Diseases

Background/Objectives: Uterine leiomyosarcoma (uLMS) shares clinical and radiological similarities with benign uterine leiomyoma (LM), while validated discriminatory markers remain scarce. We compared cyclin E1 (CCNE1) expression in uLMS and LM tissue samples. Methods: This retrospective case-control study included 61 patients (16 uLMS, 45 LM) treated at a single institution (2017–2023). Of 22 eligible uLMS cases, six were excluded because suitable tissue was unavailable and they had significantly higher FIGO stages than the included cases. CCNE1 immunoreactivity was assessed using an adapted Allred score in five non-overlapping high-power fields selected from regions of highest expression. Two blinded pathologists independently scored each field, and the patient-level median was used for primary analysis. Results: The median CCNE1 Allred score was 6 (IQR 5–6) in uLMS versus 2 (IQR 0–3) in LM (p < 0.001), with excellent interobserver agreement (ICC 0.94). The AUC was 0.941 (95% CI 0.875–0.990). A data-derived cut-off ≥4 yielded 93.8% sensitivity and 84.4% specificity. A conservative minimum-expression analysis yielded an AUC of 0.882. Postmenopausal status was strongly associated with uLMS but was nearly completely confounded with the diagnostic group (12/16 uLMS vs. 0/45 LM). A premenopausal-only analysis was directionally consistent but underpowered. Clinical symptoms and tumor size did not differ between the groups. Conclusions: CCNE1 immunoexpression was substantially higher in uLMS than LM, with excellent reproducibility. Diagnostic-performance estimates remain exploratory and were influenced by tumor-region sampling, menopausal imbalance, and under-representation of advanced-stage uLMS. Independent multicenter validation, particularly in premenopausal and advanced-stage disease, is required before clinical application. Full article

Background/Objectives: Human herpesvirus 8 (HHV-8), also known as Kaposi sarcoma-associated herpesvirus (KSHV), is a gamma-2 herpesvirus implicated in a distinctive group of lymphoproliferative disorders (LPDs) and lymphomas. In some of these entities, lesional cells are concurrently infected with Epstein–Barr virus (EBV), a gamma-1 herpesvirus, raising important questions regarding viral cooperation in lymphomagenesis. This narrative review summarizes the clinicopathological spectrum and biological significance of HHV-8/EBV co-positive lymphoproliferations. Methods: We provide a narrative synthesis of the biology of HHV-8 and EBV, including latent, abortive lytic, and productive lytic infection programmes and viral mechanisms involved in cell-cycle deregulation, apoptosis inhibition, immune evasion, and B-cell transformation. Major HHV-8-associated lymphoproliferative entities are reviewed within the current WHO-HAEM5 and International Consensus Classification frameworks, with particular attention to patterns of EBV co-infection and diagnostically atypical or overlapping lesions. Results: Primary effusion lymphoma, including its extracavitary presentation, is frequently EBV-positive, whereas HHV-8-positive germinotropic lymphoproliferative disorder is characteristically HHV-8/EBV dual-positive. In contrast, HHV-8-positive lesional cells in multicentric Castleman disease and HHV-8-positive diffuse large B-cell lymphoma are typically EBV-negative. True dual positivity requires demonstration of HHV-8 latency-associated nuclear antigen and EBV-encoded RNA within the same morphologically defined lesional cell population. Rare atypical cases show overlapping clinicopathological features among established entities. Conclusions: HHV-8/EBV co-positive lymphoproliferations comprise a biologically and diagnostically heterogeneous group. Although unusual overlapping cases suggest potential relationships among HHV-8-associated disorders, current evidence does not support a single continuous disease spectrum or a uniform mechanism of HHV-8/EBV cooperation. Full article

Background/Objectives: Multiple endocrine neoplasia type 1 (MEN1) is a rare hereditary syndrome characterized by primary hyperparathyroidism, duodeno-pancreatic and pituitary neuroendocrine tumors. Adrenal lesions are acknowledged manifestations of MEN1, but their functional characterization remains limited. Mild autonomous cortisol secretion (MACS) is associated with cardiometabolic risk and skeletal involvement in sporadic adrenal incidentaloma, significantly impacting patient morbidity, but data in MEN1 are lacking. The aims of the study were to estimate the prevalence of MACS in adult patients with MEN1 and radiological evidence of adrenal involvement, and to evaluate the associated biochemical, cardiometabolic, and skeletal features. Methods: This retrospective single-center observational study included adult patients with clinical, familial, or genetic MEN1 and adrenal involvement. MACS was defined as serum cortisol >1.8 µg/dL after a 1 mg overnight dexamethasone suppression test in the absence of overt Cushing syndrome. Cardiometabolic and skeletal characteristics were compared according to MACS status. Results: Among 101 MEN1 patients, 38 had adrenal involvement and 22 underwent complete hormonal evaluation. MACS was identified in 15 of the 22 patients (68.2%). Patients with MACS had significantly lower baseline ACTH concentrations and showed a trend toward a higher prevalence of metabolic syndrome. No significant differences were observed in osteoporosis or fracture prevalence. Conclusions: This is the first study specifically evaluating the prevalence of MACS in MEN1 patients with adrenal lesions. MACS appears to be more common than in sporadic adrenal incidentalomas and may represent an important factor for improving clinical characterization and tailoring patient management. Larger prospective studies are needed to define the optimal follow-up strategy. Full article

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. Full article

Background/Objectives: Chronic lymphocytic leukemia (CLL) is a heterogeneous B-cell malignancy in which B-cell receptor signaling, microenvironmental interactions, genomic lesions, and epigenetic deregulation cooperate to shape disease behavior. The imprinted DLK1-DIO3 locus at chromosome 14q32 contains the largest human miRNA cluster and has been implicated in cancer-related regulatory networks; however, its contribution to CLL remains incompletely defined. Methods: In the present study, we investigated the potential involvement of DLK1-DIO3 miRNAs in CLL biology by integrating public transcriptomic datasets with miRNA-centered pathway analysis. GSE70830 was used as a discovery dataset and GSE66117 as a supportive validation cohort to identify genes consistently downregulated in CLL compared with normal B cells. Results: The analyses identified 1236 and 2145 downregulated genes, respectively, and their intersection yielded a 345-gene consensus set. The overlap was significantly greater than expected by chance (odds ratio 2.33; p = 1.55 × 10⁻³¹). This set was used as gene-filter input for DIANA-miRPath v3.0 analysis of the DLK1-DIO3 miRNA cluster, identifying eight KEGG pathways mainly involving B-cell receptor/NF-κB signaling, cell adhesion, leukocyte transendothelial migration, and glycan-related processes. DIANA-miRPath v4.0 provided pathway-centered refinement. GSE216258 miRNA analysis did not show generalized locus-wide upregulation, while a GSE12366 sensitivity analysis showed that 32 of the 345 genes overlapped the strongest naïve-memory B-cell differentiation signatures. The absence of uniform locus-wide upregulation suggests that these data do not establish a direct link between DLK1-DIO3 activation and generalized repression of the 345-gene set. Future studies are needed to identify gene- and pathway-specific effects. Conclusions: Overall, our findings support an association between DLK1-DIO3 miRNA target/pathway annotations and CLL-relevant transcriptional programs, providing a hypothesis-generating framework that warrants further experimental validation. Full article

Background: Accurate early identification of sepsis remains a major clinical challenge due to its heterogeneous presentation and overlap of clinical signs with the non-infectious systemic inflammatory response syndrome (SIRS). Timely differentiation is crucial for improving patient outcomes, meeting sepsis bundle requirements and reducing inappropriate antimicrobial use. We hypothesized that clinical–laboratory data available within the first three hours of patient presentation could be used to identify patients with sepsis at a clinically useful level of diagnostic accuracy, in lieu of traditional microbiology results which would not become available until at least 12–24 h. Data from two independent studies were used to quantify the diagnostic value of demographic, vital, clinical–laboratory, and microbiological data available at three time points for distinguishing retrospectively diagnosed critically ill patients with either sepsis or non-infectious SIRS. A particular focus of this work was an assessment of the utility of SeptiCyte RAPID (Immunexpress Inc., Seattle, WA, USA) as an aid to sepsis diagnosis, producing actionable data within one hour. Methods: Data from two independent study cohorts were analyzed. The “510(k) cohort” consisted of 419 adult patients in intensive care (ICU) (MARS, VENUS, and NEPTUNE studies). The “Andalusian cohort” consisted of 353 ICU patients from the PANGEA study. Logistic regression models, selected by a greedy search algorithm and validated by repeated cross-validation, were used to determine the contributions of different variables to diagnostic accuracy. Diagnostic performance was quantified by the area under the receiver operating characteristic curve (AUC). Results: For the 510(k) cohort, a baseline AUC of 0.69–0.73 was observed using five to seven vital and demographic variables assessed immediately upon presentation (time T1). The addition of clinical–laboratory variables, in particular SeptiCyte RAPID, within one to three hours post-presentation (time T2) increased the AUC to 0.85–0.86. Finally, the addition of microbiological data 12–24 h post-presentation (time T3) further improved the AUC to 0.90–0.91. Similar results were obtained for the Andalusian cohort. AUC values at the three time points were as follows: At time T1, AUC = 0.67 based solely on vital signs and demographics; at time T2, AUC = 0.87 based on vitals + demographics + SeptiCyte RAPID ± other clinical–laboratory data; at time T3, AUC = 0.93 based on vitals + demographics + SeptiCyte RAPID ± other clinical–laboratory data + microbiology results. For both cohorts, the most significant variables included temperature, mean arterial pressure, respiratory rate, suspected infection site, SeptiCyte RAPID, procalcitonin, confirmed bacterial infection and positive blood culture confirmation. In summary, the AUC for diagnosing sepsis rose progressively from T1 (510(k) 0.69–0.73; Andalusian 0.67) to T2 (510(k) 0.85–0.86; Andalusian 0.87) with the addition of SeptiCyte RAPID to T3 (510(k) 0.90–0.91; Andalusian 0.93) as more clinical information became available over time. Conclusions: The accuracy of identification of sepsis increases markedly as demographics and vital signs are supplemented with clinical–laboratory information, and ultimately with microbiological culture results. The AUC improves in the shortest time within the first three hours when laboratory data, and particularly SeptiCyte RAPID results, become available. Integrating rapid host response testing with SeptiCyte RAPID into time-based diagnostic frameworks may enhance early sepsis recognition, improve antimicrobial stewardship, and support guideline-driven clinical decisions. Full article

Background/Objectives: Acute collective emotional events may coincide with variation across multiple dimensions of mental health and health-related behaviors. This study compared mental health outcomes and recent alcohol consumption between assessments conducted before and after a major international sporting event and explored factors associated with psychological and behavioral outcomes among young adults. Methods: An observational study was conducted among 146 adult students in western Mexico who participated in assessments surrounding the 2026 FIFA World Cup match between Mexico and England. Assessments were conducted approximately 10 h before kick-off and 11 h after completion of the match. Because individual responses could not be linked across assessment periods, comparisons were analyzed as repeated cross-sectional marginal comparisons rather than paired longitudinal analyses. Psychological outcomes were assessed using standardized instruments, and recent alcohol consumption was defined as alcohol use during the eight hours preceding each assessment. Results: Anxiety-related symptom scores were lower at the post-event assessment, whereas depressive-related symptoms remained relatively stable. Emotional well-being was also lower at the post-event assessment, while recent alcohol consumption during the eight hours preceding the assessment was substantially more frequent post-event than pre-event (41.1% vs. 0.7%). The small difference observed in sexual-attitude scores was considered exploratory. Post-event multivariable analyses identified several factors associated with psychological outcomes and recent alcohol consumption; these associations were interpreted as cross-sectional. Conclusions: Psychological and behavioral outcomes exhibited distinct patterns between assessment periods surrounding the sporting event. Given the observational design, inability to link individual responses, and presence of unmeasured co-occurring exposures, these differences should not be interpreted as within-participant changes or as effects attributable specifically to the match. Full article

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. Full article

Background/Objectives: Probiotic preparations have attracted increasing attention because of their potential to modulate the gut microbiota and improve health outcomes in a wide range of gastrointestinal and extraintestinal diseases. However, their efficacy and safety are strain-specific and remain inconsistent across many clinical indications. The aim of this review was to evaluate current evidence regarding the efficacy, safety, mechanisms of action, and clinical applications of probiotic preparations. Methods: A narrative literature review was conducted using the PubMed, Scopus, and Web of Science databases to identify publications addressing the efficacy, safety, and clinical applications of probiotic preparations. The literature search was last updated in July 2026. No publication-year restrictions were applied; the studies included in this review were published between 2000 and 2026. Priority was given to systematic reviews, meta-analyses, randomized controlled trials, international clinical practice guidelines, and mechanistic studies. Results: The reviewed evidence indicates that probiotics may contribute to intestinal homeostasis through modulation of the gut microbiota, enhancement of intestinal barrier function, and regulation of immune responses. The strongest evidence supports the use of selected probiotic strains for the prevention of antibiotic-associated diarrhea, whereas evidence for the prevention of necrotizing enterocolitis is generally favorable but depends on the specific probiotic preparation, product quality, and clinical setting. Evidence for most other gastrointestinal and extraintestinal disorders remains heterogeneous and strain-specific. Although probiotics generally exhibit a favorable safety profile, rare infectious complications have been reported in high-risk patients. Conclusions: Current evidence indicates that the efficacy and safety of probiotics depend on the specific strain, clinical indication, and patient characteristics. Further high-quality, strain-specific clinical studies are needed to optimize their use in medical practice. Full article

Cognitive tunnelling poses significant risks in OB/GYN, where rapid clinical deterioration and time-pressured decision-making are common. This critical review synthesized evidence from a comprehensive literature search across multiple databases, yielding 414 unique papers examining cognitive tunnelling mechanisms, patient safety consequences, and mitigation strategies in obstetric and gynecological contexts. Medicolegal analysis reveals that cognitive tunnelling contributes to malpractice exposure and that adoption of structured safety programs addresses root causes and strengthens the clinical record for forensic review. Mitigation strategies were critically evaluated: metacognition and individual cognitive forcing strategies such as DECLARE (Differential, Examine, Consider, List, Assess, Review, Evaluate) and Pivot-and-Cluster show theoretical promise but depend on intact executive capacity that is depleted under the very conditions that precipitate tunnelling; debriefing demonstrates consistent improvements in team situational awareness and latent threat identification but requires organizational just culture and psychological safety; and hierarchical closed-loop communication systems provide the strongest evidence of reducing preventable adverse events by distributing attentional load across teams, though authority gradients risk suppressing junior-staff dissent. Despite growing recognition, significant knowledge gaps remain regarding measurement methodologies, obstetric-specific research, intervention effectiveness, and the integration of emerging artificial intelligence technologies. Addressing cognitive tunneling through quality studies with patient-centered outcomes and validated measures is essential for reducing medical errors and enhancing patient safety in women’s healthcare. Full article

Background: Subclinical disordered eating behaviors (DEBs) are common among young women and are thought to result from complex interactions between psychological, dietary, and genetic factors. While chronic stress and unhealthy dietary habits have been implicated in the development of DEBs, the independent and interactive contributions of perceived stress, added sugar intake, and genetic susceptibility remain insufficiently understood. This pilot study investigated these associations using a two-stage case–control design. Methods: A total of 100 female university students (18–27 years) completed the Dutch Eating Behavior Questionnaire (DEBQ) during the first stage of the study. Based on DEBQ scores, 20 participants with the highest risk of DEBs and 20 with the lowest risk were selected for the second stage, forming case and control groups. Perceived stress was assessed using the Perceived Stress Scale (PSS-14), and added sugar intake was estimated using a semi-quantitative food frequency questionnaire (FFQ). Participants were also genotyped for four candidate polymorphisms (5-HTTLPR, rs6295, rs6265, and rs1800497). Group differences, correlation analyses, binary logistic regression models adjusted for BMI, and gene–environment interaction analyses were performed. Results: Perceived stress emerged as the strongest and most consistent predictor of belonging to the upper DEBQ quintile, with each one-point increase on the PSS-14 associated with a 44% increase in the odds of high-risk status after adjustment for BMI (OR = 1.44; 95% CI: 1.120–1.853; p = 0.004). Added sugar consumption did not withstand correction for multiple comparisons (p = 0.030, Bonferroni-adjusted α = 0.025). No significant main effects or gene–environment interactions were detected for any of the investigated polymorphisms or the cumulative genetic risk score. Conclusions: These preliminary findings highlight perceived stress as the important modifiable risk factor for subclinical disordered eating behaviors in young women, suggesting that stress-reduction and emotional regulation interventions may be more effective than dietary approaches in this population. However, the lack of significant associations for the genetic variants studied should be interpreted with caution given the limited sample size and statistical power. Replication in larger, longitudinal cohorts is warranted to confirm these findings and explore developmental trajectories. Full article

Background: Immunotherapy and targeted therapy have gained ground over conventional chemotherapy in treating various cancers. While pulmonary toxicity associated with these agents is rare, it represents a significant factor in both mortality and morbidity and may influence the overall success of cancer treatment. This case series report adds to the emerging evidence of cancer therapy-induced pneumonitis features and corticotherapy outcomes. Patients and methods: This single-center, retrospective case series analyzed 12 consecutive cases of patients undergoing immunotherapy (four receiving nivolumab, four receiving pembrolizumab) or targeted therapy (three receiving obinutuzumab, one receiving abemaciclib) for cancer (seven with lung cancer, three with non-Hodgkin lymphoma, one with breast cancer, one with renal cancer) who developed pneumonitis during their follow-up. Results: The interval from oncological treatment initiation to pneumonitis onset ranged from 6 to 48 months (median = 18.5), and in four patients it occurred after discontinuation of oncologic therapy. In most patients, the diagnosis was established with high probability based only on the clinical presentation, radiologic pattern, and concomitant oncologic therapy. Bronchoscopy with bronchoalveolar lavage analysis was performed in eight of the 12 patients, particularly when onset followed treatment discontinuation. The main symptom was dyspnea (10/12 cases), and three of 12 patients had respiratory failure (SpO₂ ≤ 88%). The CTCAE severity grades were: one mild, seven moderate, three severe, and one life-threatening. The CT scan showed different patterns (7 OP, 4 NSIP-like, and 1 HP). Eleven patients received oral methylprednisolone (0.40 to 0.82 mg/kg) for 5 to 16 weeks. Two patients continued oncologic treatment, and six discontinued. Pneumonitis improved or resolved in 11 of the 12 patients; one patient deteriorated after reintroduction of immunotherapy and subsequently died from cancer-related complications. Conclusions: Immunotherapy- and targeted therapy-induced pneumonitis can express various features and severities, and prompt recognition and diagnosis based on clinical, radiologic and contextual elements are mandatory. In this small, heterogeneous series the individualized corticosteroid regimens used were followed by favorable outcomes. Our observations suggest that, in selected clinically improving patients, follow-up may rely only on clinical assessment and chest X-ray, and extensive tests may be reserved for non-responsive cases. Full article

Aims: International diabetes guidelines recommend inpatient glycaemic management protocols for bolus enteral feeding in people with diabetes to improve clinical outcomes. This study aims to evaluate before and after hospital-wide implementation of an inpatient bolus enteral feeding protocol: (1) the incidence of hyperglycaemia (>13.9 mmol/L) and hypoglycaemia (<4.0 mmol/L), (2) medication prescribing practices and capillary blood glucose monitoring and (3) health care professionals’ knowledge and confidence levels. Methods: We implemented an inpatient glycaemic management protocol for bolus enteral feeding developed by a multidisciplinary team of diabetes nurse educators and endocrinologists and approved by the institutional medical board in July 2024. This before-and-after quality improvement study was conducted over 3 months across eight inpatient wards. Adult inpatients were consecutively enrolled if they met the inclusion criteria: (1) a documented diagnosis of diabetes mellitus, (2) receiving bolus enteral feeding and (3) treatment with glucose-lowering medication. Patients listed as critically ill were excluded. Nurses working in the pilot wards were also recruited. Before implementing the protocol, diabetes nurse educators trained inpatient nurses on understanding and executing the protocol for administering capillary blood glucose monitoring and medications for patients with diabetes on enteral feeding. Nurses’ pre- and post-knowledge levels and perceived confidence were assessed using a structured questionnaire. Electronic medical records were reviewed to evaluate the incidence rates of hypoglycaemia and hyperglycaemia before and during the 3 months following protocol implementation. We also assessed adherence to protocol-recommended capillary blood glucose monitoring frequencies based on the diabetes medication regimen. Results: A total of 31 patients were observed during the 6-week baseline period and 28 patients following protocol implementation. A total of 192 clinical care episodes were audited, comprising 78 in the pre-intervention phase and 114 in the post-intervention phase. The incidence of hyperglycaemia decreased from 43.6% to 10.5%, while hypoglycaemia decreased from 3.8% to 2.6%. After adjusting for protocol adoption rates, protocol implementation was associated with significantly lower odds of hyperglycaemia (odds ratio [OR] 0.22, 95% CI [0.07, 0.65], p = 0.006). A significant increase in appropriate nursing practices was observed post-intervention (p < 0.001). Adoption of the protocol by nurses decreased the odds of hyperglycaemia by 70% (p = 0.014). Nurses’ knowledge scores improved significantly from baseline to 3 months post-implementation (p < 0.001). Conclusions: Implementation of a standardised inpatient glycaemic management protocol for PWD receiving bolus enteral feeding was associated with reduced rates of hyperglycaemia and hypoglycaemia. Larger-scale studies are warranted to evaluate the effectiveness and sustainability of wider implementation in improving clinical outcomes. Full article

Objective: Exercise therapy is recommended for patients with peripheral arterial disease (PAD) to improve walking capacity and functional outcomes. However, rehabilitation programmes after lower-limb revascularisation remain poorly defined. We aimed to map the existing literature on exercise-based rehabilitation following lower-limb revascularisation in patients with PAD and summarise key intervention features and reported outcomes. Data Sources: PubMed/MEDLINE, Embase, the Physiotherapy Evidence Database (PEDro), and the Cochrane Central Register of Controlled Trials were systematically searched from inception to identify relevant studies. Review Methods: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). Studies involving adult patients with PAD or chronic limb-threatening ischaemia who underwent lower-limb revascularisation and participated in postoperative exercise or rehabilitation programmes were included. Two reviewers independently screened studies and extracted data on study characteristics, intervention components, and outcomes. Findings were synthesised descriptively and presented in tables and narrative summaries. Results: Fourteen studies were included. Rehabilitation programmes showed substantial heterogeneity in exercise modality, timing of initiation, intensity, supervision, and duration. Walking-based exercise was the most commonly reported modality. Sessions typically lasted 20–60 min. Exercise frequency ranged from daily inpatient mobilisation or 6 days/week during early rehabilitation to two to five sessions/week in outpatient or home-based programmes, and programme length ranged from inpatient-only rehabilitation to 12 months. The most frequently reported outcomes were measures of walking capacity, including treadmill walking distance and the 6 min walk test. In contrast, limb-related outcomes (e.g., wound healing, limb salvage, and reintervention) and safety outcomes were less frequently reported. Conclusions: Exercise-based rehabilitation after lower-limb revascularisation in patients with PAD demonstrates considerable variability in programme characteristics and outcome measures. Although most studies focus on walking performance, key outcomes—particularly limb-related events and safety—remain underreported. Future research should establish standardised postoperative rehabilitation protocols and evaluate a broader range of clinically relevant outcomes, especially in patients with chronic limb-threatening ischaemia. Full article

Background: Age-related macular degeneration (AMD) represents a leading cause of irreversible vision loss worldwide, driven by intricate interactions among oxidative stress, low-degree chronic inflammation, and macular pigment depletion in aging retinas. Lutein, a component of the macular pigment, has attracted significant attention in AMD management for its antioxidant and blue-light filtering properties. Its oral supplementation, however, although showing potential in slowing AMD progression, requires daily intake and results in variable macular absorption. Trans-scleral iontophoresis (TSI) is a non-invasive technique using low-intensity electric currents to deliver charged molecules into biological tissues and represents an innovative method to deliver lutein into the retina. Methods: The present narrative review synthesizes and discusses the results of lutein supplementation in AMD patients; the ocular iontophoresis basal principles, efficacy, safety and limitations in treating different ophthalmic pathologies; and the evolving clinical evidence supporting lutein TSI in the AMD management. Results: Ex-vivo studies have shown that lutein TSI may provide efficient, localized, rapid, and sustained retinal supplementation of macular pigment, overcoming oral intake limitations. Recent preliminary clinical studies have demonstrated that this technique is well-tolerated and effective in enhancing macular pigment optical density and improving some visual functions in AMD patients. Conclusions: Ex-vivo and pilot clinical studies highlight the capacity of TSI to deliver lutein inside the retina, overcoming physiological barriers that may limit the efficacy of lutein oral administration. The demonstration of the efficacy of the procedure in preserving/improving visual functions and delaying disease progression in AMD patients requires further long-term randomized controlled clinical studies. Full article

Background/Objectives: Oral structural and functional impairment and depressive outcomes frequently coexist in older adults, but the strength and interpretation of their association remain uncertain. This systematic review and meta-analysis evaluated whether poorer oral status or function is associated with depressive outcomes in older populations. Methods: Six databases were searched for observational studies published from 1 January 2016 to 5 January 2026, with an update on 19 April 2026. Eligible studies examined oral impairment as the exposure and depressive outcomes as the endpoint in older adults. Risk of bias was assessed using Newcastle–Ottawa criteria and certainty using GRADE. Comparable adjusted odds ratios (ORs) were pooled using random-effects meta-analysis with restricted maximum likelihood and Hartung–Knapp adjustment; non-comparable metrics were synthesized separately. Results: Thirty studies were included; fifteen contributed to the primary OR meta-analysis. In the primary model, poorer oral status or function was associated with higher odds of adverse depressive outcomes (OR = 1.61, 95% CI: 1.31–1.99), although between-study heterogeneity was substantial (I² = 88.1%). In the trim-and-fill sensitivity analysis, the pooled estimate decreased to OR = 1.29 (95% CI: 0.99–1.69; p = 0.0584) and no longer reached conventional statistical significance. The certainty of the primary evidence was very low. Conclusions: Poorer oral structural or functional status is associated with worse depressive outcomes in older adults, but the magnitude is heterogeneous and sensitive to small-study-effect assumptions. The evidence remains observational and of very low certainty and should be interpreted as hypothesis-generating rather than causal or treatment evidence. Full article

Background/Objectives: Severe acute respiratory syndrome (SARS) remains an important cause of hospitalization and mortality, particularly among vulnerable populations. Understanding the factors associated with previous hospitalization may support more effective prevention and vaccination strategies. This study aimed to analyze the epidemiological profile of previous hospitalization among patients with SARS in the state of Pernambuco, Brazil. Methods: A quantitative, retrospective, cross-sectional study was conducted using data from the Influenza Epidemiological Surveillance System (SIVEP-Gripe), including 79,852 adult patients (≥18 years) notified with SARS in Pernambuco between 2021 and 2024. Sociodemographic, clinical, and vaccination-related variables were analyzed to identify factors associated with previous hospitalization. Results: The prevalence of previous hospital admission (readmission history) was 6.6%. Patients with previous hospitalization had a significantly higher median age compared to those without previous hospitalization (66 vs. 63 years; p < 0.001). The prevalence of previous hospitalization was higher among individuals with chronic comorbidities, particularly hematologic diseases (prevalence ratio [PR] = 1.95; 95% confidence interval [CI]: 1.51–2.51; p < 0.001) and asthma (PR = 1.67; 95% CI: 1.42–1.96; p < 0.001). Influenza vaccination was associated with a lower prevalence of previous SARS hospitalization (PR = 1.29; 95% CI: 1.03–1.61; p = 0.023). In contrast, COVID-19 vaccination status showed no significant association with previous hospitalization. A history of previous SARS hospitalization was associated with a higher prevalence of death in subsequent hospitalizations (PR = 1.09; 95% CI: 1.01–1.18; p = 0.022). Conclusions: Older adults and individuals with chronic comorbidities showed a higher prevalence of previous SARS hospitalization in Pernambuco. The findings show an association between influenza vaccination and a lower prevalence of previous SARS hospitalization and highlight the importance of post-discharge follow-up and epidemiological surveillance. Full article

Background/Objectives: Pediatric solid tumors (PST) are a biologically distinct group of malignancies whose developmental origins and molecular drivers differ substantially from those of adult cancers, with direct implications for therapeutic strategy and clinical outcome. This review synthesizes current evidence on molecular pathogenesis, tumor microenvironment biology, and the structural conditions that shape access to care across select PST. Methods: A narrative review of peer-reviewed literature was conducted primarily using PubMed, supplemented by Google Scholar, covering publications from 2000 to 2025. Tumor types were selected based on their prevalence in the pediatric population and the availability of evidence addressing both molecular features and health disparities. Body: Across eight tumor types (neuroblastoma, Ewing sarcoma, pediatric brain tumors, rhabdomyosarcoma, Wilms tumor, retinoblastoma, osteosarcoma, and chondrosarcoma), recurrent molecular alterations including MYCN amplification, EWS-FLI1 fusions, PAX-FOXO1 rearrangements and IDH 1/2 mutations emerge as central determinants of disease behavior and eligibility for treatment. The tumor microenvironment manifests as a shared mediator of immune exclusion and therapeutic resistance across tumor types, with, but not limited to, tumor-associated macrophages, myeloid-derived suppressor cells, and checkpoint molecule expression, identified as recurrent features influencing treatment response. Immunotherapeutic strategies have shown variable efficacy across PST, with the most consistent clinical benefit established in neuroblastoma. A critical and underappreciated pattern stands out across tumor types: children carrying the most aggressive molecular subtypes are disproportionately those with the least access to therapies those subtypes demand, emphasizing an overlap of biological and structural disadvantage that is also amplified in low- and middle-income countries, where late-stage presentation, treatment abandonment and limited access to molecular diagnostics compound the biological disadvantage. Conclusions: Within the eight PST reviewed, the most aggressive molecular subtypes and the greatest structural disadvantages converge in the same children; those carrying MYCN amplification, PAX-FOXO1 fusions, or EWS-FLI1 fusions are disproportionately those with the least access to the therapies their biology demands. Genomic and immunologic advances will only reach their full clinical potential when paired with inclusive trial data, diversified genomic databases, and most importantly, equitable access to biomarker-specialized therapies across all populations. Full article

Background/Objectives: To evaluate the prognostic significance of the novel hemoglobin–albumin–C-reactive protein (HARP) index in patients with locally advanced nasopharyngeal carcinoma (LANPC) treated with definitive concurrent chemoradiotherapy (CCRT). Methods: This retrospective study included 248 patients with LANPC treated with definitive CCRT between 2011 and 2020. The HARP index [hemoglobin × (albumin ÷ C-reactive protein)] was calculated using pretreatment laboratory values. Prognostic associations between HARP and survival outcomes were evaluated using continuous and categorical Cox regression analyses, restricted cubic spline modeling, receiver operating characteristic analyses, and bootstrap-based internal validation. Results: Lower pretreatment HARP values were independently associated with inferior progression-free survival (PFS) and overall survival (OS). In continuous Cox analyses, increasing HARP values were associated with reduced risks of mortality and disease progression (both p < 0.001). ROC analysis identified 3.2 as the exploratory cut-off value for clinical stratification. Patients with HARP ≥ 3.2 (n = 112) had significantly better outcomes than those with HARP < 3.2 (n = 136). Median PFS and OS were not reached in the high-HARP group, whereas they were 47.0 and 72.0 months, respectively, in the low-HARP group. Low HARP values were associated with inferior PFS (HR, 3.86; p < 0.001) and OS (HR, 3.06; p < 0.001). Bootstrap internal validation demonstrated stable model discrimination with minimal optimism. Conclusions: The novel HARP index is an independently associated and internally validated prognostic biomarker in patients with LANPC treated with definitive CCRT. HARP may provide a practical tool for improved risk stratification, pending prospective external validation. Full article