5-year Results Research Articles

Cerebellar Mutism/Posterior Fossa Syndrome Following Resection of Posterior Fossa Tumor in Pediatric Patients: Assessing Pathophysiology, Risk Factors, and Neuroradiographic Features

Background Cerebellar mutism syndrome (CMS) is a postoperative syndrome of decreased speech seen in children associated with neurobehavioral abnormalities, the incidence of which is up to 40%. Objective To evaluate pediatric patients with posterior fossa tumors for incidence, clinical characteristics, pathophysiology, risk factors, and neuroradiographic features of this syndrome. Materials and Methods The study included 60 pediatric patients with a posterior fossa tumor who underwent surgery by a telovelar approach. Detailed pre- and postoperative clinical and radiological evaluations were done. Patients with CMS were analyzed and compared with those without mutism to find risk factors for CMS. The presentation and characteristics of cerebellar mutism were studied along with the following risk factors:The preoperative, immediate postoperative, and 1-year postoperative imaging results were reviewed to assess the neuroradiographic features in the two groups. Results The incidence of this syndrome was 20%. The mutism was accompanied by some neurobehavioral abnormalities (p-value = 0.05). The most significant finding was the presence of a period of cerebellar dysarthria after the resolution of the muteness (p-value < 0.001) in all cases. Brainstem and related structures' involvement was the most significant risk factor (p-value = 0.03). The presence of brainstem and peduncular edema in the immediate postoperative period (p-value = 0.04) and gross atrophy of posterior fossa structures at 1 year (p-value = 0.01) showed significance toward the development of CMS. There was delayed neurological recovery in patients with CMS with a poor Glasgow Outcome Score at 1 year of follow-up. Conclusion The clinical presentation of this syndrome in context with neuroradiographic features suggests that it results from transient impairment of the afferent and/or efferent pathways of dentate nuclei that are involved in initiating complex volitional movements and are associated with brainstem involvement of tumor and poor functional outcome.

Long-Term Safety and Efficacy of Bimekizumab in Axial Spondyloarthritis: 2-Year Results from Two Phase 3 Studies.

Bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)‑17F in addition to IL-17A, previously demonstrated efficacy and was well tolerated to 1 year in patients with non-radiographic (nr-) and radiographic (r-) axial spondyloarthritis (axSpA). Here, we report bimekizumab safety and efficacy to 2 years. Patients completing week 52 in the phase 3 studies BE MOBILE 1 (nr-axSpA; NCT03928704) and 2 (r‑axSpA; NCT03928743) were eligible for an ongoing open‑label extension (OLE; NCT04436640). All OLE patients received subcutaneous bimekizumab 160 mg every 4 weeks. Safety outcomes for patients who received ≥1 bimekizumab dose, and efficacy outcomes for all randomised patients, are reported to week 104. In the OLE (Weeks 52 - 104), 70.8% (367/518) of patients reported ≥1 treatment‑emergent adverse event (TEAE). Most frequent TEAEs (EAIR/100PY) were SARS-CoV-2 (COVID-19) infection (25.2), nasopharyngitis (11.0) and oral candidiasis (5.4). Fungal infection EAIR/100PY was 11.8 (majority Candida infections: 6.8; most mild/moderate, none serious/systemic). Inflammatory bowel disease and uveitis rates were low; no major adverse cardiovascular events or deaths occurred. TEAE incidence rate was generally similar across Weeks 0-52 and 52-104.At week 104, >50% of randomised patients (N = 586) achieved ASAS40; ∼60% achieved ASDAS low disease activity (<2.1) and >30% achieved ASDAS inactive disease (<1.3). Bimekizumab demonstrated sustained suppression of MRI inflammation at week 104, with >57% of patients achieving MRI remission. The safety profile of bimekizumab remained consistent with prior reports, with no new safety signals identified. 1-year efficacy was sustained to 2 years across patients with nr‑axSpA and r-axSpA.

Safety and efficacy of valoctocogene roxaparvovec with prophylactic glucocorticoids: 1-year results from the phase 3b, single-arm, open-label GENEr8-3 study.

Valoctocogene roxaparvovec, an adeno-associated virus vector that transfers a human factor VIII (FVIII) coding sequence to hepatocytes, provides bleeding protection for people with severe hemophilia A (HA). Determine the efficacy and safety of valoctocogene roxaparvovec with concomitant prophylactic glucocorticoids in the open-label, single-arm, phase 3b GENEr8-3 trial. Participants with severe HA who were using HA prophylaxis received one 6x1013 vg/kg infusion of valoctocogene roxaparvovec concomitantly with daily prophylactic glucocorticoids (40 mg prednisolone equivalent/d weeks 0‒8; taper to 5 mg/d weeks 9‒19). The primary efficacy endpoint was change from baseline in FVIII activity (chromogenic substrate assay) at week 52. Secondary efficacy endpoints included annualized rate of FVIII use and annualized bleeding rate (ABR) for treated bleeds. Safety was assessed by adverse events (AEs). Analysis populations were intent-to-treat (ITT; received valoctocogene roxaparvovec) for safety analyses and modified ITT (mITT; ≥52 FVIII infusions in the year before dosing) for efficacy analyses. Overall, 22 participants with severe HA received valoctocogene roxaparvovec. In the mITT population (n = 21), mean week 52 FVIII activity increased from baseline (imputed as 1 IU/dL) to 16.1 IU/dL (standard deviation [SD], 22.4; P = 0.0057); post-HA prophylaxis, mean treated ABR and mean annualized FVIII use decreased 67.1% and 91.6% from baseline, respectively (P <0.05). The most common AE was alanine aminotransferase elevation (20/22 participants). Glucocorticoid-related AEs occurred in 19/22 participants. No participants discontinued the study. Based on cross-trial comparisons, prophylactic glucocorticoids do not confer safety or efficacy benefits compared with reactive glucocorticoid regimens.

Efficacy and Safety of Different Atropine Regimens for the Treatment of Myopia in Children

Additional data are required regarding atropine treatment regimens for control of myopia progression. To investigate the efficacy and safety of different atropine regimens for myopia in children. This was a secondary analysis of the 3-year results of the 24-Month Myopia Outcome Study of Atropine in Children (MOSAIC) trial, called the MOSAIC2 trial. The MOSAIC trial was an investigator-led, double-masked, randomized clinical trial of different atropine concentrations and regimens. The MOSAIC2 study took place at the Centre for Eye Research Ireland, in Dublin, Ireland, and included children and adolescents with myopia from the MOSAIC trial. Data analysis was conducted from November 2023 to February 2024. Participants were randomly assigned to the following cohorts: group 1, nightly placebo for 2 years then 0.05% atropine eye drops for 1 year and group 2, nightly 0.01% atropine eye drops for 2 years then rerandomization to placebo nightly, tapering placebo, or tapering of 0.01% atropine eye drops for 1 year. Observed changes in cycloplegic spherical equivalent refraction and axial length from month 24, or baseline, to month 36. A total of 199 children with myopia (mean [SD] age, 13.9 [2.4] years; 121 female [60.8%]) of the 250 children and adolescents from the MOSAIC trial were included in the MOSAIC2 trial analysis. Of 83 participants assigned to group 1, 66 (79.5%) reconsented to year 3, and 61 (73.5%) completed the trial. Of 167 participants assigned to group 2, 133 (79.6%) continued to year 3, and 121 (72.5%) completed the trial (0.01% atropine, then nightly placebo: n = 31 and n = 29 [93.5%]; 0.01% atropine, then tapering placebo: n = 29 and n = 25 [86.2%]; 0.01% atropine then tapering 0.01% atropine: n = 73 and n = 67 [91.8%], respectively). Compared with the group taking placebo then 0.05% atropine, the combined atropine then placebo groups had more spherical equivalent progression (adjusted difference, -0.13 diopters [D]; 95% CI, -0.22 to -0.04 D; P = .01) and axial elongation (adjusted difference, 0.06 mm; 95% CI, 0.02-0.09 mm; P = .008), and the group taking 0.01% atropine then tapering 0.01% atropine had more axial elongation (adjusted difference, 0.04 mm; 95% CI, 0.009-0.07 mm; P = .04). In the group taking placebo then 0.05% atropine, 15% (n = 10) and 8% (n = 5) reported blurred near vision and photophobia, respectively, during year 3, compared with 3% (n = 2) and 0%, respectively, in the group taking 0.01% atropine then tapering 0.01% atropine, and no reports in both placebo groups. Despite more adverse events, participants using 0.05% atropine during year 3 had no differences in treatment completion rates and exhibited 0.13-D less myopia progression and 0.06-mm less axial elongation, compared with participants using placebo, supporting consideration of treatment as given to the group taking 0.05% atropine in this European population. isrctn.org Identifier: ISRCTN36732601.

Role of caffeine in slowing progression of myopia: 1-year results from a prospective, longitudinal clinical trial

Role of caffeine in slowing progression of myopia: 1-year results from a prospective, longitudinal clinical trial

Effect of sodium glucose cotransporter-2 inhibitors (SGLT-2is) on the clinical outcomes of patients with diabetic atrial fibrillation

BackgroundDiabetes mellitus (DM) and atrial Fibrillation (AF) are among the most common health issues. They are responsible for the highest rates of morbidity and mortality. The importance of sodium glucose cotransporter-2 inhibitors (SGLT-2is) in treating DM has increased significantly in recent years. In our article, we aimed to evaluate the effect of SGLT-2i on the clinical outcomes of AF patients with DM.MethodsOur study is a retrospective, observational study. The patients with AF and DM were divided into two groups: those using SGLT-2i or not using SGLT-2i, and 3-year follow-up results were examined. The endpoints of the study were defined as all-cause death, the development of myocardial infarction (MI), major bleeding requiring hospitalization, and an ischemic cerebrovascular event (CVE). Differences between groups according to SGLT-2i use were analyzed.ResultsThe study included 485 patients, 205 (42.3%) of whom were male and had an average age of 70.7 ± 9.7 years. A total of 138 of 485 patients (28.5%) received SGLT-2i. All-cause mortality was lower in the group receiving SGLT-2i (p < 0.001). Similarly, a significant reduction in major bleeding events was observed among those who received SGLT-2i treatment (p = 0.009). The incidence of CVEs was lower among SGLT-2i recipients, but the difference was not statistically significant (p = 0.066). SGLT2i usage did not mitigate the risk of MI development (p = 0.317).ConclusionsIn our study, SGLT-2i treatment was associated with a significant reduction in all-cause mortality and major bleeding in diabetic AF patients. Our study provides evidence of the clinical benefit of SGLT-2i in AF patients.

Influence of organic sources of nutrient on mungbean performance in South-eastern Rajasthan

A field experiment was conducted during the Kharif seasons of 2022 and 2023 at the organic farming block of the Agricultural Research Station, Ummedganj, Agriculture University, Kota (Rajasthan), to study the effects of organic sources of nutrient on mungbean growth and yield in the mungbean-wheat cropping system of southeastern Rajasthan. The experiment included eight treatments: T1 , Absolute control; T2 , 100% N by farm yard manure (FYM) + cow urine @ 10% spray at 15, 30, and 45 days after sowing (DAS); T3, 100% N by FYM + panchagavya @ 5% spray at 15, 30, and 45 DAS; T4 , 75% N by FYM + 25% N by vermicompost + vermiwash @ 10% spray at 15, 30, and 45 DAS; T5 , 50% N by FYM + 50% N by vermicompost + vermiwash @ 10% spray at 15, 30, and 45 DAS; T6 , 75% N by FYM + jeevamrut @ 500 liters/ha at sowing + vermiwash @ 5% spray @ 15, 30, and 45 DAS; T7 , 100% N by FYM + NPK consortia of biofertilizers + Zinc solubilising bacteria (ZSB) each @ 62.5 ml/kg seed inoculation + amrita sanjeevani @ 500 liters/ha at sowing, 15 and 30 DAS and 75% N by FYM + NPK consortia of biofertilizers @ 62.5 ml/kg seed inoculation + sasyagavya @ 10% spray at 15, 30, and 45 DAS (T8 ). The treatments were arranged in a randomized block design with 3 replications. The 2-years pooled results showed that the treatment T5 produced significantly higher values for plant height (54.62 cm), number of branches/plant (9.65), total number of effective nodules/plant (31.65), fresh and dry weight of root nodules/plant (119.94 mg and 23.98 mg, respectively), number of pods/plant (26.28), number of seeds/pod (9.39), pod length (8.17 cm), test weight (34.99 g), seed yield (1242 kg/ha), and straw yield (2,204 kg/ha) compared to the absolute control. These results were statistically on par with the T3 and T7 treatments, and the seed yield was found at par with T3 in the pooled analysis. Hence, the application of 50% N by FYM and 50% N by vermicompost, along with vermiwash spray, is highly effective mungbean yield in the South Eastern Rajasthan for enhancing.

Influence of organic sources of nutrient on mungbean performance in South-eastern Rajasthan

A field experiment was conducted during the Kharif seasons of 2022 and 2023 at the organic farming block of the Agricultural Research Station, Ummedganj, Agriculture University, Kota (Rajasthan), to study the effects of organic sources of nutrient on mungbean growth and yield in the mungbean-wheat cropping system of southeastern Rajasthan. The experiment included eight treatments: T1 , Absolute control; T2 , 100% N by farm yard manure (FYM) + cow urine @ 10% spray at 15, 30, and 45 days after sowing (DAS); T3, 100% N by FYM + panchagavya @ 5% spray at 15, 30, and 45 DAS; T4 , 75% N by FYM + 25% N by vermicompost + vermiwash @ 10% spray at 15, 30, and 45 DAS; T5 , 50% N by FYM + 50% N by vermicompost + vermiwash @ 10% spray at 15, 30, and 45 DAS; T6 , 75% N by FYM + jeevamrut @ 500 liters/ha at sowing + vermiwash @ 5% spray @ 15, 30, and 45 DAS; T7 , 100% N by FYM + NPK consortia of biofertilizers + Zinc solubilising bacteria (ZSB) each @ 62.5 ml/kg seed inoculation + amrita sanjeevani @ 500 liters/ha at sowing, 15 and 30 DAS and 75% N by FYM + NPK consortia of biofertilizers @ 62.5 ml/kg seed inoculation + sasyagavya @ 10% spray at 15, 30, and 45 DAS (T8 ). The treatments were arranged in a randomized block design with 3 replications. The 2-years pooled results showed that the treatment T5 produced significantly higher values for plant height (54.62 cm), number of branches/plant (9.65), total number of effective nodules/plant (31.65), fresh and dry weight of root nodules/plant (119.94 mg and 23.98 mg, respectively), number of pods/plant (26.28), number of seeds/pod (9.39), pod length (8.17 cm), test weight (34.99 g), seed yield (1242 kg/ha), and straw yield (2,204 kg/ha) compared to the absolute control. These results were statistically on par with the T3 and T7 treatments, and the seed yield was found at par with T3 in the pooled analysis. Hence, the application of 50% N by FYM and 50% N by vermicompost, along with vermiwash spray, is highly effective mungbean yield in the South Eastern Rajasthan for enhancing.

Dutch Nationwide Cohort Experience with a New PROMs Set in Metabolic and Bariatric Surgery: BODY-Q Obesity Module.

Patient-reported outcomes are important as obesity is a chronic disease with a substantial impact. A multidisciplinary task force selected six scales (48 questions) from the validated BODY-Q questionnaire. This subset was gradually introduced and evaluated in a mandatory nationwide registry. The focus was to assess the scale's module results and its feasibility in a quality registry. All Dutch patients undergoing bariatric surgery between 2019 and 2022 were selected. Completed questionnaires of RAND-36, EQ-5D-5L, and BODY-Q were reviewed with baseline and 1-year results. Uni- and multivariable regression analyses were performed to assess the relationship between baseline characteristics and quality of life scores over time. A total of 10,972 patients completed at least one BODY-Q scale. The lowest score was on the body image scale preoperatively (28.2, SD 20.9) and the highest on the social scale postoperatively (76.2, SD 18.8). A representative group of 510 patients with repeated measurements showed the most improvement on the body image scale (+ 32.2) followed by physical function (+ 26.3). Multivariable linear regression analysis showed a significant influence, primarily for gender, age, and BMI on BODY-Q scores. Score improvement for BODY-Q was mainly driven by weight loss, while EQ-5D-5L and RAND-36 showed no clear pattern. Comparing the three questionnaires showed significant correlations for physical and social function only. The BODY-Q obesity module demonstrates potential as a relevant PROM for inclusion in a quality registry. BODY-Q scores provide a foundation for future research, with notable improvements in quality of life observed, particularly in the body image and physical function scales.

2-year results from an observational study of proactive treatment regimens with intravitreal aflibercept 2 mg in patients with nAMD in clinical practice: XTEND study UK cohort

Abstract Objectives The 36-month XTEND (NCT03939767) multicentre, observational, prospective study examined the effectiveness of proactive treatment regimens of intravitreal aflibercept (IVT-AFL) 2 mg in treatment-naïve patients with neovascular age-related macular degeneration (nAMD) in routine clinical practice. The 12- and 24-month outcomes from the XTEND UK cohort are reported. Methods Patients aged ≥50 years with nAMD planned to receive IVT-AFL 2 mg were eligible. After three initial monthly IVT-AFL injections, treatment intervals could be extended in 2- to 4-weekly increments to a maximum of 16 weeks (8-week minimum treatment interval). Endpoints included mean change from baseline in best-corrected visual acuity (BCVA) and central subfield thickness (CST) at month (M) 12 and M24. Treatment intervals and safety were assessed. Statistics were descriptive. Results In the UK, 496 patients from 23 centres were treated (mean age 79.7 years, 64.3% female). From a baseline BCVA (mean ± SD) of 55.2 ± 15.8 letters, mean (95% confidence interval [CI]) change in BCVA was +3.4 (2.0, 4.9) letters at M12 and +1.3 (− 0.3, 2.9) letters at M24. From a baseline CST (mean ± SD) of 395 ± 143 μm, mean (95% CI) change in CST was −105 ( 121, −89) μm at M12 and −105 (− 122, −88) μm at M24. By M12 and M24, patients had received a mean ± SD of 7.4 ± 2.4 and 10.7 ± 4.6 injections, respectively. Outcomes in patients enrolled prior to and during the COVID-19 pandemic were comparable. No new safety concerns were identified. Conclusions Despite the COVID-19 pandemic, patients in the UK achieved and maintained clinically meaningful improvements in functional and anatomic outcomes through M24. Trial registration ClinicalTrials.gov identifier, NCT03939767.

Acid Reflux Management with the RefluxStop Implant: A Prospective Multicenter Trial with 3-Year Outcomes.

RefluxStop is a unique implant for laparoscopic treatment of gastroesophageal reflux disease (GERD). It restores normal function of the gastroesophageal junction without the unwanted effects of encircling the esophagus, circumventing adverse events (AEs) associated with conventional anti-reflux surgeries. Three-year follow-up of 50 patients with chronic GERD treated by RefluxStop was achieved in a prospective, single-arm, multicentric clinical trial analyzing safety and effectiveness of the procedure. The 3-year results included 47 of 50 patients. No cases of device-related AEs, erosion, device migration, or explantation occurred during the entire study period. Two AEs were reported between the 1- and 3-year results (1-year results previously published), including mild dysphagia (n = 1) and heartburn (n = 1). No subjects (n = 0/47) required regular daily proton pump inhibitor (PPI) therapy at 3-year follow-up. Subjects experienced a 93.1% reduction in median total GERD-HRQL score at 3years (2.0) from baseline (29.5). One subject (n = 1) was dissatisfied with treatment but demonstrated normal 24-h pH monitoring results. Daily regurgitation improved by 97.9% from a baseline of 86% (n = 43/50) to 2.1% (n = 1/47) at follow-up. Dysphagia GERD-HRQL subscore of > 2 (i.e., bothersome everyday) decreased from 22% at baseline to 2% at 3years. Baseline odynophagia (16%) completely resolved at 3years. RefluxStop surgery treats GERD without encircling and applying pressure on the esophagus. Three-year follow-up demonstrates that the device is safe and effective in treating GERD with substantial improvements in quality of life via GERD-HRQL (median improvement 93%), PPI usage (0%), and 98% without dysphagia.

Three-unit posterior monolithic fixed dental prostheses made from high-translucent shade-graded zirconia: 3-Year results from a prospective clinical pilot study

ObjectivesTo assess the clinical performance of tooth-supported 3-unit fixed dental prostheses (FDPs) made from shade-graded monolithic 5Y-PSZ (partly stabilized zirconia) zirconia in terms of survival rate and the quality of restorations based on modified FDI criteria over three-years.Materials and methodsHigh-translucent shade-graded monolithic zirconia (Lava Esthetic, Solventum Dental Solutions) was used to manufacture maxillary or mandibular three-unit FDPs in the posterior region (N = 22) employing subtractive milling system (Amann Girrbach). All FDPs were bonded with a universal resin cement (Rely X Universal, Solventum Dental Solutions) and evaluated 4 weeks after cementation (baseline) and after 1, 2, and 3 years. The primary objective was to assess the survival and complication rates of the restorations. Furthermore, the quality of the restorations was evaluated based on selected and modified FDI (World Dental Federation) criteria, which encompass functional, aesthetic, and biological parameters. FDI criteria were analyzed using the Fisher-Freeman-Halton exact test.ResultsTwenty-one patients were examined at 1 year, 2 years, and 3 years. The survival rate was 100%. No mechanical complications were observed. A total of 3 biological complications occurred. These were successfully managed without any residual functional impairment. All FDI criteria were found to be clinically acceptable or better.ConclusionsMonolithic shade-graded zirconia FDPs demonstrated 100% survival at 3 years with a low complication rate.Clinical relevanceFixed 3-unit FDPs made of high-translucent monolithic zirconia might be a viable treatment option in the posterior region, preventing the chipping phenomenon and providing favorable aesthetics while allowing for an efficient digital workflow.

Colposcopy referrals and CIN3 detection after triage by host cell DNA methylation and/or HPV genotyping in HPV positive women with low-grade cytology from a population-based Dutch primary HPV screening trial.

High-risk HPV (hrHPV)-based screening has led to many unnecessary colposcopy referrals, mainly because of direct referral after low-grade cytology (ASC-US/LSIL). DNA methylation and genotyping tests on ASC-US/LSIL samples have the potential to significantly improve the efficiency of screening. In this study, 12 triage strategies were constructed from FAM19A4/miR124-2 or ASCL1/LHX8 methylation, HPV16/18 or HPV16/18/31/33/45 genotyping and 1-year repeat cytology. The performance was evaluated on 215 hrHPV-positive ASC-US/LSIL samples from the IMPROVE trial (NTR5078). Performance was measured by colposcopy referral rate, positive predictive value (PPV) for detecting precancer (CIN3), and negative predictive value (NPV). To evaluate efficiency, strategies were ordered by the cumulative colposcopy referral rate after 1-year cytology and compared by the marginal PPV to detect one additional CIN3 (mPPV). The most conservative strategy (referral when HPV16/18 and FAM19A4/miR124 methylation results are positive) had a direct referral rate of 5.2%, a cumulative referral rate after 1-year cytology of 54.1%, and mPPV of 19.3%. Replacing HPV16/18 by HPV16/18/31/33/45 increased the cumulative 1-year referral rate to 54.6%, and yielded an mPPV of 10.0%. Similar results were obtained for strategies with ASCL1/LHX8 methylation. Of all strategies, referral after an HPV16/18/31/33/45 positive, ASCL1/LHX8 methylation-positive, and/or 1-year cytology-positive result yielded the highest direct and cumulative 1-year colposcopy referral rates of 64.4% and 79.1%, respectively. The NPVs after 1-year cytology varied between 98.1% and 99.4%, warranting a return to routine screening. Altogether, DNA methylation-based triage strategies are recommended as they are discriminative for CIN3 and control the number of immediate colposcopy referrals.

Neoadjuvant Modified Infusional Fluorouracil, Leucovorin, and Oxaliplatin With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Updated Results of the FOWARC Study After a Median Follow-Up of 10 Years.

We present 10-year results of the phase Ⅲ FOWARC trial, which evaluated the efficacy of modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) with or without radiation compared with fluorouracil with radiation in patients with locally advanced rectal cancer. A total of 495 patients age 18-75 years with stage Ⅱ-Ⅲ rectal cancer were randomly assigned to three treatment arms: fluorouracil plus radiotherapy, mFOLFOX6 plus radiotherapy, or mFOLFOX6 alone, followed by surgery and adjuvant chemotherapy. With a median follow-up of 10 years, the 10-year disease-free survival (DFS) rates were 52.5%, 62.6%, and 60.5%, respectively (P = .56). The 10-year locoregional recurrence (LR) rates were 10.8%, 8.0%, and 9.6% (P = .57), and the 10-year overall survival (OS) rates were 65.9%, 72.3%, and 73.4% (P = .90). Subgroup analysis identified ypTNM stage as a significant prognostic factor for DFS, LR, and OS (P < .0001, P < .006, P < .0001, respectively). Patients achieving pathologic complete response had 10-year DFS, LR, and OS rates of 84.3%, 3.0%, and 92.4%, respectively. No significant difference was observed in long-term survival outcome between mFOLFOX6 with and without radiation and fluorouracil plus radiation. These results demonstrate that neoadjuvant mFOLFOX6 chemotherapy can be considered as a therapeutic option in LARC.

Long-Term Results after Autologous Matrix-Induced Chondrogenesis for Osteochondral Lesions of the Talus: A 10-Year Cohort Study.

A gold standard surgical treatment for osteochondral lesions (OCLs) of the talus still needs to be established. Still, autologous matrix-induced chondrogenesis (AMIC) is a commonly applied 1-stage procedure that has achieved good short- and mid-term results. The present cohort study aimed to assess whether the long-term, 10-year results can confirm the previous findings. All patients underwent an open AMIC procedure using a collagen type I/III bilayer matrix for a talar OCL. General demographic data, preoperative magnetic resonance imaging findings, intraoperative details, and German version of the Foot Function Index (FFI-D) scores preoperatively and at 1, 5, and 10 years as well as European Foot and Ankle Society (EFAS) and American Orthopedic Foot & Ankle Society (AOFAS) scores at 10 years after surgery were analyzed. The primary outcome variable was the procedure's longitudinal effect, and several variables' influence on the outcome was tested. Of 47 consecutive patients, 18 (38%) were included. Of the 18 patients, 6 (33%) were female, and 12 (67%) were male, with a mean age of 39 ± 15 (range = 15-62) and an average body mass index (BMI) of 26 ± 5 (range = 20-38) kg/m². The mean defect size was 1.4 ± 0.9 (range = 0.2-4) cm². The FFI-D total score showed a significant decrease from preoperatively to 1 year postoperatively (56 ± 19 to 34 ± 27; P = 0.001) with a further nonsignificant decrease to the 5-year (34 ± 27 to 21 ± 20; P = 0.16) and 10-year follow-up (21 ± 20 to 15 ± 13; P = 1.00). All the single items decreased significantly from preoperatively to the 5- and 10-year mark. Although not significant, most items improved from 5 to 10 years postoperatively. Age positively correlated with the preoperative, 5-year, and 10-year follow-up FFI-D total score. AMIC, as a single-step surgical intervention, is a viable long-term treatment option. Patient selection regarding symptoms and findings is vital to achieve satisfying results.

Therapeutic Effect of Evenamide, a Glutamate Inhibitor, in Patients With Treatment-Resistant Schizophrenia (TRS): Final, 1-Year Results From a Phase 2, Open-Label, Rater-Blinded, Randomized, International Clinical Trial.

The results from a pilot, 1-year, randomized, open-label, add-on treatment study in treatment-resistant schizophrenia (TRS) with evenamide, a glutamate modulator, were not associated with any safety abnormalities at all doses (7.5-30 mg bid), with a high retention rate even at 6-month (~85%), and 1-year (~75%), and the absence of psychotic relapses during the 1-year treatment period. Overall, treatment with evenamide showed a gradual, sustained, and clinically important improvement up to 1 year in all efficacy measures (eg, PANSS mean change ~ -20%; CGI-S mean change ~ -1.0). In addition, compared to the results at Week 6, the responder rates generally more than doubled at 1-year (PANSS "≥20% improvement from baseline" = ~45%; CGI-S "2-category of improvement" = ~25%; CGI-C "much improved" = ~40%). These results, rarely replicated in other trials in TRS, support the use of evenamide as an add-on treatment in patients who are not benefiting from their current first- or second-generation antipsychotic medication.

A 7-year study of workplace drug testing in two major cities in Türkiye

Background Workplace Drug Testing (WDT) is a worldwide practice that is crucial in anti-drug efforts. This study aimed to provide compherensive information about the WDT applications in Türkiye with data obtained from two major cities in two different regions of Türkiye. Methods The retrospective assessment of forensic toxicological analysis results in urine, hair or urine&hair samples collected from 220 WDT cases in İzmir (3rd largest city) and Adana (5th largest city) from 2016 to 2022 years was carried. The screening and confirmation analysis were performed with immunoassay and liquid chromatography-tandem mass spectrometry (LC-MS/MS), respectively. Results Cases with a positive result from one of urine or hair tests were accepted as positive. 20.5% (n = 45) of the cases were detected positive, and most applicants were identified as drivers (84.4%, n = 38). Urine samples of 23.5% (n = 52) were screened by immunoassay, and THC (n = 1) and opiate (n = 1) were detected. In the LC-MS/MS analysis, benzodiazepines were detected most in urine as a single substance, while cannabinoids and codeine were detected in the hair. Multidrug combinations used in treatment were detected in urine and hair. It was detected both alone and among the substances accompanying cannabinoids and amphetamines. Conclusions This study presents 7-year WDT results of two different major cities in Türkiye. The method of WDT application differs across the country so a standard procedure should be performed. In our country, where zero tolerance against substance use is adopted, the detection of illegal and controlled substances in cases clearly shows that WDT practice should be routinized.

What are the comparative long-term (≥1-year) results of GLP-1 receptor agonist therapy and bariatric surgery for weight loss?

What are the comparative long-term (≥1-year) results of GLP-1 receptor agonist therapy and bariatric surgery for weight loss?

Five-year oncological outcomes after enhanced recovery after surgery (ERAS) compared to conventional care for colorectal cancer: a retrospective cohort of 981 patients.

The enhanced recovery after surgery (ERAS) protocol has been introduced over the past three decades for patients undergoing colorectal surgery. However, the effect of this program on long-term survival is poorly studied. We evaluated the effect of ERAS on 5-year overall survival (OS) and recurrence-free survival (RFS) after colorectal cancer surgery, and identified risk factors. This retrospective study used data from the comparison of oncological outcomes at 3years after ERAS or conventional care (pre-ERAS), conducted in our department between 2005 and 2017, and published in 2022. A total of 981 patients were included (ERAS, n = 486; pre-ERAS, n = 495). The 5-year OS and RFS rates were similar in the ERAS and pre-ERAS groups, respectively (63.3% [58.9;67.4] vs 57.7% [53.2;61.9]; p = 0.055) and (69.5% [65.2;73.4] vs 70.9% [66.6;74.8]; p = 0.365). The 5-year OS result was confirmed by a propensity score analysis (HR0.98 [0.71; 1.37], p = 0.911). Analysis of 5-year survival by a multivariate Cox model identified age (HR1.28 [1.15; 1.43]), BMI < 18.5 (HR1.62 [1.08;2.45]), smoking (HR1.68 [1.26;2.24]), ASA score > 2 (HR1.56 [1.22;1.98]), and laparotomy interventions (HR2.06 [1.61;2.63]) as risk factors for death. Regarding RFS, multivariate analysis adjusted on the ERAS group identified age as a protective factor with a reduction of 10% in the risk of recurrence (HR0.90 [0.81-0.99]). In contrast patients treated with neoadjuvant chemotherapy had a higher risk of recurrence (HR1.41 [1.07-1.85]). This study failed to demonstrate any advantage of the ERAS program in improving 5-year OS and RFS after colorectal cancer surgery. Age, undernutrition, smoking, ASA score > 2, and laparotomy interventions are independently associated with early mortality.

P90 JNJ-77242113 induces a strong and durable pharmacodynamic response in serum and skin of patients with moderate-to-severe psoriasis: 1-year results from FRONTIERs 1 and 2

Abstract JNJ-77242113 (JNJ-2113), a targeted oral peptide that binds the interleukin (IL)-23-receptor to inhibit IL-23 signalling, showed superior clinical efficacy vs. placebo at Week(W) 16 of FRONTIER-1 in patients with moderate-to-severe plaque psoriasis, which correlated with strong serum and skin pharmacodynamic (PD) responses (Bissonnette R, Pinter A, Ferris LK et al. An oral interleukin-23-receptor antagonist peptide for plaque psoriasis. N Engl J Med 2024; 390:510–21). Here, we evaluated JNJ-2113 systemic PD responses through W52 and further characterized the JNJ-2113 skin PD effect, including relationships with clinical response, utilizing tape-strip skin sampling. FRONTIER-1 randomized (1:1:1:1:1:1; 41-43pts/arm) participants to 25 mg QD, 25 mg BID, 50 mg QD, 100 mg QD, 100 mg BID, or placebo through W16. Patients continuing to FRONTIER-2 received the same JNJ-2113 regimen or crossed-over from placebo→100 mg QD through a total of 52-weeks of treatment. Both targeted [β-Defensin-2 (BD-2)/IL-22/IL-17A/IL-17F/IL-23] and broad (5400+ protein Olink® Explore HT) proteomics were conducted using serum samples collected through W52. The BD-2 and Olink® Explore-HT assays were performed on protein lysates extracted from tape-strip samples of lesional and non-lesional skin collected through W16, and correlation between BD-2 levels and psoriasis area and severity index (PASI) scores was evaluated. JNJ-2113 drove significant, rapid, dose-related reductions in serum psoriasis disease biomarker (BD-2/IL-22/IL-17A/IL-17F) levels that continued through W52; largest reductions were with JNJ-2113 100 mg BID [W52 fold-change (FC) from baseline: -3.63/-1.19/-1.03/-1.49, respectively]. Notably, through W52, JNJ-2113 had minimal impact on serum IL-23 (W52 FC from baseline: −0.09) or cytokines involved in broad immune response through W52 as assessed via Olink® Explore-HT. Consistent with serum results, JNJ-2113 100 mg BID significantly reduced BD-2 levels in W16 lesional skin to levels seen in non-lesional skin; this reduction correlated with PASI. Broad proteomics of tape-strip samples showed baseline lesional samples were significantly enriched for psoriasis-relevant proteins (BD-2/IL-22/IL-17A/IL-19 and others) and clustered away from non-lesional samples. Importantly, JNJ-2113 100 mg BID reduced psoriasis-related proteins in W16 tape-strip lesional samples, with a protein signature like non-lesional samples but distinct from baseline lesional and W16 placebo samples, suggesting JNJ-2113 normalized skin inflammation. JNJ-2113 selectively blocked IL-23-driven inflammation and induced a dose-related PD response, with rapid and sustained reduction of biomarkers of the IL-23 pathway and psoriasis disease severity through 1-year of treatment. JNJ-2113 also normalized skin biomarkers, which correlated with reductions in PASI, to drive disease improvement. Our novel approach to tape-strip-derived proteomics demonstrates this minimally invasive alternative to skin biopsies can be used to evaluate disease biology and characterize local treatment response in psoriatic patients.