Ahsan M. Arozullah

BACKGROUND: Pneumonia is a common postoperative complication associated with substantial morbidity and mortality. OBJECTIVE: To develop and validate a preoperative risk index for predicting postoperative pneumonia. DESIGN: Prospective cohort study with outcome assessment based on chart review. SETTING: 100 Veterans Affairs Medical Centers performing major surgery. PATIENTS: The risk index was developed by using data on 160 805 patients undergoing major noncardiac surgery between 1 September 1997 and 31 August 1999 and was validated by using data on 155 266 patients undergoing surgery between 1 September 1995 and 31 August 1997. Patients with preoperative pneumonia, ventilator dependence, and pneumonia that developed after postoperative respiratory failure were excluded. MEASUREMENTS: Postoperative pneumonia was defined by using the Centers for Disease Control and Prevention definition of nosocomial pneumonia. RESULTS: A total of 2466 patients (1.5%) developed pneumonia, and the 30-day postoperative mortality rate was 21%. A postoperative pneumonia risk index was developed that included type of surgery (abdominal aortic aneurysm repair, thoracic, upper abdominal, neck, vascular, and neurosurgery), age, functional status, weight loss, chronic obstructive pulmonary disease, general anesthesia, impaired sensorium, cerebral vascular accident, blood urea nitrogen level, transfusion, emergency surgery, long-term steroid use, smoking, and alcohol use. Patients were divided into five risk classes by using risk index scores. Pneumonia rates were 0.2% among those with 0 to 15 risk points, 1.2% for those with 16 to 25 risk points, 4.0% for those with 26 to 40 risk points, 9.4% for those with 41 to 55 risk points, and 15.3% for those with more than 55 risk points. The C-statistic was 0.805 for the development cohort and 0.817 for the validation cohort. CONCLUSIONS: The postoperative pneumonia risk index identifies patients at risk for postoperative pneumonia and may be useful in guiding perioperative respiratory care.

OBJECTIVE: To develop and validate a preoperative risk index for predicting postoperative respiratory failure (PRF). SUMMARY BACKGROUND DATA: Respiratory failure is an important postoperative complication. METHOD: Based on a prospective cohort study, cases from 44 Veterans Affairs Medical Centers (n = 81,719) were used to develop the models. Cases from 132 Veterans Affairs Medical Centers (n = 99,390) were used as a validation sample. PRF was defined as mechanical ventilation for more than 48 hours after surgery or reintubation and mechanical ventilation after postoperative extubation. Ventilator-dependent, comatose, do not resuscitate, and female patients were excluded. RESULTS: PRF developed in 2,746 patients (3.4%). The respiratory failure risk index was developed from a simplified logistic regression model and included abdominal aortic aneurysm repair, thoracic surgery, neurosurgery, upper abdominal surgery, peripheral vascular surgery, neck surgery, emergency surgery, albumin level less than 30 g/L, blood urea nitrogen level more than 30 mg/dL, dependent functional status, chronic obstructive pulmonary disease, and age. CONCLUSIONS: The respiratory failure risk index is a validated model for identifying patients at risk for developing PRF and may be useful for guiding perioperative respiratory care.

There is an urgent need for first-line treatment options for patients with human epidermal growth factor receptor 2 (HER2)-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. Claudin-18 isoform 2 (CLDN18.2) is expressed in normal gastric cells and maintained in malignant G/GEJ adenocarcinoma cells. GLOW (closed enrollment), a global, double-blind, phase 3 study, examined zolbetuximab, a monoclonal antibody that targets CLDN18.2, plus capecitabine and oxaliplatin (CAPOX) as first-line treatment for CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. Patients (n = 507) were randomized 1:1 (block sizes of two) to zolbetuximab plus CAPOX or placebo plus CAPOX. GLOW met the primary endpoint of progression-free survival (median, 8.21 months versus 6.80 months with zolbetuximab versus placebo; hazard ratio (HR) = 0.687; 95% confidence interval (CI), 0.544-0.866; P = 0.0007) and key secondary endpoint of overall survival (median, 14.39 months versus 12.16 months; HR = 0.771; 95% CI, 0.615-0.965; P = 0.0118). Grade ≥3 treatment-emergent adverse events were similar with zolbetuximab (72.8%) and placebo (69.9%). Zolbetuximab plus CAPOX represents a potential new first-line therapy for patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. ClinicalTrials.gov identifier: NCT03653507 .