Maintenance Group Research Articles

Long-term efficacy and safety of enavogliflozin in Korean people with type 2 diabetes: A 52-week extension of a Phase 3 randomized controlled trial.

To evaluate the long-term safety and efficacy of enavogliflozin monotherapy (0.3 mg/day) in individuals with type 2 diabetes mellitus (T2DM). Following a 24-week randomized, double-blind treatment period with enavogliflozin 0.3 mg/day (n = 77) or placebo (n = 69), consenting participants received enavogliflozin 0.3 mg/day for an additional 28 weeks during an open-label extension (OLE) period. The safety and efficacy of enavogliflozin were assessed at Week 52. A total of 37 participants continued enavogliflozin (maintenance group), and 26 participants switched from placebo to enavogliflozin (switch group). No additional adverse drug reactions related to enavogliflozin were observed during the OLE period. At Week 52, glycated haemoglobin (HbA1c) and fasting plasma glucose were significantly lower than at the baseline, by 0.9% and 24.9 mg/dL, respectively, in the maintenance group (p < 0.0001 for both), and by 0.7% and 18.0 mg/dL, respectively, in the switch group (p < 0.0001 and p = 0.002). The proportions of participants reaching HbA1c 7.0%(53 mmol/mol) at Week 52 were 69.4% in the maintenance group and 65.4% in the switch group. A significant increase in urine glucose-to-creatinine ratio was observed at Week 52, by 84.9 g/g and 67.1 g/g in the maintenance and switch groups, respectively (p < 0.0001 for both). Body weight in both groups decreased significantly (p < 0.0001) from baseline to Week 52, by 3.5 kg and 3.8 kg in the maintenance and switch groups, respectively. Enavogliflozin 0.3 mg monotherapy provides long-term glycaemic control in T2DM and is safe and well tolerated during a 52-week treatment period.

A single-center, retrospective study-spring-evaluating the efficacy and safety of recombinant human vascular endothelial inhibitor combined with anti-PD-1 in elderly patients aged 80 and above with NSCLC.

To investigate the efficacy and safety of combining Recombinant Human Endostatin Injection (marketed as Endo) with anti-PD-1 in elderly patients aged 80 and above with non-small cell lung cancer (NSCLC). Retrospective analysis of 181 patients with NSCLC aged 80 and above treated in the Department of Respiratory and Critical Care Medicine at Chaohu Hospital, affiliated with Anhui Medical University, from June 2019 to January 2024. Patients who received at least one cycle of combined Endo with anti-PD-1 were included based on inclusion criteria. Clinical and pathological data were collected, including complete blood count, liver and kidney function, electrocardiogram, coagulation function, thyroid function, cardiac enzymes, and whole-body imaging. Adverse events were recorded with a final follow-up on January 25, 2024. The primary endpoints were progression-free survival (PFS) and overall survival (OS), with safety as a secondary endpoint. This study involved 14 elderly patients with NSCLC aged over 80. Median progression-free survival (mPFS) was 102 days, and median overall survival (mOS) was 311 days. Subgroup analyses based on treatment cycles showed a non-significant 441-day mPFS increase in the long-term group (≥6 cycles, 5 patients) compared to the short-term group (<6 cycles, 9 patients). However, the mOS in the long-term group significantly exceeded the short-term group by 141 days, with statistical significance (P=0.048). Further categorization revealed a 204-day shorter mPFS in the monotherapy maintenance group (Endo or Immunol) compared to the combination maintenance group (Endo combined with Immunol, 441 days). The mOS of the monotherapy maintenance group was longer (686 days) than the combination maintenance group (311 days), but no statistical significance (P= 0.710, 0.920). Throughout the treatment, 77 adverse events were recorded, mainly grade 1-2, with no new treatment-related reactions occurred. Overall, the safety of Endo combined with anti-PD-1 was considered good and manageable. The combination of Endo and anti-PD-1 could be an effective treatment choice for patients with NSCLC aged 80 and above.

Effect of desflurane anesthesia on flash visual evoked potential monitoring in patients undergoing spine surgery: study protocol for a randomized controlled trial

BackgroundFlash visual evoked potentials (FVEPs) are a reliable method for protecting visual function during spine surgery in prone position. However, the popularization and application of FVEPs remain limited due to the unclear influence of various anesthetics on FVEPs. Exploring the effects of anesthetic drugs on FVEP and establishing appropriate anesthesia maintenance methods are particularly important for promoting and applying FVEP. According to the conventional concept, inhaled narcotic drugs significantly affect the success of FVEP monitoring, FVEP extraction, and interpretation. Nonetheless, our previous study demonstrated that sevoflurane-propofol balanced anesthesia was a practicable regimen for FVEPs. Desflurane is widely used in general anesthesia for its rapid recovery properties. As the effect of desflurane on FVEP remains unclear, this trial will investigate the effect of different inhaled concentrations of desflurane anesthesia on amplitude of FVEPs during spine surgery, aiming to identify more feasible anesthesia schemes for the clinical application of FVEP.Methods/ designA total of 70 patients undergoing elective spinal surgery will be enrolled in this prospective, randomized controlled, open-label, patient-assessor-blinded, superiority trial and randomly assigned to the low inhaled concentration of desflurane group (LD group) maintained with desflurane-propofolremifentanil-balanced anesthesia or high inhaled concentration of desflurane group (HD group) maintained with desflurane-remifentanil anesthesia maintenance group at a ratio of 1:1. All patients will be monitored for intraoperative FVEPs, and the baseline will be measured half an hour after induction under total intravenous anesthesia (TIVA). After that, patients will receive 0.5 minimum alveolar concentration (MAC) of desflurane combined with propofol and remifentanil for anesthesia maintenance in the LD group, while 0.7–1.0 MAC of desflurane and remifentanil will be maintained in the HD group. The primary outcome is the N75-P100 amplitude 1 h after the induction of anesthesia. We intend to use the dual measure evaluation, dual data entry, and statistical analysis by double trained assessors to ensure the reliability and accuracy of the results.DiscussionThis randomized controlled trial aims to explore the superiority effect of low inhaled concentration of desflurane combined with propofolremifentanil-balanced anesthesia versus high inhaled concentration of desflurane combined with remifentanil anesthesia on amplitude of FVEPs. The study is meant to be published in a peer-reviewed journal and might guide the anesthetic regimen for FVEPs. The conclusion is expected to provide high-quality evidence for the effect of desflurane on FVEPs and aim to explore more feasible anesthesia schemes for the clinical application of FVEPs and visual function protection.Trial registrationThis study was registered on clinicaltrials.gov on July 15, 2022. ClinicalTrials.gov Identifier: NCT05465330.

Impact of rituximab maintenance on survival of patients with mantle cell lymphoma: A north Indian tertiary care center experience.

e19047 Background: Mantle cell lymphoma (MCL) is an aggressive variant of non-Hodgkin lymphoma. Indian data is scarce owing to its rarity in south-east Asia. Till now, studies have not shown overall survival benefit with rituximab maintenance (RM). Our study aims to assess if RM improves overall survival of MCL patients. Methods: We retrospectively analysed clinicopathological data of 90 transplant-ineligible MCL patients treated between January’2013-December’2023 at Institute Rotary Cancer Hospital - All India Institute of Medical Sciences, New Delhi, India. Rituximab-based induction chemotherapy was used in all patients as per institutional protocol. RM was used in twenty-eight (31.0%) patients due to financial constraints. Primary outcome was overall survival (OS). Secondary outcomes were event free survival (EFS) and factors affecting OS, EFS. OS was defined as time from treatment initiation to demise from any cause or last follow-up. EFS was defined as time from treatment initiation to disease progression or relapse or demise from any cause. Response was assessed by modified Cheson’s lymphoma response evaluation criteria. STATA 13.0 was used to assess survival by Kaplan-Meier analysis and log rank test. Factors affecting survival were assessed by multivariate analysis (Cox proportional hazards model) and expressed as adjusted hazard ratio (aHR). p value &lt; 0.05 defined statistical significance. Results: Median age was sixty years; male-female ratio 3:1. Thirty-five (39.0%) had one or more co-morbidities, 79(88.0%) generalised lymphadenopathy, 72(80.0%) extra-nodal involvement, 49(54.0%) B symptoms, 84(93.0%) advanced stage (III/IV), 49(54.0%) high risk MCL international prognostic index (MIPI). Clinical and tumor characteristics, response rates after initial induction were similar in both maintenance and non-maintenance groups. Overall, 52(58.0%) patients were alive with median follow-up of 63.0 months (inter-quartile range 37.0-90.0 months). Median OS was 37.5 months in non-maintenance group and did not reach in maintenance group. Estimated 1.0-, 2.0, 3.0-year OS were 100.0%, 91.0%, 81.0% vs 75.0%, 63.0%, 55.0% respectively in maintenance vs non-maintenance group. RM was significantly associated with better OS [aHR (95% confidence interval): 0.31 (0.13-0.75), p=0.01]. Advanced stage, Eastern Co-operative Oncology Group performance status (ECOG PS) ≥2 at presentation were also significant factors for poor OS. Median EFS was significantly lower in non-maintenance group [14.0 vs 42.5 months; aHR (95% confidence interval): 0.34 (0.18-0.64), p=0.001]. Advanced stage, anemia, high risk MIPI at presentation were also significant factors for poor EFS. Conclusions: This was the first study from south-east Asia demonstrating impact of rituximab maintenance in MCL. Rituximab maintenance significantly improved OS and EFS of MCL patients.

Plasma triglyceride is associated with the recurrence of atrial fibrillation after radiofrequency catheter ablation: A retrospective study.

The purpose of this study was to explore the association between triglycerides (TGs) and the risk of atrial fibrillation (AF) recurrence. Included were adult patients with AF who underwent radiofrequency catheter ablation in the Affiliated Changzhou Second People's Hospital of Nanjing Medical University. The enrolled patients were divided into theAF recurrence group and the sinus rhythm (SR) maintenance group. The univariate Cox regression analysis and Kaplan-Meier survival curve were performed estimate the association between TG and the risk of AF recurrence. Of the 402 patients, 79 (19.7%) experienced recurrence of AF after ablation. The TG level was significantly higher in the AF recurrence group than in the SR-maintaining group. Patients were grouped by quartile of TG levels, with Quartile 1 and Quartile 2 defined as the low concentration group, Quartile 3 as the moderate concentration group, and Quartile 4 as the high concentration group. Multivariate Cox regression analysis showed that the moderate concentration group (p = .02, hazard ratio [HR]: 2.331, 95% confidence interval [CI]: 1.141-4.762) and high concentration group (p = .007, HR: 2.873, 95% CI: 1.332-6.199) were associated with an increased risk of AF recurrence compared with the low concentration group. The median follow-up was 1.17 years, it is indicated that a higher risk of recurrent AF was observed in the moderate concentration and high concentration group (log-rank: χ2 = 7.540, p = .023). Our data suggest that an elevated TG level measured before catheter ablation is associated with an increased risk of AF recurrence.

Long-Term Maintenance of Normal Serum Vitamin B1 Levels Is Associated with Better Outcomes in Patients with Heart Failure.

Deficiency of vitamin B1 (VB1), an essential micronutrient, causes heart failure (HF). A recent randomized controlled trial failed to show any improvement in HF prognosis after short-term VB1 supplementation. In the current study, we investigated the efficacy of long-term maintenance of normal blood VB1 levels in preventing adverse outcomes in patients with HF.This study included 88 consecutive patients with HF who received guideline-directed medical therapy at Arida Municipal Hospital. The patients were divided into 3 groups: a control group with normal VB1 levels and no VB1 supplementation (normal group, n = 25), and those presenting with VB1 deficiency, who either required short-term VB1 supplementation (short-term supplementation group, n = 25), or long-term maintenance of normal blood VB1 levels (long-term maintenance group, n = 38). The time to the first appearance of composite outcomes, including cardiovascular death and hospitalization for HF, was compared between the 3 groups.VB1 deficiency was observed in 63 (72%) patients. The Kaplan-Meier curve showed that the long-term maintenance group had better outcomes than the other 2 groups. In the multivariate analysis, long-term maintenance of normal blood VB1 levels and age were independent predictors of composite outcomes.VB1 deficiency is frequently observed, and the long-term maintenance of normal blood VB1 levels may result in better outcomes in patients with HF. Our results suggest that the detection of VB1 deficiency and long-term restoration of VB1 levels may be part of the overall therapeutic strategy for HF.

Efficacy of chidamide maintenance therapy versus autologous stem cell transplantation versus observation as a post-remission choice in the survival of adult patients with peripheral T-cell lymphoma: Post hoc analysis of a prospective, multicenter, phase 2 study in China.

In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group ( P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 .

Hemodynamic changes in the prone position according to fluid loading after anaesthesia induction in patients undergoing lumbar spine surgery: a randomized, assessor-blind, prospective study

Introduction A change from the supine to prone position causes hemodynamic alterations. We aimed to evaluate the effect of fluid preloading in the supine position, the subsequent hemodynamic changes in the prone position and postoperative outcomes. Patients and methods This prospective, assessor-blind, randomized controlled trial was conducted between March and June 2023. Adults scheduled for elective orthopaedic lumbar surgery under general anaesthesia were enrolled. In total, 80 participants were randomly assigned to fluid maintenance (M) or loading (L) groups. Both groups were administered intravenous fluid at a rate of 2 ml/kg/h until surgical incision; Group L was loaded with an additional 5 ml/kg intravenous fluid for 10 min after anaesthesia induction. The primary outcome was incidence of hypotension before surgical incision. Secondary outcomes included differences in the mean blood pressure (mBP), heart rate, pleth variability index (PVi), stroke volume variation (SVV), pulse pressure variation (PPV), stroke volume index and cardiac index before surgical incision between the two groups. Additionally, postoperative complications until postoperative day 2 and postoperative hospital length of stay were investigated. Results Hypotension was prevalent in Group M before surgical incision and could be predicted by a baseline PVi >16. The mBP was significantly higher in Group L immediately after fluid loading. The PVi, SVV and PPV were lower in Group L after fluid loading, with continued differences at 2–3 time points for SVV and PPV. Other outcomes did not differ between the two groups. Conclusion Fluid loading after inducing general anaesthesia could reduce the occurrence of hypotension until surgical incision in patients scheduled for surgery in the prone position. Additionally, hypotension could be predicted in patients with a baseline PVi >16. Therefore, intravenous fluid loading is strongly recommended in patients with high baseline PVi to prevent hypotension after anaesthesia induction and in the prone position. Trial number KCT0008294 (date of registration: 16 March 2023)

The role of upfront lenalidomide maintenance for primary central nervous system lymphoma following first-line methotrexate treatment: A retrospective study.

Consolidation therapy improves the duration of response among patients with primary central nervous system lymphoma (PCNSL). Lenalidomide maintenance has shown encouraging results in older patients with PCNSL. Herein, we performed a retrospective, single-center analysis to evaluate the effect of lenalidomide maintenance on the duration of response in patients with newly-diagnosed PCNSL. Sixty-nine adult patients with PCNSL who achieved complete remission or partial remission (PR) after induction therapy were enrolled. The median age of patients was 58.0 years. The maintenance group (n = 35) received oral lenalidomide (25 mg/day) for 21 days, every 28 days for 24 months; the observation group did not undergo any further treatment. After a median follow-up of 32.6 months, the maintenance group experienced fewer relapse events. However, the median progression-free survival (PFS) was similar between groups (36.1 vs. 30.6 months; hazard ratio, 0.78; 95% confidence interval, 0.446). Lenalidomide maintenance significantly improved PFS and overall survival (OS) only among patients who experienced PR after induction. The median duration of lenalidomide maintenance was 18 months; lenalidomide was well tolerated and minimally impacted the quality of life. The present study was the first to evaluate lenalidomide maintenance as a frontline treatment among patients with PCNSL, PFS and OS did not improve, although the safety profile was satisfactory.

The joint maintenance operation selection and technician routing problem

Numerous studies have explored the challenge of optimizing maintenance grouping, aiming to efficiently manage maintenance resources and reduce costs associated with various maintenance opportunities. Maintenance grouping is even more important when the systems to maintain are geographically distributed because it significantly reduces travel costs. In this research, we tackle a novel problem that integrates condition-based maintenance with the selection of maintenance operations and technician routing. The problem involves the selection of machines requiring maintenance for each time period, determining the nature of required operations (based on the uncertain degradation state of the machines), selecting suitable technicians based on their skills and availability, and planning their routes. We formulate this problem as a mixed-integer program and propose a heuristic approach for its solution. Our method constructs a solution by iteratively adding maintenance operations to technician routes. To assess the method’s performance, we conduct experiments that evaluate both running times and solution quality.

Exploring the optimal indicator of short-term peridiagnosis weight dynamics to predict cancer survival: A multicentre cohort study.

Body weight and its changes have been associated with cancer outcomes. However, the associations of short-term peridiagnosis weight dynamics in standardized, clinically operational time frames with cancer survival remain largely unknown. This study aimed to screen for and evaluate the optimal indicator of short-term peridiagnosis weight dynamics to predict overall survival (OS) in patients with cancer. This multicentre cohort study prospectively collected data from 7460 patients pathologically diagnosed with cancer between 2013 and 2019. Body weight data were recorded 1month before, at the time of and 1month following diagnosis. By permuting different types (point value in kg, point height-adjusted value in kg/m2, absolute change in kg or relative change in percentage) and time frames (prediagnosis, postdiagnosis or peridiagnosis), we generated 12 different weight-related indicators and compared their prognostic performance using Harrell's C-index, integrated discrimination improvement, continuous net reclassification improvement and time-dependent C-index. We analysed associations of peridiagnosis relative weight change (RWC) with OS using restricted cubic spine (RCS), Kaplan-Meier analysis and multivariable-adjusted Cox regression models. The study enrolled 5012 males and 2448 females, with a median age of 59years. During a median follow-up of 37months, 1026 deaths occurred. Peridiagnosis (1month before diagnosis to 1month following diagnosis) RWC showed higher prognostic performance (Harrell's C-index=0.601, 95% confidence interval [CI]=[0.583, 0.619]) than other types of indicators including body mass index (BMI), absolute weight change, absolute BMI change, prediagnosis RWC and postdiagnosis RWC in the study population (all P<0.05). Time-dependent C-index analysis also indicated that peridiagnosis RWC was optimal for predicting OS. The multivariable-adjusted RCS analysis revealed an N-shaped non-linear association between peridiagnosis RWC and OS (PRWC<0.001, Pnon-linear<0.001). Univariate survival analysis showed that the peridiagnosis RWC groups could represent distinct mortality risk stratifications (P<0.001). Multivariable survival analysis showed that, compared with the maintenance group (weight change<5%), the significant (gain >10%, hazard ratio [HR]=0.530, 95% CI=[0.413, 0.680]) and moderate (gain 5-10%, HR=0.588, 95% CI=[0.422, 0.819]) weight gain groups were both associated with improved OS. In contrast, the moderate (loss 5-10%, HR=1.219, 95% CI=[1.029, 1.443]) and significant (loss >10%, HR=1.280, 95% CI=[1.095, 1.497]) weight loss groups were both associated with poorer OS. The prognostic performance of peridiagnosis RWC is superior to other weight-related indicators in patients with cancer. The findings underscore the importance of expanding the surveillance of body weight from at diagnosis to both past and future, and conducting it withinclinically operational time frames, in order to identify and intervene with patients who are at risk of weight change-related premature deaths.

An integrated framework of preventive maintenance and task scheduling for repairable multi-unit systems

Preventive maintenance and task scheduling are both crucial activities in industrial practice. Although they are interdependent and mutually influential, most existing studies typically analyze them separately. In this paper, an integrated framework of preventive maintenance planning and task scheduling is explored. On one hand, while most scholars focus on the system as a whole in scheduling studies, we further take into account the degradation and maintenance of multiple units during the task scheduling process. On the other hand, instead of only using "direct replacement" as the main maintenance method, we further consider the repairability of the unit by incorporating imperfect maintenance effects into the maintenance modeling. Additionally, the lifecycle partitioning method is proposed to analyze the maintenance groups for multiple units at the completion of scheduling tasks and their corresponding probabilities. Based on this foundation, an integrated decision model is established with the preventive maintenance threshold and scheduling task sequence as decision variables to minimize the total weighted expected completion time. Finally, a novel genetic algorithm based on hybrid encoding is proposed, and the effectiveness of integrated decision-making was validated using a practical example.

Risk of post-operative bleeding after dentoalveolar surgery in patients taking anticoagulants: a cohort study using the common data model

This retrospective study aimed to determine risk factors associated with post-operative bleeding after dentoalveolar surgery in patients taking anticoagulants. Patients taking anticoagulants who were planned to undergo periodontal flap operation, tooth extraction or implant surgery were included. Patients were divided into two subgroups according to the maintenance of anticoagulants following medical consultation: (1) maintenance group and (2) discontinuation group. The analysed patient-related factors included systemic diseases, maintenance of anticoagulants and types of anticoagulant. Intra- and post-operative treatment-related factors, haemostatic methods and post-operative bleeding were collected for statistical analyses. There were 35 post-operative bleeding complications (6.5%) in the 537 included patients: 21 (8.6%) in maintenance group and 14 (4.8%) in discontinuation group. The type of anticoagulant (p = 0.037), tooth extraction combined with bone grafting (p = 0.016) and type of implant surgery (p = 0.032) were significantly related to the post-operative bleeding rate. In the maintenance group, atrial fibrillation [odds ratio (OR) = 6.051] and vitamin K inhibitors (OR = 3.679) were associated with a significantly higher bleeding risk. From this result, it can be inferred that the decision to continue anticoagulants should be made carefully based on the types of anticoagulant and the characteristics of dentoalveolar surgeries performed: extraction with bone grafting, multiple implantations and involvement of maxillary arch.

Efficacy of programmed cell death 1 inhibitor maintenance after chimeric antigen receptor T cells in patients with relapsed/refractory B-cell non-Hodgkin-lymphoma.

Chimeric antigen receptor (CAR)-T cells obtained long-term durability in about 30% to 40% of relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL). Maintenance therapy after CAR-T is necessary, and PD1 inhibitor is one of the important maintenance therapy options. A total of 173 r/r B-NHL patients treated with PD1 inhibitor maintenance following CD19/22 CAR-T therapy alone or combined with autologous hematopoietic stem cell transplantation (ASCT) from March 2019 to July 2022 were assessed for eligibility for two trials. There were 81 patients on PD1 inhibitor maintenance therapy. In the CD19/22 CAR-T therapy trial, the PD1 inhibitor maintenance group indicated superior objective response rate (ORR) (82.9% vs 60%; P = 0.04) and 2-year progression-free survival (PFS) (59.8% vs 21.3%; P = 0.001) than the non-maintenance group. The estimated 2-year overall survival (OS) was comparable in the two groups (60.1% vs 45.1%; P = 0.112). No difference was observed in the peak expansion levels of CD19 CAR-T and CD22 CAR-T between the two groups. The persistence time of CD19 and CD22 CAR-T in the PD1 inhibitor maintenance group was longer than that in the non-maintenance group. In the CD19/22 CAR-T therapy combined with ASCT trial, no significant differences in ORR (81.4% vs 84.8%; P = 0.67), 2-year PFS (72.3% vs 74.9%; P = 0.73), and 2-year OS (84.1% vs 80.7%; P = 0.79) were observed between non-maintenance and PD1 inhibitor maintenance therapy groups. The peak expansion levels and duration of CD19 and CD22 CAR-T were not statistically different between the two groups. During maintenance treatment with PD1 inhibitor, all adverse events were manageable. In the multivariable analyses, type and R3m were independent predictive factors influencing the OS of r/r B-NHL with PD1 inhibitor maintenance after CAR-T therapy. PD1 inhibitor maintenance following CD19/22 CAR-T therapy obtained superior response and survival in r/r B-NHL, but not in the trial of CD19/22 CAR-T cell therapy combined with ASCT.

Summary of Failure Conditions Recorded in Selected Helicopters Operated by Army Air Corps

This paper has been drawn up for the Air Operations Group and the Technical Maintenance Group of the 56th Air Force Base in Inowrocław (Poland). Its primary purpose is to compare the frequency of failure conditions and their impact on the safety of flights performed on Mi-24 and W-3PL helicopters. Special attention has been paid to the values of flight parameters recorded and any anomalies identified. The data were analyzed using the "Objective Record Analysis" software, with two aspects taken into consideration. The first aspect – failure conditions which do not affect flight safety, i.e. when the crew exceeded the permissible flight parameters for a given exercise, an interference took place, a calculation error occurred in the system or the equipment became uncalibrated. A total of 534 failure states were singled out, with 18% of them caused by the human factor. The remaining 82% occurred due to interference and errors in the recording system or due to an incorrect flight parameter recording process (with this factor remaining beyond the control of the flight crew or maintenance personnel). The second aspect focused on failure conditions having an impact on flight safety, i.e. when the crew exceeded the aircraft's operating envelope or damage to the aircraft's systems and components occurred. 1,075 states have been recorded, with safety violations caused by exceeding the aircraft’s operating limits accounting for 5% of them. Damage to aircraft systems and components was the root cause of the 95% of the failures (with emergency landings required in 6 cases). It was shown that 80% of the failure conditions studied occurred on the Mi-24, with the number of missions performed on this particular type being nearly twice as high as on the W-3PL. Analysis of the years to which the available data was related (2012-2016) has led to the conclusion that the number of flights performed and the number of failure conditions was on an increase. However, the share of failure conditions in the total number of flights decreased. Authors 1 and 2 serve in the 56th Air Force Base and were granted permission to access and publish the data presented in this paper.

Longitudinal BMI change and outcomes in Chronic Obstructive Pulmonary Disease: a nationwide population-based cohort study

BackgroundThe association between longitudinal body mass index (BMI) change and clinical outcomes in patients with chronic obstructive pulmonary disease (COPD) has not fully investigated.MethodsThis retrospective cohort study included 116,463 COPD patients aged ≥ 40, with at least two health examinations, one within 2 years before and another within 3 years after COPD diagnosis (January 1, 2014, to December 31, 2019). Associations between BMI percentage change with all-cause mortality, primary endpoint, and initial severe exacerbation were assessed.ResultsBMI decreased > 5% in 14,728 (12.6%), while maintained in 80,689 (69.2%), and increased > 5% in 21,046 (18.1%) after COPD diagnosis. Compared to maintenance group, adjusted hazard ratio (aHR) for all-cause mortality was 1.70 in BMI decrease group (95% CI:1.61, 1.79) and 1.13 in BMI increase group (95% CI:1.07, 1.20). In subgroup analysis, decrease in BMI showed a stronger effect on mortality as baseline BMI was lower, while an increase in BMI was related to an increase in mortality only in obese COPD patients with aHRs of 1.18 (95% CI: 1.03, 1.36). The aHRs for the risk of severe exacerbation (BMI decrease group and increase group vs. maintenance group) were 1.30 (95% CI:1.24, 1.35) and 1.12 (95% CI:1.07, 1.16), respectively.ConclusionsA decrease in BMI was associated with an increased risk of all-cause mortality in a dose-dependent manner in patients with COPD. This was most significant in underweight patients. Regular monitoring for weight loss might be an important component for COPD management.

Abstract 3824: Efficacy of trastuzumab in combination with capecitabine and cisplatin vs 5-FU and cisplatin therapy for Korean patients with HER2-positive advanced gastric cancer Health Insurance Review and Assessment service (HIRA) data retrospective analysis

Abstract The combinations of oral fluoropyrimidines and cisplatin such as capecitabine and cisplatin (XP) or 5-FU and cisplatin (FP) are regarded as a standard therapy against HER-2 positive advanced gastric cancer (AGC). Trastuzumab-XP(HXP) and trastuzumab-FP(HFP) is the most common regimen against AGC in Korea. The aim of the present study is to evaluate the effectiveness of trastuzumab-XP vs trastuzumab-FP. Patients with HER2-positive AGC were assigned to the trastuzumabXP or trastuzumabFP group. We then retrospectively compared the efficacy and safety between both groups. As a first-line chemotherapy, trastuzumab in combination with XP or FP was administered to 2,399 patients: 1,913 with HXP and 486 with HFP. In the HXP group vs HFP group, median progression-free survival (mPFS), and median overall survival (mOS) were 8.02 vs 6.08 months (p &amp;lt;0.0001) and 13.27 vs 9.89 months (p &amp;lt;0.0001). In HFP group, mPFS and mOS were 10.15 vs 5.36 months (p &amp;lt;0.0001) and 15.15 vs 8.90 months (p &amp;lt;0.0001) in comparison HFP-H maintenance to HFP group. In HXP group, mPFS and mOS were 10.64 vs 13.44 vs 5.03 months (p &amp;lt;0.0001) and 20.14 vs 22.18 vs 9.10 months (p &amp;lt;0.0001) in comparison HXP-H maintenance, HXP-HX maintenance, and HXP group. Trastuzumab in combination with XP and HX maintenance is a potential first-line therapeutic option for patients with HER2-positive AGC. Citation Format: hyun woo Lee, Jang-Hee Kim, Seok Yun Kang, Tae Jun Park, Yong Won Choi. Efficacy of trastuzumab in combination with capecitabine and cisplatin vs 5-FU and cisplatin therapy for Korean patients with HER2-positive advanced gastric cancer Health Insurance Review and Assessment service (HIRA) data retrospective analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3824.

Pragmatic Implementation of Online Obesity Treatment and Maintenance Interventions in Primary Care

Behavioral weight loss interventions have achieved success in primary care; however, to our knowledge, pragmatic implementation of a fully automated treatment that requires little researcher oversight has not been tested. Moreover, weight loss maintenance remains a challenge. To evaluate the long-term effectiveness of an automated, online, behavioral obesity treatment program (Rx Weight Loss [RxWL]) at 12 months (primary end point) and 24 months when delivered pragmatically in primary care and to compare the effectiveness of 3 weight loss maintenance approaches. This randomized clinical trial of RxWL, an online weight loss program, recruited patients from a Rhode Island primary care network with approximately 60 practices and 100 physicians. Eligible participants were primary care patients aged 18 to 75 years with overweight or obesity who were referred by their nurse care manager and enrolled between 2018 and 2020. All participants were included in the intention-to-treat analysis, whereas only those who engaged with maintenance intervention were included in the per-protocol analysis. Data were analyzed from August 2022 to September 2023. All participants were offered the same 3-month weight loss program, with randomization to one of three 9-month maintenance programs: control intervention (monthly online newsletters), monthly intervention (9 monthly video lessons and 1 week of self-monitoring per month), or refresher intervention (an introductory session and two 4-week periods of lessons and self-monitoring at 7 and 10 months). The primary outcome was weight change at 12 months using height and weight data collected from electronic medical records through 24 months. Among the 540 participants (mean [SD] age, 52.8 [13.4] years; 384 females [71.1%]) in the intention-to-treat analysis, mean estimated 3-month weight loss was 3.60 (95% CI, -4.32 to -2.88) kg. At the 12-month primary end point, the amount of weight regained in the monthly (0.37 [95% CI, -0.06 to 0.81] kg) and refresher (0.45 [95% CI, 0.27 to 0.87] kg) maintenance groups was significantly less than that in the newsletter control maintenance group (1.28 [95% CI, 0.85 to 1.71] kg; P = .004). The difference in weight regain between the monthly and refresher maintenance groups was not statistically significant. This pattern persisted at 24 months. In the per-protocol analysis of 253 participants, mean weight loss at the end of the initial 3-month intervention was 6.19 (95% CI, -7.25 to -5.13) kg. Similarly, at 12 months there was less weight regain in the monthly (0.61 kg) and refresher (0.96 kg) maintenance groups than in the newsletter control maintenance group (1.86 kg). Results of this randomized clinical trial indicate that pragmatic implementation of a 12-month automated, online, behavioral obesity treatment that includes 9 months of active maintenance produces clinically significant weight loss over 2 years in primary care patients with overweight or obesity. These findings underscore the importance of providing ongoing maintenance intervention to prevent weight regain. ClinicalTrials.gov Identifier: NCT03488212.

A 52-week efficacy and safety study of enavogliflozin versus dapagliflozin as an add-on to metformin in patients with type 2 diabetes mellitus: ENHANCE-M extension study.

To evaluate the long-term safety and efficacy of enavogliflozin 0.3 mg/day added to metformin in patients with type 2 diabetes mellitus. After 24 weeks of a randomized, double-blind treatment period with enavogliflozin 0.3 mg/day (n = 101) or dapagliflozin 10 mg/day (n = 99) added to metformin, all patients received enavogliflozin 0.3 mg/day plus metformin for an additional 28 weeks during the open-label extension period. Eighty-two patients continued enavogliflozin (maintenance group), and 77 were switched from dapagliflozin to enavogliflozin (switch group). All adverse drug reactions (ADR) were mild in severity. In the maintenance group, ADRs (cystitis and vaginal infection) were reported in two patients (2.44%) during 52 weeks. In the switch group, ADR (hypoglycaemia) was reported in one patient (1.30%) during a 28-week open-label extension period. At week 52, glycated haemoglobin and fasting plasma glucose were significantly lower than at the baseline, by 0.85% and 29.08 mg/dl, respectively, in the maintenance group (p < .0001 for both), and by 0.81% and 32.77 mg/dl, respectively, in the switch group (p < .0001 for both). At week 52, 68.92% of patients from the maintenance group and 64.29% from the switch group achieved glycated haemoglobin <7%. A significant increase in the urine glucose-creatinine ratio was observed at week 52, by 58.81 g/g and 63.77 g/g in the maintenance and switch groups, respectively (p < .0001). Enavogliflozin added to metformin was tolerated well for up to 52 weeks and provided continual glycaemic control in type 2 diabetes mellitus, along with a significant increase in the urine glucose-creatinine ratio.

Determinants of the operational performance of community-managed handpumps in rural Mozambique: An analysis of five years of cross-sectional sustainability assessments

Improving rural water supply sustainability in sub-Saharan Africa remains a major challenge. This study analysed five-years of cross-sectional sustainability check data collected annually between 2011 and 2016 (except 2015) to investigate factors influencing the operational performance of community-managed handpumps in rural Mozambique. Logistic and negative binomial regression was performed using multiple outcome measures of functionality, reliability and continuity. Average marginal effects (AMEs) were estimated to assess the effects of the predictors and mediation analysis was conducted to examine the role of women's participation.Higher levels of handpump performance were associated with financial records quality and update frequency, water committees with spare parts in stock, and committee annual revenue. The AME of high quality or recently updated financial records for non-functionality was estimated to be −0.40 (95% confidence interval [CI], −0.56 to −0.25), which is interpreted as a 40% lower probability of a water point being non-functional compared to the reference group. Water committees with a spare part stock exhibited a preventive effect on both non-functionality and breakdowns in the past 12 months, reducing their probability by 10% (AME, 95% CI, −0.17 to −0.03) and by 18% (AME, 95% CI, −0.30 to −0.05), respectively. Annual committee revenue up to 2,000 MZN (57 USD) reduced the probability of breakdowns by 25% (AME, 95% CI, −0.45 to 0.05). Handpumps were 10% (AME, 95% CI, 0.03 to 0.17) more likely to be non-functional when women were in the committee management positions. Conversely, female maintenance group members were associated with reduced breakdowns in the multivariate regression analysis (odds ratio, 0.48; 95% CI, 0.24 to 0.95).Increasing outreach of post-construction support on capacity building for water committees, particularly on user fee collection, maintaining financial records, replenishing spare parts, and increased participation of women in the maintenance group, may contribute to greater sustainability of rural water points.