Search Results (5,680)

Background/Objectives: Diabetic macular edema (DME) is a major cause of vision impairment in patients with diabetes mellitus, and intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is widely used for its management. However, the longitudinal effects of anti-VEGF treatment on the ganglion cell complex (GCC) remain unclear. This study evaluated changes in GCC thickness in eyes with DME following intravitreal bevacizumab injections over a one-year period. Methods: In this retrospective observational study, 55 eyes from 55 patients with DME who received intravitreal bevacizumab injections were analyzed. Central foveal thickness (CFT), total macular volume (TMV), and retinal layer thicknesses including the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), and GCC were measured using spectral-domain optical coherence tomography and compared with those of fellow eyes without DME. Results: At baseline, eyes with DME showed significantly greater CFT, TMV, RNFL, IPL, and GCC thickness compared with fellow eyes. After one year of treatment, CFT and TMV decreased significantly, and significant reductions were also observed in RNFL, GCL, IPL, and GCC thickness. At the one-year follow-up, GCC and inner retinal layer thicknesses were no longer significantly different between DME and fellow eyes. Multiple regression analysis showed that final visual acuity was associated with baseline visual acuity and CFT at one year, but not with GCC thickness. Conclusions: These findings suggest that the reduction in GCC thickness after bevacizumab treatment may reflect anatomical normalization following edema resolution rather than true ganglion cell loss. Further studies with larger cohorts and longer follow-up are required to clarify the long-term effects of anti-VEGF therapy on retinal neurostructure. Full article

Objectives: Reconstruction of complex midfacial defects remains challenging due to the need to restore three-dimensional anatomy, functional integrity, and facial symmetry. This study aimed to evaluate the clinical effectiveness, safety, and functional and aesthetic outcomes of patient-specific custom implants (PSCIs) in complex midfacial reconstruction. Additionally, we assessed whether virtual surgical planning (VSP) combined with PSCIs reduces operative time and improves postoperative symmetry and patient-reported outcomes. Materials and Methods: A retrospective comparative cohort study was conducted using prospectively recorded clinical data from patients treated with PSCI/VSP between January 2021 and June 2025 and a historical control cohort treated with standard pre-shaped implants. Eighty-seven consecutive patients undergoing reconstruction of acquired or post-oncologic midfacial defects using titanium or PEEK patient-specific implants were enrolled. Preoperative VSP was performed in all cases. The principal endpoint was postoperative facial symmetry assessed by three-dimensional photogrammetry. Secondary functional outcomes included ocular position and nasal airway patency. Secondary outcomes included operative time, complication rates, implant-related morbidity, and patient-reported outcome measures (FACE-Q) at 12 months. Outcomes were compared with a historical cohort reconstructed with standard pre-shaped implants. Results: Eighty-two patients completed at least 12 months of follow-up. PSCI reconstruction demonstrated significantly improved postoperative symmetry (mean deviation 1.8 ± 0.6 mm vs. 3.4 ± 1.1 mm in controls, p < 0.001) and higher patient satisfaction scores at 12 months (FACE-Q overall satisfaction score 82.8 ± 9.3 vs. 69.7 ± 11.2, p < 0.001). Mean operative time was reduced by approximately 24.7%, and intraoperative implant modification was required in only 6% of cases compared with 48% in the control group. The overall complication rate was 11%, with implant removal required in 2.4% of patients. Functional outcomes showed significant improvements in orbital positioning and nasal airway patency. Conclusions: Patient-specific custom implants combined with virtual surgical planning provide reliable and reproducible reconstruction of complex midfacial defects. This approach significantly improves facial symmetry, patient satisfaction, and operative efficiency while maintaining low complication rates. PSCIs should be considered a preferred reconstructive option in selected patients requiring complex maxillofacial reconstruction. Full article

Osteogenesis imperfecta (OI) is the most common heritable bone-fragility disorder, with type I (non-deforming OI) representing its mildest classical phenotype (historically referred to as Lobstein disease). Intramedullary (IM) rodding is essential for managing recurrent long-bone fractures and progressive deformities, with the Fassier–Duval (FD) telescopic rod now being the standard choice. This narrative review, based on a structured search from the seminal 1959 description of IM rodding to 2026, synthesizes the design principles, the minimally invasive technique and the comparative outcomes of FD rodding of the lower limb, with explicit attention to type I disease. Across cohort studies, comparative series and a recent systematic review, telescopic rods consistently achieve lower revision rates and longer implant survival than static or non-telescopic devices, reducing reoperation odds by roughly three-quarters. Overall complication rates nonetheless remain high (commonly 33–55%) and are dominated by implant migration and failure of telescoping. Younger age and eccentric epiphyseal positioning after incomplete deformity correction increase migration risk. Type-I-specific evidence remains limited. A report published under the “Lobstein” designation involved a Sillence type IV patient and therefore does not constitute type-I-specific evidence. Retrospective data nevertheless suggest favorable implant survival with telescopic fixation, but definitive conclusions cannot yet be drawn. Proper technique, adjunctive bisphosphonate therapy and multidisciplinary care remain decisive. Phenotype-stratified prospective data are the principal unmet need. Full article

Background/Objectives: Topical hemostatic agents are widely used in thyroid surgery, but their clinical value remains uncertain. We evaluated whether intraoperative use of a collagen-based hemostatic patch during bilateral thyroidectomy was associated with patient-reported recovery and postoperative complications. Methods: This retrospective cohort study included 193 patients undergoing bilateral thyroidectomy (98 received Hemopatch and 95 underwent conventional hemostasis without a patch). Pain and swallowing scores were summarized as medians with interquartile ranges and compared using two-sided Mann–Whitney U tests. Unadjusted mean differences with 95% percentile-bootstrap confidence intervals based on 10,000 independent-group resamples were reported as effect estimates. Multivariable proportional-odds ordinal logistic regression adjusting for age, sex, operative time, intraoperative blood loss, and pathology was performed as a sensitivity analysis. Results: Major postoperative complications were infrequent, with no statistically significant between-group differences. Patch use was associated with lower pain scores on POD7 (mean difference −0.34, 95% CI −0.59 to −0.09; p = 0.0008), POD30 (−0.11, 95% CI −0.22 to 0.01; p = 0.0223), and POD90 (−0.12, 95% CI −0.18 to −0.05; p = 0.0005), but not POD1. Swallowing disturbance was also associated with lower scores on POD7 (−0.35, 95% CI −0.67 to −0.03; p = 0.0068), POD30 (−0.17, 95% CI −0.38 to 0.05; p = 0.0272), and POD90 (−0.23, 95% CI −0.38 to −0.09; p = 0.0005), but not POD1. Scar satisfaction was associated with a higher mean score at 6 months (+0.46, 95% CI +0.21 to +0.71; p = 0.0018). Several associations remained significant after multivariable adjustment and Holm correction, although not all comparisons were robust to multiplicity adjustment. Conclusions: Collagen-based hemostatic patch use was associated with modest differences in selected patient-reported recovery measures. The magnitude and clinical importance of these differences remain uncertain. No statistically significant differences in major complications were observed, but the study was not powered to establish comparative safety for uncommon events. These exploratory findings require confirmation in prospective multicenter studies. Full article

Background: Pancreatoduodenectomy (PD) is a complex surgical procedure with substantial postoperative morbidity and mortality. Postoperative outcomes following PD are typically determined by measuring preoperative liver function in the form of serum albumin and bilirubin levels. In this study, the prognostic value of the preoperative ALBI grade was compared with that of albumin and bilirubin alone in predicting postoperative complications and short-term mortality after PD. Methods: This retrospective cohort study included 1149 patients who underwent partial or total PD between 2014 and 2017 at a high-volume surgical center. The preoperative ALBI grade (I–III) was calculated in these patients as well as the preoperative levels of bilirubin and albumin. The associations between ALBI grade, albumin and bilirubin levels with postoperative complications and 30- and 90-day mortality were analyzed using univariate and multivariable logistic regression models. The predictive performance of the ALBI grade and albumin and bilirubin levels was assessed using receiver operating characteristic (ROC) curves and area under the curve (AUC) analysis. Results: Higher ALBI grades were significantly associated with worse perioperative outcomes, including increased incidence of liver perfusion failure (42.4%) and postpancreatectomy hemorrhage (15.2%). In a pre-specified reduced multivariable model adjusted for BMI, ASA physical status as well as surgical complexity, ALBI grade III remained associated with 30- and 90-day mortality (OR 6.21; 95% CI, 1.62–23.78; p = 0.008 and OR 8.97; 95% CI, 2.91–27.62; p < 0.001) but was attenuated compared to univariate analyses. Seven of the 8 patients with ASA grade IV physical status were in ALBI grade III and accounted for 5 of the 6 30-day and 6 of the 8 90-day deaths in this group; in a sensitivity analysis excluding these patients, the association between ALBI grade III and 30-day mortality was no longer statistically significant, and the univariable association with 90-day mortality was also attenuated to non-significance, although the BMI-adjusted 90-day estimate remained significant (OR 5.02; 95% CI, 1.07–23.54; p = 0.041). ROC analysis showed that the ALBI score (AUC, 0.74 and 0.74) did not outperform albumin alone (AUC, 0.69 and 0.70) in predicting 30- and 90-day mortality (DeLong p = 0.21–0.24), although both outperformed bilirubin alone (AUC, 0.54–0.56). Conclusions: Preoperative ALBI grade III is associated with short-term morbidity and mortality after PD, but this association is confounded in part by baseline surgical risk (ASA physical status), and the ALBI score does not outperform albumin alone as a predictor of mortality. As a simple, readily available composite marker, the ALBI grade may still help flag patients who warrant closer perioperative surveillance, although this retrospective study does not establish that correcting albumin or bilirubin levels before surgery improves outcomes. Full article

Purpose: To compare the clinical and functional outcomes of two successive generations of a trifocal intraocular lens (IOL), the original Liberty 677MY and the optimized Liberty 677CMY. To the best of our knowledge, this is the first head-to-head comparison between two successive generations of any IOL model reported. Methods: This retrospective study included 42 patients (84 eyes) who underwent bilateral phacoemulsification with implantation of either the Liberty 677MY (26 eyes) or the Liberty 677CMY (58 eyes). The primary outcome was postoperative binocular intermediate visual acuity (VA). Secondary outcomes included monocular intermediate VA, monocular and binocular distance and near VA, the proportion of patients or eyes achieving ≤0.1 LogMAR, and defocus curves. Exploratory outcomes included spectacle independence, patient-reported satisfaction (Quality of vision—QoV- and Catquest-9SF), photic phenomena, and intraoperative or postoperative complications. Results: At 3 months, binocular UIVA differed by approximately 0.10 LogMAR in favor of the 677CMY cohort, which was considered clinically significant, although the difference did not reach statistical significance (p = 0.052). Supporting this tendency, monocular UIVA was significantly better with the 677CMY IOL (p = 0.012). Also, a significantly higher percentage of patients and eyes achieved binocular and monocular UIVA ≤ 0.1 LogMAR with the 677CMY IOL (p = 0.025). Defocus curves additionally showed significant between-group differences at intermediate defocus levels (−1.00 and −1.50 D; p < 0.05), favoring the 677CMY cohort. No between-group differences were observed for any distance VA parameter. Binocular near VA and near-vision thresholds were also comparable between groups, although a greater proportion of eyes achieved monocular UNVA ≤ 0.1 LogMAR with the 677CMY IOL (p = 0.016). Spectacle use, overall satisfaction, photic phenomena profile, and postoperative complications were comparable between groups. Conclusions: The optimized Liberty 677CMY exhibited a favorable pattern of intermediate visual performance compared with the 677MY while maintaining comparable distance and near VA and a similar safety profile. These findings suggest potential clinical benefits of the design modifications, although larger prospective studies are warranted to confirm these observations. Full article

Introduction: Ventilator-associated pneumonia (VAP) is associated with increased morbidity and mortality. Early-onset (EOVAP) and late-onset (LOVAP) VAP differ in risk factors, microbiology, and outcomes. Methods: A retrospective cohort study of adult ICU patients admitted to a tertiary hospital between May 2020 and May 2022 compared EOVAP and LOVAP. Results: 194 patients were included (73.7% male), with a median age of 61 years. A total of 70.6% were admitted to the ICU for infection-related respiratory failure, predominantly due to COVID-19 (59.3%). EOVAP represented 21% and LOVAP 79% of cases, with median days to diagnosis of 4 and 11, respectively. Empirical antibiotic therapy was adequate in both groups; de-escalation was possible in 26.8%, and escalation due to treatment failure was required in 13.4%. The most commonly prescribed initial antibiotic was piperacillin–tazobactam (45%). Broad-spectrum antibiotic use did not differ between groups. Amoxicillin–clavulanate resistance was high in both groups (LOVAP 62.1%; EOVAP 48.8%), and piperacillin–tazobactam resistance was more frequent in LOVAP (41.2%). Follow-up cultures showed a high persistence rate (73.2%), with no significant change in resistance patterns. Conclusions: VAP remains common in the ICU, and the COVID-19 pandemic significantly impacted the already complex epidemiology of VAP. High resistance rates to amoxicillin–clavulanate and frequent isolation of MDR pathogens challenge empirical treatment based on onset timing, supporting empiric antibiotic selection guided by local microbiological ecology. Full article

Background: Organized cervical cancer screening aims to reduce the burden of advanced disease through earlier detection. However, a substantial proportion of women continue to present with locally advanced cervical cancer (LACC) requiring definitive chemoradiation. This study evaluated temporal changes in the demographic and clinicopathological characteristics of women with LACC treated with definitive chemoradiation before and after implementation of the organized cervical cancer screening program in Serbia. Methods: This retrospective single-center cohort study included 200 consecutive women with histologically confirmed LACC treated with definitive chemoradiation at the Institute of Oncology and Radiology of Serbia. Two cohorts were analyzed: a pre-screening cohort (2010–2011, n = 100) and a post-screening cohort (2022–2023, n = 100). Demographic and clinicopathological characteristics, including age, histopathology, FIGO stage, lymph node involvement, and geographic distribution, were compared. For study purposes, all patients were retrospectively restaged according to the FIGO 2018 classification using the best available clinical, radiological, and pathological data. Results: Women in the post-screening cohort were significantly older at diagnosis than those in the pre-screening cohort (mean age 54.9 vs. 49.7 years, p = 0.0046), with a substantially higher proportion of patients older than 64 years (28% vs. 2%, p < 0.0001). Although the overall distribution of FIGO stages II–IV did not differ significantly, a marked redistribution of FIGO 2018 substages was observed (p < 0.0001), characterized by an increased proportion of stage IIIC disease and significantly more frequent lymph node involvement (63% vs. 41%, p = 0.0018). Geographic distribution remained stable, with most patients referred from the Belgrade administrative district. Conclusions: This study demonstrated clinically relevant temporal changes in the demographic and clinicopathological characteristics of women requiring definitive chemoradiation for LACC in Serbia. More than a decade after implementation of organized cervical cancer screening, tertiary referral centers continue to manage a substantial burden of patients with locally advanced disease requiring complex, resource-intensive treatment. These findings should not be interpreted as a direct evaluation of the national screening program but may provide valuable insights for healthcare planning in Serbia and other countries with similarly resource-constrained healthcare systems. Strengthening participation in organized screening, ensuring timely diagnostic evaluation, and improving HPV vaccination uptake remain essential to reduce the burden of advanced cervical cancer. Full article

Background and Objectives: Fingolimod, a sphingosine-1-phosphate receptor modulator, is an effective disease-modifying therapy for relapsing forms of multiple sclerosis (MS). Although lymphopenia is a well-recognized pharmacological effect, its clinical significance remains uncertain. This study evaluated the frequency and severity of fingolimod-associated lymphopenia, longitudinal hematological changes and their relationship with clinical outcomes in a real-world MS cohort. Materials and Methods: This retrospective observational study included 143 adults with MS who initiated fingolimod treatment between May 2019 and October 2020. Demographic, clinical and laboratory data were collected at baseline and at 3- and 6-month follow-up visits. Lymphopenia was graded according to the Common Terminology Criteria for Adverse Events version 4.0. Laboratory parameters and infection outcomes were compared according to lymphopenia severity. Logistic regression analysis was performed to identify factors associated with Grade 4 lymphopenia at 6 months. Results: At 6 months, lymphopenia was present in 124 patients (86.7%), including Grade 4 lymphopenia in 15 (10.5%). Leukocyte, neutrophil and lymphocyte counts decreased, whereas ALT, AST, GGT, NLR and SII increased significantly during treatment (all p < 0.001). Infection frequency did not differ among lymphopenia severity groups (p = 0.530). No statistically significant association was detected between Grade 3–4 lymphopenia and infection risk (OR, 1.41; 95% CI, 0.42–4.71; p = 0.545). Lower baseline lymphocyte count was independently associated with Grade 4 lymphopenia (adjusted OR 0.078, 95% CI 0.018–0.325; p < 0.001). Conclusions: Fingolimod-associated lymphopenia was common, with Grade 4 lymphopenia affecting approximately one-tenth of patients. No statistically significant association between lymphopenia severity and infection was detected; however, the small number of Grade 4 cases, low event rate and wide confidence interval limited the statistical power to exclude clinically meaningful differences. These findings should therefore be interpreted cautiously and do not establish the absence of infection risk associated with severe lymphopenia. Regular hematological monitoring and individualized clinical decision-making remain essential, particularly in patients with lower baseline lymphocyte counts. Full article

Objectives: To compare sexual function and other clinical outcomes after transobturator tape (TOT) alone versus TOT with concomitant anterior colporrhaphy (AC) in sexually active women with stress urinary incontinence (SUI) and asymptomatic stage ≥ 2 cystocele. Methods: This single-center retrospective cohort study included 173 sexually active women aged 30–50 years who underwent TOT alone (n = 78) or TOT with concomitant AC (TOT+AC, n = 95) between January 2021 and April 2025. Sexual function was assessed using the Female Sexual Function Index (FSFI) preoperatively and at 12 months postoperatively. The primary endpoint was the change in FSFI total score. Secondary outcomes included FSFI domain scores, International Consultation on Incontinence Questionnaire–Short Form (ICIQ-SF), Pelvic Organ Prolapse Symptom Score (POP-SS), Visual Analog Scale (VAS) scores, continence status, complications, and patient satisfaction. Results: Both groups showed significant improvements in FSFI total scores at 12 months, with a significantly greater increase in the TOT+AC group than in the TOT group (1.13 ± 0.76 vs. 0.57 ± 0.63, p < 0.001), corresponding to a between-group difference of 0.56 points (95% CI, 0.35–0.77). Improvements in desire (p = 0.004) and arousal (p < 0.001) were also greater in the TOT+AC group, whereas between-group differences in changes in lubrication, orgasm, satisfaction, and pain were not significant. At 12 months, the TOT+AC group had lower ICIQ-SF (2.18 ± 0.97 vs. 2.74 ± 1.11, p < 0.001) and POP-SS (4.02 ± 0.89 vs. 6.62 ± 1.61, p < 0.001) scores and higher patient satisfaction (7.71 ± 1.25 vs. 6.63 ± 1.12, p < 0.001). However, the magnitude of improvement in ICIQ-SF did not differ significantly between groups (p = 0.606). In multivariable linear regression, TOT alone remained independently associated with a smaller improvement in FSFI total score after adjustment for baseline FSFI total score and POP-Q stage (B = −0.610, 95% CI −0.842 to −0.378; p < 0.001). Conclusions: In sexually active women with SUI and asymptomatic stage ≥ 2 cystocele, concomitant AC at the time of TOT was associated with a greater improvement in overall sexual function and prolapse-related symptoms at 12 months compared with TOT alone. However, the absolute between-group difference in FSFI improvement was modest, and its clinical significance remains uncertain. Although postoperative ICIQ-SF scores were lower with TOT+AC, the magnitude of improvement in incontinence symptoms did not differ significantly between groups. These findings suggest that concomitant AC may provide additional functional benefits when individualized preoperative assessment supports combined surgery; however, the present findings do not establish specific selection criteria or support routine AC for all women with asymptomatic stage ≥ 2 cystocele. Prospective randomized studies are needed to confirm these associations and better define which patients may benefit from concomitant repair. Full article

Background and Objectives: Fifth metacarpal neck fractures are commonly encountered in hand surgery, yet optimal surgical fixation remains debated. This study compares Kirschner wire (K-wire) fixation and locking plate osteosynthesis in terms of radiological and functional outcomes. Materials and Methods: A retrospective cohort of 30 patients (mean age 45) from 2003–2022 was reviewed. Patients underwent either antegrade K-wire fixation or dorsal/volar locking plate fixation. Outcomes assessed included union time, angular and length deformity correction, return to work, and complication rates. Results: Both groups achieved similar final angulation correction (85%, p = 0.72). K-wire fixation achieved significantly faster radiographic union (K-wire: 3.5 months; plate: 4.5 months, p = 0. 019). K-wires allowed earlier intervention (6.0 (3.0–9.0) vs. 14.0 (9.0–22.0) days to surgery, p < 0.05) but had a 6.7% malunion rate. Plating allowed earlier return to work and avoided pin-tract issues. Functional scores (QuickDASH) and grip strength restoration (>90%) were statistically similar. Conclusions: Both K-wire fixation and locking plate osteosynthesis achieved bone union and satisfactory functional recovery in this retrospective cohort. However, given the small sample size and observational nature of the study, surgical selection should be tailored to individual patient presentation and surgeon preference until larger prospective trials are available. Full article

Background: The comparative prognostic value of the Endothelial Activation and Stress Index (EASIX) and the Inflammatory Prognostic Index (IPI) in extensive-stage small-cell lung cancer remains unclear. This study aimed to compare the prognostic value of EASIX and IPI and assess their contribution beyond established clinical factors. Methods: This retrospective single-center study included 129 patients with de novo extensive-stage small-cell lung cancer who initiated first-line systemic therapy between December 2022 and October 2025. Pretreatment EASIX and IPI values were analyzed as log₂-transformed continuous variables in multivariable Cox models. Overall survival was the primary outcome, and first-line progression-free survival was the secondary outcome. Results: During a median follow-up of 26.91 months, 116 deaths and 123 progression-or-death events occurred. Each doubling of the EASIX value was independently associated with a higher hazard of death (adjusted hazard ratio, 1.14; 95% confidence interval, 1.01–1.28; p = 0.019), whereas IPI was not independently associated with overall survival. Neither index was independently associated with first-line progression-free survival. Adding EASIX to the clinical model improved model fit and increased the C-index from 0.619 to 0.650, whereas IPI provided no additional prognostic contribution. Conclusions: EASIX may provide prognostic information beyond established clinical factors for overall survival in extensive-stage small-cell lung cancer. These findings warrant validation in larger multicenter cohorts. Full article

Background/Objectives: The combined goal of achieving both clinical and endoscopic remission has highlighted the need for strategies that support a treat-to-target approach in inflammatory bowel disease (IBD). A proactive monitoring strategy involves scheduled assessments regardless of symptoms to detect subclinical disease activity and enable timely treatment adjustments, whereas a reactive approach initiates evaluation only in response to clinical deterioration or objective signs of active disease. This study investigated whether proactive monitoring improves the achievement of treatment goals compared with a reactive strategy. Methods: In this prospective cohort study carried out between September 2020 and July 2022, patients with IBD receiving biologic therapy were managed according to a predefined proactive monitoring schedule and prospectively followed for one year. A control group, matched for age, sex, diagnosis, and treatment, was enrolled from another tertiary IBD center using a reactive monitoring strategy; their clinical course over one year was reconstructed retrospectively from medical records. All patients underwent colonoscopy assessment at one year. The primary outcome was treatment failure, defined as inadequate mucosal healing or symptom control, the need for intestinal surgery, or discontinuation of biologic therapy due to insufficient efficacy. Results: A total of 162 patients were included (91 managed proactively and 71 managed reactively). In the intention-to-treat population, treatment failure occurred in 67 patients (74%, 95% confidence interval (CI) 63–84%) in the intervention group and 60 patients (85%, 95% CI 75% to 94%) in the control group (difference 11%, CI −3% to 25%, p = 0.13). In the per-protocol analysis, 44 of 69 patients (64%, CI 50% to 78%) in the intervention group experienced treatment failure compared with 43 of 53 patients (81%, CI 60% to 93%) in the control group (difference 17%, CI −1% to 36%, p = 0.06). Patients in the proactive monitoring group underwent significantly more disease-monitoring assessments than those managed reactively. Conclusions: Proactive monitoring numerically improved combined clinical and endoscopic outcomes compared with reactive management, but this did not reach statistical significance and resulted in substantially greater healthcare resource utilization. Full article

Background: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with highly variable biological behavior. Somatostatin receptor (SSTR)-based imaging with ⁶⁸Ga-DOTATATE PET/CT has become an important functional imaging modality for evaluating these tumors. In contrast, ¹⁸F-FDG PET/CT reflects tumor glucose metabolism and has been associated with more aggressive tumor phenotypes. This study aimed to evaluate associations between ⁶⁸Ga-DOTATATE and ¹⁸F-FDG PET/CT-derived parameters and postoperative PASS and GAPP scores in patients with pheochromocytoma. Materials and Methods: Thirty patients with histologically confirmed pheochromocytoma who underwent ⁶⁸Ga-DOTATATE PET/CT were retrospectively reviewed. Among them, 11 patients also underwent ¹⁸F-FDG PET/CT and were included in the comparative imaging analysis. Results: Tumor size showed strong positive correlations with both SSTR-TV (ρ = 0.725, p < 0.001) and SSTR-TL (ρ = 0.755, p < 0.001). ¹⁸F-FDG SUVmax was positively correlated with PASS (ρ = 0.616, p = 0.044) and GAPP scores (ρ = 0.720, p = 0.012). ¹⁸F-to-⁶⁸Ga SUVmax ratio showed significant positive correlations with the PASS (ρ = 0.737, p = 0.010) and the GAPP score (ρ = 0.661, p = 0.027). Conclusions: In this exploratory study, ⁶⁸Ga-derived volumetric parameters were primarily associated with tumor size, whereas ¹⁸F SUVmax and the ¹⁸F/⁶⁸Ga SUVmax ratio were associated with PASS and GAPP scores in the small dual-tracer subgroup. These findings require validation in larger cohorts. Full article

Background: Methotrexate-induced neurotoxicity (MTX-NTX) is a severe complication during childhood acute lymphoblastic leukemia (ALL) treatment, yet its underlying pharmacogenetic determinants remain incompletely understood. Methods: A multicenter retrospective nationwide case–control study was performed including 71 pediatric ALL patients (34 MTX-NTX cases and 37 controls). Targeted next-generation sequencing of 17 genes involved in MTX transport, intracellular metabolism and folate pathways was performed. Results: Transport-related genes accounted for 61.4% of all detected variants and showed the highest number of nominally significant variants. Pathway-level burden analysis demonstrated a significant enrichment of transporter-related variants in patients with MTX-NTX compared with controls (FDR-adjusted p = 0.004), whereas the analysis for folate/metabolism-related genes did not remain significant after multiple-testing (FDR-adjusted p = 0.096). Similar findings were observed in the stroke-like syndrome (SLS) subgroup (FDR-adjusted p = 0.014 and 0.108, respectively). Gene-level burden analysis identified ABCG2 and ABCC4 as the predominant contributors, harboring both 18.4% of significant variants in the overall MTX-NTX analysis and 20.6% and 17.6%, respectively in the SLS phenotype. Moreover, the distribution of significant variants was strongly correlated between the overall MTX-NTX and SLS analyses (Spearman’s ρ = 0.549, p = 0.022). Volcano plot analysis revealed ABCG2 as the gene showing the most prominent pattern of nominal associations, containing both the variants associated with a protective direction (e.g., c.1728-46G>A, p = 2.6 × 10⁻⁴) and variants associated with increased risk, including c.34G>A and c.203+36A>G (p = 0.002) and c.263+10A>G (p = 0.0097). Phenotype-specific analyses revealed distinct genetic signatures across neurological manifestations, with transporter genes predominating in focal neurological deficits. Conclusions: Our findings suggest that genetic variability in ABC transporter genes may contribute to susceptibility to MTX-NTX, whereas folate metabolism genes may represent complementary phenotype-modifying factors. These findings are exploratory and require validation in larger, independent cohorts and functional studies. Full article