The failure of conventional therapies for bovine theileriosis in Khorasan-Razavi province and other regions of Iran has led to significant economic losses and raised concerns about rural livestock sustainability and national food security. This study identified specific cytochrome b mutations in Theileria annulata isolates collected from cattle showing clinical unresponsiveness to buparvaquone treatment in the Khorasan-Razavi province of Iran. Blood samples were collected, and parasite DNA was extracted and amplified via PCR using specific primers. Sequencing and subsequent BLAST analysis revealed two novel cytochrome b variants, OQ230576 and OQ230577, registered in the NCBI GenBank. These variants exhibited multiple non-synonymous mutations compared to sensitive reference strains from Iran (MH248139/1) and Ankara. The OQ230576 sequence demonstrated six to ten mutations, while OQ230577 exhibited eight to ten mutations, suggesting structural alterations linked to drug resistance. These findings confirm the emergence and spread of resistant Theileria annulata strains in the studied regions. The progressive decline in treatment efficacy underscores the urgent need for alternative therapeutic approaches and more robust disease management strategies to safeguard livestock productivity and rural economies.
This study examined whether repeated incarceration among justice-involved male adolescents with substance use disorder (SUD) reflects not only a legal consequence but also a marker of a more severe clinical risk profile. It also evaluated the roles of addiction severity, family criminal history, psychological resilience, and meaning in life in repeated incarceration. The sample comprised 203 male adolescents with a history of substance use who were incarcerated in a closed correctional facility. Participants were classified as first-time incarcerated or repeatedly incarcerated. Addiction severity was assessed with the Addiction Profile Index for Adolescents, psychological resilience with the Brief Resilience Scale, and meaning in life with the Meaning in Life Questionnaire. Group differences were examined using chi-square tests and independent-samples t-tests, and independent predictors of repeated incarceration were analyzed with binary logistic regression. Overall, 32.5% of participants had a history of repeated incarceration. Compared with first-time incarcerated adolescents, this group showed greater addiction severity and lower psychological resilience and meaning in life, whereas age and offense type did not differ significantly. In binary logistic regression, the model was significant and explained 34.2% of the variance in repeated incarceration. Family history of crime was the strongest predictor, increasing the risk 5.20-fold. Higher addiction severity increased the likelihood of repeated incarceration, whereas meaning in life was protective. Age and psychological resilience were not independently significant in the multivariable model. Repeated incarceration may represent not merely a legal outcome, but a clinical indicator of greater addiction burden, adverse family context, and limited psychological protective resources. Rehabilitation should therefore extend beyond containment and address clinical severity, family functioning, and purpose-related psychological resources simultaneously.
Photovoltaic (PV) power generation plays a critical role in the global transition toward sustainable energy systems. However, accurate PV power forecasting remains challenging due to the non-stationary nature of PV power time series and the presence of structural zeros. Most existing studies rely on parametric models or treat zero inflation as a secondary issue. In this study, a hybrid hurdle modeling framework is implemented to explicitly account for both structural zeros and continuous positive power values through a two-part structure. The zero component is modeled using Bayesian logistic regression (BLR), random forest classifier (RFC), and support vector classifier (SVC). The positive values are analyzed using the parametric models Gamma regression (GR), Log-normal regression (LNR), and Weibull regression (WR) and the non-parametric machine learning (ML) techniques random forest regression (RFR), extreme gradient boosting (XGBoost), and support vector regression (SVR). The proposed framework is validated using the target variable active power (AP, kW) based on a real-world data from a 110 kWe (129.6 kWp) PV plant located in Çaycuma, Zonguldak, Türkiye. Four metrics were used to compare the predictive performances of the models: mean squared error (MSE), mean absolute (scaled) error (MAE and MASE), and the coefficient of determination ([Formula: see text]). Among the 18 distinct hurdle models, the lowest error values and the highest [Formula: see text] were obtained when the positive component was modeled by either RFR, such as BLR-RFR (MSE = 67.425 kW, MAE = 3.974 kW, MASE = 0.615, [Formula: see text] = 0.899) or XGBoost, such as RFC-XGBoost (MSE = 69.252 kW, MAE = 4.075 kW, MASE = 0.630, [Formula: see text] = 0.898). The findings indicate that hybrid modeling approaches where the zero component is modeled using BLR, RFC, or SVC, and the positive component is modeled with either RFR or XGBoost provide a reliable framework for PV power forecasting, when predicting continuous data characterized by excessive structural zeros.
Lymphoproliferative disorders (LPDs) associated with inborn errors of immunity (IEI) are rare entities and their genetic basis is not well defined. We performed targeted deep sequencing using a panel of 529 genes to investigate the single nucleotide variants (SNVs), insertion/deletions (INDELs), structural rearrangements (SVs), and copy number variants (CNVs) in 16 lymphoproliferations associated with IEI belonging to a cohort of 14 patients. Histomorphologically, the cases were classified into B-cell hyperplasia (n = 1); polymorphic B-lymphoproliferative disorder (n = 8); polymorphic B-lymphoproliferative disorder with focal increased large cell component bordering large B cell lymphoma (n = 3); and large B-cell lymphoma (n = 4). Fourteen of the 16 cases were EBV positive. Across the patients, 40 variants were identified. The majority of the genes affected were those involved in DNA damage response pathways and transcriptional regulation. Pathogenic SNVs, INDELs, and CNVs were increased in cases with a large B cell component vs other cases. Heterozygous SNVs in protein interaction domains of EMSY were identified in 3 cases, suggesting that it may have a predisposing role in the development of lymphoproliferations. Deletions involving the TNFAIP3 gene (copy number losses) were also recurrent, identified in 3 of 16 cases (18.8%) and correlated with large cell morphology.
This scoping review aimed to characterize antimicrobial stewardship (AMS) interventions in transplant recipients, compare antibacterial, antifungal, and antiviral stewardship strategies, summarize clinical and economic outcomes, and identify knowledge gaps relevant to health policy. The study was conducted according to the Joanna Briggs Institute methodology and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. Original research articles published between January 2015 and March 2025 were identified through searches of the PubMed, Scopus, and Web of Science databases. Data were synthesized using thematic analysis. Fifteen studies published between 2017 and 2025 were included. Thematic analysis categorized the interventions into the following domains: intervention structure, individualized strategies, diagnostic management, clinical and economic outcomes, comparative findings by population and transplant type, and implementation barriers. All studies included an antibacterial stewardship component (100%), whereas antifungal (20%) and antiviral (7%) interventions were comparatively limited. Interventions were primarily implemented as guideline-based optimization and prospective audit-and-feedback models. Infectious disease specialists participated in 87% of the studies, while clinical pharmacists were involved in 33%. Clinical effects were predominantly reported using process indicators. A reduction in antimicrobial treatment duration (47%) and improved guideline adherence (33%) were the most frequently reported outcomes. Studies evaluating mortality and graft survival were limited (27%), and most did not demonstrate significant differences. Economic outcomes were reported in 73% of the studies, with program-level cost reductions ranging from 20% to 40%. The most common implementation barriers were high resource requirements and heterogeneity of guidelines. Antimicrobial stewardship practices in transplant recipients are primarily focused on antibacterial management and are associated with improvements in short-term process indicators. However, evidence regarding long-term clinical outcomes and antifungal and antiviral stewardship practices remains limited. Developing transplant-specific, multidisciplinary, and sustainable AMS models is essential for antimicrobial resistance control and patient safety in this high-risk population.
Caesarean scar defects, known as isthmocele, are increasingly recognized in women with secondary infertility, yet hysterosalpingographic (HSG) criteria remain poorly defined. We describe a reproducible HSG feature, the "pocket sign," observed in seven women with prior caesarean delivery. This finding appears as contrast pooling in the anterior lower uterine segment near the internal cervical os. In all cases, it correlated with transvaginal ultrasound and hysteroscopic findings. Although non-specific and not diagnostic, the pocket sign may serve as an adjunctive indicator prompting further evaluation. Given anatomical variability and intrinsic limitations of HSG, multimodal imaging remains essential.
A superior titanium glycolate-based catalyst for thermo- and photocatalytic formic acid dehydrogenation (FADH) is synthesized for hydrogen evolution. Carbon-decorated mesoporous anatase TiO2 nanospheres (CTNSs) are obtained by the hydrolysis of titanium glycolate nanospheres (TGNSs). The selection of TGNSs as the precursor of the support allows varying the extent of carbon decoration, crystallinity, mean crystallite size, Ti-(III)/Ti-(IV) ratio, and oxygen vacancy of TiO2-based catalyst by controlling the hydrolysis time. A series of catalysts are obtained by immobilization of ultrafine PdAu nanoalloy onto amine-functionalized CTNSs with different crystalline properties and carbon contents. The nanocatalyst obtained using CTNSs with the lowest crystallinity (78.4%), smallest crystallite size (3.98 nm), and densely carbon-decorated anatase phase with a high oxygen vacancy (40.65%) and high Ti-(III)/Ti-(IIV) ratio (0.409) with a band gap energy of 1.255 eV (PdAu@ACTNSs-1) provides an exceptional TOF of 20,924 h-1 with 100% H2 selectivity in catalytic FADH at 60 °C. A TOF of 34,877 h-1 was obtained at 80 °C. TOFs up to 1507 h-1 are observed in visible-light-driven photocatalytic FADH at 25 °C via 1O2, •OH radicals, and electron holes. PdAu@ACTNS-1 exhibits high stability over thermo-/photocatalytic FADHs. The synthetic route presents an innovative strategy for developing new high-performance catalysts for organic reactions.
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This mixed-methods study explores audiologists' perspectives on remote programming (RP) for cochlear implants (CIs) and compares patient satisfaction between initial activation and follow-up sessions. A mixed-methods approach combined qualitative interviews with audiologists and a survey of CI users. Thematic analysis was applied to interview data, and survey responses were analysed descriptively and comparatively. Six experienced audiologists participated in semi-structured interviews, while 136 CI users (44 initial activation, 92 follow-up) completed satisfaction surveys. Audiologist interviews revealed four key themes: RP advantages, implementation challenges, technical requirements, and professional satisfaction. Survey data showed significantly higher satisfaction among follow-up users across seven of eight items. Both groups rated technical quality and communication highly, but follow-up users reported greater ease, confidence, and willingness to use RP again. RP is a viable alternative for CI programming, particularly for follow-ups, while initial activations pose unique challenges best managed through hybrid care models. Incorporating both patient and clinician perspectives, this study underscores the need for robust infrastructure, enhanced communication strategies, and standardised professional training to ensure consistent, high-quality remote audiological care.
Kinesio taping is widely used as a non-pharmacological adjunct in knee osteoarthritis (OA), although its mechanisms and clinical value remain debated. This narrative review synthesizes current evidence on kinesio taping in knee OA, addressing mechanisms and effects on pain, function, muscle activation, proprioception, and range of motion (ROM). PubMed/MEDLINE, Scopus, Web of Science, Directory of Open Access Journals (DOAJ), and Google Scholar were searched through 19 May 2026 using MeSH terms "Osteoarthritis, Knee" and "Athletic Tape" with related keywords. Eligible sources included systematic reviews, meta-analyses, randomized controlled trials, observational studies, and appraised qualitatively with interpretive weight ranked by study design. Kinesio taping may provide short-term pain reductions that fall below minimal clinically important difference (MCID) (15-20 mm VAS). Functional gains are modest and inconsistent, mostly below WOMAC MCID (17%). Although kinesio taping does not increase muscle strength, it may modulate quadriceps-hamstring coactivation and neuromuscular control during low-load tasks. Proprioceptive gains are reportedly angle-specific (significant at 15° and 30°). Flexion ROM increases modestly, whereas extension changes little. Compared with other adjunctive treatments, it shows lower or comparable effects. Adverse effects are confined to minor, self-limiting skin reactions. Current evidence does not support the routine use of kinesio taping as a standalone treatment for knee OA. Kinesio taping may be considered as a short-term adjunct to exercise and education in selected patients, as it may facilitate symptom relief, sensory feedback, and low-load activity. Methodological heterogeneity remains a significant limitation, and randomized controlled trials are needed.
Gastrointestinal cancer surgery commonly leads to postoperative complications and other adverse outcomes. While prehabilitation shows promise in reducing adverse postoperative outcomes, most hospitals have resource limitations that preclude its use as standard of care. Additionally, the need to expedite surgery from diagnosis often creates a narrow window for prehabilitation initiatives. Online, self-reported screening tools may address these challenges by facilitating early identification of high-risk patients and enabling targeted preoperative interventions, thereby allowing equitable allocation of limited resources. Therefore, the primary aim of this study is to evaluate the predictive utility of a tri-modal (physical, nutritional, psychological) screening tool for patients undergoing gastrointestinal cancer surgery. This prospective international cohort study will recruit 1214 adults undergoing elective gastrointestinal cancer surgery across 35 sites from 19 countries. Participants will complete an online screening tool developed through a comprehensive, multistep, predefined process. The screening tool comprises the Duke Activity Status Index, Patient-Generated Subjective Global Assessment Short Form and the Patient Health Questionnaire-4, in English, Spanish, French or Portuguese. These tools were selected based on a scoping review, followed by an international Delphi consensus process. The primary outcomes include rate of postoperative complications, major complications (Clavien-Dindo Classification grade III-V) and overall complication severity assessed by the Comprehensive Complications Index; all assessed 30 days postoperatively. Secondary outcomes include hospital length of stay, readmission rate within 30 days, discharge destination (home vs other), days at home and alive in 30 days postsurgery, 30-day all-cause mortality and 12-month survival. Primary analyses will establish optimal screening tool cut-points to stratify patients into clinically actionable risk categories for postoperative complications and examine the independent predictive value of these screening scores after adjusting for established clinical risk factors. This study has received ethical approval from the Sydney Local Health District Human Research and Ethics Committee (X25-0333 and 2025/ETH02465) and has been registered on the Open Science Framework (10.17605/OSF.IO/HVCGD). The results of Preoperative Risk Evaluation for Cancer Treatment will be submitted to reputable journals and presented at national and international conferences.
We evaluated the relationships between demographic, metabolic and biochemical risk factors and the presence, localisation and severity of carpal tunnel syndrome (CTS) in a large Turkish cohort. In total, 3144 participants were retrospectively included in this 2-year study. Among these, 1458 had an electrophysiologically confirmed diagnosis of CTS, while the remaining 1686 individuals served as the control group. Demographic characteristics, comorbidities and biochemical parameters were recorded for all participants. The CTS patients were further stratified by electrophysiological severity and the anatomical localisation of the involvement. The median age (57 vs 48 years) and body mass index (BMI) (30.6 vs 27.9 kg/m2) were significantly higher in the CTS group. Regarding comorbidities, diabetes mellitus (DM), hypertension (HT) and hyperlipidemia were more frequent among CTS patients, with these differences persisting in severe cases. Furthermore, advanced age and the presence of DM and HT were more prevalent in the bilateral CTS subgroup. In a multivariate model, age and BMI remained independently associated with the presence of CTS. Advanced age and high BMI were confirmed as independent predictors of CTS, whereas female sex was not. Furthermore, components of metabolic syndrome were the most common comorbidities identified in this Turkish cohort.
Cystic fibrosis (CF) results from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, causing multisystem disease and impaired quality of life. CFTR modulators have improved pulmonary and nutritional outcomes, yet potential metabolic effects such as dyslipidemia remain a concern, particularly in adults. Pediatric data are limited. This study evaluated the effects of CFTR modulators on lipid and lipoprotein profiles in children with CF. This retrospective study was conducted at a tertiary pediatric pulmonology center. Body mass index (BMI) Z-scores, lung function tests, and serum lipid profiles were compared between baseline and six months after initiation of CFTR modulator therapy. Twenty-six patients were included finally. The median age was 11 (5.9-15.6) years; 53.8% were female, and 80.8% received elexacaftor/tezacaftor/ivacaftor. After six-month therapy, significant improvements were observed in BMI (p = 0.047), FEV₁ (p = 0.005), and FVC Z-scores (p = 0.001). Although HDL, LDL, VLDL, triglycerides, and total cholesterol increased numerically, none reached statistical significance. No difference was found between BMI changes and lipid alterations. Over six months of continuous CFTR modulator therapy, we observed improvements in pulmonary and nutritional outcomes without evidence of clinically meaningful lipid deterioration. This study adds real-world pediatric data regarding lipid profile changes during CFTR modulator therapy. While these therapies significantly improve pulmonary and nutritional outcomes, we observed no evidence of lipid deterioration over six months of treatment. These findings contribute to the evolving understanding of the systemic effects of CFTR modulators in childhood and underscore the importance of ongoing cardiometabolic evaluation as survival improves.
This study aimed to investigate the fermentation of reduced-calorie sour cherry-based beverages using three individual probiotic strains (Lactiplantibacillus plantarum SH5, Limosilactobacillus fermentum SH10, and Lactiplantibacillus pentosus SH14) and one mixed-strain formulation, and to evaluate these beverages together with unfermented control beverages in terms of their physicochemical, microbiological, bioactive, and cytotoxic properties during 28 days of cold storage. The fermented beverages exhibited pH values of 3.54-3.63, turbidity of 0.614-0.779, total soluble solids of 24.93-29.87 °Brix, and dry matter content of 27.62%-30.75%, with color parameters recorded as L* (15.08-16.66), a* (12.80-18.21), and b* (-5.78 to -3.05). Phenolic profiling identified catechin (31.05-32.90 ppm), chlorogenic acid (10.82-11.05 ppm), and myricetin (5.05-6.90 ppm) as the predominant compounds, although most phenolics gradually declined during storage. Despite higher initial total phenolic content (TPC) in control samples, lacto-fermented beverages exhibited superior recovery values (%), indicating enhanced bioaccessibility during in vitro digestion. Calorie reductions reached up to 46.46% in SCN9-SH10, while viable LAB populations remained above 106 CFU/mL throughout 21 days of storage (7.01-7.65 log CFU/mL). TPC ranged from 214.75 to 353.67 mg gallic acid equivalent (GAE)/100 mL, DPPH scavenging activity from 213.54 to 274.02 mg Trolox equivalent (TE)/100 mL, and cupric reducing antioxidant capacity (CUPRAC) values from 924.46 to 1576.71 mg TE/100 mL, with fermented samples consistently demonstrating higher antioxidant capacity than controls. Antibacterial activity was observed only in SCN9-Mix and control samples against Bacillus cereus ATCC 11778, while cytotoxicity assays indicated modest inhibitory effects toward MCF-7 breast cancer cells, with cell viability ranging from 87.64% to 94.45% in freshly prepared samples and decreasing over 28 days. Collectively, these findings demonstrate that lactic acid fermentation effectively enhances the functional, microbiological, and bioactive properties of reduced-calorie sour cherry-based beverages.
By reducing the duration of the vitrification-warming procedure to 1 min does ultra-rapid vitrification-warming (URV/W) effectively maintain oocyte viability and improve clinical outcomes compared to conventional vitrification-warming (CV/W) timing (14 min) and what is the effect of the two procedures on cellular stress? URV/W shortens procedure time, reduces cryoprotectant exposure, improves oocyte survival, and is associated with fewer transcriptomic alterations in oocytes than CV/W. CV/W techniques require extended cryoprotectant exposure and micromanipulation, which elevate cellular stress and the risk of cryoinjury. URV/W procedures address these challenges by reducing exposure and manipulation, though comparative data on clinical outcomes and transcriptomic signatures in human oocytes remain limited. The study was performed between August 2024 and December 2024 and included a clinical cohort and a transcriptomic cohort to provide a thorough assessment of the effects of cryopreservation methodology on oocyte and embryo viability, development, and cellular stress. The clinical cohort comprised 1077 oocytes used to evaluate clinical outcomes following CV/W and URV/W. The study also included a prospective analysis involving 68 oocytes from 4 donors in the transcriptomic cohort. Oocytes and trophectoderm biopsy samples from blastocyst-stage embryos were assigned to three groups: fresh, CV/W, and URV/W. The clinical study was performed using a total of 1077 oocytes from 46 donors, which were matched and allocated for the comparison of clinical outcomes between CV/W (n = 519) and URV/W (n = 558). Following vitrification-warming, the oocytes were fertilized via ICSI for assessment of embryo development and clinical outcomes. In the transcriptomic cohort of the study, transcriptomic testing and analysis were performed as part of the prospective analysis to compare CV/W and URV/W in terms of their effectiveness in oocyte freezing and warming, their impact on embryo development, and their effects at the molecular level. A total of 68 samples were obtained from 4 donors, including eight oocytes and eight trophectoderm biopsy samples from each of the three groups. These samples were analyzed to investigate the cellular effects of cryopreservation-induced stress through transcriptomic profiling. The single-cell transcriptomic study included preparation of cDNA libraries followed by next-generation sequencing to investigate differential gene expression across oocytes and embryonic trophectoderm cells in the three groups. This method allowed for the comprehensive monitoring of transcriptional activity, enabling the detection and quantification of mRNA molecules to evaluate the transcriptomic signatures of the study groups. In addition, functional enrichment analyses of up- and downregulated genes were conducted and classified based on gene ontology to identify potential pathways associated with embryo quality and cellular stress. Transcriptomic analysis indicated that gene expression patterns following URV/W were more similar to fresh oocytes than those undergoing CV/W. Differences in gene expression patterns among blastocysts from the three groups were minimal, as the total number of differentially expressed genes was limited. Oocytes subjected to URV/W demonstrated a significantly higher survival rate, lower post-ICSI degeneration, and produced more high-quality Day-5 blastocysts compared to those vitrified using CV/W methods (P < 0.001 for all comparisons). These findings are unlikely to be solely attributable to differences in procedural timing, as fertilization, cleavage, euploidy, clinical pregnancy, and live birth rates were comparable between groups (P > 0.05 for all comparisons). All oocyte samples donated (1145) for research purposes were included in the study without quality-based selection. Only embryos reaching the blastocyst stage on Days 5 or 6 using the URV/W method were included in the transcriptomic analysis. Embryos not reaching these stages were excluded. Consequently, only data from embryos with optimal development and good quality were analyzed, and compared among the three groups. Obtaining cDNA in single-cell studies is a novel and challenging process, particularly due to the limited availability of RNA. While advanced clinical evaluations can still be conducted on biopsied oocytes and embryos, the failure to obtain cDNA from the same samples may result in incomplete data, which can limit the overall scope and outcomes of the study. The comprehensive single-cell transcriptomic data obtained from this expanded dataset will help delineate pathways altered by different vitrification methods, providing critical insights into their efficacy and potential risks in clinical practice. Additionally, the findings will illuminate key genes and pathways involved in embryonic stress, enabling the development of more cost-effective, targeted gene panels for evaluating these factors. This study was funded by the Sanatórium pre liečbu neplodnosti SPLN's, Ovogene and Mikrogen Genetic Diagnosis Laboratory's own resources. A.V.P. is a Medical Science Liaison for Kitazato Corporation-Dibimed. His role in the study was strictly scientific and unrelated to any commercial interest. All the other co-authors declare no conflicts of interest. n/a.
The aim of this study was to evaluate the real-world efficacy and safety of intravitreal faricimab for macular edema (ME) secondary to retinal vein occlusion (RVO) across a multicenter cohort with up to 52 weeks of follow-up. Data from 17 centers across Türkiye were retrospectively analyzed between 22 November 2024 and 1 March 2026. Patients with branch RVO (BRVO) or central RVO (CRVO) complicated by ME who received at least one intravitreal faricimab injection and had complete ophthalmic and optical coherence tomography (OCT) data with a minimum 4-week follow-up were included. Demographics, diagnosis, prior treatments, best-corrected visual acuity (BCVA; decimal converted to logMAR), central macular thickness (CMT), intraocular pressure (IOP), injection number, follow-up duration, and ocular/systemic adverse events were recorded at baseline, day 7, monthly after each of the first three injections, and at the final visit. A total of 70 patients (37 BRVO [52.9%], 33 CRVO [47.1%]) were included, with a mean follow-up of 23.69 ± 8.54 weeks; 44 (62.8%) were treatment-naïve and 26 (37.2%) were switch patients. When comparing baseline and final visits, treatment-naïve patients showed a mean CMT reduction of 306.9 ± 231.3 µm (from 594.1 ± 206.9 µm at baseline to 287.2 ± 89.9 µm at final visit; p < 0.001), while switch patients demonstrated a mean CMT reduction of 290.6 ± 114.3 µm (from 562.1 ± 107.3 to 271.5 ± 90.7 µm; p < 0.001). The mean logMAR BCVA gain was 0.77 (p < 0.001) in naïve and 0.38 (p < 0.001) in switch patients. IOP remained stable throughout, and no serious ocular or systemic adverse events were recorded. Faricimab demonstrated rapid anatomical and functional improvements in the RVO cohort, evident as early as day 7 after the initial injection. These findings support faricimab as a potent and reliable therapeutic option across both RVO subtypes in routine clinical practice. Retinal vein occlusion (RVO) is a condition where one of the veins draining blood from the back of the eye becomes blocked, causing fluid to build up in the retina and leading to blurred or reduced vision, the second most common cause of vision loss from retinal blood vessel disease. Faricimab is a new medicine that works by blocking two proteins, vascular endothelial growth factor-A (VEGF-A) and angiopoietin-2, which cause fluid leakage and blood vessel instability in the eye. While faricimab has shown promising results in clinical trials, less is known about how it performs in everyday clinical practice. This study looked at real-world outcomes in 70 patients with RVO treated across 17 eye centers in Türkiye. Faricimab led to rapid and meaningful improvements in both vision and retinal swelling, detectable as early as 1 week after the first injection, in both patients who had never received eye injections before and those switching from other treatments. No serious side effects were recorded. These findings support faricimab as an effective and well-tolerated treatment for RVO in routine clinical practice, though longer follow-up studies are needed to confirm lasting benefits, and the safety of rare inflammatory events cannot be fully assessed in a cohort of this size.
Type II endoleak (T2EL) is the most frequently reported complication following endovascular aneurysm repair (EVAR). Although generally considered benign and often self-limiting, spontaneous resolution does not always occur, and secondary intervention may be required. In this study, morphological and morphovolumetric parameters were compared between patients who developed T2EL and those without endoleak, in order to identify predictors of T2EL development in the pre-EVAR period. Additionally, our experience in the management of T2EL was reviewed in the context of the existing literature. A total of 472 patients who underwent EVAR were initially evaluated. After exclusion of other endoleak types, 408 patients were included in the final analysis, of whom 53 (13%) developed T2EL. The no-endoleak group comprised 355 patients (87%). Overall, T2EL accounted for 45.2% of all detected endoleaks. Primary endpoints were the identification of factors influencing T2EL development and the assessment of morphological and morphovolumetric parameters associated with endoleak formation. Secondary endpoints included secondary intervention rates, as well as post-EVAR mortality and morbidity. No early mortality was observed. The mean follow-up duration was 33.2±21.2 months (median: 25 months; range: 12-99 months). All patients had at least one year of follow-up. Both univariate and multivariate analyses identified age, antiplatelet therapy regimen, inferior mesenteric artery (IMA) diameter, number of patent lumbar arteries, thrombus localisation, and the intraluminal thrombus-to-aneurysm volume ratio as significant predictors of T2EL development. Late mortality for the entire cohort was 23.0%, with cardiac-related causes being the most common (11.0%). Mean intensive care unit stay was 5.2±5.1 hours, and mean hospital stay was 2.6±1.0 days. Although EVAR effectively reduces aneurysm diameter and volume during follow-up, the presence of T2EL may limit this benefit. Lumbar arteries were the most common source of T2EL. An IMA diameter >3 mm, female sex, double antiplatelet therapy, presence of four or more lumbar arteries, absence of coronary artery disease, and thrombus characteristics were associated with increased T2EL risk. D-dimer appears to be a useful biomarker for T2EL detection. Morphovolumetric analysis is more sensitive than maximum diameter measurement in the surveillance of low-flow endoleaks.
Renal cell carcinoma (RCC) rarely metastasizes to the carpal bones. We describe a 43-year-old woman with a history of RCC who presented with ulnar-sided wrist pain. Imaging demonstrated complete osteolytic destruction of the hamate. Treatment consisted of excision of the hamate, intralesional curettage, cement reconstruction, and internal fixation to the adjacent carpal bones and the fourth and fifth metacarpals. At 15 months of follow-up, no local recurrence, carpal instability, or implant-related complications were observed. Surgical excision with cementation and internal fixation achieved local tumor control, maintained carpal stability, and enabled early functional recovery in this rare case of hamate metastasis from RCC.
Many cancer monotherapies demonstrate limited clinical efficacy, making combination therapies a relevant treatment strategy. The extensive number of potential drug combinations and context-specific response profiles complicates the prediction of drug combination responses. Existing computational models are typically trained to predict a single aggregated synergy score, which summarises drug responses across different dosage combinations, such as Bliss or Loewe scores. This oversimplification of the drug-response surface leads to high prediction uncertainty and limited actionability, as these models fail to distinguish between potency and efficacy. We introduce DeepSynBa, an actionable model that predicts the complete dose-response matrix of drug pairs instead of relying on an aggregated synergy score. This is achieved by predicting parameters describing the response surface as an intermediate layer in the model. Evaluated on the NCI-ALMANAC and the O'Neil datasets, DeepSynBa outperforms the state-of-the-art methods in the dose-response matrix prediction task across most evaluation scenarios, including testing on novel drug combinations, cell lines, and drugs, across nine different tissue types. We also show that DeepSynBa yields reliable synergy score predictions. More importantly, DeepSynBa can predict drug combination responses across different dosages for untested combinations. The intermediate dose-response parameter layer enables the separation of efficacy from potency, informing the selection of dosage ranges that optimise efficacy while limiting off-target toxicity in experimental screens. The predictive capability and the downstream actionability make DeepSynBa a powerful tool for advancing drug combination research beyond the limitations of the current approaches. The code and the dataset for DeepSynBa are available at https://github.com/hikuru/DeepSynBa.