Middlemore Hospital is a major public hospital in the suburb of Otahuhu, Auckland, New Zealand. The hospital has approximately 800 beds. There are 24 operating theatres across two sites.
To compare perioperative, oncological, and survival outcomes of total gastrectomy (TG) versus subtotal gastrectomy (SG) in patients with locally advanced distal diffuse gastric adenocarcinoma treated with perioperative 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) chemotherapy. Diffuse distal gastric cancer is characterized by infiltrative growth patterns and early nodal metastasis. Whilst radical resection remains the cornerstone of curative treatment, the optimal extent of surgery with TG or SG, remains debated. This international multicenter cohort study analyzed data from patients with histologically confirmed diffuse gastric adenocarcinoma, located > 5 cm from the gastroesophageal junction. Endpoints included surgical margin status, nodal yield, perioperative morbidity, recurrence patterns, time-to-recurrence (TTR), and overall survival (OS). Outcomes were compared using multivariate analyses. In total, 188 (39.0
BACKGROUND:Obinutuzumab, a glycoengineered type II anti-CD20 monoclonal antibody, induces potent B-cell depletion and is approved for the treatment of active lupus nephritis. Its efficacy and safety in patients with active systemic lupus erythematosus (SLE) are yet to be determined. METHODS:We conducted a phase 3, multicenter, double-blind, placebo-controlled trial involving adults with active SLE but without proliferative or membranous lupus nephritis who were receiving standard therapy. Patients were randomly assigned in a 1:1 ratio to receive obinutuzumab (1000 mg) or placebo on day 1 and weeks 2, 24, and 26. In the prespecified analysis, the primary end point at week 52 was a response on the SLE Responder Index 4 (SRI-4), defined by a reduction from baseline of at least 4 points in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, no worsening of disease as assessed by the British Isles Lupus Assessment Group (BILAG) 2004 index and Physician's Global Assessment, and no intercurrent events (i.e., major concomitant-therapy violation, receipt of rescue medication, or early discontinuation of trial participation due to death, lack of efficacy, or adverse events). RESULTS:Of 303 patients who underwent randomization, 151 were assigned to receive obinutuzumab and 152 to receive placebo. At week 52, an SRI-4 response was observed in 76.7% of the patients in the obinutuzumab group and in 53.5% of those in the placebo group (adjusted difference, 23.1 percentage points; 95% confidence interval [CI], 12.5 to 33.6; P<0.001). In an additional analysis whereby nonfatal intercurrent events did not affect response status, the respective percentages were 85.4% and 68.5% (adjusted difference, 16.8 percentage points; 95% CI, 7.1 to 26.4). Obinutuzumab was superior to placebo with respect to all key secondary end points: BILAG-based Composite Lupus Assessment response, sustained reduction in glucocorticoid dose, sustained SRI-4 response, SRI-6 response, and time to first BILAG-defined flare. Adverse events were reported in 88.7% of the patients in the obinutuzumab group and in 81.5% of those in the placebo group, and serious adverse events in 15.9% and 11.9%, respectively. One patient in the obinutuzumab group and 3 in the placebo group died during the double-blind period. CONCLUSIONS:Among adults with active SLE, treatment with obinutuzumab was superior to placebo with respect to the primary and all key secondary end points. (Funded by F. Hoffmann-La Roche; ALLEGORY ClinicalTrials.gov number, NCT04963296.).
Importance:Clesrovimab is a long-acting monoclonal antibody approved for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants who are born during or entering their first RSV season; data concerning clesrovimab from a second RSV season among children who remain at risk for severe disease are needed. Objective:To evaluate the safety and tolerability of clesrovimab (105 mg) vs palivizumab in RSV season 1 in infants at increased risk for severe RSV disease. Key secondary objectives include describing the safety of 210 mg of clesrovimab in RSV season 2 in children who remain at increased risk for severe RSV disease, clesrovimab pharmacokinetics, and the incidence of RSV-associated disease. Design, Setting, and Participants:SMART (MK-1654-007) was a randomized, partially masked, palivizumab-controlled, phase 3 clinical trial, conducted at 110 sites in 27 countries and territories between November 30, 2021, and November 20, 2025. The population constituted palivizumab-eligible infants, including those with prematurity, chronic lung disease of prematurity, or hemodynamically significant congenital heart disease. Interventions:Participants, randomized 1:1 and stratified by region and condition, received clesrovimab (105 mg) on day 1 followed by placebo on day 28 or monthly palivizumab (15 mg/kg) up to 5 doses (1 dose per month). Eligible infants received open-label clesrovimab (210 mg) before their second RSV season. Main Outcomes and Measures:The primary outcome was the observed proportions of participants experiencing adverse events (AEs) after clesrovimab or palivizumab in season 1. Results:Overall, 997 infants (500 [50.2%] male; median age, 2.6 [range, 0.0-12.0] months) received clesrovimab, 105 mg (n = 498) or palivizumab (n = 499) in season 1; 276 received clesrovimab, 210 mg open-label in season 2. In season 1, the proportions of participants experiencing AEs were comparable between treatment groups. In season 2, clesrovimab, 210 mg was well tolerated. Incidence rates of RSV-associated medically attended lower respiratory infection (MALRI) were comparable between clesrovimab and palivizumab (3.2% [95% CI, 1.8%-5.2%] and 3.4% [95% CI, 2.0%-5.6%], respectively) through day 150 in season 1; total RSV-associated MALRI incidence through day 180 after a 210-mg dose in season 2 was 7.3% (95% CI, 4.4%-11.4%). Conclusions and Relevance:In this randomized clinical trial, clesrovimab was well tolerated in infants at increased risk for severe RSV disease through 2 RSV seasons. These findings support the use of clesrovimab in children who remain at risk for severe RSV disease in their second RSV season. Trial Registration:ClinicalTrials.gov Identifier: NCT04938830.
BACKGROUND:Approximately 10% of hospitalized patients globally report a penicillin allergy, leading to inappropriate antibiotic prescribing and inferior healthcare outcomes. Evidence supporting the effectiveness and widespread implementation of inpatient penicillin direct oral challenge (DOC) is limited. METHODS:A prospective, multicenter, international type 2 hybrid effectiveness-implementation study was conducted in 40 hospitals across 8 countries between November 2022 and May 2025. Adult inpatients with a penicillin allergy underwent assessment using a digital penicillin allergy toolkit (National Antibiotic Allergy Network [NAAN] App). According to site clinical practice, participants received penicillin DOC (effectiveness intervention) or assessment only. Participating sites received bimonthly audit and feedback at least 3 months after site activation (implementation strategy). Observational data were used to emulate a target trial to examine secondary effectiveness outcomes, including antibiotic prescribing at 90 days in DOC versus non-DOC participants. The primary implementation outcome was adoption of the NAAN App within 6 months of site activation. RESULTS:Among 5121 participants assessed, 1573 (30.7%) underwent DOC, of which 1502 (95.5%) were delabeled. Of 71 (4.5%) participants with a positive DOC, 6 (0.4%) had a serious adverse event. Of 1852 inpatients in the target trial analysis, 892 underwent DOC and 960 underwent assessment only. Participants who underwent DOC were more likely to be prescribed penicillin (risk ratio [RR], 13.25 [95% confidence interval {CI}, 7.82-22.46]), and less likely to be prescribed World Health Organization (WHO) "Watch" or "Reserve" antibiotics (RR, 0.73 [95% CI, .60-.89]) at 90 days post evaluation. Within 6 months of site activation, 77 clinicians adopted the NAAN App. CONCLUSIONS:Multidisciplinary adoption of inpatient penicillin DOC was safe and significantly improved penicillin prescribing and reduced use of WHO restricted antibiotics.
BACKGROUND:The management of reproductive health in individuals with autoimmune rheumatic diseases (AIRDs) has evolved into a primary clinical priority. Wide variations in clinical practice and drug availability in the Asia-Pacific regions necessitate localized frameworks. These consensus statements, developed by the Asia Pacific League of Associations for Rheumatology (APLAR) Special Interest Group for Women's Health & Reproductive Issues in Rheumatic and Musculoskeletal Diseases, aim to bridge the gaps within the region, foster multidisciplinary collaboration, and address regional knowledge deficits. METHODS:An expert panel comprising 16 members of the 13 APLAR member nation organizations formulated 23 research questions using the PICO framework. A systematic review of English-language literature up to July 2025 was conducted across the MEDLINE, Scopus, Google Scholar, and Cochrane Library databases, supplemented by a manual search of journals from the APLAR regions. Evidence from the APLAR region was appraised using the GRADE system. A modified Delphi online voting process was employed to reach consensus, pre-defined as ≥ 75% agreement. RESULTS:The panel approved four overarching principles and 86 statements, organized into 16 broad categories. These statements cover all three phases of pregnancy in AIRDs, the safety of medications during pregnancy and lactation, contraception, assisted reproductive techniques, fertility preservation, and hormonal replacement therapy, covering both female and male aspects as relevant. CONCLUSION:In a field often lacking high-quality data, these consensus statements from APLAR provide expert opinion-based guidance to support clinical decision-making. It is envisaged that it will assist in educational and training purposes and help shape future research priorities.
