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.
Sex-related differences in left ventricular (LV) remodeling in response to severe aortic stenosis (AS) and post-transcatheter aortic valve implantation (TAVI) remain unclear. Previous studies have demonstrated inconsistent and discordant findings regarding the relationships between LV remodeling and clinical endpoints across sexes following TAVI. More importantly, it has been shown that females with severe AS are often diagnosed later and less likely to be referred for TAVI. We sought to evaluate sex-based differences in LV remodeling prior to and after TAVI, and to assess whether these differences were associated with long-term clinical outcomes. We conducted a retrospective study of 977 patients with severe AS undergoing TAVI (2013-2020). Serial echocardiograms were performed at baseline (before TAVI) and at various timepoints post-TAVI. Echocardiographic parameters related to LV remodeling were extracted. Clinical outcomes (myocardial infarction [MI], heart failure hospitalization [HFH], stroke, and survival) were tracked over 10 years. Compared with males, females had larger baseline indexed LV end-diastolic dimension (26.5 ± 4.0 mm/m2 vs. 25.3 ± 3.5; p < 0.001), lower LV mass index[LVMI] (101.5 ± 28.0 vs. 111.5 ± 30.1 g/m2; p < 0.001), higher left ventricular ejection fraction (59.5 ± 11.13 vs. 53.8 ± 13.5%; p < 0.001), and higher LV filling pressures as indicated by a higher E/e' (18.7 ± 6.9 vs. 15.6 ± 6.2, p < 0.001). However, changes in LVMI, LV chamber size, and diastolic parameters post-TAVI were similar across sexes. Within-group analyses demonstrated that both males and females experienced favorable reverse remodeling in LV mass, LVMI, and wall thicknesses post-TAVI. No significant sex differences were observed in MI, HFH, stroke, or survival post-TAVI. Our results support that males and females present with distinct baseline cardiac phenotypes in the setting of severe AS, but both sexes experience comparable LV reverse remodeling and clinical outcomes post-TAVI. This reinforces the structural and prognostic benefit from TAVI across sexes, underscoring the importance of equitable referral and access to this intervention.
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.
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.
Argonautes (AGOs) are the effectors for the action of microRNAs (miRNAs). Plant genomes harbor large numbers of AGO genes whose functions remain to be fully understood. Here, we elucidated a function of AGO5 in the ecological model plant Nicotiana attenuata during its interactions with the specialist herbivore Manduca sexta. Plants silenced in NaAGO5 expression using inverted-repeat technology (irAGO5) were indistinguishable from the wild type (WT) in growth and development but were highly susceptible to M. sexta herbivory. M. sexta caterpillars grew faster and accumulated significantly more biomass on irAGO5 than on WT plants. Herbivory-elicited irAGO5 plants accumulated significantly lower amounts of auxin-dependent defense metabolites such as phenolamides, flavonoids, and diterpenoid glycosides, but not nicotine and trypsin protease inhibitors (TPI). Nicotine and TPI levels, which require intact jasmonate signaling, were attenuated in plants silenced in NaAGO8 expression (irAGO8). irAGO5 plants showed compromised herbivore-induced auxin levels and YUCCA gene expression but accumulated more salicylic acid; however, jasmonate accumulations were at WT levels. Exogenous auxin treatments restored resistance against M. sexta and auxin-dependent defense metabolites. Substantial temporal changes in the miRNome were observed in irAGO5 and were largely different from those in irAGO8. An AGO5-dependent miRNA-mRNA regulatory interaction network was inferred for defense-signaling components. Furthermore, double knockdowns of NaAGO5 and NaAGO8 revealed cooperative functions of the two genes during herbivory. We infer that AGO5 is a central component of the herbivore-induced smRNA pathway that modulates multiple nodes in the auxin-dependent metabolic space of the defense signaling network when N. attenuata plants interact with the specialist herbivore M. sexta.
Geochemical partitioning of phosphorous (P) in surface sediments of Ashtamudi wetland was undertaken to assess the nutrient mobility, bioavailability and ecological risks. The fraction composition implied the dominance of calcium carbonate-bound P (326.92 ± 26.61 mg/kg) during non-monsoon and alkali-bound organic P (439.25 ± 11.54 mg/kg) during monsoon. Iron-bound P was the major component of bioavailable P; its retention, mobility, and bioavailability in sediments was controlled by iron (oxyhydr) oxides, pH, redox, and salinity. The elevated alkali-bound P content during monsoon highlights the allochthonous contribution of humic associated P via run-off. Increased salinity favours the formation of carbonate minerals (adsorption sites for P in sediments), resulting in dominance of calcium-bound P during non-monsoon. Sedimentary OP was relatively higher and the microbially mediated remineralisation triggers the transformation of organic P to bioavailable form. Enriched levels of total P in sediments were substantiated by relatively lower average organic carbon to total P [70.45 (non-monsoon) and 25.74 (monsoon)] and organic nitrogen/total P ratios [4.53 (non-monsoon) and 1.68 (monsoon)]. Estimated bioavailable P (~ 34-60%) indicated the possibility for rise in P content of the water column and may induce eutrophication risk if nutrient release occurs from sediments. Total P concentration > 700 mg/kg at majority of sites implied P contamination due to anthropogenic sources. Severe pollution at ~ 50% of the sites (as per phosphorous pollution index) endorses the fact that the wetland sediments are susceptible to eutrophication.
The camel has received very little attention in contrast to other domesticated animals, especially in developing nations such as Ethiopia. As a result, camels are susceptible to several illnesses, including mange mites. In the present study, a camel whose main complaint was itching, rubs against an object and is kept extensively was treated clinically at Kombolcha City Administration Veterinary Clinic, Northeast, Ethiopia. Upon physical examination, the body temperature was 37.2 °C. The camel was emaciated, and the hair was rough. The clinical manifestations of the camel mange in the present study included hair loss on the head, with skin crust around the lower flank, hand quarters and the head and inside of the thigh and thickening and corrugation of the skin of the inguinal area, including the skin of the prepuce. The patient was clinically diagnosed with camel mange and not confirmed by laboratory diagnosis. However, therapeutic diagnosis based on three subcutaneous injections of ivermectin (1 ml/50 kg body weight) administered at ten-day intervals, together with two topical applications of amitraz applied midway between consecutive injections, this treatment was followed by the disappearance of clinical signs. Additionally, the owner was instructed to separate healthy camels from those that were contaminated, clean the fomites before and after usage, and treat the herds whenever one or more camels had clinical symptoms. There was no recurrence of infestation within five months of follow-up. Therefore, the combination of ivermectin and topical amitraz appeared effective in the clinical management of camel mange in this case. Detailed epidemiological and therapeutic investigations are warranted.
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.
Religiosity, trust in physicians, and trust in government health agencies influence individual decision-making and behavior toward public health programs. However, trust in information about cancer from these sources and their association with public awareness of human papillomavirus (HPV) as a cause of cervical cancer remain understudied. To assess the association of trust in cancer information sources with awareness that HPV causes cervical cancer among US adults. This cross-sectional study used the nationally representative 2022 Health Information National Trends Survey (HINTS) data on noninstitutionalized US adults aged 18 years or older collected between March 7 and November 8, 2022 and analyzed between July 23, 2025 and April 9, 2026. Trust in government health agencies, physicians, and religious organizations for cancer information. The primary outcome was awareness of HPV as a cause of cervical cancer among US adults who have heard of HPV. Our study included 3914 respondents who had heard of HPV. Of these, 625 (15.0%) were Hispanic, 558 (10.0%) were non-Hispanic Black, 2290 (65.2%) were non-Hispanic White, and 2557 (55.8%) were female. Overall, 2910 (75.1%), 1173 (30.3%), and 157 (3.5%) US adults had a lot of trust in physicians, government health agencies, and religious organizations for cancer information, respectively. The prevalence of awareness that HPV causes cervical cancer was 870 (70.2%), 1922 (64.8%), and 86 (48.9%) among individuals with a lot of trust in government health agencies, physicians, and religious organizations for cancer information, respectively. In the logistic regression model, compared with individuals with a lot of trust, those with some trust (aOR, 0.71; 95% CI, 0.52-0.96) and little or no trust (aOR, 0.68; 95% CI, 0.49-0.95) in government health agencies for cancer information had lower odds of awareness that HPV causes cervical cancer. Similarly, compared with individuals with a lot of trust, those with some trust in physicians (aOR, 0.71; 95% CI, 0.52-0.98) had lower odds of awareness that HPV causes cervical cancer. In contrast, individuals with little or no trust in religious organizations (aOR, 1.88; 95% CI, 1.10-3.24) had higher odds of awareness of HPV as a cause of cervical cancer. Compared with non-Hispanic White respondents, non-Hispanic Asian respondents had lower odds of awareness of HPV as a cause of cervical cancer (aOR, 0.31; 95% CI, 0.18-0.52). Compared with female respondents, male respondents had lower odds (aOR, 0.62; 95% CI, 0.47-0.81) of awareness of HPV as a cause of cervical cancer. Compared with individuals who had college or postgraduate education, individuals with up to high school (aOR, 0.42; 95% CI, 0.30-0.60) and after high school or some college education (aOR, 0.47; 95% CI, 0.35-0.62) had lower odds of awareness of HPV as a cause of cervical cancer. In this cross-sectional study of US adults, trust in government health agencies and physicians was positively associated with public awareness of HPV as a cause of cervical cancer. Through public health promotion campaigns, we must address the decreasing trends in trust in physicians and government health agencies to achieve the goal of cervical cancer elimination in the US.
Investigation of nanofluids under microbial movement is a potential topic from applications point of view. This study focuses on the analysis of hybrid nanomaterial based microorganism model between finite boundaries. These boundaries consist of two walls having expansion or contraction property. Formulation of the problem comprises governing laws representing the flow of microorganism in the presence of physical effects and hybrid nanofluid effective characteristics. Similarity functions are adopted for conversion of the primary model into final form and then studied through Variational Iteration scheme. Successful implementation of the scheme provided considerable convergence and better results for the model with fluctuating physical parameters. It is found that increasing permeation and magnetic field significantly controlled the velocity in the channel. Presence of heat generation influentially enhances the temperature for both expansion and contraction cases; while the Soret effects help to augment the density motile of microorganism. The shear drag varies from 0.9057 to 1.1458 ([Formula: see text]), 0.9076 to 0.2470 ([Formula: see text]) in contraction case at the lower surface. This magnitude changes from 0.6762 to 0.6774 ([Formula: see text]), 0.6793 to 0.1558 ([Formula: see text]) at upper expanding surface. Contracting of the walls promoting this factor from 1.9017 to 1.8970 and 1.3982 to 1.3964, for [Formula: see text] and [Formula: see text], respectively. Further, the expanding walls heat transfer rate improves from 0.0509 to 0.0568, 1.4957 to 1.4981 and it depreciates from 0.0480 to 0.0461, and 1.4922 to 1.4839 in contracting walls.
The optimal duration of dual antiplatelet therapy (DAPT) in patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI) remains uncertain. To evaluate the safety and efficacy of abbreviated DAPT durations in patients at HBR undergoing PCI. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched from inception to October 26, 2025. Randomized clinical trials (RCTs) comparing abbreviated (ie, 1- to 3-month) vs standard (ie, 6- to 12-month) DAPT durations in patients at HBR without an indication for oral anticoagulation. A pairwise meta-analysis was performed to compare abbreviated (ie, 1-month to 3-month) vs standard (ie, ≥6-month) DAPT durations. A frequentist network meta-analysis was performed to compare 1-month, 3-month, and standard DAPT. The coprimary safety and efficacy end points were major or clinically relevant nonmajor bleeding (MCRB) and major adverse cardiovascular events (MACE; ie, a composite of cardiovascular death, myocardial infarction, or stroke). A total of 14 RCTs encompassing 11 398 patients at HBR (mean [range] age, 74.7 [68.6-80.0] years; 39.1% female and 60.9% male) were included. Compared with standard DAPT, abbreviated DAPT was associated with lower MCRB (risk ratio [RR], 0.71; 95% CI, 0.55-0.92; P = .009) and major bleeding (RR, 0.76; 95% CI, 0.59-0.99; P = .04). The risks of MACE (RR, 0.97; 95% CI, 0.81-1.16; P = .76) and its individual components did not differ between abbreviated and standard regimens. An increased risk of MACE was observed with 1-month vs 3-month DAPT in the single trial comparing these regimens, but the network estimate was nonsignificant (RR, 1.28; 95% CI, 0.96-1.72). In this systematic review and meta-analysis, for patients at HBR undergoing PCI, abbreviated DAPT was associated with a lower risk of bleeding and, at least for 3-month regimens, was not associated with an increase in fatal or nonfatal ischemic cardiovascular or cerebrovascular events compared with standard 6- to 12-month DAPT.
Medial unicompartmental knee arthroplasty (UKA) provides reliable outcomes in appropriately selected patients with medial compartment knee osteoarthritis. However, the effect of proximal tibia vara on implant positioning, alignment correction and patient-reported outcome measures (PROMs) is not completely defined. This study aimed to evaluate the association between proximal tibia vara, tibial component positioning, postoperative coronal alignment and clinical outcomes after medial UKA. Two hundred twelve patients who underwent medial UKA between 2014 and 2020 were included. Analysed parameters included medial proximal tibial angle (MPTA), hip-knee-ankle angle (HKA), joint line convergence angle (JLCA) and lateral distal femoral angle (LDFA). CPAK (Coronal Plane Alignment of the Knee) type and functional knee phenotypes were calculated. Patients were stratified into a normal tibia group (MPTA ≥ 85°, n = 118) and a tibia vara group (MPTA < 85°, n = 94). Clinical outcomes were assessed using the Oxford Knee Score (OKS), Knee Society Score (KSS clinical [KSS] and functional [KSS-F] subscales) and the Forgotten Joint Score-12 (FJS-12). Outcomes were significantly better in the normal group, with higher KSS (p = 0.036), OKS (p = 0.005) and FJS-12 (p = 0.006) scores. The majority of patients were classified as CPAK Type 1 (n = 80), while the most frequent phenotype was Var9Var3Var3 (n = 15). Alignment correction was smaller in the tibia vara group, with a lower mean ΔHKA (3.0 ± 2.8° vs. 3.7 ± 2.7°, respectively, p = 0.015). In subgroup analysis, mobile-bearing UKA demonstrated a significantly lower FJS-12 in tibia vara knees (p = 0.018), whereas fixed-bearing results were comparable between groups. The presence of component overhang was associated with worse clinical outcomes. Proximal tibial vara was associated with lower postoperative scores after medial UKA. Tibial component overhang independently impaired all clinical outcomes, underscoring the clinical relevance of tibial morphology and precise component positioning in medial UKA. Level III.
Left atrial (LA) mechanical function may change after catheter ablation for atrial fibrillation (AF); however, the determinants of follow-up LA function remain unclear. We aimed to characterize 6-month changes in LA strain and identify baseline determinants of follow-up LA strain after ablation for paroxysmal AF. This prospective study enrolled consecutive patients undergoing first-time pulmonary vein isolation for paroxysmal AF. Two-dimensional speckle-tracking echocardiography from apical four- and two-chamber views was performed at baseline and 6 months to assess LA reservoir strain (LASr) and contraction strain (LASct). Factors associated with 6-month LASr and ΔLASr (6-month minus baseline) were examined using multivariable linear regression. Of 167 enrolled patients, 121 without structural heart disease and with analyzable echocardiograms in sinus rhythm at baseline and 6 months were included (67 ± 11 years; 68% men). LASr decreased (25.9 ± 7.9% to 23.1 ± 6.4%, p < 0.001) and LASct declined (11.8 ± 5.5% to 10.4 ± 4.8%, p = 0.007), while LA volume index (LAVI) was unchanged. Baseline LAVI was independently associated with 6-month LASr (standardized β = 0.32, p < 0.001), and higher baseline LAVI was associated with greater ΔLASr (standardized β = 0.33, p < 0.001). These associations were unchanged after adjustment for ablation modality (pulsed-field ablation vs thermal ablation). Post-ablation changes in LA strain were continuously associated with baseline LA remodeling; lower baseline LAVI was independently associated with a less favorable change in LASr. Post-ablation LA function should be interpreted in conjunction with baseline remodeling.
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.
Smoking prevalence in Germany remains high (30%) and uptake of cessation services is low. E-cigarettes are promoted as a cessation aid but whether they are preferred over established methods is unknown. To improve cessation efforts, understanding the extent different characteristics of a smoking cessation program are preferred are important. This study estimated preferences and willingness-to-pay for a smoking cessation program using a discrete choice experiment (DCE). Potential participants who resided in Germany and smoked ≥5 cigarettes daily (cpd) were recruited for the main study between July-September 2023. The DCE included 12 choice tasks. Attributes were cessation aids (nicotine replacement, medication, and e-cigarettes), counseling, referral by a health professional, effectiveness, and out-of-pocket costs. The study sample (N=1052) was 51.4% female with a mean cpd of 17 (SD=8.2). Mixed logit regression found counseling, referrals, and program effectiveness significantly influenced choices (p<0.001). None of the levels for cessation aids were significant. However, in subgroup analyses the use of e-cigarettes for quitting was preferred by those with prior e-cigarette use, while evidence-based cessation aids were preferred by several other subgroups. While low costs were preferred, particularly among those with no experience using cessation aids, participants were willing to pay a high cost for an effective program (€91.48/month). To increase engagement, smoking cessation programs in Germany should include counseling and be explicit on the evidence of cessation therapies, as program effectiveness is highly valued. Improving access to cessation aids through referrals and lower costs can increase cessation efforts. Our findings suggest that German adults who smoke are most likely to engage in cessation programs that demonstrate proven effectiveness, include counseling support, and are recommended by a health professional. The lack of preference for specific cessation aids, except e-cigarettes among prior users, indicates that better communication about the effectiveness of evidence-based pharmacotherapies is needed. Health professionals should provide clear, evidence-based guidance on all cessation methods, including transparent discussion of the current evidence regarding e-cigarettes for smoking cessation, to support informed decision-making and optimize treatment selection.
Vaginal hysterectomy with suture apical suspension (hysterectomy) is commonly performed for uterovaginal prolapse, and a vaginal sacrospinous hysteropexy with graft (hysteropexy) is a uterine-sparing alternative. Ten-year outcomes for prolapse surgeries are rarely reported. To compare the efficacy and adverse events of these 2 procedures over 10 years. At 9 clinical sites in the US Pelvic Floor Disorders Network, postmenopausal women with symptomatic uterovaginal prolapse were enrolled in a multisite superiority randomized clinical trial between April 2013 and February 2015. Study data were analyzed from February 2018 to November 2025. Women were originally randomized to vaginal mesh hysteropexy or to vaginal hysterectomy with uterosacral ligament suspension. Participants had 5 years of masked follow-up at 6-month intervals followed by an extended unmasked annual follow-up from 6 to 10 years. The primary treatment failure composite outcome (retreatment of prolapse, prolapse beyond the hymen, or prolapse symptoms) was evaluated with time-to-failure models. Secondary outcomes included individual anatomic Pelvic Organ Prolapse Quantification measures, bothersome symptoms measured by validated questionnaires, complications and adverse events. A total of 183 participants (mean [SD] age, 66 [7] years) were randomized, and 175 were included in the intention-to-treat analysis after ineligibility exclusions (88 hysteropexy group and 87 hysterectomy group), 112 of whom (64%; 55 hysteropexy group and 57 hysterectomy group) participated in the 6- to 10-year follow-up extension. There were fewer failures for hysteropexy (35 of 88 [40%]) compared with hysterectomy (46 of 87 [53%]) through 10 years. Time-to-failure analysis showed lower failure risk in hysteropexy (adjusted hazard ratio, 0.64; 95% CI, 0.41-1.00; P = .05). Both groups had sustained improvements in patient reported outcomes with no group differences demonstrated in patient-reported prolapse, urinary, or bowel symptoms, sexual function, dyspareunia, or clinically important complications. Results show that vaginal mesh hysteropexy continued to have a lower composite failure rate through 10 years than vaginal hysterectomy with uterosacral ligament suspension, although an expected increase in durability over the native tissue procedure in years 6 to 10 was not observed. Both procedures are reasonable options for patients. If available, hysteropexy with mesh augmentation for patients who desire uterine preservation is a low risk and effective option. ClinicalTrials.gov Identifier: NCT01802281.
To examine associations between smoking and Sjögren's disease (SjD) diagnosis, compared with non-Sjögren's sicca syndrome (sicca) and population controls, and to explore immunomodulatory effects of smoking on disease phenotype. Adults referred for suspected SjD to the OASIS cohort from 2014 until 2023 were classified as SjD or sicca. Smoking status, exposure (pack-years), and passive smoking history were recorded through standardised questionnaires. Associations with diagnosis, clinical and serological parameters, and patient-reported outcomes were analysed using multivariate logistic and linear regression. Smoking patterns were further compared to matched controls from the 2018 UK Annual Population Survey. 317 SjD patients and 170 sicca controls were included. Of these, 257 SjD met 2016 classification criteria, and were used for primary analyses. Smoking data were available for 85.0% of the cohort. SjD patients were more frequently never smokers than sicca (70.5% vs 53.1%, p = 0.002). In the multivariate analysis, current smoking (OR 0.37, 95%CI 0.15-0.92) was independently associated with lower odds of SjD. Never smokers exhibited higher IgG levels (p = 0.003) and more frequent biological ESSDAI activity (p = 0.038). Smoking exposure correlated with reduced IgG, rheumatoid factor levels, and seropositivity, independent of DMARD use. Compared with population controls, sicca, but not SjD, showed higher ever-smoking rates (49.6% vs 39.1%, p = 0.049). Smoking was negatively associated with SjD diagnosis compared to sicca, but not population controls. Smoking exposure linked to lower immunoglobulin and autoantibody levels, suggesting an immunomodulatory effect rather than true disease protection. Findings support a potential metabolically-influenced, non-autoimmune, sicca phenotype linked to smoking.
Adrenocortical carcinoma (ACC) is a rare tumor with highly aggressive malignancy. Its two main pathological subtypes, conventional ACC (CAC) and oncocytic ACC (OAC), are hypothesized to differ in clinical behavior, but comparative studies are limited due to the rarity of OAC. This study aimed to compare the clinical characteristics, pathological features, and prognosis between CAC and OAC. A retrospective review was conducted on 128 ACC patients (105 CAC, 23 OAC) during the period of October 2015 and October 2025. Data on clinical presentation, hormonal status, pathological findings, and survival outcomes were collected and analyzed. Statistical comparisons were performed using t-tests, Mann-Whitney U tests, chi-square tests, Cox proportional hazards regression analysis, multivariable Cox proportional hazards regression analysis, and Kaplan-Meier survival analysis with log-rank test. Compared with CAC, OAC patients had a significantly lower prevalence of Cushing's syndrome (13.0% vs. 39.0%, P < 0.05) and hypertension (17.4% vs. 48.6%, P < 0.01). In contrast, adrenal-derived sexual characteristics abnormalities were more common in OAC (65.2% vs. 26.0%, P < 0.001). Pathologically, compared with CAC, the Ki-67 index was significantly lower in OAC (median: 14% vs. 20%, P < 0.05). Also, Kaplan-Meier survival analysis revealed a more favorable overall survival(OS) for OAC, with a 5-year OS rate of 70.4% compared to 48.4% for CAC (P < 0.05). After multivariate adjustment for ENSAT stage and Ki‑67, pathological subtype lost independent prognostic significance, while ENSAT stage and Ki‑67 remained independent predictors. CAC was associated with a higher frequency of glucocorticoid excess symptom, a higher proliferative index (Ki-67). OAC was characterized by a higher prevalence of androgen excess symptoms. OAC demonstrated similar OS to CAC after adjustment for ENSAT stage and Ki‑67.