5-year Results Research Articles

Restrictive Strategy vs Usual Care for Cholecystectomy in Patients With Abdominal Pain and Gallstones

The 1-year results of the SECURE trial, a randomized trial comparing a restrictive strategy vs usual care for select patients with symptomatic cholelithiasis for cholecystectomy, resulted in a significantly lower operation rate after restrictive strategy. However, a restrictive strategy did not result in more pain-free patients at 1 year. To gauge pain level and determine the proportion of pain-free patients, operation rate, and biliary and surgical complications at the 5-year follow-up. This randomized clinical trial was a multicenter, parallel-arm, noninferiority, prospective study. Between February 2014 and April 2017, patients from 24 hospitals with symptomatic, uncomplicated cholelithiasis were included. Uncomplicated cholelithiasis was defined as gallstone disease without signs of complicated cholelithiasis, ie, biliary pancreatitis, cholangitis, common bile duct stones, or cholecystitis. Follow-up data for this analysis were collected by telephone from July 11, 2019, to September 23, 2023. Patients were randomized (1:1) to receive usual care or a restrictive strategy with stepwise selection for cholecystectomy. The primary, noninferiority end point was proportion of patients who were pain free as evaluated by Izbicki pain score at the 5-year follow-up. A 5% noninferiority margin was chosen. The secondary end points included cholecystectomy rates, biliary and surgical complications, and patient satisfaction. Among 1067 patients, the median (IQR) age was 49.0 years (38.0-59.0 years); 786 (73.7%) were female, and 281 (26.3%) were male. At the 5-year follow-up, 228 of 363 patients (62.8%) were pain free in the usual care group, compared with 216 of 353 patients (61.2%) in restrictive strategy group (difference, 1.6%; 1-sided 95% lower confidence limit, -7.6%; noninferiority P = .18). After cholecystectomy, 187 of 294 patients (63.6%) in the usual care group and 160 of 254 patients (63.0%) in the restrictive strategy group were pain free, respectively (P = .88). The restrictive care strategy was associated with 387 of 529 cholecystectomies (73.2%) compared with 437 of 536 in the usual care group (81.5%; 8.3% difference; P = .001). No differences between groups were observed in biliary and surgical complications or in patient satisfaction. In the long-term, a restrictive strategy results in a significant but small reduction in operation rate compared with usual care and is not associated with increased biliary and surgical complications. However, regardless of the strategy, only two-third of patients were pain free. Further criteria for selecting patients with uncomplicated cholelithiasis for cholecystectomy and rethinking laparoscopic cholecystectomy as treatment is needed to improve patient-reported outcomes. CCMO Identifier: NTR4022.

Netakimab for the treatment of psoriatic arthritis: 3-year results of the phase III BCD-085-8/PATERA study

Netakimab for the treatment of psoriatic arthritis: 3-year results of the phase III BCD-085-8/PATERA study

86. Intraosseous basivertebral nerve ablation for the treatment of vertebrogenic pain: pooled 4-year results from two long-term follow-up studies

86. Intraosseous basivertebral nerve ablation for the treatment of vertebrogenic pain: pooled 4-year results from two long-term follow-up studies

Clinical Outcomes of Excisional Goniotomy with the Kahook Dual Blade: 6-Year Results.

This study aims to evaluate the long-term clinical outcomes of excisional goniotomy with the Kahook Dual Blade (KDB) in the management of various types of glaucoma. This was a retrospective, noncomparative chart review of 90 eyes of 53 patients with glaucoma that underwent standalone KDB goniotomy (KDB-alone group) or KDB goniotomy with concomitant phacoemulsification (KDB-phaco group) between October 2015 and October 2017. Surgical success was defined as an intraocular pressure (IOP) reduction by ≥ 20% at the last follow-up with no surgical reinterventions required and a final IOP ≥ 4mmHg and ≤ 21mmHg. We also report on changes from baseline in IOP, number of glaucoma medications, best-corrected visual acuity (BCVA), and visual field parameters, for up to 72months. At 72months, mean (standard deviation [SD]) IOP was reduced from 17.5 (5.7) to 13.6 (3.0) mmHg (P < 0.0001) in the KDB-phaco group and from 23.3 (5.9) to 15.1 (6.2) mmHg (P = 0.0593) in the KDB-alone group. The mean (SD) number of glaucoma medications was reduced from 1.3 (1.0) to 0.8 (0.9) (P < 0.0001) in the KDB-phaco group and from 1.2 (1.0) to 0.7 (0.8) (P = 0.3409) in the KDB-alone group. During the 72-month follow-up, surgical success was achieved in 24 of the 52 available eyes (46.2%). Four eyes underwent a glaucoma surgical reintervention by 72months. Excisional goniotomy with the KDB effectively lowered the IOP (by an average of 28.0% from baseline) and maintained or further reduced glaucoma medication burdens (by an average of 30.8% from baseline) under an excellent safety profile, independent of phacoemulsification status. The procedure exhibited favorable success for up to 6years, providing valuable insights into its long-term efficacy as a glaucoma treatment.

Treating acid reflux without compressing the food passageway: 4-year safety and clinical outcomes with the RefluxStop device in a prospective multicenter study

IntroductionRefluxStop is an implantable device for laparoscopic surgical treatment of gastroesophageal reflux disease (GERD) to restore and maintain lower esophageal sphincter and angle of His anatomy without encircling and putting pressure on the food passageway, thereby avoiding side effects such as dysphagia and bloating seen with traditional fundoplication. This study reports the clinical outcomes with RefluxStop at 4 years following implantation of the device.MethodsA prospective, single arm, multicenter clinical investigation analyzing safety and effectiveness of the RefluxStop device in 50 patients with chronic GERD.ResultsAvailable data are presented for 44 patients at 4 years with the addition of three patients at 3 years carried forward. At 4 years, median GERD-HRQL score was 90% reduced compared to baseline. Two patients (2/44) used regular daily proton pump inhibitors (PPIs) despite subsequent 24-h pH monitoring off PPI therapy yielding normal results. There were no device-related adverse events (AEs), esophageal dilations, migrations, or explants during the entire study period. AEs reported between 1 and 4 years were as follows: one subject with heartburn and a pathologic pH result with device positioned too low at surgery; one subject with dysphagia, thus, 46/47 patients reported no dysphagia-related AEs between years 1 and 4. Two patients (2/47) were dissatisfied with treatment despite normal 24-h pH monitoring, of whom one had manometry-verified dysmotility at 6 months, indicating dissatisfaction for reasons other than acid reflux.ConclusionThese results confirm the excellent and already published 1-year results as stable in the long-term, supporting the safety and effectiveness of the RefluxStop device in treating GERD for over 4 years. GERD-HRQL score, pH testing, and PPI usage indicate treatment success without dysphagia or gas-bloating and only minimal incidence of other AEs. This favorably low rate of AEs is likely attributable to RefluxStop’s dynamic physiologic interaction and non-encircling nature.

Long-Term Outcomes (10 Years) of Sacrospinous Ligament Fixation for Pelvic Organ Prolapse Repair.

The purpose of this study was to evaluate the 10-year results of sacrospinous ligament suspension as primary repair for apical prolapse and to evaluate long-term side effects. A retrospective study analyzed 10-year follow-up after prolapse repair using sacrospinous ligament suspension. A subjective recurrence was identified as the postoperative occurrence of swelling symptoms based on a particular item on the Italian Prolapse Quality of Life (P-QoL) questionnaire. An objective recurrence was defined as a postoperative decline to stage II or below in any compartment based on the POP-Q system or the requirement for additional surgery. The assessment of postoperative subjective satisfaction was conducted using the Patient Global Impression of Improvement (PGI-I) score. In total, 40 patients underwent sacrospinous ligament fixation. Objective recurrence was remarkably high, as it was observed in 17 (56.7%) patients. Subjective recurrence was reported by ten (33.3%) women, and reintervention occurred in two (6.7%) of patients. From the point of view of quality of life, according to the PGI-I, twenty-three (76.7%) patients described some degree of improvement after surgery, four (13.3%) described their status as unmodified, and three (10%) reported some form of worsening after primary treatment. Transvaginal repair with sacrospinous fixation is a long-lasting option for prolapse repair, with improvement in every POP-q parameter. Some degree of anterior recurrence, recurrence of symptoms with swelling, or an overall worsening of quality of life after surgery is possible.

Posterior capsule opacification with two similar-design hydrophobic acrylic intraocular lenses: 3-year results of a randomized controlled trial.

To compare intraindividually the incidence and intensity of posterior capsule opacification (PCO) and Nd:YAG capsulotomy rates between two similar open-loop single-piece hydrophobic acrylic intraocular lenses (IOLs) differing slightly in their particular material, optic surface and sharp posterior edge design over a period of 3 years. Department of Opthalmology, Medical University Vienna. Randomized, prospective, patient- and examiner-masked clinical trial with intraindividual comparison. 100 patients randomly received a Vivinex XY1 IOL in one eye and a Clareon CNA0T0 IOL in the fellow eye. The amount of PCO (score: 0 - 10) was assessed subjectively and objectively with digital retroillumination picturs using automated image analysis software (AQUA). Best-corrected distance visual acuity (CDVA) as well as the presence of glistenings, subjective visual symptoms and Nd:YAG laser capsulotomy rate were noted. 67 of 100 patients were available for the 3-years follow-up examination. The objective PCO score of the Vivinex XY1 IOLs was 1.0 ± 1.0 compared to the PCO score of 1.5 ± 1.2 for the Clareon CNA0T0 IOLs (p < 0.001). 7.5% of patients had a neodymium:yttrium-aluminium-garnet (Nd:YAG) capsulotomy in the Vivinex XY1 eye, and 9.0% had a capsulotomy in the Clareon CNA0T0 eye (p = 1.0). Both hydrophobic acrylic IOLs showed low PCO and YAG rates with a small but significant favor of the Vivinex XY1 IOL compared to the Clareon CNA0T0 IOL. The interaction of various factors such as hydrophobic material, smooth optic surface and sharp posterior optic edge is the major key for PCO prevention.

CCL2/CCR2 Expression in Locally Advanced Prostate Cancer and Patient Long-Term Outcome: 10-Year Results from the TROG 03.04 RADAR Trial.

This study investigated the prognostic value of the chemokine C-C motif ligand 2 (CCL2) and its receptor C-C motif chemokine receptor 2 (CCR2) expression in locally advanced prostate cancer treated with radiotherapy and androgen deprivation using the 10-year outcome data from the TROG 03.04 RADAR clinical trial. CCL2 and CCR2 protein expression in prostate cancer biopsies at the time of diagnosis were quantified by immunohistochemistry and digital quantification. CCR2 protein expression was detected in prostate cancer cells and was associated with prostate-specific antigen serum concentration (p = 0.045). However, neither CCL2 nor CCR2 tissue expression could predict prostate cancer progression, or other clinicopathological parameters including perineural invasion and patient outcome. In serum samples, CCL2 concentration at the time of diagnosis, as assayed by enzyme-linked immunosorbent assay, was significantly higher in patients with prostate cancer compared with benign prostatic hyperplasia (median difference 0.22 ng/mL, 95% CI, 0.17-0.30) (p < 0.0001) and normal controls (median difference 0.13 ng/mL, 95% CI, 0.13-0.17) (p < 0.0001). However, circulating CCL2 was not statistically significant as a predictor of disease progression and patient outcome. In conclusion, this study shows that although CCL2 and CCR2 are expressed in prostate cancer, with an increased level of CCL2 in the serum, neither CCL2 nor CCR2 expression has a clinical prognostic value in locally advanced prostate cancer.

The significance of total quality management implementation challenges in service delivery

Background: Many of the total quality management (TQM) implementation challenges substantiated in the literature seem oriented towards various facets, including organisation, management, or clients, casting doubts about the effectiveness of the concept in service delivery. The ever-increasing demand for quality services solicits more attention to the desired performance outcomes that define and reflect more of clients’ needs. Such demand presents quality management concerns for many healthcare organisations targeting service delivery.Aim: The TQM concept gets less logical given the increasing challenges in its implementation for service delivery. This research aimed to determine the significance of such challenges.Setting: Queen ‘Mamohato Memorial Hospital (QMMH), Lesotho.Methods: Based on a questionnaire survey of 297 participants, comprising 98 staff and 199 clients, the study obtains survey data from a 5-year result of TQM implementation attempts at Queen ‘Mamohato Memorial Hospital (QMMH), Lesotho.Results: TQM demonstrates great potential to support service delivery as a strategic approach. The study isolates the management-oriented facet of TQM implementation challenges and finds them considerably influenced by the various TQM components.Conclusion: This study establishes and classifies the TQM implementation challenges in QMMH, which are mostly organization, management, and client-oriented. It further addresses assumptions relating to their classifications. Overall, the result suggests that the significance of the underlying challenges in service delivery is more management-oriented.Contribution: The study provides directions that strengthen the effectiveness of the TQM concept and its implementation. It suggests the capacity-building of a hospital’s management team drives TQM implementation.

Selective industry adoption of a voluntary front-of-pack nutrition label results in low and skewed uptake: 10-year results for the Health Star Rating

Front-of-pack nutrition labelling (FOPNL) on packaged foods is recommended by the World Health Organization to promote healthier diets. Our aim was to assess uptake of Australia’s FOPNL, the Health Star Rating (HSR), overall and by HSR score received (0.5 (less healthy) to 5.0 (more healthy) in 0.5 increments) after ten years of voluntary implementation. In a sample of 21,197 products, we found HSR uptake of 37% overall in 2023. Uptake was unevenly distributed, with 24% of products with an HSR ≤ 3 displaying the label, compared to 53% of products scoring ≥3.5 (p < 0.001). Low HSR uptake on poorly rated products demonstrates that most food manufacturers will only display FOPNL where marketing value exists in a voluntary system. Poor and uneven HSR uptake limits consumers’ ability to meaningfully use the label to compare and choose healthier products. Government action is urgently required to make the HSR system mandatory.

Preoperative Magnetic Resonance Guided Single-Dose Partial Breast Irradiation: 5-Year Results of the Prospective Single-Arm ABLATIVE Trial

Preoperative partial breast irradiation (PBI) can increase accuracy of target volume definition and decrease irradiated volumes compared with postoperative PBI. In the ABLATIVE trial (NCT02316561), 15/36 patients achieved pathologic complete response (pCR) 6-8 months after preoperative PBI and breast conserving surgery (BCS). We now present the 5-year results. The ABLATIVE trial is a Dutch prospective cohort study in four hospitals. Women aged ≥ 50 years with unifocal, non-lobular breast cancer, ER-positive, HER2-negative, and a tumor negative sentinel node were treated between 2015-2018 with preoperative single-dose PBI followed by BCS after six or eight months. The primary endpoint was pCR. Secondary endpoints were yearly evaluated oncological outcomes, toxicity, cosmetic outcome (assessed by patients and physicians) and quality of life. Thirty-six patients were treated with BCS six (n=15) and eight (n=21) months following PBI. Median tumor size was 13 mm (IQR 9-16). After a median follow-up of 5.5 years (IQR 5.1-6.0 years), two (6%) patients had ipsilateral breast events and two (6%) distant metastases. The 5-years overall survival was 94% [95% CI 87-100%]. The 5-year cumulative incidence of clinician-reported grade 1/2 breast fibrosis and breast discomfort/pain were 94%/6% and 75%/6%, respectively. The proportion of patients (very) satisfied with the cosmetic results was 89% at baseline and 78% at 5 years. Cosmetic results evaluated using the BCCT.core software were excellent or good in all patients. The 4-year median global quality of life score was 83 (IQR 67-92), similar to baseline (83 (IQR 75-83), p=0.42). Preoperative single-dose PBI and BCS may be an oncologically safe treatment with mild late toxicity, and no decline in cosmetic results and quality of life during 5 years of follow-up. This means that preoperative instead of standard postoperative irradiation has the potential to challenge the current clinical practice.

Bridge-Enhanced Anterior Cruciate Ligament Restoration: 6-Year Results From the First-in-Human Cohort Study.

Bridge-enhanced anterior cruciate ligament restoration (BEAR) combines suture repair of the anterior cruciate ligament (ACL) with an extracellular matrix implant plus autologous blood to facilitate native ACL healing. The purpose of this study was to compare the 6-year follow-up outcomes of patients who underwent the BEAR procedure with those of a nonrandomized concurrent control group receiving autograft ACL reconstruction (ACLR) in the first-in-human safety study of the BEAR implant (BEAR I trial). Based on the 2-year results, it was hypothesized that isometric hamstring strength after the BEAR procedure would be greater than that after ACLR and that there would be no other differences in outcomes at 6 years. Cohort study, Level of evidence, 2. Ten patients underwent BEAR and 10 received ACLR with a 4-stranded hamstring autograft. Outcomes assessed included the record of subsequent surgeries, the International Knee Documentation Committee (IKDC) Subjective Knee Score, IKDC physical examination grade, the Knee injury and Osteoarthritis Outcome Score, instrumented knee laxity, functional outcomes (ie, muscle strength assessments and hop testing), and qualitative magnetic resonance imaging assessment. Comparisons between treatments were based on computations of the mean differences and the associated 95% CIs. One patient in the BEAR group and 3 patients in the ACLR group were lost to follow-up. In the period between 2 and 6 years, 1 patient in each group underwent revision surgery. There were no differences between groups at the 6-year follow-up in any of the outcome measures except for isometric hamstring strength, which was approximately equal to that of the contralateral knee in the BEAR group and <44% of that in the contralateral knee in the ACLR group (P < .01). This preliminary study suggests that the outcomes of BEAR and ACLR with a hamstring tendon graft may be similar at the 6-year follow-up and warrants investigation of the BEAR procedure in a larger cohort of patients.

Ten-Year Effectiveness and Safety of Trabecular Micro-BypassStentImplantation with Cataract Surgery in Patients with Glaucoma or Ocular Hypertension.

This study evaluated 10-year results of implanting one iStent trabecular micro-bypass stent during cataract surgery in eyes with open-angle glaucoma (OAG) or ocular hypertension. This retrospective, non-randomized study examined 10-year outcomes of iStent trabecular micro-bypass stent implantation with cataract surgery by one surgeon in eyes with OAG [including primary OAG (POAG) and pseudoexfoliative glaucoma (PXG)] or ocular hypertension at a multi-specialty German ophthalmology center. Study visits were conducted preoperatively and at 2.5, 3, 5, and 10years postoperatively; examinations included intraocular pressure (IOP), medications, corrected-distance visual acuity (CDVA), and adverse events. A total of 63 eyes of 45 patients with OAG (n = 60 eyes) or ocular hypertension (n = 3 eyes) and data through 10years were analyzed. Mean preoperative IOP was 18.6 ± 4.4mmHg on 1.83 ± 1.03 mean medications. At study visits through 10years postoperative, mean IOP reduced by 12.9-19.0% (p < 0.005 at all points), and mean medication burden reduced by 37.8-51.4% (p ≤ 0.006 at all points). At 10years postoperatively, 77.8% of eyes had IOP ≤ 18mmHg and 47.6% had IOP ≤ 15mmHg (vs. 50.8% and 25.4% preoperatively, respectively; p = 0.016). One-third (33.3%) of eyes were medication-free vs. 3.2% preoperatively (p < 0.001); 17.5% were on 2-5 medications (vs. 55.6% preoperatively, p = 0.005); and 93.7% of eyes were on the same or fewer medications vs. preoperative. Post-phacoemulsification CDVA improvement was maintained; no filtering surgeries were completed over 10-year follow-up. Significant and safe IOP and medication reductions were observed through 10years after iStent implantation with cataract surgery in patients with OAG or ocular hypertension.

Efficacy, durability, and safety of faricimab with extended dosing up to every 16 weeks in diabetic macular edema: 2-year results from the Japan subgroup of the phase 3 YOSEMITE trial

PurposeTo evaluate the 2-year efficacy, durability, and safety of faricimab in patients with diabetic macular edema (DME) in the YOSEMITE Japan subgroup.Study designYOSEMITE/RHINE (NCT03622580/NCT03622593) subgroup analysis: global, multicenter, randomized, double-masked, active-comparator–controlled, phase 3 faricimab trials.MethodsPatients were randomized 1:1:1 to intravitreal faricimab 6.0 mg every 8 weeks (Q8W) and per treat-and-extend (T&E) dosing, or aflibercept 2.0 mg Q8W. Outcomes were assessed through year 2 for the YOSEMITE Japan subgroup (N = 60) and the pooled YOSEMITE/RHINE global cohort (N = 1891).ResultsIn the YOSEMITE Japan subgroup, 21, 19, and 20 patients were randomized to faricimab Q8W, faricimab T&E, and aflibercept Q8W, respectively (632, 632, and 627 patients in the pooled YOSEMITE/RHINE cohort). Vision gains and anatomic improvements with faricimab at year 1 were maintained over 2 years and were generally consistent between groups. Mean best-corrected visual acuity changes from baseline at year 2 (weeks 92–100 average) for the YOSEMITE Japan subgroup were +12.5, +9.0, and +5.0 letters in the faricimab Q8W, faricimab T&E and aflibercept Q8W arms, respectively (+10.8, +10.4, and +10.3 letters in the pooled YOSEMITE/RHINE cohort). At week 96, 61.1% of the YOSEMITE Japan subgroup and 78.1% of the pooled YOSEMITE/RHINE cohort were on ≥ Q12W dosing. Faricimab was well-tolerated with a safety profile comparable with aflibercept.ConclusionFaricimab up to Q16W offered durable vision gains and anatomic improvements up to 2 years in patients with DME in the YOSEMITE Japan subgroup. Outcomes were generally consistent with the pooled YOSEMITE/RHINE cohort.

Esthetically driven immediate provisionalization in the anterior zone: 5-year results from a prospective study evaluating 3.0-mm-diameter tapered implants

ObjectivesEvaluate the 5-year safety and efficacy of a narrow-diameter (3.0 mm) implant that was immediately provisionalized with a single crown in the maxillary lateral incisor or mandibular central or lateral incisor area.Materials and methodsAn open, prospective, single-cohort, multicenter study was conducted, in which narrow-diameter implants were placed in fresh, healed extraction, or congenitally missing sites. All patients were required to meet strict criteria for immediate loading. The primary endpoints were marginal bone levels (MBL) and MBL changes (MBLC) from implant placement to 5-year follow-up. Secondary endpoints included cumulative 5-year survival and success rates, soft tissue health, and esthetic parameters.ResultsA total of 91 implants were placed in 77 patients. The mean MBL remained stable from the 1-year (− 0.79 ± 0.73 mm, n = 75) to 5-year (− 0.74 ± 0.87 mm, n = 65) follow-up. A marginal bone gain of 0.11 ± 0.83 mm was observed from the 1-year to 5-year follow-up. The cumulative 5-year survival rate was 96.5%, and the cumulative 5-year success rate was 93%. The clinical parameters, including the modified plaque index, modified sulcus bleeding index, Jemt’s papilla index, and pink esthetic score improved throughout the 5-year study.ConclusionsThe study demonstrated that narrow-diameter implants represent a safe and predictable treatment option for subjects suitable for immediate loading and with limited bone volume or limited inter-dental space.Clinical relevanceNarrow-diameter implants with immediate provisionalization can be considered for use to restore missing or damaged teeth with predictable functional and esthetic outcomes. This trial was registered with ClinicalTrials.gov (NCT02184845).

Effects of Irrigation Amount and Nitrogen Rate on Cotton Yield, Nitrogen Use Efficiency, and Soil Nitrogen Balance under Drip Irrigation

Water and nitrogen (N) are major constraints for cotton growth and yield formation in arid regions. Irrigation and N application have been widely investigated to improve crop yield and water and N use efficiency (NUE). However, further optimization of water and N management is needed because the effects of N application on soil N balance and N loss under different irrigation levels remain unclear. In this study, a field experiment was conducted in 2020 and 2021 to investigate the effects of different irrigation amounts (full irrigation (100% ETc), moderate irrigation (80% ETc), low irrigation (60% ETc)) and N application rates (control (without N application, N0), low N (150 kg ha−1, N150), medium N (225 kg ha−1 and 300 kg ha−1, N225 and N300), and high N (375 kg ha−1, N375)) on cotton yield, NUE, and soil N balance. The 2-year results showed that under the 60% ETc treatment, cotton dry matter accumulation, N uptake, and yield were significantly enhanced by increasing N application. Under the 80% and 100% ETc treatments, these parameters peaked with the N300 treatment; the N375 treatment showed no significant difference or decrease compared to the N300 treatment. The 80% ETc N300 treatment had the highest cotton yield and NUE, which increased by 17.49–106.57% and 12.28–88.78% compared with other treatments, respectively. Residual soil N accumulation (RSNmin), apparent N loss (ANL), and apparent N surplus (ANS) increased as the N application rate increased under the 60% and 100% ETc treatments. While under the 80% ETc treatment, the ANS did not significantly differ between the N225 and N300 treatments, ANL significantly decreased by 43.51–88.56% when the N application rate increased from 150 to 225 and 300 kg ha−1. The ANL of the 80% ETc N300 treatment was the lowest, but ANS did not significantly increase. The regression analysis and spatial analysis results showed that under irrigation of 336–348 mm and N application of 254–327 kg ha−1, cotton yield, NUE, and WPI reached more than 80% of the maximum value, with less apparent N loss, thus maintaining the soil N balance in drip-irrigated cotton fields. This study helps to improve the utilization of water and N resources in cotton production. Future research on optimizing water and N management needs to more fully consider environmental pollution to achieve sustainable development of agricultural ecosystems.

Switching to Intravitreal Brolucizumab after Ranibizumab or Aflibercept Using Treat and Extend Regimen for Neovascular Age-Related Macular Degeneration in Japanese Patients: 1-Year Results and Factors Associated with Treatment Responsiveness.

Objective: To purpose of this study was to retrospectively evaluate the 1-year outcomes and factors associated with the treatment responsiveness of switching to intravitreal brolucizumab (IVBR) for neovascular age-related macular degeneration (nAMD) in Japanese patients refractory to ranibizumab or aflibercept using a treat and extend (TAE) regimen. Methods: A total of 48 eyes of 47 nAMD patients were switched to IVBR, and 36 eyes of 35 patients (27 males and 8 females) underwent 1-year treatment after the switch. Results: The rate of dry macula was significantly higher 12 months after the switch to IVBR (p < 0.001), with a significant decrease in the mean central macular thickness (CMT) and the mean central choroidal thickness (CCT) (p < 0.01 and p < 0.01, respectively). The injection interval was significantly extended from 7.0 ± 1.7 weeks to 10.3 ± 2.5 weeks 12 months after the switch (p < 0.001). In the multivariate analysis, a smaller number of prior anti-VEGF injections (p = 0.025; odds ratio: 0.947; 95% confidence interval: 0.903-0.994) and a pre-switching CCT of less than 250 µm (p = 0.023; odds ratio: 0.099; 95% confidence interval: 0.013-0.731) were associated with the good response group. Conclusions: These results suggest that IVBR may suppress disease activity and prolong the injection interval by switching for AMD patients with an insufficient response to treatment with ranibizumab and aflibercept.

Deucravacitinib in Plaque Psoriasis: 4-Year Safety and Efficacy Results From the Phase 3 POETYK PSO-1, PSO-2, and LTE Trials

Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was superior to placebo and apremilast in the phase 3 POETYK PSO-1 and PSO-2 trials in moderate to severe plaque psoriasis. Upon trial completion, patients could enroll in the ongoing POETYK long-term extension (LTE) trial. Here, deucravacitinib safety and efficacy are reported through 4 years. Methods: PSO-1/PSO-2 randomized patients 1:2:1 to placebo, deucravacitinib 6 mg QD, or apremilast 30 mg BID. At Week 52, patients in the LTE received open-label deucravacitinib 6 mg QD. Safety was evaluated in patients receiving ≥1 deucravacitinib dose. Exposure-adjusted incidence rate (EAIR) per 100 person-years (PY) was used to assess adverse events (AEs). Efficacy outcomes included PASI 75, PASI 90, and sPGA 0/1 and were analyzed using mNRI in LTE patients receiving continuous deucravacitinib from Day 1 of the parent trials. Results: 1519 patients received ≥1 deucravacitinib dose; cumulative exposure was 4392.8 PY. EAIRs/100 PY were decreased/comparable from the 1- to 4-year cumulative period, respectively: AEs (229.2, 131.7), serious AEs (5.7, 5.0), deaths (0.2, 0.3), discontinuation due to AEs (4.4, 2.2), herpes zoster (0.8, 0.6), malignancies (1.0, 0.9), MACE (0.3, 0.3), and venous thromboembolism (0.2, 0.1). With continuous deucravacitinib treatment (n = 513), clinical response rates were maintained from Year 3 (PASI 75, 73.8% [95% CI, 69.6, 78.0]; PASI 90, 49.0% [95% CI, 44.4, 53.7]; sPGA 0/1, 55.2% [95% CI, 50.5, 59.9]) to Year 4 (PASI 75, 71.7% [95% CI, 67.0, 76.3]; PASI 90, 47.5% [95% CI, 42.6, 52.4]; sPGA 0/1, 57.2% [95% CI, 52.1, 62.2]) by mNRI. Conclusion: Deucravacitinib demonstrated durable efficacy with continuous treatment and a safety profile through 4 years consistent with that at 3 years, without new or long-term safety signals.

Long-term efficacy and safety of tofacitinib in patients with ulcerative colitis: 3-year results from a real-world study.

The efficacy and safety of tofacitinib for the treatment of refractory ulcerative colitis (UC) has been demonstrated in clinical trials. Although, a series of reports with real-world evidence of its short-term efficacy and safety profiles have already been published, reports of long-term real-world data have been limited. We aimed to show our 3-year evidence on the clinical use of tofacitinib for the treatment of UC, focusing on its efficacy and safety profiles. A retrospective observational study was conducted on patients who started tofacitinib for active refractory UC at our hospital. The primary outcome was the retention rate until 156 weeks after initiating tofacitinib. The secondary outcomes were short-term efficacy at 4, 8, and 12 weeks; long-term efficacy at 52, 104, and 156 weeks; prognostic factors related to the cumulative retention rate; loss of response; and safety profile, including adverse events. Forty-six patients who were able to be monitored for up to 156 weeks after tofacitinib initiation, were enrolled in this study. Continuation of tofacitinib was possible until 156 weeks in 54.3%, with > 50% response rates and > 40% remission rates. Among patients in whom response or remission was achieved and tofacitinib was deescalated after 8 weeks of induction treatment, 54.3% experienced relapse but were successfully rescued by and retained on reinduction treatment, except for 1 patient. No serious AEs were observed in the study. Tofacitinib is effective and safe as long-term treatment in a refractory cohort of UC patients in real-world clinical practice.

Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized phase 3 CLL14 study

AbstractIn the CLL14 study, patients with previously untreated chronic lymphocytic leukemia (CLL) and coexisting conditions were randomized to 12 cycles of venetoclax-obinutuzumab (Ven-Obi, n = 216) or chlorambucil-obinutuzumab (Clb-Obi, n = 216). Progression-free survival (PFS) was the primary end point. Key secondary end points included time-to-next-treatment (TTNT), rates of undetectable minimal residual disease (uMRD), overall survival (OS), and rates of adverse events. Patient reported outcomes of time until definitive deterioration (TUDD) in quality of life (QoL) were analyzed. At a median observation time of 76.4 months, PFS remained superior for Ven-Obi compared with Clb-Obi (median, 76.2 vs 36.4 months; hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.31-0.52; P < .0001). Likewise, TTNT was longer after Ven-Obi (6-year TTNT, 65.2% vs 37.1%; HR, 0.44; 95% CI, 0.33-0.58; P < .0001). In the Ven-Obi arm, presence of del(17p), unmutated immunoglobulin heavy-chain variable region, and lymph node size of ≥5 cm were independent prognostic factors for shorter PFS. The 6-year OS rate was 78.7% in the Ven-Obi and 69.2% in the Clb-Obi arm (HR, 0.69; 95% CI, 0.48-1.01; P = .052). A significantly longer TUDD in global health status/QoL was observed in the Ven-Obi than in the Clb-Obi arm (median, 82.1 vs 65.1 months; HR, 0.70; 95% CI, 0.51-0.97). Follow-up–adjusted second primary malignancies incidence rates were 2.3 and 1.4 per 1000 patient-months in the Ven-Obi and Clb-Obi arm, respectively. The sustained long-term survival and QoL benefits support the use of 1-year fixed-duration Ven-Obi in CLL. This trial was registered at www.ClinicalTrials.gov as #NCT02242942.