventions and outcomes. Result: Wearables and mobile applications can enable continuous self-monitoring of physical activity, dietary intake, sleep, and physiological measures. Artificial intelligence may improve dietary personalization, risk prediction, glycemic control, and adaptive feedback. VR offers an immersive way to tackle behavioral and cognitive mechanisms related to overeating such as cravings, food cue reactivity, and inhibitory control. However, the evidence is heterogeneous, with many studies limited by short follow-up periods, small samples, variable adherence, and insufficient clinical validation. Conclusions: Artificial intelligence, wearable technologies, and VR are promising tools for precision obesity management, but their long-term clinical effectiveness remains uncertain. Future research should prioritize adequately powered trials, longer follow-up, standardized outcomes, transparent algorithms, ethical data governance, and integration with multidisciplinary nutrition and obesity care.
Background/Objectives: Intestinal diseases are a major global health problem due to their high prevalence, chronic course, and significant impact on quality of life. Increasing attention has been given to the extra-skeletal effects of vitamin D, particularly its role in immune regulation, maintenance of intestinal barrier integrity, and modulation of the gut microbiota. The aim of this review was to evaluate current evidence regarding the role of vitamin D in immune regulation, intestinal barrier function, and the pathogenic mechanisms of intestinal diseases, including inflammatory and functional gastrointestinal disorders. Methods: A structured narrative review was conducted using the PubMed, Scopus, and Web of Science databases to identify publications addressing the role of vitamin D in intestinal diseases. The literature search was updated in May 2026 and included studies published between 2004 and 2026. The aim of this review was to summarize current evidence on the effects of vitamin D on immune regulation, intestinal barrier integrity, gut microbiota, and their clinical relevance in intestinal diseases. Results: The included studies demonstrated that vitamin D plays an important role in maintaining intestinal homeostasis through regulation of innate and adaptive immune responses, preservation of epithelial barrier integrity, and modulation of gut microbiota composition. Vitamin D deficiency was associated with impaired VDR-dependent signalling, increased intestinal permeability, dysbiosis, and enhanced pro-inflammatory immune responses, which may contribute to the development and progression of inflammatory bowel disease, Crohn’s disease, ulcerative colitis, irritable bowel syndrome, and celiac disease. Conclusions: Current evidence supports the important role of vitamin D in immune regulation, intestinal barrier protection, and maintenance of gut microbial balance. Further clinical studies are required to better understand its therapeutic potential in intestinal diseases.
Background/Objectives: Melanoma remains one of the most aggressive skin cancers worldwide, with rising incidence and persistent therapeutic challenges, particularly in advanced diseases. Drug repositioning has emerged as a cost- and time-efficient strategy for identifying adjunctive treatments, and antihypertensive medications have attracted attention for their potential off-target antitumor and immunomodulatory effects. This scoping review aimed to map and critically appraise the evidence on the repositioning of antihypertensive drugs for melanoma management. Methods: The review followed the JBI methodology, and the results were reported in accordance with the PRISMA-ScR guidelines. Searches were conducted in July 2025 and updated in May 2026 in PubMed, Scopus, and Web of Science. For Methodological Quality and Risk-of-bias assessment, the SYRCLE Risk of Bias tool was employed for animal studies. Results: This review included 37 studies. β-Blockers, particularly propranolol, were the most frequently investigated agents (n = 21). Several studies reported antiproliferative, pro-apoptotic, antiangiogenic, and immunomodulatory effects; however, these findings were not uniform. Absent direct antiproliferative effects, biphasic dose responses, lack of angiogenic effects, and outcomes dependent on drug concentration, treatment schedule, and experimental model were also reported. Agents targeting the renin–angiotensin system and calcium channels similarly produced heterogeneous and context-dependent findings. The animal studies frequently presented high or unclear risk of bias, particularly because of incomplete reporting of randomization, allocation concealment, and blinding. No formal methodological quality assessment was performed for the in vitro studies. Conclusions: Antihypertensive agents, particularly β-blockers, show promising but heterogeneous preclinical signals in melanoma. However, the available evidence is not sufficient to establish reproducible efficacy or translational validity. Standardized and methodologically rigorous preclinical studies are required before these agents can be considered for clinical investigation as adjunctive melanoma therapies.
Background: Malakoplakia is a rare chronic granulomatous inflammatory disorder characterized by defective macrophage phagolysosomal activity and accumulation of Michaelis–Gutmann bodies on histopathology. It occurs predominantly in immunocompromised individuals and may mimic infectious, inflammatory, or neoplastic processes, creating significant diagnostic challenges. We describe four cases of malakoplakia occurring in distinct immunocompromised states and review the published literature to better characterize its clinical spectrum, management, and outcomes. Methods: We conducted a retrospective case series of four patients diagnosed with histologically confirmed malakoplakia at our institution. Cases occurred in the setting of liver transplantation, kidney transplantation, relapsed acute myeloid leukemia, and ulcerative colitis treated with immunosuppressive therapy. A literature review was performed using PubMed and Google Scholar to identify published cases of malakoplakia in immunocompromised hosts. Demographic, clinical, microbiological, therapeutic, and outcome data were extracted and analyzed descriptively. Results: Four patients with malakoplakia involving the gastrointestinal tract or renal allograft were identified. Clinical presentations ranged from incidental endoscopic findings and tumor-like colonic masses to recurrent bacteremia and graft dysfunction. Histopathologic examination demonstrated characteristic Michaelis–Gutmann bodies in all cases. Management included antimicrobial therapy, observation, and surgical intervention when necessary. Two patients achieved complete clinical and histologic resolution, one required transplant nephrectomy because of persistent allograft infection, and one died from progressive acute myeloid leukemia. Combined with 48 cases identified in the literature, 52 patients were analyzed. The gastrointestinal tract was the most frequently affected site (76.9%), followed by the genitourinary tract (19.2%). Malignancy (32.7%), solid-organ transplantation (26.9%), and autoimmune disease (21.2%) were the most common underlying conditions. Conclusions: Malakoplakia should be considered in the differential diagnosis of mass lesions, persistent infections, and inflammatory lesions in immunocompromised patients, particularly those with malignancy or receiving immunosuppressive therapy. Early histopathologic diagnosis is essential to distinguish malakoplakia from malignancy and guide appropriate management. Our findings highlight the heterogeneous clinical manifestations and outcomes of this uncommon condition and emphasize the importance of multidisciplinary evaluation in affected patients.
Background: Cancer-associated thrombosis is a clinically important complication of malignancy. The systemic immune–inflammation index (SII), calculated from platelet, neutrophil, and lymphocyte counts, may reflect the inflammatory background of cancer, but its value in matched heterogeneous cancer cohorts remains unclear. Objective: To evaluate whether SII is associated with thrombotic status and recorded all-cause mortality in patients with solid cancers. Methods: This retrospective matched cohort study was derived from 2020 consecutive adult patients hospitalized with solid malignancies between September 2023 and December 2025 at the Oncology Clinic of University Hospital “Tsaritsa Yoanna—ISUL”, Sofia, Bulgaria. Patients with documented thrombosis were matched 1:2 to non-thrombotic controls using a nearest propensity-score approach, with preference for exact matching on sex and cancer type. The final cohort included 110 thrombotic patients and 220 matched controls. SII was analyzed in relation to thrombotic status and recorded all-cause mortality using logistic regression. Results: Thrombotic patients and controls were well balanced for matching variables. Mortality was similar between groups: 29.1% versus 28.2%. SII did not differ significantly between thrombotic patients and controls: 772 (516–1471) versus 783 (501–1292), p = 0.655, and showed poor discrimination for thrombotic status, with an AUC of 0.515. In the overall matched cohort, higher SII was associated with recorded all-cause mortality after adjustment for thrombotic status, age, sex, cancer type, stage, and metastatic disease: OR 1.31 per 1000-unit increase, 95% CI 1.05–1.64, p = 0.016. The association was numerically stronger among thrombotic patients, but interaction testing was not statistically significant. Conclusions: SII was not associated with thrombotic status in this matched cancer cohort. Higher SII was associated with recorded all-cause mortality, suggesting that SII may better reflect systemic inflammatory burden than cancer-associated thrombosis itself.
Introduction: Delayed gastric emptying (DGE) is a common complication after pancreatoduodenectomy, occurring in up to two-thirds of patients. Although rarely life-threatening, DGE prolongs hospitalization and increases healthcare costs. The International Study Group of Pancreatic Surgery (ISGPS) definition enables retrospective grading but lacks objective physiological assessment. This pilot study evaluated the feasibility and clinical relevance of standardized postoperative gastric scintigraphy. Methods: Six patients undergoing pancreatoduodenectomy between January and May 2025 received one or two standardized liquid gastric emptying scintigraphies on postoperative days (POD) 4–6 and 10–13. Quantitative analysis included half-emptying time (T½) and residual activity (RA%) at 30 and 60 min. Findings were correlated with ISGPS-defined DGE. Results: Eleven scintigraphic examinations were performed. Clinically relevant ISGPS Grade B/C DGE occurred in two patients and was associated with persistently elevated RA% at 60 min and prolonged T½ on early scintigraphy. Two additional patients showed scintigraphic abnormalities without meeting clinical DGE criteria, without confirmed outcome-level consequences. Conclusions: Standardized gastric scintigraphy may provide an objective and reproducible method for evaluating DGE after pancreatoduodenectomy and may complement clinically based ISGPS definitions.
Background: Complex wounds present significant reconstructive challenges owing to impaired healing, infections, and tissue loss. Skin grafting remains a widely used reconstructive technique; however, outcome data from the Gulf region are limited to a few studies. This study aimed to evaluate early graft outcomes and complications following skin graft reconstruction for complex wounds at a tertiary hospital. Methods: A retrospective, hospital-based study was conducted at Sultan Qaboos University Hospital (SQUH), including all patients who underwent split-thickness or full-thickness skin grafting between 2023 and 2025. Demographic, clinical, surgical, and wound-related data were collected. The main outcomes were graft take on postoperative days 5–7, time to complete re-epithelialization, and the occurrence of postoperative complications. Results: A total of 50 patients were included; 72% were males, with a median age of 45.5 years. Diabetes mellitus was present in 34% of patients. Trauma (28%) and infection/necrotizing causes (22%) were the most common etiologies of wounds. Complete graft take (>90%) was achieved in 90% of the patients, whereas 10% had partial graft take. The median time to complete re-epithelialization was 13 days. Complications were infrequent and minor, including postoperative infection (8%), hypertrophic scar formation (6%), and wound dehiscence (2%). No significant differences in healing time were observed between the diabetic and non-diabetic patients. Conclusions: In this descriptive institutional cohort, a combined protocol of wound-bed preparation, skin graft reconstruction, and postoperative NPWT-assisted stabilization was associated with favorable early graft take and fewer complications. These findings should be interpreted cautiously because of wound heterogeneity, unavailable wound size measurements, and limited subgroup sizes. Larger prospective studies are needed to evaluate the predictors of graft success.
Background/Objectives: Subclinical hypothyroidism (SCH) has been reported to be associated with chronic kidney disease (CKD). Anti–thyroid peroxidase antibody (TPO-Ab) positivity, a known cause of autoimmune thyroid disease, has been reported to be positively associated with SCH with hypertension, but not with SCH without hypertension. Therefore, hypertension status might indicate latent thyroid damage among individuals with SCH. This distinction suggests that categorizing SCH by hypertension status could be useful for evaluating its association with CKD. Methods: A cross-sectional study of 1479 Japanese aged 40–69 years, all of whom had thyroid hormone levels (free triiodothyronine and free thyroxine) within the normal range, was conducted to evaluate the association between CKD and SCH categorized by hypertension status. Results: No significant association between SCH without hypertension and CKD was observed. However, a significant positive association between SCH with hypertension and CKD was identified. The potential confounders-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 0.96 (0.39, 2.38) for SCH without hypertension and 2.76 (1.37, 5.59) for SCH with hypertension. Conclusions: Although further investigation is warranted, categorizing SCH by hypertension status may be useful for understanding the association between SCH and CKD. These findings may help clarify the biological significance of SCH in the development of CKD.
Gastric mucosa-associated lymphoid tissue (MALT) lymphoma, also known clinically as gastric MALT lymphoma (GML) or MALToma, is an indolent B-cell neoplasm strongly associated with chronic Helicobacter pylori (H. pylori) infection. While early-stage disease is based on persistent antigenic stimulation and chronic inflammation, the metabolic and molecular transitions that drive monoclonal B-cell autonomy remain poorly understood. Importantly, H. pylori maintain this long-term colonization by defusing the host’s innate immunity; specifically, its lipid A portion features unique elongated acyl chains, composed of 16–18 carbon atoms, that fail to bind to and activate host TLR4/MD2 receptors, resulting in exceptionally weak endotoxic potency. Persistent colonization relies on key oncoproteins, particularly cytotoxin-associated gene A (CagA) and vacuolar cytotoxin A (VacA), which orchestrate early inflammatory infiltration (neutrophils, Th1, Th2 and Th17 cells) before shifting the microenvironment toward a suppressive regulatory T cell (Treg) phenotype. In this study, we propose a new critical step in the oncogenesis of gastric metastasis: chronic mitochondrial and immunometabolic adaptation within the gastric microenvironment. We claim that H. pylori act not only as a trigger for infection but also as a chronic driver of mitochondrial adaptation to oxidative stress and hypoxia, which subsequently results in defective mitophagy. CagA- and VacA-mediated mitochondrial damage induces reactive oxygen species (ROS) and functional hypoxia, stabilizing HIF-1α to force a glycolytic metabolic shift, while incomplete mitophagy rescues metabolically altered, apoptosis-resistant clones to drive monoclonal B-cell expansion. Within this ecological-microenvironmental framework, the predominantly cytoplasmic sequestration of BCL10 and the NF-κB subunit p65 observed in GML is reinterpreted not as evidence of signaling inactivity, but as a dynamically regulated adaptive state. This configuration is orchestrated by mitochondrial stress responses that enable adaptation to the chronic microenvironmental pressures imposed by H. pylori, acting in concert with the metabolic programs governed by MYC, NRF2, and BCL2. Overall, this review outlines the multi-step pathogenesis of H. pylori-mediated GML, highlighting how mitochondrial dysfunction and metabolic remodeling drive the transition from chronic infection to malignant transformation.
Background/Objectives: Evidence suggests that inflammation contributes to the pathogenesis of neurodegenerative disorders. The utility of blood-derived inflammatory biomarkers in differentiating neurodegenerative disorders remains incompletely understood. The aim of this study was to compare peripheral inflammatory markers in patients with essential tremor (ET), Parkinson’s disease (PD), progressive supranuclear palsy (PSP), and control participants. Methods: This retrospective study included 44 patients with ET, 47 with PD, 44 with PSP, and 45 control participants. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) were calculated from routine complete blood counts. Between-group comparisons were performed using the Kruskal–Wallis test, with a Holm correction across the six indices. The effect sizes were also estimated. Results: The PLR was the only inflammatory marker that significantly differentiated the analyzed groups (p = 0.045), with the highest value observed in PSP patients and the lowest in ET patients. A post hoc analysis indicated different PLR values in PSP than in ET patients (Cliff’s delta = 0.336, small-to-moderate effect). However, the overall association did not remain statistically significant after Holm correction across the six indices (adjusted p = 0.268), and the diagnostic group was not independently associated with PLR after adjustment for age and sex. No statistically significant differences were observed for the NLR, MLR, SII, SIRI, or AISI. Nevertheless, PSP patients consistently exhibited the highest median values of the NLR, SII, and AISI, whereas ET patients generally showed lower inflammatory marker levels. Conclusions: PLR was the only inflammatory marker that significantly differentiated the analyzed groups and was the highest among patients with PSP. The observed trends suggest a tendency toward greater peripheral immune activation in PSP compared with PD and ET. Larger prospective studies incorporating both inflammatory and neurodegenerative biomarkers are warranted to validate these findings.
Background/Objective: Melanoma is an aggressive skin malignancy characterized by significant molecular heterogeneity. Among the molecular alterations identified in melanoma, BRAF mutations represent one of the most common genetic abnormalities and play an important role in activating the MAPK signaling pathway. BRAF mutation status has become clinically important because of its prognostic significance and implications for targeted therapy. This study aimed to evaluate the frequency of BRAF mutations and their associations with demographic, histopathological, and clinicopathological characteristics in melanoma patients at the only referral center for BRAF testing in Kosova, the Institute of Pathology, University Clinical Center of Kosova (UCCK). Methods: This retrospective study included 127 melanoma patients. Descriptive statistics, frequency analysis, Spearman’s correlation and multivariable binary logistic regression analyses were performed to evaluate associations between BRAF mutation status and clinicopathological variables, including age, gender, Breslow thickness, histological type, ulceration, and anatomical localization. Results: BRAF mutation was identified in 76 of 127 melanoma patients (59.8%). The BRAF V600E/V600E2/V600D variants represented the predominant molecular subtype (75%). BRAF-positive melanoma was more frequently observed in younger patients and was significantly associated with increased Breslow thickness, nodular melanoma, ulceration, and trunk localization. Conclusions: BRAF mutations were highly prevalent in melanoma patients from Kosova and were associated with clinicopathological features of a more aggressive disease. The findings establish an important baseline for molecular epidemiology in the country and support the integration of routine BRAF testing into personalized melanoma management and future regional research.
Background: A complex interplay between viral activity and host immune responses drives the progression of liver fibrosis in chronic hepatitis B. The T helper 17 (Th17) immune pathway, which produces the pro-inflammatory cytokine interleukin-17A (IL-17A), has been implicated in hepatic fibrogenesis. However, the relationship between IL-17A levels, IL-17A G197A (rs2275913) gene SNP, and the degree of liver fibrosis across different phases of the natural history of chronic hepatitis B remains insufficiently explored. Methods: This study employed an analytical observational design with a cross-sectional approach in treatment-naïve patients with chronic hepatitis B. The degree of liver fibrosis was assessed using liver elastography. IL-17A (rs2275913) gene SNP was analysed using Real-Time PCR, while serum IL-17A levels were measured using enzyme-linked immunosorbent assay. Statistical analyses included Spearman’s correlation, the contingency coefficient, the Chi-square test, the Kruskal–Wallis test, and the Mann–Whitney test, with a significance level set at p < 0.05. Results: A total of 76 patients with chronic hepatitis B were included in this study. The phase of disease progression was significantly associated with the degree of liver fibrosis (p = 0.016). Median IL-17A levels increased in parallel with fibrosis severity (p = 0.003), with a particularly significant association observed during the R phase (p = 0.002). However, no significant association was found between the IL-17A G197A (rs2275913) gene SNP and either liver fibrosis severity or serum IL-17A levels. Conclusions: Elevated serum IL-17A levels were associated with greater liver fibrosis severity, particularly during the reactivation phase of chronic hepatitis B. These findings suggest a potential relationship between IL-17A-mediated immune responses and liver fibrosis in patients with chronic hepatitis B.
Background: Cardiovascular (CV) risk estimation is usually based on the assessment of classic risk factors and the extent of coronary artery stenosis. However, a substantial rate of acute coronary syndromes (ACS) and sudden cardiac deaths (SCD) is observed in patients with high-risk atherosclerotic plaques (HRP), even in the absence of significant stenosis. Therefore, this study aimed to evaluate the predictive value of traditional clinical risk factors for the presence of HRP in patients scheduled for coronary computed tomography (CCT). Methods: This single-center study included 123 patients undergoing CCT for suspected coronary artery disease (CAD). Atherosclerotic plaque morphology (HRP) and the degree of coronary artery stenosis (CAD-RADS categories) were assessed in all the patients. CV risk factors, including LDL serum levels and CT Calcium score (CS), were analyzed. Results: The study cohort was mostly males (54.5%), with an average age of 60.40 ± 12.45 years and typical risk factors: hypertension (70%), diabetes (22%), obesity (30%), and smoking (20%). Most patients (88%) were found to have coronary atherosclerosis with nonobstructive disease (CAD-RADS 1–2) in 39% of patients. HRP was confirmed in over one-fifth of the participants (22%), with half of the patients in the CAD-RADS 2 category. There were no differences in CV risk factors between patients with and without HRP in CCT. No significant clinical predictor of HRP in CCT was identified. Conclusions: CV risk factors do not predict HRP in CCT, which may underestimate the real risk of ACS and SCD.
In recent years, numerous countries have recorded a steady increase in opioid use. Although prescribing practices vary considerably among them, fentanyl is among the most frequently prescribed strong opioids in several European countries and in Spain. In this study, we analyzed the evolution of outpatient fentanyl dispensing in Galicia, Spain, between January 2019 and December 2025, using the Anatomical Therapeutic Chemical Classification/Defined Daily Dose (ATC/DDD) system. We paid particular attention to differences between provinces and explored temporal trends broken down by route of administration (buccal, nasal, sublingual and transdermal). Dispensing data were obtained from the General Sub-directorate of Pharmacy of the Galician Health Service (SERGAS) from the monthly billing database of official prescriptions dispensed in Galician pharmacies and were expressed as defined daily dose per 1000 inhabitants per day (DID). Dispensing rates between provinces were compared using the non-parametric Kruskal–Wallis test, considering a p-value less than 0.05 as statistically significant. We observed an increase in fentanyl use between 2019 and 2021, followed by a systematic decrease during the 2022–2025 period. Significant differences (p < 0.001) were found in the defined daily dose per 1000 inhabitants per day (DID) among the four Galician provinces, and demographic and socioeconomic factors partially explain the observed disparities. Regarding pharmaceutical presentations, transdermal patches were the most frequently used form during the study period. While some limitations should be noted, the results suggest that the observed decrease in fentanyl dispensing in Galicia could be associated with the implementation of the Ministry of Health’s 2021 optimization plan, with a sustained reduction in its dispensing from 2022 onwards. However, it is necessary to maintain pharmacovigilance at the provincial level.
Background: Osteoporosis is increasingly understood as a complex population health condition shaped by interacting behavioral, metabolic, pharmacological, and healthcare system determinants rather than isolated skeletal risk factors. However, comparative studies integrating these dimensions across distinct healthcare and sociocultural settings remain scarce. We aimed to characterize cross-national differences in osteoporosis-related risk clustering between Romanian and Tunisian adults using an integrative multidimensional framework. Methods: We performed a comparative cross-sectional analysis of harmonized data from two pharmacy-based studies conducted in Romania and Tunisia, including adults aged ≥ 40 years (n = 349). Osteoporosis-related knowledge, lifestyle and metabolic risk factors, pharmacological exposures, preventive behaviors, and treatment patterns were assessed. Multivariable regression and mediation analyses were used to identify independent predictors of screening uptake and to evaluate the relationship between knowledge and preventive behavior. An exploratory cumulative preventive deficit score was used to estimate overall preventive burden within the pharmacy-based study sample. Results: Romanian participants demonstrated significantly higher osteoporosis knowledge than Tunisian participants (8.90 ± 2.20 vs. 7.83 ± 2.99; p < 0.001); however, knowledge was not independently associated with Dual-Energy X-ray Absorptiometry (DXA) uptake and did not mediate country-related differences in screening behavior. Compared with the Romanian cohort, the Tunisian cohort exhibited lower DXA screening rates (11.2% vs. 22.8%; p = 0.005), lower vitamin D supplementation (11.9% vs. 38.6%; p < 0.001), greater sedentary behavior, and a significantly higher cumulative preventive deficit burden (3.39 ± 1.08 vs. 2.77 ± 1.26; p < 0.001). Medication-related osteoporosis risk was also greater in Tunisia, particularly due to markedly higher corticosteroid exposure (7.5% vs. 0.5%; p = 0.002). Despite this less favorable preventive profile, the treatment gap among participants with diagnosed osteoporosis was significantly lower in Tunisia than in Romania (4.8% vs. 42.9%; p = 0.003). Conclusions: Distinct but convergent osteoporosis-related risk patterns were identified across the two populations, suggesting that osteoporosis vulnerability emerges through context-specific clustering of behavioral, pharmacological, and healthcare-access determinants rather than through isolated risk factors alone. The dissociation between knowledge and preventive behavior highlights the limited impact of awareness-based strategies when structural barriers remain unaddressed. These findings support a shift toward integrated, population-tailored osteoporosis prevention models that incorporate healthcare-system, medication-related, and behavioral determinants, in addition to conventional educational approaches.
