Search Results (596)

Small mammals in temperate areas frequently face fluctuations in food resources, and food shortage is a key factor affecting their immune function. In order to understand whether immune function and gut microbiota change under food shortage, adult male Brandt’s voles (Lasiopodomys brandtii) were used and divided into Fed (Fed, n = 8), 80% food restriction (80% FR, n = 10) and 60% food restriction (60% FR, n = 9) groups. The experimental course lasted for 35 days. Food restriction reduced body mass (p < 0.001) but did not affect total fat mass (p = 0.532) or blood glucose levels (p = 0.777) compared with the Fed voles. Immunological parameters—including wet masses of thymus and spleen, phytohemagglutinin (PHA) responses at 6 h, 12 h, 24 h, and 48 h post PHA injection, interleukin-4 (IL-4) levels (p = 0.700), the counts of white blood cells (p = 0.864), lymphocytes (p = 0.692), and neutrophils (p = 0.729)—were not influenced by food restriction, indicating that voles could maintain stable immune function under food shortage. Similarly, leptin (p = 0.219) and corticosterone (CORT) (p = 0.282) levels were also not impacted by food restriction, and no correlation existed between these two hormones and the above immunological indices. However, interferon-γ (IFN-γ) (p < 0.001) levels in the 80% FR group were the highest among the three groups. Food restriction had no effect on alpha (α)-diversity of the gut microbiota, indicating that food restriction does not affect their diversity or richness. Food restriction did not affect relative abundance at the phylum or genus levels, nor at most family levels, but reduced Erysipelotrichaceae at the family level. In summary, Brandt’s voles could maintain stable energy status, leptin and corticosterone levels, and the diversity and richness of the gut microbiota under food restriction, which may help us to understand this species’ ability to survive well in times of food shortage. Full article

Objective: Axonal injury is a key determinant in irreversible disability in multiple sclerosis (MS). Reliable biomarkers of neuroaxonal damage are essential for improving diagnosis, monitoring disease progression, and evaluating treatment response. This study investigated the relationship between phosphorylated neurofilament heavy chain (pNF-H), clinical characteristics, and conventional cerebrospinal fluid (CSF) and serum biomarkers in Algerian patients with MS. Methods: A total of 102 participants were enrolled. Clinical, immunological, and biochemical parameters were assessed, including the Expanded Disability Status Scale (EDSS), oligoclonal bands (OCBs), IgG index, albumin quotient, and pNF-H concentrations in paired CSF and serum samples. Results: OCBs were detected in 85.5% of patients, and 65.21% exhibited intrathecal immunoglobulin synthesis, with a median IgG index of 0.87. Patients with progressive MS were significantly older and more disabled than those with relapsing–remitting MS (age: p = 0.01; EDSS: p = 0.0007). OCB-positive patients had significantly higher IgG index values (p = 0.0004), but OCB status was not associated with age, EDSS, or albumin quotient. EDSS correlated positively with age (p = 0.0007), albumin quotient (p = 0.01), and IgG index (p = 0.001). Both CSF and serum pNF-H levels were significantly elevated in MS patients compared with NSDs group (p < 0.001). Increased pNF-H concentrations were associated with progressive disease and greater disability (EDSS ≥ 5). Conclusions: Elevated pNF-H levels in CSF and serum are associated with disease severity and progressive MS, supporting their potential as complementary biomarkers of neuroaxonal damage and clinical disability in routine MS assessment. Full article

Background/Objectives: Lung cancer remains the leading cause of cancer-related mortality worldwide, and surgical resection is the primary curative treatment for patients with early-stage non-small cell lung cancer (NSCLC). Patients undergoing lung cancer surgery are frequently affected by malnutrition, systemic inflammation, sarcopenia, and cancer-related cachexia, which may adversely affect postoperative recovery and clinical outcomes. Perioperative immunonutrition has been proposed as a strategy to support immune and metabolic responses associated with surgical stress. This narrative review summarizes current evidence regarding the role of perioperative immunonutrition in patients undergoing lung cancer surgery. Methods: This narrative review summarizes current evidence regarding perioperative immunonutrition in patients undergoing lung cancer surgery. Relevant studies evaluating perioperative immunonutrition, including formulations enriched with arginine, omega-3 fatty acids, glutamine, and nucleotides, were analyzed. Particular attention was given to clinical studies in thoracic surgical oncology, perioperative outcomes, inflammatory response, and current nutritional guideline recommendations. Results: Available evidence suggests that perioperative immunonutrition may improve nutritional and immunological status in patients undergoing lung cancer surgery. Clinical studies have reported reductions in postoperative complications, shorter chest drainage duration, improved nutritional indices, and decreased inflammatory markers in patients receiving immunonutritional support. Experimental and translational studies also indicate potential beneficial effects on immune cell function and inflammatory regulation. However, current thoracic-specific evidence remains limited because of small study populations, heterogeneity of nutritional protocols, and variability in study design. Conclusions: Perioperative immunonutrition appears to be a promising adjunct to comprehensive perioperative care in patients undergoing lung cancer surgery. Although preliminary evidence suggests potential benefits in postoperative recovery and nutritional optimization, its implementation should be individualized according to the patient’s nutritional status, disease stage, and overall treatment strategy. As immunonutrition modulates metabolic and immune pathways that may also influence tumor biology, nutritional interventions should be evidence-based, carefully monitored, and integrated within multidisciplinary perioperative care to maximize clinical benefits while minimizing potential unintended effects. Further large, well-designed randomized clinical trials are needed to establish standardized protocols and clarify the role of immunonutrition in thoracic surgical oncology. Full article

Background: Nutritional abnormalities, alterations in body composition, and impaired muscle function are increasingly recognized as clinically relevant features in patients with Systemic Lupus Erythematosus (SLE). However, the relationship between multidimensional nutritional assessment and disease activity remains incompletely characterized. This study aimed to evaluate the associations between nutritional status, body composition, muscle strength, nutritional risk indices, and disease activity in patients with SLE. Materials and Methods: This exploratory retrospective study included hospitalized patients with SLE. Clinical data, anthropometric measurements, and nutritional status were assessed using the body mass index (BMI), prognostic nutritional index (PNI), controlling nutritional status (CONUT), and nutritional risk index (NRI). Muscle function was evaluated using the SARC-F scale. Disease activity was measured using the SLE Disease Activity Index 2000 (SLEDAI-2K). Multivariable linear regression models were constructed to assess the independent association between nutritional indices and disease activity, adjusting for age, sex, glucocorticoid exposure, and immunosuppressive therapy. Correlation analyses were performed between nutritional indices and disease activity-related variables, and supplementary exploratory Spearman correlations were performed between the SARC-F score and SLEDAI-2K, CRP, complement C3, complement C4, and ESR. False discovery rate correction using the Benjamini–Hochberg procedure was applied to exploratory correlation analyses. Results: A total of 67 patients were included. Nutritional indices (BMI, PNI, CONUT, and NRI) were not independently associated with SLEDAI-2K in multivariable regression analyses. In correlation analyses, after FDR adjustment, the PNI remained significantly associated with SLEDAI-2K, lymphocyte counts, and complement C3 levels, while CONUT remained significantly associated with lymphocyte count and C3 levels. The BMI and NRI were not significantly associated with disease activity or inflammatory markers after correction. SARC-F showed a weak positive correlation with SLEDAI-2K (r = 0.328; p = 0.008; qFDR = 0.040), which remained statistically significant after FDR correction. No significant correlations were observed between SARC-F and CRP, complement C3, complement C4, or ESR after FDR adjustment. Conclusions: Nutritional indices showed limited independent association with disease activity in SLE after adjustment for available confounders. Although the PNI and CONUT retained selected correlations with disease activity-related or immunological markers after FDR correction, these associations should be interpreted cautiously, as albumin- and lymphocyte-based indices may reflect inflammatory activity or disease burdens rather than nutritional status alone. SARC-F remains significantly associated with disease activity (SLEDAI-2K) after FDR adjustment. These findings should be validated in future prospective studies with a larger number of patients. Full article

Hepatitis B virus (HBV) infection remains a major driver of liver-related morbidity and mortality among people living with HIV (PLWH), yet vaccine-induced protection is frequently suboptimal. HIV-associated immune dysfunction, including CD4⁺ T-cell depletion, altered antigen presentation, impaired T follicular helper cell support, and B-cell dysregulation, reduces seroprotection after standard recombinant HBV vaccines and may limit durability of antibody responses. Vaccine response is further influenced by HIV viral suppression, age, comorbidities, prior vaccine history, and baseline HBV serologic status, including isolated hepatitis B core antibody (anti-HBc) and occult HBV infection (OBI) considerations. Although antiretroviral therapy (ART) improves vaccine responsiveness, many PLWH fail to achieve protective hepatitis B surface antibody (anti-HBs) titers (≥10 mIU/mL) after conventional schedules, or experience antibody waning over time. Current guidelines recommend HBV vaccination for all susceptible PLWH with post-vaccination serologic testing and revaccination for nonresponders. Persistent implementation barriers, including incomplete series, vaccine hesitancy, stigma, and logistical constraints, continue to limit real-world impact. Emerging clinical trial data support CpG-adjuvanted HBV vaccines (HepB-CpG/Heplisav-B) and intensified dosing and schedules (double-dose or four-dose regimens) to improve seroprotection and generate higher peak anti-HBs titers, which may enhance durability. This review synthesizes guideline recommendations, immunologic mechanisms of hyporesponsiveness, predictors of vaccine response, and practical strategies to optimize HBV vaccination in PLWH. Full article

Background: Neonatal sepsis caused by multidrug-resistant (MDR) Gram-negative pathogens poses significant therapeutic challenges in neonatal intensive care units (NICUs), particularly in surgical neonates. Ceftazidime-avibactam (CAZ-AVI), a novel β-lactam/β-lactamase inhibitor combination, offers activity against extended-spectrum β-lactamases (ESBLs), AmpC, and serine carbapenemases, but neonatal experience remains limited. Methods and Results: We present a 35-week preterm neonate with long-gap esophageal atresia who developed late-onset sepsis caused by MDR Enterobacter hormaechei, including a KPC-producing carbapenem-resistant isolate, during postoperative recovery. After a multidisciplinary review, the patient received off-label CAZ-AVI at 25 mg/kg/dose (20/5 mg/kg) every 8 h, infused over 2 h, informed by available neonatal pharmacokinetic evidence and weight-adjusted dosing recommendations. Amikacin was administered contextually. Consecutive blood cultures obtained 48–72 h after dual antibiotic therapy initiation became negative and remained sterile, with concordant decline in inflammatory biomarkers, confirming rapid microbiological clearance. Unfortunately, the newborn died in the hours immediately following the final surgery performed to repair the esophageal atresia via end-to-end anastomosis; the cause was complications (hemothorax) unrelated to infectious diseases, although the onset of such severe sepsis may have compromised an already impaired immunological status. Discussion: This case shows mechanism-concordant antimicrobial selection and the feasibility of neonatal dosing when MDR Enterobacterales drive invasive infection. Our experience supports prospective evaluation of CAZ-AVI in carefully selected septic newborns while emphasizing the importance of rapid carbapenemase genotyping, susceptibility testing, and multidisciplinary oversight. Full article

Background: Intestinal parasitic infections are common in tropical settings and may influence immune regulation, allergic responses, and respiratory health. In children with sickle cell disease (SCD), respiratory morbidity is multifactorial, and the contribution of intestinal parasites remains uncertain. This study assessed whether documented intestinal parasitic infections, particularly helminth infections, were associated with asthma-like respiratory phenotypes and clinical morbidity in children with SCD in French Guiana. Methods: We conducted a multicenter cross-sectional analysis of children and adolescents younger than 18 years with confirmed SCD who were being followed by the pediatric SCD centers of Saint-Laurent-du-Maroni, Cayenne, and Kourou between January 2022 and December 2025. Clinical, respiratory, and parasitological data were extracted from routine-care medical records. Intestinal parasitic infection was defined as at least one documented stool parasitology result identifying Strongyloides stercoralis, hookworm, or Entamoeba histolytica, according to the variables consistently available in the database. Respiratory outcomes included physician-diagnosed asthma, bronchial obstruction, bronchodilator reversibility, and an asthma-like respiratory phenotype. Results: Among 233 included children, 105 (45.1%) had at least one documented intestinal parasitic infection and 82 (35.2%) had a helminth infection. Hookworm was the most common parasite (75/233, 32.2%), followed by Entamoeba histolytica (33/233, 14.2%) and Strongyloides stercoralis (24/233, 10.3%). An asthma-like respiratory phenotype was observed in 32/105 infected children (30.5%) versus 44/128 non-infected children (34.4%). Bronchial obstruction and bronchodilator reversibility were also similar between groups. After adjustment for age, sex, genotype, hydroxyurea treatment, rural residence, site of follow-up, and environmental tobacco smoke exposure, intestinal parasitic infection was not associated with asthma-like respiratory phenotype (adjusted OR: 0.94, 95% CI: 0.51–1.72; p = 0.844), recurrent hospitalization, or history of acute chest syndrome. Conclusions: In this routine-care multicenter pediatric SCD cohort from French Guiana, intestinal parasitic infections were common but were not associated with respiratory phenotype or selected morbidity outcomes. Because testing and respiratory assessment were not systematic, these findings should be interpreted as showing that routine parasitological status alone could not identify children with respiratory morbidity. Prospective studies with standardized repeated parasitological, immunological, environmental, and respiratory assessments are needed. Full article

Soluble immune checkpoints (sICs) have emerged as potential biomarkers in various cancers. However, their role in extensive-stage small cell lung cancer (ES-SCLC), an aggressive tumor type with limited therapeutic options and poor prognosis, remains poorly characterized. We analyzed 14 circulating sICs, leukocyte–platelet (PLT) complexes, and PD-L1 surface expression in ES-SCLC patients treated with chemoimmunotherapy (n = 41) prior to treatment and healthy donors (HD, n = 10). We assessed their associations with clinical and demographic factors and performed survival analyses using Kaplan–Meier and log-rank tests. Levels of soluble (s) PD-L1, PD-L2, BTLA, HVEM, TIM-3, and CD27 were higher in plasma from ES-SCLC patients compared to those from HD (p < 0.05). Patients with liver metastases exhibited higher sIC levels, and a multivariate model demonstrated discriminative power. Network analyses revealed distinct patterns of immune dysregulation between ES-SCLC and HD. We observed correlations among sICs and leukocyte–PLT complexes and leukocyte PD-L1 expression, indicating links between systemic immune status and tumor–immune interactions. Furthermore, increased concentrations of sTIM-3, sCD27, sHVEM and sPD-L1 were associated with a poor prognosis. Overall, sICs reflect relevant clinical, prognostic, and immunological features in ES-SCLC. Their plasma measurement could aid in non-invasive patient stratification regarding liver metastases and survival risk. Full article

Background: Cigarette smoking promotes persistent systemic alterations in COPD, yet the interplay among genetic susceptibility, oxidative stress, immune dysregulation, impaired control of persistent viral replication, and long-term outcomes remains incompletely understood. Methods: We conducted an observational study in 102 patients aged ≥70 years with severe-to-very-severe COPD undergoing pulmonary rehabilitation. Current smokers (n = 38) were compared with never/former smokers (n = 64). Analyses included Chr15q25 genotyping (rs16969968), oxidative stress biomarkers (tail intensity, 8-OHdG, MDA, and bilirubin), hematological and immunological parameters, α7nAChR expression, TTV load as a surrogate marker of immune competence, latent virus prevalence, and five-year survival assessed by multivariable Cox regression. Results: Current smokers exhibited significantly higher DNA damage (tail intensity, p = 0.001; 8-OHdG, p = 0.002), lower bilirubin levels (p = 0.031), increased neutrophil and CD4⁺ T-cell counts (p = 0.031 and p = 0.028, respectively), altered α7nAChR expression on CD4⁺ T cells (p = 0.030), and higher TTV load (p = 0.002) than never/former smokers. The rs16969968 AA genotype was more frequent among current smokers. In survival analyses, an elevated WBC count was independently associated with increased mortality risk (HR 1.12, 95% CI 1.01–1.23; p = 0.035), whereas higher bilirubin levels showed a protective association. TTV load, smoking status, and FEV1 were not independently associated with mortality. Conclusions: In severe-to-very-severe COPD, smoking is associated with a distinct biological profile characterized by enhanced oxidative DNA damage, systemic inflammation, immune remodeling, reduced antioxidant defenses, and impaired control of persistent viral replication. WBC and bilirubin emerged as the biomarkers most consistently associated with long-term outcomes. These findings support integrated biological profiling as a tool for risk stratification and precision-guided rehabilitation in advanced COPD. Full article

Background: KRAS mutations are among the most common oncogenic drivers in non-small cell lung cancer (NSCLC) and are associated with substantial molecular and immunological heterogeneity. However, the clinicopathological associations and prognostic relevance of KRAS mutation subtypes and co-occurring genomic alterations in relation to PD-L1 expression and survival outcomes remain incompletely understood, particularly in the immunotherapy era. Methods: This retrospective single-center study included 93 KRAS-mutant NSCLC patients identified among 543 consecutively sequenced cases between March 2024 and March 2025. KRAS mutation subtypes, co-mutations involving TP53, STK11, and KEAP1, PD-L1 expression status, clinicopathological features, and survival outcomes were evaluated. Overall survival was assessed using Kaplan–Meier analysis and Cox proportional hazards regression models. Results: KRAS mutations were detected in 17.1% of NSCLC patients. G12C was the most frequent KRAS subtype (38.7%), followed by G12V (18.3%) and G12D (14.0%). Co-occurring mutations were identified in 73.1% of cases, most commonly involving TP53 (40.9%) and STK11 (33.3%). PD-L1 expression was negative in 48.4% of patients, low in 28.0%, and high in 23.7%. No significant association was identified between KRAS mutation subtype and PD-L1 expression (p = 0.663). STK11-mutated tumors demonstrated a trend toward lower PD-L1 expression levels compared with STK11 wild-type tumors. However, none of the molecular variables retained independent prognostic significance. Immunotherapy was associated with significantly prolonged overall survival (median OS: 24 vs. 7 months, p = 0.013) and remained independently associated with improved survival in multivariate analysis (HR: 0.376, 95% CI: 0.204–0.694, p = 0.002). Advanced-stage disease independently predicted worse survival outcomes (HR: 13.43, 95% CI: 1.81–99.79, p = 0.011). Conclusions: KRAS mutation subtypes and co-occurring genomic alterations demonstrated limited independent prognostic significance in this real-world NSCLC cohort. In contrast, immunotherapy was associated with improved overall survival in this retrospective cohort. These findings should be interpreted as observational and hypothesis-generating rather than evidence of predictive treatment benefit. Larger prospective studies integrating genomic and immune biomarkers are warranted. Full article

Background: Vitamin D is involved not only in calcium–phosphate homeostasis but also in immune and endothelial regulation. Vitamin D deficiency has been suggested to worsen disease activity in systemic lupus erythematosus (SLE). Environmental and lifestyle factors, including seasonal sun exposure, smoking, diet, and supplementation, may influence vitamin D status and disease manifestations. This study aimed to evaluate the association between serum 25-hydroxyvitamin D [25(OH)D] levels, disease activity, and anti-double-stranded DNA (anti-dsDNA) antibody titers in patients with SLE, taking selected lifestyle and environmental factors into account. Methods: Serum 25(OH)D concentrations, SLE disease activity assessed by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, and anti-dsDNA antibody titers were measured in patients with SLE and healthy controls. Blood samples were collected during sunny (April–September) and non-sunny (October–March) months. Information on vitamin D supplementation, smoking status, and dietary habits was obtained using a structured questionnaire. Associations between vitamin D status, disease activity, anti-dsDNA seropositivity, season of blood collection, supplementation, smoking, and diet were analyzed statistically. Results: Patients with SLE had significantly higher mean serum 25(OH)D levels than controls, mainly due to frequent vitamin D supplementation. No significant associations were observed between serum 25(OH)D levels and SLEDAI-2K scores or anti-dsDNA antibody positivity. Seasonality, smoking status, and adherence to special diets were not significantly related to disease activity or anti-dsDNA seropositivity. Vitamin D supplementation was strongly associated with sufficient 25(OH)D levels but did not translate into reduced disease activity or lower anti-dsDNA prevalence. Conclusions: Serum 25(OH)D concentration was not associated with clinical or immunological activity of SLE in this cross-sectional study, despite effective correction of deficiency through supplementation. These findings likely reflect the heterogeneity of SLE and the limitations of single time-point assessments, although regular monitoring and individualized vitamin D supplementation may still be considered in SLE care, particularly in the context of recommended photoprotection. Full article

Background: Rheumatoid arthritis (RA) is associated with increased cardiovascular risk beyond traditional risk factors. Carotid intima–media thickness (IMT) is a marker of subclinical atherosclerosis and may be influenced by chronic inflammation in RA. Objectives: This study aimed to compare carotid IMT between women with RA and age-matched controls, and to investigate the associations between IMT and RA-related factors, including disease duration, menopausal status, anti-cyclic citrullinated peptide (anti-CCP) antibodies and the CD4/CD8 T-cell ratio. Methods: This cross-sectional study included 59 women with RA and 55 age-matched controls. All RA patients received methotrexate and had no recent biologic DMARD exposure. Carotid IMT was measured by B-mode ultrasonography. Clinical, laboratory, and immunologic parameters, including anti-CCP antibodies and CD4/CD8 ratio, were analyzed. Results: Mean carotid IMT was significantly higher in RA patients than in controls (0.85 ± 0.09 vs. 0.63 ± 0.08 mm, p < 0.0001). Within the RA group, IMT correlated positively with disease duration (r = 0.48, p < 0.001), years since menopause (ρ = 0.44, p = 0.001), anti-CCP titers (r = 0.31, p = 0.018) and CD4/CD8 ratio (r = 0.42, p < 0.001), and inversely with CD8 T-cell counts (r = −0.34, p = 0.009). In multivariable analysis, RA duration and CD4/CD8 ratio remained independently associated with IMT after adjustment for age, lipids and blood pressure. Conclusions: Women with RA had greater carotid IMT than age-matched controls. Longer disease duration and a higher CD4/CD8 ratio were independently associated with IMT, supporting a link between cumulative disease burden, T-cell imbalance and subclinical carotid atherosclerosis in RA. These findings support routine cardiovascular risk assessment and consideration of vascular imaging in high-risk RA subgroups. Full article

Purpose: Lymphopenia is a common adverse event following radiotherapy, but its prognostic relevance following comprehensive involved-site radiation (ISRT) for oligometastatic disease is unknown. We evaluated lymphocyte kinetics after ISRT for oligometastases and tested whether treatment-related lymphopenia was associated with overall survival (OS) and modified progression-free survival (mPFS). Patients and Methods: We performed a single-institution registry study of consecutive patients with 1 to 5 distant metastases treated with comprehensive ISRT by a single radiation oncologist from 2014 to 2023. Systemic therapy was administered at clinician discretion. Absolute lymphocyte count (ALC) was collected at baseline, during radiation and at 1, 3 and 12 months after radiotherapy. Lymphopenia was graded using CTCAE v5.0 (grade 1, ALC < 1000 cells/µL; grade ≥ 3, ALC < 500 cells/µL). OS and mPFS (defined as death or metastatic progression not salvageable with further local therapy) were estimated by the Kaplan–Meier method. Associations were evaluated using univariable and multivariable Cox proportional hazards models. Results: Among 177 patients, the 5-year OS was 39.6% and the median OS was 42.8 months. Median ALC declined from 1400 cells/µL at baseline to 800 cells/µL during radiotherapy (p < 0.01) and 700 cells/µL at a median of 0.7 months after radiation (p < 0.01). Partial recovery was observed at 1000 cells/µL at 3 months (p < 0.001) and 1000 cells/µL at 1 year (p < 0.01). Baseline ALC <1000 cells/µL was associated with worse OS on univariable analysis (p = 0.04) but not on multivariable analysis. Although 27% developed grade ≥ 3 lymphopenia within 3 months of radiation, the 5-year overall survival was 41.4% without lymphopenia versus 31.9% with lymphopenia (p = 0.60). On multivariable analysis, ECOG performance status (HR 1.9, p < 0.01), age (HR 1.04, p < 0.01), albumin (HR 0.6, p = 0.03), and pre-radiation chemotherapy (HR 3.1, p < 0.01) independently predicted overall survival. Conclusions: Comprehensive ISRT for oligometastatic disease was associated with a sustained decrease in median ALC. Treatment-related lymphopenia was not independently associated with OS in this heterogeneous cohort. The disease control benefit of metastasis-directed therapy may outweigh potential detrimental immunologic effects of radiation-induced lymphopenia. Full article

Background: Torque teno virus (TTV) is a ubiquitous, non-pathogenic component of the human virome whose role in people living with HIV (PLWH), particularly during antiretroviral therapy (ART)-mediated immune reconstitution, remains unclear. This systematic review aimed to synthesize available evidence on TTV viral load in PLWH, focusing on its relationship with immunological markers. Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A comprehensive literature search was conducted in MEDLINE, Web of Science, and Scopus in January 2026 to identify studies assessing plasma TTV viral load before and/or during ART and reporting immunological outcomes. Eligible studies included prospective and retrospective longitudinal studies, cross-sectional studies, and mixed designs assessing plasma TTV viral load in relation to ART status and immune recovery markers. Results: Thirteen studies (n = 1700 PLWH) were included, predominantly observational and conducted in adult populations. Most studies (76.9%) reported a significant inverse association between TTV viral load and CD4 T-cell count, while all studies assessing HIV viral load found a direct correlation with TTV levels. An inverse relationship with the CD4/CD8 ratio was consistently observed where evaluated. Higher TTV loads were reported in ART-naïve individuals and in those with advanced immunosuppression, with longitudinal studies indicating a general decline during ART. Overall, methodological heterogeneity and moderate risk of bias were common. Conclusions: TTV viral load shows a consistent inverse association with CD4 cell count and may reflect global immune dysfunction in PLWH beyond conventional markers. However, its clinical utility remains investigational due to the heterogeneity in the study design, limited data on longitudinal dynamics, and lack of standardized assays and thresholds. Full article

Background: Immune mechanisms are increasingly implicated in the heterogeneity of schizophrenia spectrum disorders. Cytomegalovirus (CMV), a latent immunomodulatory herpesvirus, is linked to cognitive and immunological alterations, but its electrophysiological correlates remain largely unexplored. This study investigates the relationships among CMV serostatus, EEG features, inflammatory markers, and clinical–cognitive variables. Methods: In this prospective cross-sectional study, 123 patients with schizophrenia spectrum disorders underwent integrated clinical, cognitive, laboratory, and qualitative visual EEG assessments. CMV exposure was determined via IgG serology. Results: Global electroencephalographic EEG organization did not differ by CMV serostatus. However, a descriptive increase in resting-state sharp-wave discharges was observed in CMV-seronegative patients, independent of baseline cortical rhythms. Immunologically, CMV-seropositive individuals exhibited significantly higher total leukocyte counts, consistent with latent viral immune remodeling rather than overt systemic inflammation. Clinically, CMV-seropositive patients demonstrated descriptively higher scores on the disorganization dimension derived from the PANSS (Positive and Negative Syndrome Scale) five-factor consensus model. While these variations did not retain statistical significance after multiple testing correction, separate dimensional analyses revealed that patients exhibiting sharp waves demonstrated better overall cognitive functioning and superior performance within a memory-related item grouping. Notably, the presence of sharp-wave activity was independent of both peripheral inflammatory profiles and treatment-resistant status, underscoring a distinct electrophysiological phenotype. Conclusions: CMV exposure represents a modulating biological background associated with corrected leukocyte elevations and subtle electrophysiological variability, rather than a direct determinant of global clinical severity. The nominal EEG variations and their independent link to better-preserved memory performance highlight non-linear neuroimmune interactions. Given the cross-sectional design, these exploratory patterns warrant a non-causal interpretation but outline a foundation for future longitudinal investigations. Full article