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We would like to thank the authors of the comment [...].
We read with great interest the comprehensive 20-year review of orbital metastases by Ulaş and co-authors [...].
To provide a nationwide epidemiological assessment of upper limb amputations (ULAs) in Germany, including incidence trends, underlying aetiologies, amputation levels and revision patterns, with a comparative analysis between 2019 and 2023. Nationwide retrospective cross-sectional analysis of routinely collected inpatient hospital data. All acute-care hospitals in Germany reporting to the national Diagnosis-Related Groups and Operation and Procedure Classification System (OPS) from 2019 to 2023. All patients undergoing ULA procedures (OPS 5-862 and 5-863) or revision procedures (OPS 5-866) within the study period. No exclusion criteria were applied. Primary measures were annual incidence of ULAs, the distribution of amputation levels and underlying medical aetiologies. Secondary measures included the incidence of revision procedures and revision aetiologies stratified by anatomical level. A total of 5427 ULAs were performed in 2023, representing a 7.3% decrease compared with 2019 (5,852). Distal amputations remained most frequent, though proximal amputations increased proportionally over time. Above-wrist amputations were predominantly associated with malignancy (40.3%) and vascular disease (23.7%), whereas distal amputations were mainly trauma-related (43.6%). Infection-related distal amputations increased from 23.4% in 2019 to 30.4% in 2023. Revision procedures occurred in 32.4% of proximal amputations and 6.1% of distal amputations in 2023. Infection was the most common indication for distal revisions (53.3%), while infection and neuroma formation each accounted for 29.4% of proximal revisions. This nationwide analysis provides a comprehensive epidemiological overview of ULAs in Germany, demonstrating stable overall incidence but clear level-specific differences in underlying aetiologies. Proximal amputations were mainly associated with malignant and vascular disease, whereas trauma predominated at distal levels. High rates of infection-related and neuroma-related revisions, particularly after proximal amputations, highlight the complexity of surgical management and the need for level-specific perioperative and follow-up strategies.
To evaluate the clinical efficacy of probing with or without bicanalicular intubation (BCI) for congenital nasolacrimal duct obstruction (CNLDO) in children at least 3 years of age and to identify factors influencing surgical success. The medical records of children treated between 2014 and 2024 at Health Sciences University Beyoğlu Eye Training and Research Hospital were reviewed retrospectively. All patients underwent probing with or without bicanalicular silicone intubation (BCI) using the square knot technique. Surgical success was defined as resolution of symptoms and a normal fluorescein dye disappearance test. A total of 95 children (116 eyes) were included. Mean patient age was 4.57 ± 1.98 years (range, 3-14). Mean follow-up was 15.5 ± 15.4 months. BCI was performed initially in 102 eyes. Mean tube retention was 66.8 ± 43.0 days. Overall success was 87%, increasing to 95% after reprobing and BCI in failed cases. Age, sex, obstruction type, canalicular stenosis, Rosenmüller's valve hypertrophy, and inferior turbinate infracture were not significantly associated with success (P > 0.05). Tube retention for 45-90 days was significantly associated with higher success compared with retention <45 days (P = 0.013; OR = 12.75; 95% CI, 1.72-94.48). In our study cohort of children undergoing surgery for CNLDO at 3 years of age and older, probing and BCI achieved high success, especially if the tube was successfully retained for at least 45 days. Reintubation in failed cases can improve outcomes.
To evaluate the surgical outcomes of blepharoptosis in patients with no light perception (NLP) who used prostheses and to assess eyelid symmetry and functional improvement following appropriate surgical management. This retrospective study included 15 patients with prosthesis-related ptosis treated between 2020 and 2024. Demographic characteristics, prosthesis type and duration of use, type of ptosis, preoperative levator function, and surgical technique were recorded. Margin reflex distance 1 (MRD-1) was measured preoperatively and at postoperative 1 week, 1 month, 3 months and 6 months, using standardized digital photographs. Eyelid symmetry, complications, and need for revision surgery were evaluated. Repeated measurements were analyzed using the Friedman test with Wilcoxon signed-rank post hoc comparisons. The mean age was 40.13±17.41 years (range 15-70 years); 10 patients were female and 5 were male. The mean preoperative levator function was 11.80±3.52. Regarding the underlying causes of eye loss/prosthesis use, 9 (60.0%) were due to trauma, 1 (6.7%) was due to infection, 2 (13.3%) were due to glaucoma, and 3 (20.0%) were due to other causes. 12 patients had evisceration, and 3 patients used a prosthesis over a phthisis bulbi eye. 13 patients underwent Müller Muscle-Conjunctival Resection (MMCR) and 2 patients underwent levator surgery. MRD-1 increased significantly from 1.20±0.94 mm preoperatively to 3.27±0.70 mm at 6 months. Further analysis to determine the source of the difference revealed statistically significant differences between preoperative MRD-1 and postoperative MRD1 at 1 week, 1 month, 3 months, and 6 months. The Friedman test showed a significant improvement over time (p<0.001). Technique comparisons were exploratory due to the small levator subgroup. No significant difference was found between the duration of eye prosthesis use and preoperative MRD-1 (p=0.761). MRD-1 improved from 1.20±0.94 mm preoperatively to 3.27±0.70 mm at 6 months, and eyelid symmetry (≤1 mm) was achieved in 86.6% of patients, demonstrating that ptosis of the upper eyelid in ocular prosthesis patients can be effectively corrected with appropriately selected surgical techniques based on levator function.
Prediabetes, a condition defined by the World Health Organization (WHO), has become a significant global health issue affecting a substantial portion of the world's population. This study aims to investigate the levels of adipocyte fatty acid-binding protein-4 (a-FABP or FABP-4), a biomarker found in individuals with prediabetes. FABP-4 is a protein released by both adipocytes and macrophages and plays a crucial role in influencing insulin resistance and lipid metabolism. The focus of this study is to evaluate FABP-4 levels in individuals with prediabetes and its correlation with metabolic parameters and CRP levels. The study was conducted on 90 participants, including individuals diagnosed with prediabetes (n = 44) and a healthy control (n = 44) group. The findings reveal that FABP-4 levels are significantly elevated in individuals with prediabetes. Furthermore, positive correlations were observed between FABP-4 levels and fasting and postprandial blood glucose, HbA1c, and C-reactive protein (CRP). Regression analysis indicates that FABP-4 is independently associated with prediabetes and, when considered alongside the triglyceride-to-high-density lipoprotein (HDL) ratio, is associated with prediabetes. This study underscores the association between FABP-4 and prediabetes, highlighting its potential role in fundamental processes such as insulin resistance, lipolysis, and inflammation. Additionally, it suggests that the triglyceride/HDL ratio is significantly associated with prediabetes. In conclusion, FABP-4 and the triglyceride/HDL ratio have the potential to be utilized as biomarkers in the assessment of prediabetes, contributing to the development of new treatment targets in this context.
Mesenchymal stem/stromal cells (MSCs) exhibit broad differentiation capability and strong immunoregulatory potential mediated through intercellular communication and the release of diverse paracrine mediators. They represent a promising but still investigational therapeutic approach for managing complications associated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). This review provides an updated synthesis of MSC biology, their bidirectional interaction with immune cells, and their functional contribution to the hematopoietic niche. It also evaluates current clinical evidence regarding the therapeutic roles of MSCs and MSC-derived extracellular vesicles (EVs) in acute and chronic graft-versus-host disease (aGVHD/cGVHD), as well as in poor graft function. Mechanistic insights encompass macrophage polarization toward an anti-inflammatory phenotype, inhibition of dendritic cell maturation, enhancement of regulatory T-cell expansion, and modulation of cytokine signaling pathways. Within the bone marrow milieu, MSCs contribute to stromal restoration and angiogenic repair. Recent phase II/III trials in steroid-refractory (SR)-aGVHD have demonstrated overall response rates ranging from 48 to 71%. Efficacy appears particularly enhanced in pediatric patients and with early MSC administration. Across studies, MSC therapy shows a favorable safety profile; however, heterogeneity in response and inconsistent survival outcomes remain notable limitations. For poor graft function, limited prospective studies indicate hematopoietic recovery following third-party MSC infusions, and combination approaches such as co-administration with thrombopoietin receptor agonists are under investigation. MSC-derived EVs emulate many immunomodulatory effects of their parental cells with a potentially safer profile, though clinical validation remains in its infancy. MSC-oriented interventions hold substantial biological and therapeutic promise, offering a favorable safety margin; however, clinical translation is hindered by product variability, suboptimal engraftment and persistence, and inconsistent efficacy across studies. Future directions should emphasize standardized manufacturing and potency assays, biomarker-driven patient and timing selection, optimized conditioning and dosing strategies, and the systematic appraisal of EV-based or genetically modified MSC products through controlled trials.
Climate change significantly impacts agricultural ecosystems through rising temperatures, changing precipitation patterns, increasing atmospheric CO2 levels, and more frequent extreme weather events. These environmental changes have a pronounced effect on plant-parasitic nematodes (PPNs; phylum Nematoda), which cause serious crop losses on a global scale. This review aims to provide a comprehensive evaluation of current knowledge on how major climate change drivers influence the biology, population dynamics, host-plant interactions, and geographic distribution of PPNs in agricultural systems. Recent studies show that rising temperatures accelerate nematode development, increasing the number of generations within a production season and facilitating the spread of many economically important species toward higher latitudes and elevations. Changes in precipitation patterns and soil moisture directly affect nematode survival, mobility, and infection success, and these effects often vary depending on regional conditions and nematode species. Elevated atmospheric CO2 levels modify plant-nematode interactions by increasing root biomass, altering rhizosphere processes, and regulating plant defense pathways (e.g., jasmonic acid and salicylic acid signaling), which may enhance host susceptibility and infection intensity. Furthermore, extreme climate events can disrupt the natural balance in soil ecosystems, weakening natural antagonist-nematode relationships. However, responses of PPNs to climate change are not uniform, and contrasting findings across studies indicate that these responses are strongly shaped by species-specific traits and environmental variability. In addition, future research should focus on long-term and multi-factorial field studies to better capture the combined effects of climate drivers. Overall, climate change is expected to increase PPN prevalence and drive shifts in their geographic distribution, highlighting the need for climate-sensitive and regionally adapted nematode management strategies.
Artificial intelligence (AI)-based decision support systems are increasingly explored in surgical oncology. However, their concordance with multidisciplinary tumor board (MTB) decisions, particularly in complex gastrointestinal malignancies, remains insufficiently characterized. This retrospective observational study included 47 patients who underwent oncological surgery and were discussed at a multidisciplinary tumor board during an eighteen-month period. For each patient, concordance between MTB-established treatment decisions and subsequent AI-generated recommendations (ChatGPT-based) was assessed. Concordance was categorized as discordant (0), partially concordant (1), or fully concordant (2). Discordant cases were further analyzed across predefined domains, including staging discrepancies, resectability assessment, interpretation of metastatic disease burden, and treatment sequencing. Full concordance was observed in 18 cases (38.3%), partial concordance in 22 cases (46.8%), and discordance in 7 cases (14.9%). Overall, 85.1% of cases demonstrated at least partial concordance. Discordance was more frequent among male patients (5 of 19; 26.3%) compared with female patients (2 of 28; 7.1%). Qualitative analysis revealed that discordance most commonly arose from differences in resectability assessment and staging interpretation. AI recommendations tended to favor broader surgical candidacy, whereas MTB decisions more frequently excluded surgery based on nuanced clinical and contextual factors. AI-generated recommendations show substantial overlap with MTB decisions in most cases but diverge at critical surgical decision points, particularly regarding resectability and staging. These findings suggest that AI may serve as a complementary decision-support tool rather than a substitute for multidisciplinary clinical judgment for oncological surgery care.
The performance of healthcare organisations with their considerably complex structures is often on the agenda due to limited resources. Service quality, commonly assessed using the SERVQUAL scale, represents a key performance dimension in healthcare delivery. This paper aims to investigate the extent of meeting the expectations in health service provision in Turkiye and countries in Asia. We searched electronic databases, namely Web of Science, Google Scholar, PubMed, and Turkish Council of Higher Education National Thesis Centre, to find relevant and accessible English and Turkish studies published until 1 January 2023. Eligible studies were empirical research conducted in healthcare settings using the SERVQUAL scale and reporting expectation-perception gaps. Mean differences with 95% confidence intervals were calculated. Heterogeneity was assessed using the I2 and τ2 statistics, and publication bias was evaluated using funnel plots and Egger's test. A total of 47 studies (N = 13,581) were included. The highest quality gap occurred in the responsiveness (0.59) and reliability (0.54) dimensions. Patients had high levels of expectations from healthcare organisations in all five subdomains examined for both Turkiye and other Asian countries. Highly significant quality gaps in the examined domains emphasise the need for improvements in appropriate and quality service delivery and the implementation of compassionate patient-centred approaches. We have concluded that healthcare managers and decision-makers should regularly monitor the quality level of provided healthcare services, find the gaps that need to be improved, and better understand how client expectations in healthcare might be shaped in different settings and countries. Limitations include the restriction to English and Turkish languages, the cross-sectional design of studies, and variability in hospital settings. No protocol was registered.
Introduction & Objective: Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), with limited treatment options for steroid-resistant cases. Ruxolitinib, a JAK1/2 inhibitor, has shown promise in treating steroid-resistant acute (aGVHD), chronic (cGVHD), and overlap GVHD (oGVHD), but real-world data remain limited. This study evaluated the real-world efficacy and safety of ruxolitinib in allo-HSCT patients with steroid-resistant GVHD. Materials & Methods: This retrospective, multicenter study included adult patients treated with ruxolitinib for Grade II or higher aGVHD or moderate-to-severe cGVHD at nine centers in Turkey (2017-2024). Clinical characteristics, treatment responses, and adverse events were recorded. Primary outcomes were overall response rate (ORR) and overall survival (OS). Results: Among 80 patients (mean age: 39.3 ± 13.3 years; 60 males), 39 had aGVHD, 68 cGVHD, and 15 oGVHD. The ORR was 72 of 80 patients (90.0%) (complete response: 37 of 80 [46.3%], partial response: 35 of 80 [43.8%]). The 1-year and 2-year OS rates were 91.3% and 82.5%. Severe cGVHD (p < 0.001) and lack of response to ruxolitinib (p = 0.018) were associated with reduced OS. Adverse events included infections in 40 of 80 patients (50.0%), cytopenias in 23 of 80 (28.7%), and cytomegalovirus reactivation in 20 of 80 (25.0%). Conclusion: In this retrospective multicenter cohort, ruxolitinib was associated with high response rates in steroid-refractory GVHD, while disease severity remained a key determinant of survival, and findings should be interpreted as exploratory.
Background/Objectives: Accurate post-mortem interval (PMI) estimation becomes increasingly difficult when bodies decompose under extreme heat. Hyperthermal Mediterranean environments accelerate soft-tissue degradation, induce early mummification, and distort classical thanatological indicators, often resulting in substantial PMI overestimation. This study analyzes three forensic cases affected by climate-driven decomposition anomalies and presents a climate-adaptive, AI-assisted diagnostic framework applied uniformly across all cases to improve PMI interpretation. Methods: A retrospective case series analysis was conducted on three individuals recovered during summer heatwaves. Crime scene investigation, post-mortem computed tomography (PMCT), autopsy, and genetic identification were integrated with 5-15-year meteorological datasets. Classical PMI estimations were compared with circumstantial data. A multimodal AI model, incorporating environmental features, decomposition morphology, and microenvironmental modifiers, was operationalized for each case using a hybrid Random Forest-LSTM architecture. Engineered indices included Accumulated Degree Days (ADD), a Decomposition Index, and climate-stress metrics (Thermal Load Index, Desiccation Pressure Factor, Microenvironmental Distortion Coefficient). Quantile regression provided calibrated prediction intervals. Results: Morphological assessments overestimated PMI in every case, suggesting intervals of 1-6 months despite true PMIs of approximately 20 days (Cases 1-2) or 36-48 h (Case 3). The AI model yielded conceptual outputs more consistent with verified PMIs, ~21 days (Case 1), ~23 days (Case 2), and ~42 h (Case 3), each accompanied by 50% and 90% prediction intervals. Explainability analyses identified thermal load, desiccation pressure, and microenvironmental distortion, particularly insulation in Case 3, as dominant drivers. Conclusions: Extreme heat fundamentally alters decomposition trajectories, rendering classical PMI methods unreliable. Applying a climate-aware, AI-assisted diagnostic framework across all three cases improved interpretability, providing uncertainty-aware estimates aligned with true PMIs. The AI framework is presented as a conceptual, non-trained, proof-of-concept system, and reported outputs represent operational demonstrations rather than validated predictions, offering a promising foundation for next-generation PMI diagnostics in hyperthermal forensic settings.
Fungal infections affect especially to patients with cancer and those who are immunocompromised. We analyzed the prevalence of filamentous fungi in patients at Ankara Oncology Education and Research Hospital from 2022 to 2024; antifungal susceptibility tests were also carried out. Filamentous fungi were analyzed by MALDI-TOF (matrix-assisted laser desorption ionization-time of flight), and antifungal susceptibility was tested by the broth microdilution method. Filamentous fungi were recovered from 66 (6.5%) of 1020 samples: 31(47%) deep tracheal aspirates, 13 (19.7%) sputum, 10 (15.2%) ear swabs, nine (13.6%) biopsies, and three (4.5%) bronchoalveolar lavage samples. Filamentous fungi other than Aspergillus grew from 10 (15.2%) samples, while Aspergillus species were recovered in 56 (84.8%). Of the 56 Aspergillus, 21 (31.8%) were Aspergillus fumigatus, 15 (22.7%) were Aspergillus flavus, 14 (21.2%) were Aspergillus niger, three (4.5%) were Aspergillus terreus, and one strain (1.5%) each of the following species were identified: Aspergillus tamarii, Aspergillus nidulans, and Aspergillus calidoustus. Of 66 patients from whom a fungal isolate was recovered, 50 (75.8%) had cancer. Minimum inhibitory concentrations (MICs) were determined in 45 (80.4%) Aspergillus isolates. Eight (8/19) A. fumigatus, seven (7/13) A. flavus, and three (3/11) A. niger were non-wild type (WT) according to amphotericin B MIC values. Four (4/13) A. flavus and two (2/19) A. fumigatus were non-WT according to itraconazole MIC values. One (1/13) A. flavus was non-WT according to voriconazole MIC value. The filamentous fungi recovered from the patients showed high antifungal MIC/MEC values, and some isolates had high amphotericin B MICs. Voriconazole was effective in vitro against A. fumigatus.
We aimed to evaluate the sensitivity and specificity of Recent Thymic Emigrant (RTE) levels for diagnostic discrimination among various Inborn Errors of Immunity (IEI) subgroups. We analysed 205 paediatric patients diagnosed with IEI at the Paediatric Immunology and Allergy Department of Başakşehir Çam and Sakura City Hospital in Istanbul between January 2021 and January 2024. An age- and sex-matched control group consisting of 31 healthy children was also included for comparison. Demographic, clinical and laboratory data were evaluated. Reduced RTE levels were identified in 39% of all patients. Low RTE levels were most pronounced in patients with syndromic combined immunodeficiency (77%) and immune dysregulation (100%), and were also observed at high frequencies in combined immunodeficiency (CID) (60%) and autoinflammatory disorders (57.1%). For the syndromic CID group, the diagnostic performance of RTE yielded an area under the curve (AUC) of 0.80, with a sensitivity of 92% and a specificity of 52%. In the immune dysregulation group, the AUC was 0.79, with a sensitivity of 83.5% and a specificity of 57.1%. Assessment of RTE levels represents a valuable diagnostic biomarker, particularly for patients within the syndromic CID and immune dysregulation categories. This parameter may contribute meaningfully to clinical practice by facilitating early diagnosis, guiding genetic testing and enabling assessment of thymic function. Incorporating thymic output assessment into routine immunophenotyping panels may shorten the diagnostic timeline for IEI and allow earlier initiation of appropriate therapies.
Response to anti-programmed cell death protein-1 (anti-PD-1) immunotherapy remains limited in patients with metastatic non-small cell lung cancer (NSCLC), whose tumors exhibit low or absent programmed death-ligand 1 (PD-L1) expression, and subsequent second-line therapy has poor efficacy. To address this limitation, we evaluated the efficacy and safety of combined ipilimumab and nivolumab (IPI/NIVO) with subablative radiotherapy (RT) in patients with metastatic NSCLC with negative or low PD-L1 expression, who had progressed on prior anti-PD-1 therapy. This single-arm, prospective phase II trial aimed to enroll 30 evaluable patients with metastatic NSCLC exhibiting low (1-49%) or negative (<1%) PD-L1 tumor expression who had progressed after first-line anti-PD-1 therapy. Primary endpoints were safety, disease control rate (DCR), and objective response rate (ORR) at 6 and 12 weeks, assessed in non-irradiated tumor lesions. Treatment consisted of IPI 1 mg/kg every 6 weeks (Q6W) and NIVO 240 mg every 2 weeks for 6 weeks combined with subablative RT (3×8 Gy to 1-4 lesions). Thereafter, IPI 1 mg/kg Q6W and NIVO 360 mg every 3 weeks were continued. In 31 patients of the intention-to-treat population, ORR was 7% and 10% at 6 and 12 weeks, and reached 29% as the best response. DCR was 58% and 39% at 6 and 12 weeks. Overall survival (OS) differed significantly by best response, with a median OS of 3.1, 13.5 and 22.5 months for progressive disease, stable disease and partial/complete response (p<0.001). Baseline sum of longest diameters, together with age, blood inflammatory markers and albumin levels, were prognostic of treatment response. All patients experienced treatment-related adverse events (AEs), with grade 3 as the highest severity in eight patients (26%). Immune-related AEs led to treatment discontinuation in five patients (16%). Early T-cell activation in peripheral blood samples (day 8) was detectable and more pronounced in responders than in progressors. In patients with metastatic NSCLC and low or negative tumor PD-L1 expression, IPI/NIVO/RT was able to induce objective clinical responses in a subset of patients who had progressed after first-line anti-PD1 therapy. Treatment was associated with a strong T-cell activation, improved OS and an acceptable safety profile. 2020-001097-29.
Natural disasters such as earthquakes disrupt individuals' sense of safety and temporal continuity. In response to uncertainty, individuals may increasingly engage with digital environments, which may evolve into maladaptive patterns of use. Drawing on Uncertainty Reduction Theory, this study examined whether problematic social media use and doomscrolling function as indirect pathways linking post-earthquake traumatic stress to future time perspective. A total of 414 undergraduate students from a public university in Kahramanmaraş, Türkiye, participated in this cross-sectional study. Data were collected using validated self-report measures. The hypothesized indirect effects model was tested using path analysis with bootstrapping (5,000 resamples). Post-earthquake traumatic stress was positively associated with problematic social media use and limited future time perspective. Problematic social media use significantly predicted both doomscrolling and limited future time perspective. Doomscrolling did not emerge as a significant predictor of future time perspective. Indirect effects analyses indicated that problematic social media use accounted for the relationship between traumatic stress and future time perspective, whereas the indirect pathway through doomscrolling was not significant. The findings suggest that problematic social media use may represent a key behavioral pathway linking post-earthquake traumatic stress to individuals' perceptions of the future. Although doomscrolling is associated with problematic social media use, it does not independently contribute to future time perspective. These results highlight the importance of distinguishing between different forms of digital engagement in understanding psychological responses to trauma.
BackgroundCDK4/6 inhibitors are standard treatments for HR+/HER2- metastatic breast cancer. While effective, hepatotoxicity is a significant clinical concern. This study aimed to evaluate the incidence and clinical predictors of hepatotoxicity in a real-world setting.MethodsThis retrospective study included 70 patients treated with palbociclib or ribociclib between 2020 and 2024. Hepatotoxicity was defined as Grade ≥1 elevation of ALT and/or AST per CTCAE v5.0. Independent predictors were identified using multivariable binary logistic regression, and model performance was assessed via ROC curve analysis.ResultsThe mean age was 55.7 ± 10.8 years, and 12.9% had baseline liver metastasis. Hepatotoxicity occurred in 20% (n = 14) of patients. Multivariable analysis identified liver metastasis (OR = 39.3; 95% CI: 4.4-351.9; p = 0.001), hypercholesterolemia (OR = 14.9; 95% CI: 2.0-112.1; p = 0.009), and higher body mass index (OR = 1.19; 95% CI: 1.00-1.41; p = 0.045) as independent predictors. Age and specific CDK4/6 inhibitor type were not significantly associated with toxicity. The predictive model demonstrated strong discriminative ability with an AUC of 0.878.ConclusionsHepatotoxicity is common in routine practice. Baseline liver metastasis, hyperlipidemia, and higher BMI are key predictors of risk. These findings suggest that readily available clinical characteristics can identify high-risk patients, supporting the need for individualized liver function monitoring during treatment.
Recombination-activating genes (RAG1 and RAG2) encode lymphoid-specific proteins that are essential for V(D)J recombination during early T- and B-lymphocyte development. Biallelic mutations in these genes result in a broad spectrum of primary immunodeficiency phenotypes, ranging from classical severe combined immunodeficiency (SCID) to combined immunodeficiency, immune dysregulation, autoimmunity, and inflammatory complications. The immunological phenotype varies widely, from T-B-NK+ severe combined immunodeficiency (SCID) to combined immunodeficiency (CID), or near-normal T and B cell counts, and even antibody deficiencies despite preserved pathogen-specific antibody responses. In this cohort, we aimed to characterize the clinical, immunological, and genetic features, as well as the disease course, of patients diagnosed with RAG1 and RAG2 deficiencies.
Inborn errors of immunity (IEI), previously referred to as primary immunodeficiencies, are a heterogeneous group of genetic disorders affecting immune development and function. While once considered rare, IEIs are increasingly recognized, particularly in regions with high consanguinity rates. Cutaneous manifestations, as well as ocular and hair abnormalities, may provide early and clinically relevant diagnostic clues. This study aimed to assess the prevalence, types, and diagnostic value of cutaneous, ocular and hair manifestations in patients with IEI. A total of 386 patients with confirmed IEI, classified according to the 2024 IUIS criteria, were retrospectively analyzed. Cutaneous, ocular (e.g., conjunctivitis, keratitis, scleral telangiectasia), and hair manifestations (e.g., alopecia areata, pigmentary abnormalities) were systematically reviewed from medical records. Skin findings were categorized as infectious, immune-allergic (eczema, alopecia areata, urticaria, erythroderma), disease-specific, or other. Cutaneous, ocular, and/or hair manifestations were identified in 198 patients (51.3%), with 59.1% present at diagnosis. Infectious manifestations were the most common (71.8%), followed by immune-allergic findings (34.8%), including eczema (30.3%), and disease-specific manifestations (17.7%). Ocular findings were observed in 15.7% of patients, while hair abnormalities were present in 4.04%. Skin infections were predominantly bacterial (53.1%) and were most frequent in phagocytic and innate immunity defects. Eczema was most frequent in hyper-IgE syndrome (85.8%), while non-eczematous allergic findings were most common in immune dysregulation. Ocular involvement, including viral retinitis and scleral telangiectasia, and hair abnormalities, such as syndromic hair shaft defects and alopecia areata, were observed across multiple IEI subgroups. Cutaneous, ocular, and hair abnormalities are frequent in IEI and may support early diagnosis. Recognition of recurrent, atypical, or treatment-resistant skin, eye, or hair findings should prompt immunological evaluation, particularly in pediatric patients.
Acquired aplastic anemia (AA) is a rare blood disorder causing hypocellular bone marrow due to immune damage to hematopoietic stem cells, leading to low blood cell counts. This study investigates the demographics, treatment patterns, and clinical outcomes of AA in Turkiye. In this non-interventional, retrospective descriptive study, data of 274 patients (Female/Male: 4/5) diagnosed with AA between September 1, 2011, and September 1, 2021, were collected from 16 centers. Severe and very severe AA was diagnosed in 72% and 27.7% of patients, respectively. The mean time from diagnosis to first treatment was 119 ± 287 days, while time to hematopoietic stem cell transplantation (HSCT) was 212 ± 321 days, and to Anti-Thymocyte Globulin (ATG) was 87 ± 242.5 days. The mean time to response after first-line and second-line treatment was 172.9 ± 264.6 days and 191.9 ± 211.9 days, respectively. The mean overall survival of patients with AA was 3.56 ± 3.12 years, with a 5-year overall survival rate of 72.6%. HSCT and other initial treatments led to full or partial remission for most patients, improving survival rates for over half of them. The study observed comparable patterns to previous studies, providing vital insights into Turkiye's acquired AA treatment landscape.