Systemic lupus erythematosus (SLE) is a chronic autoimmune disease associated with substantial cardiovascular, metabolic, and renal morbidity. Sodium-glucose cotransporter 2 inhibitors (SGLT2i), initially developed for type 2 diabetes (T2D), have demonstrated beneficial effects beyond glucose lowering, including improvements in metabolic, cardiovascular, and renal outcomes. These effects span multiple domains, including glycemic control, body weight and blood pressure reduction, heart failure and atherosclerotic cardiovascular disease outcomes, kidney function preservation, and potential immunomodulatory pathways. This narrative review summarizes the metabolic, cardiovascular, renal, and immunomodulatory effects of SGLT2i relevant to SLE. Evidence from the general population supports cardiometabolic and renal benefits, while observational studies and early-phase trials in SLE and lupus nephritis (LN) suggest potential benefits in selected patients. However, SLE-specific evidence remains limited, and important gaps persist regarding efficacy and safety in active disease. Further studies are needed to define the role of SGLT2i in SLE.
National and international guidelines for the treatment of arterial hypertension have changed significantly over the last decades. Until 2009, most hypertension guidelines suggested: "the lower the better". This point of view had been revised in the second decade of this century, mainly due to the lack of data supporting low target values. However, the next turnaround was prompted by interpretation of the data from the Systolic Blood Pressure Intervention Trial (SPRINT) in 2015, which provided evidence for a lower rate of cardiovascular events when systolic blood pressure was lowered below 120 mm Hg. Since the SPRINT trial had excluded patients with diabetes, the Blood Pressure Control Target in Diabetes (BPROAD) trial (2025), which included diabetics, received major attention. The BPROAD trial came to similar conclusions as the SPRINT trial, now supporting the benefit of lowering systolic blood pressure below 120 mm Hg for a broader range of patients. However, the method of measuring blood pressure, as well as the individual tolerability of low blood pressure targets, must also be taken into consideration. Nationale und internationale Leitlinien zur Behandlung der arteriellen Hypertonie haben sich über die letzten Jahrzehnte erheblich verändert. Bis 2009 wurde in den meisten Hypertonieleitlinien empfohlen, dem Prinzip „je niedriger, desto besser“ zu folgen. Diese Sichtweise wurde in der zweiten Dekade dieses Jahrhunderts revidiert, hauptsächlich wegen eines Mangels an Daten, die niedrige Zielwerte stützten. Allerdings kam es bald zur nächsten Kehrtwende, angestoßen durch die Interpretation der Daten des Systolic Blood Pressure Intervention Trial (SPRINT) 2015, der eine geringere Rate kardiovaskulärer Ereignisse bei Senkung des systolischen Blutdrucks unter 120 mm Hg belegte. Da die SPRINT-Studie Patienten mit Diabetes ausgeschlossen hatte, erregte der Blood Pressure Control Target in Diabetes (BPROAD) Trial 2025 große Aufmerksamkeit; hier waren Patienten mit Diabetes eingeschlossen. BPROAD kam zu ähnlichen Schlussfolgerungen wie SPRINT und stützte nun den Nutzen einer Senkung des systolischen Blutdrucks unter 120 mm Hg bei einer breiteren Gruppe von Patienten. Berücksichtigt werden müssen jedoch auch das Blutdruckmessverfahren und die individuelle Verträglichkeit niedriger Blutdruckziele.
To highlight the overlooked role of ocular surface disease (OSD) in glaucoma, explore its pathophysiological links to treatment, and propose integrated strategies to improve patient care. A narrative review of current literature on the relationship between glaucoma therapies and ocular surface health was conducted. Evidence on prevalence, mechanisms, diagnostic approaches, and management strategies for OSD in glaucoma patients was reviewed. Glaucoma remains the leading cause of irreversible blindness worldwide, with treatment adherence being a critical determinant of long-term outcomes. Chronic use of topical intraocular pressure (IOP)-lowering eye drops, particularly those containing benzalkonium chloride (BAK), induces epithelial and goblet cell toxicity, tear film instability, and ocular inflammation. The prevalence of OSD in glaucoma patients is markedly higher than in the general population, affecting up to 60%. Symptoms such as dryness, burning, and blurred vision significantly reduce quality of life and compromise adherence to treatment. Emerging alternatives, including preservative-free formulations, selective laser trabeculoplasty, and minimally invasive glaucoma surgery, provide opportunities to reduce ocular surface burden. Structured evaluation using questionnaires, slit-lamp examination, and diagnostic tests can facilitate early detection and tailored management. The ocular surface, long considered secondary in glaucoma care, is central to optimizing both adherence and visual outcomes. Protecting ocular surface health through preservative-sparing regimens, procedural interventions, and patient-centered strategies is essential. Reframing OSD as an integral component of glaucoma management may improve long-term quality of life and enhance treatment success.
Equine Asthma (EA) is a common, lower airway disease. Yet current diagnostic standards rely on bronchoalveolar lavage fluid (BALF) cytology, which is moderately invasive and not always feasible in field conditions. This review aimed to synthesize current evidence on candidate biomarkers of EA, with a primary focus on blood-based matrices and BALF, while also including data on biomarkers measured in tracheal wash (TW), saliva and exhaled breath condensate (EBC), where available. Searches were performed in PubMed, Scopus and Google Scholar, and original studies in horses with mild-to-moderate or severe EA reporting potential biomarkers were included. Across 57 unique studies, a broad spectrum of candidate biomarkers was evaluated. Blood-derived biomarkers, including surfactant protein D (SP-D), secretoglobin (SCGB), haptoglobin showed variable but generally limited specificity when assessed individually, although several combinations improved diagnostic accuracy. BALF-derived biomarkers more consistently reflected local airway inflammation and disease severity. Among these, neutrophil extracellular traps (NETs) related markers, neutrophil gelatinase-associated lipocalin (NGAL) and allergen-specific IgE profiles emerged as the most promising candidates, particularly in multimarker panels and phenotype-stratified analyses. Overall, current evidence supports the potential of integrated biomarker panels, especially those derived from BALF and complemented by blood-based markers, to refine the diagnosis and monitoring of EA, but robust validation in large, well-characterised study group is still required before routine clinical implementation.
Ketamine exerts rapid antidepressant effects. However, currently available ketamine-based treatments are associated with dissociative and cardiovascular adverse effects. To evaluate the antidepressant efficacy and tolerability of KET01, a novel, oral, prolonged-release racemic ketamine tablet formulation. KET01-03 was an active-comparator, double-blind, double-dummy, crossover phase 1 randomized clinical trial (RCT) conducted among healthy adult male volunteers (aged ≥18 years) between July and August 2023 at a single trial site in Germany. KET01-02 was a placebo-controlled, double-blind phase 2 RCT conducted between May 2022 and May 2023 among adult outpatients (aged ≥18 years) with treatment-resistant depression across 29 trial sites in the Czech Republic, Germany, and Poland. KET01-02 data were analyzed from May to October 2023 and KET01-03 data from August to October 2024. KET01-03 investigated a single dose of KET01 (240 mg) vs intranasal esketamine (84 mg), and KET01-02 evaluated KET01 dosages of 120 or 240 mg/d (adjunctive to ongoing standard therapy) against placebo for 3 weeks. The primary end points were the difference in mean maximum change in Clinician-Administered Dissociative States Scale (CADSS) score between KET01 and intranasal esketamine within the first 24 hours in KET01-03 and the least squares (LS) mean change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to day 21 for 240 mg/d of KET01 vs placebo in KET01-02. KET01-03 randomized 26 males (median age, 32 years [range, 21-45 years]), and KET01-02 randomized 122 outpatients with treatment-resistant depression (72 [59.0%] female; median age, 41 years [range, 19-65 years]). In KET01-03, intranasal esketamine but not KET01 induced significant dissociation within 24 hours after dosing (mean [SD] maximum change in CADSS score, 29.6 [12.5] points vs 0.7 [1.7] points; P < .001). The maximum plasma concentration was lower for KET01 (39.1 ng/mL) than esketamine (104.1 ng/mL); conversely, exposure to metabolites was higher for KET01 (eg, area under the curve [AUC] from baseline to last measurement for norketamine was 3.5 µg × h/mL) than esketamine (AUC for [S]-norketamine, 1.4 µg × h/mL). Pulse and blood pressure did not change markedly in the KET01 group in both trials, in contrast to rapid increases after intranasal esketamine in KET01-03. In KET01-02, the primary efficacy end point at day 21 was not met: LS mean MADRS score difference for 240 mg/d of KET01 vs placebo was -1.82 points (95% CI, -6.21 to 2.57 points; P = .41). However, a reduction in MADRS scores was observed 7 hours after administering the first 240 mg dose of KET01, with an LS mean difference vs placebo at day 4 (-3.66 [95% CI, -6.74 to -0.59] points; nominal P = .02) and day 7 (-3.95 [95% CI, -7.75 to -0.15] points; nominal P = .04). During follow-up, the LS mean MADRS point difference vs placebo at 4 weeks was -3.35 (95% CI, -7.62 to 0.93; nominal P = .13). The antidepressant properties and tolerability profile of KET01 in these RCTs, including minimal dissociation and cardiovascular effects, support further development of oral KET01 formulation for at-home administration. EU Clinical Trials Register Identifiers: 2023-503971-45-00 and 2021-004927-34.
To compare clinical and functional outcomes after primary anterior cruciate ligament reconstruction (ACLR) using quadriceps tendon (QT) autografts versus bone-patellar tendon-bone (BPTB) and, separately, QT versus hamstring tendon (HT) autografts, to inform evidence-based graft selection. We performed a Cochrane-guided systematic review and meta-analysis. Searches of PubMed, Scopus, Cochrane Library, SPORTDiscus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science and major trial registries through November 2025 identified randomized controlled trials (RCTs) comparing QT with HT or BPTB in adults undergoing primary ACLR. Random-effects models (REML) were used to pool mean differences/standardized mean differences and risk ratios. Heterogeneity was quantified using I2 and Q statistics. Sensitivity analyses (leave-one-out) and the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach were applied. When pooling was infeasible, a structured narrative synthesis was provided. Fifteen RCTs (2014-2025) were included. Objective anterior stability (KT-1000) showed no significant difference between QT and HT at 12 or 24 months and no significant difference between QT and BPTB at 12 months. Patient-reported outcomes (International Knee Documentation Committee, Lysholm, Knee Injury and Osteoarthritis Outcome Score [KOOS], Tegner) were largely equivalent at 12-24 months. After resolving inconsistencies due to non-exchangeable constructs/comparators, a small 12-month KOOS signal favoured QT, while 24-month effects remained null. Graft failure rates were comparable for QT versus HT and QT versus BPTB. Donor-site morbidity was substantially lower with QT versus BPTB; QT versus HT showed no significant difference. Pivot-shift favoured QT, but not significantly; postoperative stiffness did not differ. Overall certainty was mostly moderate (downgrades for imprecision and occasional indirectness); donor-site morbidity versus BPTB reached high certainty. Across randomized evidence up to 24 months, QT provides stability and patient-reported outcomes comparable to HT and BPTB, with clearly lower donor-site morbidity compared to BPTB and no excess failure compared to HT. QT is an evidence-supported alternative for primary ACLR; longer, adequately powered, construct-specific RCTs are needed for guideline-level certainty. Level I, systematic review of Level I randomized controlled studies.
Riemerella anatipestifer (RA) is a major pathogen in waterfowl, responsible for severe septicemia and serositis, leading to significant economic losses. As antibiotic resistance becomes more widespread, there is an urgent need for effective, novel vaccine strategies. In this study, we engineered three recombinant RA antigens, PorQ, YaeT, and YiaD, onto the surface of outer membrane vesicles (OMVs) derived from a Salmonella Typhimurium mutant strain using the lipoprotein signal peptide (Lpp). The engineered OMVs were shown to induce robust humoral and cellular immune responses in ducks. Immunization with these OMVs resulted in 80% survival for ducks immunized with OMVs displaying YaeT and YiaD antigens and 70% survival for ducks immunized with OMVs displaying PorQ, following challenge with RA-SD-1 (serotype 2). Furthermore, ducks immunized with OMVs displaying YaeT and YiaD exhibited reduced pathological damage and lower bacterial loads in key organs. These findings demonstrate that OMVs displaying YaeT and YiaD provide strong protection against RA infections, suggesting the potential of OMVs as an effective vaccine platform for waterfowl across various RA serotypes. The study addresses a growing challenge in poultry health, as Riemerella anatipestifer (RA) infections continue to cause substantial losses in waterfowl farming. The development of novel vaccines is crucial due to the rise in antibiotic resistance. This study highlights the potential of using outer membrane vesicles (OMVs) as a versatile vaccine platform to display multiple RA antigens. The promising results, including high survival rates and reduced organ damage, indicate that OMVs could provide an effective means to prevent RA infection in waterfowl, paving the way for future vaccine development targeting various serotypes of RA.
Gastrointestinal nematodes (GINs) significantly limit small ruminant production in Southern Africa, causing substantial economic losses and reduced livestock productivity. Control largely depends on anthelmintic drugs, but intensive and improper use has accelerated the development of anthelmintic resistance (AHR). This review synthesizes published evidence on AHR in GINs of sheep and goats across Southern Africa, drawing on studies from six countries, and summarizes resistant parasite species, drug classes, diagnostic methods, and associated risk factors. Comparative analyses showed a significant association between anthelmintic class and the proportion of farms exhibiting resistance (P < 0.05). Macrocyclic lactone (ML) resistance, particularly to ivermectin, was most prevalent, with significantly more farms harbouring resistant GIN populations than susceptible ones (P < 0.05). In contrast, the proportions of farms showing resistance to benzimidazoles (BZ) and imidazothiazoles (IMD) did not differ significantly from those with susceptible populations, reflecting variability in resistance patterns at farm level. Salicylanilide compounds exhibited significantly lower resistance prevalence (P < 0.05). Haemonchus spp. was the dominant resistant genus, with 62.2% of farms reporting resistant populations, significantly exceeding those retaining susceptibility (P < 0.05). In contrast, lower resistance levels were observed in Teladorsagia, Trichostrongylus, Oesophagostomum, and Cooperia species. These findings indicate growing evidence of resistance to BZ, ML, and IMD compounds in GINs of small ruminants in Southern Africa. The underlying reasons are unclear but are likely driven by frequent whole-flock treatments, improper dosing, limited drug rotation, reduced refugia, cross-border livestock trade, communal grazing, and non-prescription use of anthelmintics.
While some vaccines appear to be associated with lower risk of lymphoma, their impact on outcomes is largely unknown. Data from a large prospective lymphoma cohort study was utilized to estimate associations of self-reported history of vaccination against hepatitis A, hepatitis B, influenza, and yellow fever with event-free survival (EFS) and overall survival (OS) using Cox proportional hazard models. None of the vaccines were associated with EFS (HRs 0.77-1.00) or OS (HRs 0.96-1.04). Similarly, there were no significant associations between the vaccines and outcome for each lymphoma subtype. Prior vaccination against selected viruses was not associated with EFS or OS among patients with lymphoma. We did not find evidence for an impact of prior vaccination on lymphoma prognosis.
Germline deletions of UDP-glycosyltransferase (UGT) UGT2B17 and UGT2B28 genes are common in human populations, yet their association with aging remains unclear. In this exploratory study, we analyzed data from 12,934 participants, mostly Caucasian, in the Canadian Longitudinal Study on Aging (CLSA) to assess cross-sectional and prospective associations between UGT deficiencies and aging-related health outcomes, including mortality, multimorbidity, allostatic load, disease burden and polypharmacy. Sex-specific associations emerged from cross-sectional analyses: UGT2B17-deficient males were less likely to report arthritis (adjusted odds ratio (ORadj) = 0.73, 95% confidence interval (0.58-0.92), P = 0.008), UGT2B17-deficient females were less likely to report neurological problems (ORadj = 0.69 (0.51-0.91), P = 0.01), and UGT2B28-deficient females were less likely to report thyroid disorders (ORadj = 0.50 (0.29-0.82), P = 0.009). Despite these associations, multimorbidity remained prevalent across all groups and no significant associations were observed with all-cause mortality or longevity. Physiological dysregulation, assessed by the allostatic load index, was more prevalent in males. Among males aged ≥ 65, UGT2B28-deficiency was associated with reduced high dysregulation compared to UGT-proficient males (40.0% vs. 53.0%, P = 0.05), whereas UGT2B17 deficiency was associated with a higher prevalence in males (60.4% vs. 53.0%, P = 0.03). In addition, UGT2B17-deficient males had a lower prevalence of polypharmacy than UGT-proficient males (9.3% vs. 13.9%; P = 0.02). Overall, these findings indicate sex-specific associations between UGT2B17 and UGT2B28 deletions and selected healthspan-related phenotypes, suggesting that UGT-related genetic variation may modulate physiological pathways relevant to aging. Given the exploratory nature of this study and its reliance on prevalence data, the results are intended to be hypothesis-generating and will require confirmation in longer-term longitudinal studies.
To determine whether photopic negative response (PhNR) parameters obtained using a handheld electroretinography (ERG) device reflect quantitative indicators of residual retinal ganglion cell (RGC)-driven inner retinal function and how these functional measures relate to OCT-derived structural metrics in chronic unilateral non-glaucomatous optic neuropathy (ON). In this retrospective observational study, 27 patients (54 eyes) with unilateral chronic ON were examined using handheld full-field photopic ERG (RETeval™, LKC Technologies) without pupil dilation or corneal electrodes. Several ERG parameters, including the PhNR72 amplitude, PhNR minimum amplitude, P-ratio, and W-ratio, were analyzed. Optical coherence tomography (OCT)-derived ganglion cell-inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) thicknesses, and Humphrey field analyzer (HFA) indices were acquired on the same day. Linear mixed-effects models accounting for intereye correlation and false discovery rate (FDR) correction were used to assess structure-function relationships. ON eyes showed significantly reduced PhNR72 and PhNR minimum amplitudes, and lower P-ratio (PhNR72/b-wave) and W-ratio (PhNR minimum/(b-wave minus a-wave) (all p < 0.01) compared with unaffected eyesof the patients. In multivariable models, the W-ratio was independently associated with GCIPL thickness in the inferotemporal sector (β = 0.45; 95% CI, 0.22-0.68; FDR-adjusted p < 0.05), whereas no significant associations were found with RNFL thickness or HFA indices. Handheld photopic ERG-derived PhNR parameters, particularly the W-ratio, are selectively associated with GCIPL thickness, suggesting preferential coupling with RGC-driven inner retinal function rather than axonal or field-level measures. Thus, portable ERG provides a practical functional biomarker complementary to OCT for evaluating residual RGC-driven inner retinal function in chronic ON.
Children of parents with psychopathology generally perform less well in school than their peers. Parental symptoms might not, however, account for their lower achievement, as other familial factors might contribute. To examine the role of parental symptoms, we analyse data from 9,000 families in the Norwegian Mother, Father, and Child Study (MoBa). Parents reported their symptoms of anxiety, depression, ADHD, eating disorders, and alcohol use disorder during pregnancy and during their child's childhood. Children in 5th grade (aged 10) completed nationally-standardised tests of mathematics, reading comprehension, and English (as an additional language). Comparing children who are cousins (children-of-siblings design), we controlled for unmeasured factors shared among family members that confound the relationship between parental mental health and children's academic achievement. We found small associations between greater parental symptoms and lower scores in reading and mathematics (- 0.060 ≤ β ≤ -0.013). However, these associations were no longer significant when comparing cousins whose parents differ in mental health. Results suggest that parental symptoms do not exert a direct, clinically meaningful effect on children's academic achievement. Although non-significant, associations with parental symptoms measured close to the child's academic test are less attenuated than those measured during pregnancy. Notably, comparison between the overall MoBa sample and the children-of-siblings samples suggests ascertainment differences that hinder strong generalisations. Our findings underscore the importance of quasi-experimental family designs in identifying modifiable targets in intergenerational health and education research. Supporting parental mental health is crucial but its direct effect on children's achievement may be smaller than often thought.
GSM1, a potential DEAH-box RNA helicase, is involved in the glucose-ABA signaling pathway and RNA silencing. Here, MOS2 was identified to interact with GSM1 in the nucleus, and the G-patch domain of MOS2 promoted RNA helicase activity of GSM1 in vitro. In gsm1-2, reduced levels of several miRNAs and increased levels of their respective target genes were observed. The lack of MOS2 in gsm1-2 (gsm1-2 mos2-3) severely inhibited growth, resulting in seedling lethality and greater reduction of some miRNA levels, implying a genetic interaction between GSM1 and MOS2. HYL1 encodes a double-stranded RNA-binding protein that functions in the DCL1 complex to facilitate pri-miRNA processing. By contrast, gsm1-2 hyl1-2 strongly resembled hyl1-2 in the dwarf phenotype, and the expression levels of several mature miRNAs in gsm1-2 hyl1-2 were comparable to those in hyl1-2, but lower than in gsm1-2. Impaired D-body localization of HYL1 was also observed in gsm1-2, which was detected previously in mos2-2. Moreover, HYL1-pre-miR159a binding affinity was reduced in the presence of GSM1 in vitro. Collectively, these results suggest that GSM1 and MOS2 contribute to miRNA biogenesis, which is largely associated with HYL1-engaged pri-miRNA processing.
The Modified Checklist for Autism in Toddlers - Revised (M-CHAT-R) is widely used for screening children at age 2 for autism spectrum disorders (ASD), but it also identifies children at risk for broader developmental challenges. We aimed to examine whether M-CHAT-R risk status at age 2 is associated with cognitive, behavioral, adaptive, and school-related outcomes at ages 3 to 4. We used data from the French national birth Cohort ELFE, including children assessed with the M-CHAT-R at age 2. Children were classified as low or medium risk. Outcomes at ages 3-4 included general cognitive development (Child Development Inventory), non-verbal reasoning (Picture Similarities test), family and daily activities, school engagement and performance, attention regulation (teacher-rated ADHD symptoms), specific neurodevelopmental care and school-based assistance. Multivariate analyses used modified Poisson regression for binary outcomes and linear regression for continuous outcomes, adjusted for sociodemographic, child-related, and school-related factors. 9,223 children were classified as low-risk and 1,248 children as medium-risk. Medium-risk children were more often boys and from socioeconomically disadvantaged families. At 3.5 years, medium-risk children had increased likelihood of developmental delay (16.6% vs. 6.1%, RR 2.2 after adjustment) and lower cognitive and language scores (up to -0.4 SD). Despite these differences, most children attended school, and their school life was similar to that of low-risk peers. Children classified as medium-risk by the M-CHAT-R at age 2 have an increased likelihood of subtle but widespread developmental challenges at school entry. Strategies to improve access to neurodevelopmental care and school support could enhance outcomes for this group.
Few studies have evaluated whether modifiable aspects of red blood cell (RBC) transfusions are associated with recipient outcomes in very-low-birth-weight (VLBW) infants. To determine whether blood donor, RBC modifications and storage, or transfusion thresholds and characteristics are associated with serious adverse outcomes in VLBW infants undergoing transfusion. Transfusion in Preterm Infants was a prospective birth cohort study that recruited VLBW infants (<1500 g at birth) between April 1, 2019, and December 31, 2023, at 5 university-affiliated and 3 community birth hospitals in the US. Electronic medical record data linking blood donor and component data to infants were obtained and linked with Vermont Oxford Network outcome data, with additional outcome review by site. The analysis was completed in January 2026. RBC transfusion and transfusion characteristics, evaluated up to the first outcome event. The primary outcome was a composite outcome of severe intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), late-onset sepsis, severe bronchopulmonary dysplasia (BPD), retinopathy of prematurity, or death (and secondary individual outcomes), with follow-up through 90 days or death. Blood donor characteristics (sex, age, and hemoglobin), anticoagulant preservative solution and/or unit characteristics, transfused volumes, transfusion number, and infants' pretransfusion hemoglobin values were evaluated using multivariable generalized estimating equation regression models to account for correlation within hospital, adjusted for illness severity. The study enrolled 2605 VLBW infants, and 1283 (586 [45.7%] female; 713 [55.6%] <27 weeks' gestational age) received RBC transfusion. Median pretransfusion hemoglobin level was associated with higher odds of the composite outcome (odds ratio [OR] per 1 g/dL increase, 1.15; 95% CI, 1.07-1.25; P < .001). In contrast, use of additive solution (AS)-1 or AS-5 vs the reference of citrate phosphate dextrose adenine or citrate phosphate dextrose as the anticoagulant preservative solution was associated with lower odds of the composite outcome (OR, 0.72; 95% CI, 0.53-0.97; P = .03). There were no significant associations with other examined modifiable factors and the composite outcome. Among secondary outcomes, anticoagulant preservative solution was associated with lower risk of BPD (AS-1 and AS-5, OR, 0.48; 95% CI, 0.33-0.69; AS-3, OR, 0.65; 95% CI, 0.56-0.77) and higher risk of NEC (AS-3, hazard ratio [HR], 5.33; 95% CI, 1.22-23.29). Transfusion dose was associated with higher risk of mortality (HR per 5 mL/kg, 1.25; 95% CI, 1.17-1.35), and donor age was associated with a lower risk of mortality (HR for age ≥60 years, 0.63; 95% CI, 0.44-0.92). Shorter postirradiation storage duration (<1 day) was associated with lower risk of NEC (HR, 0.44; 95% CI, 0.22-0.89). Female donor sex was associated with lower risk of IVH (HR, 0.60; 95% CI, 0.36-0.99). In this cohort study of VLBW infants, pretransfusion hemoglobin and anticoagulant preservative solution were associated with a composite of morbidities and mortality, unlike other modifiable blood banking practices. For individual outcomes, select donor and blood banking factors were identified that may be modifiable targets for further evaluation.
Carbonic anhydrase IX (CAIX), a hypoxia-induced enzyme, contributes to tumor acidosis and may modulate antitumor immunity. Its role in pediatric central nervous system (CNS) tumors remains poorly understood. This study examined CAIX and immune biomarker expression in pediatric gliomas and glioneuronal tumors (GNTs) and their associations with clinical outcomes. CAIX and selected immune biomarkers were evaluated using immunohistochemistry in 34 pediatric patients (ages 0-17 years) with low-grade gliomas (LGGs; n = 21), GNTs (n = 6), and high-grade gliomas (HGGs; n = 7). CAIX was expressed in 58.8% of tumors, with no statistically significant difference between the combined LGG/GNT and HGG groups. CD3 (87.9%), CD8 (81.8%), CD44 (93.9%), CD68 (100%), CD163 (75.8%), and CCR2 (69.7%) were the most frequently detected biomarkers, whereas PD-L1 (15.2%), PD-1 (0%), and CD206 (24.2%) were rarely detected. CAIX correlated positively with CD44 (p = 0.01) and CD206 (p = 0.009). Strong CD68 expression (> 30%) was associated with significantly better 2-year event-free survival (EFS) than lower expression (91.7% vs. 53.8%; p = 0.011). No significant associations between EFS and CAIX or other immune biomarkers were observed (all p > 0.05). Pediatric gliomas and GNTs frequently express CAIX and monocyte/macrophage-related biomarkers but exhibit a low immune checkpoint profile (PD-1 and PD-L1). Unlike findings from adult studies, CAIX was neither enriched in HGGs nor associated with a worse prognosis. Strong CD68 expression may represent a candidate target for combination therapeutic strategies, although validation in a larger, homogeneous pediatric CNS tumor cohort is needed.
The clinical evaluation of lumbar degenerative disease (LDD) severity relies on symptoms and imaging, lacking biologically specific diagnostic markers. This study investigated the role of serum complements in LDD to assess their potential as diagnostic biomarkers, their correlation with anatomical stenosis, and their ability to predict postoperative recovery. We hypothesized that specific serum complement levels correlate with both structural severity and clinical outcomes. A prospective investigation was conducted on 82 patients with LDD and 90 healthy controls. To minimize selection bias, a 1:1 propensity score matching (PSM) was performed for age and gender, resulting in a matched cohort of 112 participants. Serum levels of C1q, C3, and C4 were compared, while CRP and ESR were screened to exclude systemic inflammation. Anatomical severity was quantified using the S1/S0 ratio (dural sac area ratio) on MRI. Pain intensity was evaluated via Visual Analogue Scale (VAS) scores; quality of life was appraised using ODI and Barthel scales. Surgical prognosis was defined by achieving the Minimal Clinically Important Difference (MCID, ΔVAS ≥ 1.6) at 2-month follow-up. Serum C1q levels were significantly higher in the LDD group compared to controls (184.62 vs. 156.51 g/L, P = 0.001), whereas C3 and C4 showed no significant difference. Baseline CRP and ESR levels were within normal ranges, confirming the specificity of complement activation. ROC analysis demonstrated that C1q effectively distinguished LDD patients (AUC = 0.688), with an optimal cut-off of 154.40 g/L. Serum C4 levels exhibited a significant inverse correlation with the S1/S0 ratio (β = -0.867, P = 0.004). Baseline C1q was an independent predictor of failing to achieve MCID (OR = 0.980, P = 0.010). Patients who did not attain MCID had significantly higher baseline C1q levels. The rate of achieving MCID was lower in the highest C1q quartile (Q4: 52.6%) compared to the lowest (Q1: 75.0%). Serum C1q and C4 serve as dual biomarkers in LDD. C4 correlates with anatomical stenosis severity, while C1q predicts surgical prognosis. Integration of serum complement profiling and radiological imaging improves preoperative risk stratification and facilitates surgical decision-making.
This study investigates the postoperative mobility following partial semitendinosus tendon harvesting performed during pelvic organ prolapse (POP) repair using the Hornemann Tendon Transplantation (HoTT®) method. The aim was to evaluate whether the procedure causes functional impairments and which patient-related factors influence postoperative mobility outcomes. A single-arm prospective observational study was conducted involving 142 women with POP-Q stage II-IV prolapse who underwent laparoscopic sacropexy with partial autologous semitendinosus tendon harvest. Mobility was assessed preoperatively and at 6 weeks, 3 months, and 6 months postoperatively using the validated Prosthetic Limb Users Survey of Mobility (PLUS-M™). Statistical analysis included mixed logistic regression with age, BMI, and time as fixed effects and patient identity as a random effect. Mean age was 60.1 ± 10.3 years; mean BMI was 24.3 ± 3.7 kg/m2. Median mobility (T-score) increased from 64.5 before surgery to 67.1 at 6 weeks and 71.4 at both 3 and 6 months (p < 0.001). Higher age (OR 0.94; p = 0.022) and BMI (OR 0.82; p = 0.009) were independently associated with lower odds of achieving a high mobility score (T ≥ 71.4). No significant change in continence status was observed. Patient satisfaction and quality of life improved markedly, with 96.6% recommending the procedure. Partial semitendinosus tendon harvesting in HoTT® surgery does not impair mobility and is associated with significant improvements in function and quality of life. Advanced age and higher BMI mildly reduce postoperative mobility potential but do not contraindicate the procedure.
The experience of parenting a child with autism spectrum disorder (ASD) often entails unique psychological challenges. Although research on parental stress and adjustment has expanded considerably, the mechanisms through which parents' self-stigma (PSS) influences parental burnout, perceived competence, and socio-emotional adjustment remain insufficiently theorized. The aim of this study was to examine the longitudinal links among PSS, parental burnout, parental competence, and socio-emotional adjustment among parents of children with ASD. The study employed a cross-lagged panel design with two waves of longitudinal research conducted at six-month intervals. The sample consisted of 182 parents (54.9% female) with a mean age of 40.59 years (Standard deviation = 7.12). Correlational analyses were conducted to examine associations among PSS, parental burnout, parental competence, and socio-emotional adjustment variables, while mediation analyses were performed using structural equation modelling. The results indicated that higher levels of PSS significantly increased parental burnout, which in turn reduced parental competence. Lower parental competence was subsequently associated with poorer socio-emotional adjustment. These results provide important insights for mental health professionals and intervention programs, highlighting the need to address self-stigma and burnout to foster parental competence and socio-emotional well-being in families of children with ASD.
Across tauopathies-Alzheimer's disease (AD), frontotemporal lobar degeneration due to tau (FTLD-tau)-we compared cerebrospinal fluid (CSF) biomarkers of phosphorylated-tau (p-tau) p-tau181, p-tau212, tau368, total tau (t-tau), and the tau368/t-tau ratio, and tested differentiation from non-tau (FTLD-TDP, neuronal α-synuclein disease (αSyn), and controls). In AD, CSF p-tau181 and p-tau212 were significantly higher than in all other groups, including FTLD-tau, while tau368/t-tau was significantly lower. With the aim to combine tau phosphorylation biomarkers (p-tau181 and p-tau212) with biomarkers for severity of tau pathology (tau368), we made ratios between these biomarkers and examined their diagnostic accuracy in FTLD after excluding high/intermediate AD neuropathologic change (ADNC). CSF p-tau181 and p-tau212, as well as p-tau181/tau368 and p-tau212/tau368, were higher in FTLD-tau compared with non-tau groups, and the diagnostic accuracy to discriminate FTLD-tau from FTLD-TDP improved. Levels of the ratios were increased in behavioral and primary progressive aphasia variants of tauopathies when compared to FTLD-TDP. Furthermore, the biomarkers showed significant correlation with both FTLD-tau and AD tau burden at autopsy across brain regions. These results suggest unique patterns of increased relative levels of p-tau epitopes in CSF among ADNC and FTLD-tau could improve the diagnosis of tauopathies and inform inclusion criteria in clinical trial design.