Long-term Outcomes with Spinal versus General Anesthesia for Hip Fracture Surgery: A Randomized Trial.

BACKGROUND: The effects of spinal versus general anesthesia on long-term outcomes have not been well studied. This study tested the hypothesis that spinal anesthesia is associated with better long-term survival and functional recovery than general anesthesia. METHODS: A prespecified analysis was conducted of long-term outcomes of a completed randomized superiority trial that compared spinal anesthesia versus general anesthesia for hip fracture repair. Participants included previously ambulatory patients 50 yr of age or older at 46 U.S. and Canadian hospitals. Patients were randomized 1:1 to spinal or general anesthesia, stratified by sex, fracture type, and study site. Outcome assessors and investigators involved in the data analysis were masked to the treatment arm. Outcomes included survival at up to 365 days after randomization (primary); recovery of ambulation among 365-day survivors; and composite endpoints for death or new inability to ambulate and death or new nursing home residence at 365 days. Patients were included in the analysis as randomized. RESULTS: A total of 1,600 patients were enrolled between February 12, 2016, and February 18, 2021; 795 were assigned to spinal anesthesia, and 805 were assigned to general anesthesia. Among 1,599 patients who underwent surgery, vital status information at or beyond the final study interview (conducted at approximately 365 days after randomization) was available for 1,427 (89.2%). Survival did not differ by treatment arm; at 365 days after randomization, there were 98 deaths in patients assigned to spinal anesthesia versus 92 deaths in patients assigned to general anesthesia (hazard ratio, 1.08; 95% CI, 0.81 to 1.44, P = 0.59). Recovery of ambulation among patients who survived a year did not differ by type of anesthesia (adjusted odds ratio for spinal vs. general, 0.87; 95% CI, 0.67 to 1.14; P = 0.31). Other outcomes did not differ by treatment arm. CONCLUSIONS: Long-term outcomes were similar with spinal versus general anesthesia.

The snapshot audit methodology: design, implementation and analysis of prospective observational cohort studies in surgery.

PURPOSE: For some surgical conditionns and scientific questions, the "real world" effectiveness of surgical patient care may be better explored using a multi-institutional time-bound observational cohort assessment approach (termed a "snapshot audit") than by retrospective review of administrative datasets or by prospective randomized control trials. We discuss when this might be the case, and present the key features of developing, deploying, and assessing snapshot audit outcomes data. METHODS: A narrative review of snapshot audit methodology was generated using the Scale for the Assessment of Narrative Review Articles (SANRA) guideline. Manuscripts were selected from domains including: audit design and deployment, statistical analysis, surgical therapy and technique, surgical outcomes, diagnostic testing, critical care management, concomitant non-surgical disease, implementation science, and guideline compliance. RESULTS: Snapshot audits all conform to a similar structure: being time-bound, non-interventional, and multi-institutional. A successful diverse steering committee will leverage expertise that includes clinical care and data science, coupled with librarian services. Pre-published protocols (with specified aims and analyses) greatly helps site recruitment. Mentored trainee involvement at collaborating sites should be encouraged through manuscript contributorship. Current funding principally flows from medical professional organizations. CONCLUSION: The snapshot audit approach to assessing current care provides insights into care delivery, outcomes, and guideline compliance while generating testable hypotheses.

Use of Vasoactive Medications after Cardiac Surgery in the United States.

Rationale: Patients undergoing cardiac surgery often require vasopressor or inotropic ("vasoactive") medications, but patterns of postoperative use are not well described.Objectives: This study aimed to describe vasoactive medication administration throughout hospitalization for cardiac surgery, to identify patient- and hospital-level factors associated with postoperative use, and to quantify variation in treatment patterns among hospitals.Methods: Retrospective study using the Premier Healthcare Database. The cohort included adult patients who underwent coronary artery bypass grafting or open valve repair or replacement (or in combination) from January 1, 2016, to June 30, 2018. Primary outcome was receipt of vasoactive medication(s) on the first postoperative day (POD1). We identified patient- and hospital-level factors associated with receipt of vasoactive medications using multilevel mixed-effects logistic regression modeling. We calculated adjusted median odds ratios to determine the extent to which receipt of vasoactive medications on POD1 was determined by each hospital, then calculated quotients of Akaike Information Criteria to compare the relative contributions of patient and hospital characteristics and individual hospitals with observed variation.Results: Among 104,963 adults in 294 hospitals, 95,992 (92.2%) received vasoactive medication(s) during hospitalization; 30,851 (29.7%) received treatment on POD1, most commonly norepinephrine (n = 11,427, 37.0%). A median of 29.0% (range, 0.0-94.4%) of patients in each hospital received vasoactive drug(s) on POD1. After adjustment, hospital of admission was associated with twofold increased odds of receipt of any vasoactive medication on POD1 (adjusted median odds ratio, 2.07; 95% confidence interval, 1.93-2.21). Admitting hospital contributed more to observed variation in POD1 vasoactive medication use than patient or hospital characteristics (quotients of Akaike Information Criteria 0.58, 0.44, and <0.001, respectively).Conclusions: Nearly all cardiac surgical patients receive vasoactive medications during hospitalization; however, only one-third receive treatment on POD1, with significant variability by institution. Further research is needed to understand the causes of variability across hospitals and whether these differences are associated with outcomes.

Tuberous sclerosis complex: diagnostic challenges, presenting symptoms, and commonly missed signs.

OBJECTIVE: To describe presenting symptoms and signs according to age group in a cohort of 243 patients with tuberous sclerosis complex (TSC) and identify earlier symptoms and signs that did not lead to immediate diagnosis. PATIENTS AND METHODS: We performed a retrospective chart review for 278 patients with TSC who were examined at Children's Hospital Boston in Massachusetts and at the Herscot Center for Tuberous Sclerosis Complex, Massachusetts General Hospital. The presenting symptom or sign was the first symptom or sign to cause suspicion for TSC and lead to diagnosis. Missed symptoms or signs were those that were documented in the patient's chart but did not immediately lead to diagnosis. RESULTS: There were 243 patients for whom there were sufficient data for inclusion in this study. Patients were diagnosed with TSC at ages ranging from birth to 73 years. The average age at diagnosis was 7.5 years. Of the patients, 81% were diagnosed before the age of 10. Diagnosis during adolescence and adulthood was not uncommon. The most common presenting symptoms and signs included new onset of seizures, history of seizures, infantile spasms, family history of TSC, cardiac rhabdomyomas, and hypopigmented macules. Of the patients, 39% reported missed symptoms or signs of TSC, most commonly seizures (including infantile spasms) and dermatologic features. CONCLUSIONS: Many patients had symptoms or signs of TSC that did not lead to immediate diagnosis. Clinicians should be aware of the myriad potential presenting symptoms and signs of TSC. Early diagnosis may reduce morbidity and mortality.

Anti-GD(2) with an FC point mutation reduces complement fixation and decreases antibody-induced allodynia.

Monoclonal antibodies against GD(2) ganglioside, such as ch14.18, the human-mouse chimeric antibody, have been shown to be effective for the treatment of neuroblastoma. However, treatment is associated with generalized, relatively opiate-resistant pain. We investigated if a point mutation in ch14.18 antibody (hu14.18K332A) to limit complement-dependent cytotoxicity (CDC) would ameliorate the pain behavior, while preserving antibody-dependent cellular cytotoxicity (ADCC). In vitro, CDC and ADCC were measured using europium-TDA assay. In vivo, allodynia was evaluated by measuring thresholds to von Frey filaments applied to the hindpaws after injection of either ch14.18 or hu14.18K332 into wild type rats or rats with deficient complement factor 6. Other rats were pretreated with complement factor C5a receptor antagonist and tested following ch14.18 injection. The mutation reduces the antibody's ability to activate complement, while maintaining its ADCC capabilities. Injection of hu14.18K322 (1 or 3mg/kg) produced faster resolving allodynia than that engendered by ch14.18 (1mg/kg). Injection of ch14.18 (1mg/kg) into rats with C6 complement deficiency further reduced antibody-induced allodynia, while pre-treatment with complement factor C5a receptor antagonist completely abolished ch14.18-induced allodynia. These findings showed that mutant hu14.18 K322 elicited less allodynia than ch14.18 and that ch14.18-elicited allodynia is due to activation of the complement cascade: in part, to formation of membrane attack complex, but more importantly to release of complement factor C5a. Development of immunotherapeutic agents with decreased complement-dependent lysis while maintaining cellular cytotoxicity may offer treatment options with reduced adverse side effects, thereby allowing dose escalation of therapeutic antibodies.