Search Results (27,366)

Background and Objectives: Effective myocardial protection is essential for successful cardiac surgery outcomes, especially in complex and prolonged procedures. To this end, Del Nido (DN) and histidine-tryptophan-ketoglutarate (HTK) cardioplegia solutions are widely used; however, their comparative efficacy in adult surgeries with prolonged aortic cross-clamp (ACC) times remains unclear. This study aimed to compare the efficacy and safety of DN and HTK for myocardial protection during prolonged ACC times in adult cardiac surgery and to define clinically relevant thresholds. Materials and Methods: This retrospective study included a total of 320 adult patients who underwent cardiac surgery under cardiopulmonary bypass (CPB) with an aortic cross-clamp time ≥ 90 min. Data were collected from the medical records of elective adult cardiac surgery cases performed at a single center between 2019 and 2025. Patients were categorized into two groups based on the type of cardioplegia received: Del Nido (n = 160) and HTK (n = 160). The groups were compared using 1:1 propensity score matching. Clinical and biochemical outcomes—including troponin I (TnI), CK-MB, lactate levels, incidence of low cardiac output syndrome (LCOS), and need for mechanical circulatory support—were analyzed between the two cardioplegia groups. Subgroup analyses were performed according to ACC duration (90–120, 120–150, 150–180 and >180 min). The predictive threshold of ACC duration for each complication was determined by ROC analysis, followed by the analysis of independent predictors of each endpoint by multivariate logistic regression. Results: Intraoperative cardioplegia volume and transfusion requirements were lower in the DN group (p < 0.05). HTK was associated with lower TnI levels and less intra-aortic balloon pump (IABP) requirement at ACC times exceeding 180 min. Markers of myocardial injury were lower in patients with an ACC duration of 120–150 min in favor of HTK. The propensity for ventricular fibrillation after ACC was significantly lower in the DN group. Significantly lower postoperative sodium levels were observed in the HTK group. Prolonged ACC duration was an independent risk factor for LCOS (odds ratio [OR]: 1.023, p < 0.001), VIS > 15 (OR, 1.015; p < 0.001), IABP requirement (OR: 1.020, p = 0.002), and early mortality (OR: 1.016, p = 0.048). Postoperative ejection fraction (EF), troponin I, and CK-MB levels were associated with the development of LCOS and a VIS > 15. Furthermore, according to ROC analysis, HTK cardioplegia was able to tolerate ACC for up to a longer duration in terms of certain complications, suggesting a higher physiological tolerance to ischemia. Conclusions: ACC duration is a strong predictor of major adverse outcomes in adult cardiac surgeries. Although DN cardioplegia is effective and economically advantageous for shorter procedures, HTK may provide superior myocardial protection in operations with long ACC duration. This study supports the need to individualize cardioplegia choice according to ACC duration. Further prospective studies are needed to establish standard dosing protocols and to optimize cardioplegia selection according to surgical duration and complexity. Full article

Candidiasis arises from the proliferation of Candida species in the human body, especially in individuals with compromised immune systems. Efficient therapeutic management of candidiasis is often hampered by the limited availability of potent antifungal drugs and the emergence of drug-resistant strains. We have previously identified the N-[(4-sulfamoylphenyl)methyl][1,1′-biphenyl]-4-carboxamide to have fungistatic and fungicidal properties, likely due to the hydrophobic biphenyl–chemical features affecting the structural organization of Candida spp. cell membrane. Here, we designed and synthesized a novel series of twelve 5-arylfuran-2-carboxamide derivatives bearing a new hydrophobic tail as bioisosteric replacement of the diphenyl fragment. Its antifungal effectiveness against C. albicans, C. glabrata, and C. parapsilosis, including ATCC and clinically isolated strains, was assessed for all compounds. The most active compound was N-benzyl-5-(3,4-dichlorophenyl)furan-2-carboxamide (6), with fungistatic and fungicidal effects against C. glabrata and C. parapsilosis strains (MIC = 0.062–0.125 and 0.125–0.250 mg/mL, respectively). No synergistic effects were observed when combined with fluconazole. Interestingly, fluorescent microscopy analysis after staining with SYTO 9 and propidium iodide revealed that compound 6 affected the cell membrane integrity in C. albicans strain 16. Finally, carboxamide 6 exhibited a dose-dependent cytotoxicity on erythrocytes, based on assessing the LDH release. Full article

This study examined the distribution and disease associations of non-HLA-B*27 HLA-B alleles in Romanian spondyloarthritis (SpA) patients, aiming to address the underrepresentation of Eastern European populations in immunogenetic research. Methods: We analyzed 263 HLA-B*27-negative patients from Northeastern Romania fulfilling ASAS criteria. HLA-B genotyping was performed at two-digit resolution, and allele distributions were compared with two Romanian HLA-B*27-negative control groups (n = 335 and n = 1705 cases), using chi-square testing and logistic regression. Compared to controls, HLA-B*47 (p = 0.0007) and HLA-B*54 (p = 0.0013) were significantly enriched, while HLA-B*40 was underrepresented (p = 0.0287). Notably, HLA-B*54 was observed exclusively in axial SpA. Within the cohort, both HLA-B*13 and HLA-B*57 alleles were associated with psoriasis, while HLA-B*37 and HLA-B*41 alleles were clustered within the reactive arthritis group. The HLA-B*35 and HLA-B*18 alleles were the most frequently observed alleles across most clinical phenotypes. When comparing the frequency of HLA-B associations, the most common genotypes among SpA patients were B*08-B*18, B*13-B*35, and B*35-B*51. Notably, B*08-B*18 was more frequent in patients with radiographic sacroiliitis grade ≥ 2, while B*35-B*51 was more frequent in those with confirmed systemic inflammation, as indicated by elevated CRP or ESR levels. Analysis of peptide-binding patterns revealed a cluster of risk alleles, HLA-B*08, B*18, B*35, B*40, and B*54, sharing similar features, distinct from the canonical profile of B*27. These findings highlight the contribution of non-B*27 HLA-B alleles to SpA susceptibility in an Eastern European population and support the notion that HLA-B*27-negative SpA may represent a distinct clinical and immunological entity, driven by alternative pathogenic mechanisms. They also emphasize the importance of population-specific immunogenetic profiling and support expanding genetic characterization in HLA-B*27-negative patients. Full article

Background/Objectives: Mumps remains a relevant vaccine-preventable disease globally, especially in settings where immunization coverage fluctuates or vaccine-induced immunity wanes. This study aimed to assess long-term trends in mumps incidence, vaccination coverage, clinical outcomes, and demographic characteristics in the Autonomous Province of Vojvodina (AP Vojvodina), Serbia, over a 47-year period. Methods: We conducted a retrospective observational study using surveillance data from the Institute of Public Health of Vojvodina. Analyses included annual mumps incidence rates (1978–2024), coverage with mumps-containing vaccines (MuCVs; 1986–2024), monthly case counts, and individual-level case data for the 1997–2024 period. Variables analyzed included age, month of notification, gender, vaccination status, presence of clinical complications, and the method used for case confirmation. Results: Following the introduction of MuCV in 1986, the mumps incidence markedly declined, with limited resurgences in 2000, 2009, and 2012. Between 1997 and 2024, a total of 1358 cases were reported, with 62.7% occurring in males. Over time, the age distribution shifted, with adolescents and young adults being increasingly affected during the later (2011–2024) observed period. In 2012, the highest age-specific incidence was observed among individuals aged 10–19 and 20–39 years (49.1 and 45.5 per 100,000, respectively). Vaccination coverage for both MuCV doses was suboptimal in several years. The proportion of unvaccinated cases decreased over time, while the proportion with unknown vaccination status increased. Mumps-related complications—such as orchitis, pancreatitis, and meningitis—were rare and predominantly affected unvaccinated individuals: 84.2% of orchitis, 40.0% of pancreatitis, and all meningitis cases. Only two pancreatitis cases (40.0%) were reported after one MMR dose, while fully vaccinated individuals (two doses) had one orchitis case (5.3%) and no other complications. Laboratory confirmation was applied more consistently from 2009 onward, with 49.6% of cases confirmed that year (58 out of 117), and, in several years after 2020, only laboratory-confirmed cases were reported, indicating improved diagnostic capacity. Conclusions: Despite substantial progress in controlling mumps, gaps in vaccine coverage, waning immunity, and incomplete vaccination records continue to pose a risk for mumps transmission. Strengthening routine immunization, ensuring high two-dose MuCV coverage, improving vaccination record keeping, and enhancing laboratory-based case confirmation are critical. Consideration should be given to booster doses in high-risk populations and to conducting a seroepidemiological study to estimate the susceptible population for mumps in AP Vojvodina. Full article

Objective: This study aimed to evaluate the mean age of eruption of permanent teeth and their clinical emergence sequence in a longitudinal sample of children from a multi-ethnic urban population. Methods: A total of 854 children (413 females and 441 males), aged between 4 and 13 years, were examined annually for a minimum of 4 consecutive years, as part of their annual dental screening appointment. The presence of permanent teeth was recorded at each examination. Mean and median ages, with standard deviations, of individual tooth eruption were calculated, in addition to the eruption sequence, and the analysis of the data was performed using the lognormal distribution model. Regarding the error of the method, two examiners reviewed all relevant dental screening forms, and any discrepancies were resolved through consultation with the senior author. Results: The sequence of permanent tooth eruption followed a consistent pattern across sexes, with distinct differences between the maxillary and mandibular arches. In the maxilla, eruption began with the first molar, while in the mandible, it started with the central incisor. Mandibular teeth generally erupted earlier than maxillary teeth, with girls experiencing earlier eruption than boys, with some exceptions, and prolonged eruption periods. No statistically significant differences were found in the timing of eruption between contralateral homologous teeth. Conclusions: Based on the present data, the observed sequence of tooth eruption in a multi-ethnic urban population showed similar patterns across sexes. Mandibular teeth generally erupt earlier than maxillary teeth, with girls experiencing earlier eruption than boys. Full article

Background/Objectives: Health education plays a vital role in training health professionals and caregivers, supporting both prevention and the promotion of self-care. In this context, technology serves as a valuable ally by enabling continuous and flexible learning. Among the various domains of health education, nutrition stands out as a key element in the management of Amyotrophic Lateral Sclerosis (ALS), helping to prevent malnutrition and enhance patient well-being. Accordingly, this study aimed to evaluate the effectiveness of the teaching and learning processes within a learning pathway focused on food and nutrition in the context of ALS. Methods: This study adopted a longitudinal, quantitative design. The learning pathway, titled “Food and Nutrition in ALS,” consisted of four self-paced and self-instructional Massive Open Online Courses (MOOCs), offered through the Virtual Learning Environment of the Brazilian Health System (AVASUS). Participants included health professionals, caregivers, and patients from all five regions of Brazil. Participants had the autonomy to complete the courses in any order, with no prerequisites for enrollment. Results: Out of 14,263 participants enrolled nationwide, 182 were included in this study after signing the Informed Consent Form. Of these, 142 (78%) completed at least one course and participated in the educational intervention. A significant increase in knowledge was observed, with mean pre-test scores rising from 7.3 (SD = 1.8) to 9.6 (SD = 0.9) on the post-test across all courses (p < 0.001). Conclusions: The self-instructional, technology-mediated continuing education model proved effective in improving participants’ knowledge about nutrition in ALS. Future studies should explore knowledge retention, behavior change, and the impact of such interventions on clinical outcomes, especially in multidisciplinary care settings. Full article

Background: Patients in Intensive Care Units (ICUs) often develop non-thyroidal illness syndrome. Potentially, thyroid hormones may be removed during continuous veno-venous hemodiafiltration (CVVHDF), as their molecular size is smaller than the filter pores’ cutoff. The study’s main aim was to assess whether the serum concentration of thyroid hormones changes over time during CVVHDF. Methods: This was a prospective observational trial that included 30 patients treated in an ICU. All patients developed acute kidney injury (AKI) and had clinical indications for implementation of CVVHDF. Blood samples were collected before initiation of CVVHDF and at 1, 2, 3, 6, 9 and 12 days after. The last sample was collected three days after CVVHDF withdrawal. Thyroid function was evaluated by determining the serum concentration of TSH, thyrotropin-releasing hormone (TRH), free triiodothyronine (fT₃), free thyroxine (fT₄), total triiodothyronine (tT₃), total thyroxine (tT₄) and reverse triiodothyronine (rT₃). We additionally calculated the total activity of peripheral deiodinases (G_D) using a mathematical model. Results: TRH and TSH levels remained mostly within normal ranges. fT4 and tT4 were in normal range or slightly below. In contrast, fT3 and tT3 were undetectably low in most patients throughout. Reverse T3 levels remained within normal limits. There were no statistically significant changes in any thyroid hormone levels over the CVVHDF treatment period. The calculated peripheral G_D activity was lower than normal, but importantly, it did not change significantly over time. Conclusions: Thyroid hormones are not lost due to hemodiafiltration. Decreased deiodinases activity is responsible for alterations in serum concentrations of thyroid hormones in patients during CVVHDF. Full article

Background/Objectives: Orbital reconstruction remains one of the most demanding procedures in maxillofacial surgery. It requires not only precise anatomical knowledge but also poses multiple intraoperative challenges. Limited surgical visibility—especially in transconjunctival or transcaruncular approaches—demands exceptional precision from the surgeon. At the same time, the complex anatomical structure of the orbit, its rich vascularization and innervation, and the risk of severe postoperative complications—such as diplopia, sensory deficits, impaired ocular mobility, or in the most serious cases, post-traumatic blindness due to nerve injury or orbital compartment syndrome—necessitate the highest level of surgical accuracy. In this context, patient-specific implants (PSIs), commonly fabricated from zirconium oxide or ultra-high-density polyethylene, have become invaluable. Within CAD-based reconstructive planning, especially for orbital implants, critical factors include the implant’s anatomical fit, passive stabilization on intact bony structures, and non-interference with orbital soft tissues. Above all, precise replication of the orbital dimensions is essential for optimal clinical outcomes. This study compares the morphological accuracy of orbital structures based on anthropometric measurements from 3D models generated from fan-beam computed tomography (FBCT) and cone-beam computed tomography (CBCT). Methods: A cohort group of 500 Caucasian patients aged 8 to 88 years was analyzed. 3D models of the orbits were generated from FBCT and CBCT scans. Anthropometric measurements were taken to evaluate the morphological accuracy of the orbital structures. The assessed parameters included orbital depth, orbital width, the distance from the infraorbital rim to the infraorbital foramen, the distance between the piriform aperture and the infraorbital foramen, and the distance from the zygomatico-orbital foramen to the infraorbital rim. Results: Statistically significant differences were observed between virtual models derived from FBCT and those based on CBCT in several key parameters. Discrepancies were particularly evident in measurements of orbital depth, orbital width, the distance from the infraorbital rim to the infraorbital foramen, the distance between the piriform aperture and the infraorbital foramen, and the distance from the zygomatico-orbital foramen to the infraorbital rim. Conclusions: The statistically significant discrepancies in selected orbital dimensions—particularly in regions of so-called thin bone—demonstrate that FBCT remains the gold standard in the planning and design of CAD/CAM patient-specific orbital implants. Despite its advantages, including greater accessibility and lower radiation dose, CBCT shows limited reliability in the context of orbital and infraorbital reconstruction planning. Full article

Background/Objectives: Dry eye (DE) can cause persistent eye rubbing, contributing to keratoconus (KC) development and progression. Both keratoconus (KC) and dry eye (DE) significantly impact patients’ functional and emotional well-being, with KC patients exhibiting a higher prevalence of DE symptoms and signs. This study examined whether functional (KEPAQ-F) and emotional (KEPAQ-E) quality of life, assessed by the Keratoconus End-Points Assessment Questionnaire, differ when influenced by symptoms and clinical signs of general DE versus meibomian gland dysfunction (MGD) in KC patients. Methods: Volunteers with KC (ages 18–70) underwent DE and MGD assessments, completing OSDI, MGD (MGDQ), and KEPAQ questionnaires. Clinical measures included NITBUT, Schirmer, and meibography. Pearson correlations and path analysis assessed relationships between DE and MGD symptoms and KEPAQ-F/E. Results: Forty-five KC participants (mean age: 45 ± 13, range: 20–69 years, 25 males) were enrolled; 22 (49%) had DE, and 15 (33%) had MGD. Significant correlations were observed between KEPAQ-E (2.9 ± 3.0 Logit) and KEPAQ-F (1.7 ± 3.0 Logit) scores with OSDI (26.5 ± 26.7) and MGDQ (3.3 ± 2.2) scores, and all Belin outcome measures A-D for all participants. In participants with diagnosed dry eye, KEPAQ E and F were also significantly correlated with loss of meibomian glands in the lower eyelids (R = −0.44, p = 0.04). Path analysis showed both DE and MGD were negatively correlated with lower KEPAQ-E and KEPAQ-F scores, with DE symptoms were more influential (p < 0.05). The model explained 42% of the KEPAQ-E variance and 41% of the KEPAQ-F variance. Conclusions: Emotional and functional quality of life in KC is significantly and negatively related to DE and MGD symptoms, with DE symptoms exhibiting a greater impact. Furthermore, greater loss of meibomian glands in the lower eyelids is significantly associated with reduced emotional and functional KEPAQ scores in DE patients. These results underscore the critical importance of evaluating DE in KC to improve patient-reported outcomes. Full article

Background/Objectives: The TOPAZ-1 phase III trial reported a survival benefit of using durvalumab, an anti-programmed death ligand 1 (anti-PD-L1) antibody, in combination with gemcitabine and cisplatin (GCD) treatment in patients with advanced biliary tract cancer. This retrospective study investigated the efficacy and safety of GCD treatment for advanced biliary tract cancer in real-world conditions. Methods: The study subjects were 52 patients with biliary tract cancer who received GCD therapy between January 2023 and May 2024. The observation parameters included the modified Glasgow Prognostic Score (mGPS), neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), tumor markers (CEA, CA19-9), overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events. Results: The cohort included 36 men and 16 women, with a median age of 73.0 years. There were 36 cases of cholangiocarcinoma (distal: 10, perihilar: 19, intrahepatic: 7), 13 cases of gallbladder cancer, and 3 cases of ampullary carcinoma. The stages were locally advanced in 30 cases and metastatic in 22 cases. Biliary drainage was performed in 30 cases. There were 38 cases receiving first-line therapy and 14 cases receiving second-line or later treatments. The median values at the start of GCD therapy were ALB 3.7 g/dL, CRP 0.39 mg/dL, NLR 2.4, PLR 162.5, CEA 4.8 ng/mL, and CA19-9 255.9 U/mL. The mGPS distribution was 0:23 cases, 1:18 cases, and 2:11 cases. The treatment outcomes were ORR 25.0% (CR 2 cases, PR 11 cases), DCR 78.8% (SD 28 cases, PD 10 cases, NE 1 case), median PFS 8.6 months, and median OS 13.9 months. The PLR was suggested to be useful for predicting PFS. A decrease in CEA at six weeks after the start of treatment was a significant predictor of PFS and OS. Gallbladder cancer had a significantly poorer prognosis compared to other cancers. The immune-related adverse events included hypothyroidism in two cases, cholangitis in one case, and colitis in one case. Conclusions: The ORR, DCR, and PFS were comparable to those in the TOPAZ-1 trial. Although limited by its retrospective design and small sample size, this study suggests that GCD therapy is an effective treatment regimen for unresectable biliary tract cancer in real-world clinical practice. Full article

Multidrug-resistant (MDR) strains of Klebsiella pneumoniae present an acute threat as they continue to disseminate globally. Phage therapy has shown promise as a powerful approach to combat MDR infections, but narrow phage host ranges make development of broad acting therapeutics more challenging. The goal of this effort was to use in vitro directed evolution (the “Appelmans protocol”) to isolate K. pneumoniae phages with broader host ranges for improved therapeutic cocktails. Five myophages in the genus Jiaodavirus (family Straboviridae) with complementary activity were mixed and passaged against a panel of 11 bacterial strains including a permissive host and phage-resistant clinical isolates. Following multiple rounds of training, we collected phage variants displaying altered specificity or expanded host ranges compared with parental phages when tested against a 100 strain diversity panel of K. pneumoniae. Some phage variants gained the ability to lyse previously phage-resistant strains but lost activity towards previously phage-susceptible strains, while several variants had expanded activity. Whole-genome sequencing identified mutations and recombination events impacting genes associated with host tropism including tail fiber genes that most likely underlie the observed changes in host ranges. Evolved phages with broader activity are promising candidates for improved K. pneumoniae therapeutic phage cocktails. Full article

Anomalies of coronary artery origins are rare but significant conditions that can range from benign to life-threatening. Early detection through imaging is crucial in preventing adverse outcomes. The treatment strategy varies depending on the type and severity of the anomaly, ranging from pharmacological treatment to surgery. A 22-year-old male patient, after syncope, after excluding other causes, had an exercise drill test, which was clinically negative and ECG-positive. Angio-CT revealed an undeveloped left main coronary artery (LMCA), and the circulation was supplied through the right coronary artery (RCA). The RCA provides the left anterior descending artery (LAD), and the LAD retrogradely supplies the left circumflex artery (LCX). The myocardial perfusion scintigraphy showed a slight lack of perfusion in the anterior wall (6% of total perfusion). The patient was qualified for further observation. A 77-year-old female underwent cardiac CT due to stenocardia. CT showed a lack of LMCA. The initial segment of the RCA gave rise to the left coronary artery (LCA), which encircled the aortic bulb posteriorly and bifurcated into branches resembling the LCX and LAD. After the Heart Team consultation, the patient was deemed eligible for conservative treatment. Angio-CT is a valuable tool for detecting coronary artery anomalies. Full article

Background: Electrocardiograms (EKGs) are essential tools in emergency medicine, often used to evaluate chest pain, dyspnea, and other symptoms suggestive of cardiac dysfunction. Yet, EKGs are not universally administered to all emergency department (ED) patients. Understanding and predicting which patients receive an EKG may offer insights into clinical decision making, resource allocation, and potential disparities in care. This study examines whether integrating structured clinical data with free-text patient narratives can improve prediction of EKG utilization in the ED. Methods: We conducted a retrospective observational study to predict electrocardiogram (EKG) utilization using data from 13,115 adult emergency department (ED) visits in the nationally representative 2021 National Hospital Ambulatory Medical Care Survey–Emergency Department (NHAMCS-ED), leveraging both structured features—demographics, vital signs, comorbidities, arrival mode, and triage acuity, with the most influential selected via Lasso regression—and unstructured patient narratives transformed into numerical embeddings using Clinical-BERT. Four supervised learning models—Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF) and Extreme Gradient Boosting (XGB)—were trained on three inputs (structured data only, text embeddings only, and a late-fusion combined model); hyperparameters were optimized by grid search with 5-fold cross-validation; performance was evaluated via AUROC, accuracy, sensitivity, specificity and precision; and interpretability was assessed using SHAP values and Permutation Feature Importance. Results: EKGs were administered in 30.6% of adult ED visits. Patients who received EKGs were more likely to be older, White, Medicare-insured, and to present with abnormal vital signs or higher triage severity. Across all models, the combined data approach yielded superior predictive performance. The SVM and LR achieved the highest area under the ROC curve (AUC = 0.860 and 0.861) when using both structured and unstructured data, compared to 0.772 with structured data alone and 0.823 and 0.822 with unstructured data alone. Similar improvements were observed in accuracy, sensitivity, and specificity. Conclusions: Integrating structured clinical data with patient narratives significantly enhances the ability to predict EKG utilization in the emergency department. These findings support a personalized medicine framework by demonstrating how multimodal data integration can enable individualized, real-time decision support in the ED. Full article

Background: HIV-associated neurocognitive disorders (HANDs) continue to be a significant concern, despite the advancements in prognosis achieved through Combination Antiretroviral Therapy (cART). Neuropsychological assessment, recommended by international guidelines for HANDs diagnosis, can be resource-intensive. Brief screening tools, like the International HIV Dementia Scale (IHDS) and the Montreal Cognitive Assessment (MoCA), are crucial in facilitating initial evaluations. This study aims to assess the Italian IHDS (IHDS-IT) and evaluate its sensitivity and specificity in detecting cognitive impairment in HIV patients. Methods: This cross-sectional study involved 294 patients aged ≥30 years, evaluated at the Immunology Unit of the University of Cagliari. Cognitive function was assessed using the MoCA and IHDS. Laboratory parameters, such as CD4 nadir, current CD4 count, and HIV-RNA levels, were also collected. Statistical analyses included Spearman’s correlation, Receiver Operating Characteristic analysis, and the Youden J statistic to identify the optimal IHDS-IT cut-off for cognitive impairment detection. Results: The IHDS and MoCA scores showed a moderate positive correlation (Spearman’s rho = 0.411, p < 0.0001). ROC analysis identified an IHDS-IT cut-off of ≤9, yielding an Area Under the Curve (AUC) of 0.76, sensitivity of 71.7%, and specificity of 67.2%. At this threshold, 73.1% of patients with MoCA scores below 23 also presented abnormal IHDS scores, highlighting the complementary utility of both cognitive assessment instruments. Conclusions: The IHDS-IT exhibited fair diagnostic accuracy for intercepting cognitive impairment, with a lower optimal cut-off than previously reported. The observed differences may reflect this study cohort’s demographic and clinical characteristics, including advanced age and long-lasting HIV infection. Further, longitudinal studies are necessary to validate these findings and to confirm the proposed IHDS cut-off over extended periods. Full article

Background/Objectives: The Fanconi anemia (FA) pathway is essential for the repair of DNA interstrand crosslinks and maintenance of genomic stability. Germline loss of FA pathway function in the inherited Fanconi anemia syndrome leads to increased DNA damage and a range of clinical phenotypes, including a heightened risk of head and neck squamous cell carcinoma (HNSCC). Non-synonymous FA gene mutations are also observed in up to 20% of sporadic HNSCCs. The mechanistic target of rapamycin (mTOR) is known to stimulate cell growth, anabolic metabolism including protein synthesis, and survival following genotoxic stress. Methods/Results: Here, we demonstrate that FA− deficient (FA−) HNSCC cells exhibit elevated intracellular amino acid levels, increased total protein content, and an increase in protein synthesis indicative of enhanced translation. These changes are accompanied by hyperactivation of the mTOR effectors translation initiation factor 4E Binding Protein 1 (4E-BP1) and ribosomal protein S6. Treatment with the mTOR inhibitor rapamycin reduced the phosphorylation of these targets and blocked translation specifically in FA− cells but not in their isogenic FA− proficient (FA+) counterparts. Rapamycin-mediated mTOR inhibition sensitized FA− but not FA+ cells to rapamycin under nutrient stress, supporting a therapeutic metabolism-based vulnerability in FA− cancer cells. Conclusions: These findings uncover a novel role for the FA pathway in suppressing mTOR signaling and identify mTOR inhibition as a potential strategy for targeting FA− HNSCCs. Full article