Improving Cognitive Function Through High-Intensity Interval Training in Breast Cancer Patients Undergoing Chemotherapy: Protocol for a Randomized Controlled Trial.

BACKGROUND: More than 75% of patients with breast cancer treated with chemotherapy experience cognitive impairments (eg, memory and attention problems), commonly known as chemo-brain. Exercise, especially aerobic high-intensity interval training (HIIT), is associated with better cognitive function in healthy populations. However, clinical trials testing the impact of exercise interventions on chemotherapy-induced cognitive decline in patients with cancer are lacking, and the mechanisms through which exercise could improve cognitive function are unclear. OBJECTIVE: The objective of the Improving Cognitive Function Through High-Intensity Interval Training in Breast Cancer Patients Undergoing Chemotherapy trial is to examine the effects of HIIT on cognitive function in patients with breast cancer undergoing chemotherapy. METHODS: This 2-arm, single-center, pilot randomized controlled trial will randomize 50 patients with breast cancer undergoing chemotherapy to HIIT or attention control. The HIIT group will perform a supervised 16-week, thrice-weekly intervention, with each session including a 5-minute warm-up at 10% maximal power output (POmax), 10 sets of alternating 1-minute high-intensity (90% POmax) and 1-minute recovery (10% POmax) intervals, and a 5-minute cooldown (10% POmax). The attention control group will receive a stretching program with no exercise components and be asked to maintain their exercise levels for 16 weeks. The primary outcomes of the study are executive function and memory measured using the National Institutes of Health toolbox and resting-state connectivity and diffusion tensor imaging microstructure evaluated using magnetic resonance imaging. The secondary and tertiary outcomes include cardiorespiratory fitness, body composition, physical fitness, and psychosocial health. The study has been approved by the institutional review board of the Dana-Farber Cancer Institute (20-222). RESULTS: The trial was funded in January 2019, with recruitment started in June 2021. As of May 2022, a total of 4 patients have consented and been randomized (n=2, 50% to exercise; n=1, 25% to control; and n=1, 25% nonrandomized). Trial completion is expected in January 2024. CONCLUSIONS: This first-of-its-kind study incorporates a novel exercise intervention (ie, HIIT) and comprehensive cognitive measures. If positive, our findings will establish the pilot efficacy of HIIT on chemotherapy-induced cognitive function in patients with breast cancer, providing the foundation for future larger phase-II and phase-III trials to confirm the findings and potentially establish HIIT as a standard of care for women undergoing chemotherapy for breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT04724499; https://clinicaltrials.gov/ct2/show/NCT04724499. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39740.

Back to the Future: Whole Blood Resuscitation of the Severely Injured Trauma Patient.

ABSTRACT: Following advances in blood typing and storage, whole blood transfusion became available for the treatment of casualties during World War I. While substantially utilized during World War II and the Korean War, whole blood transfusion declined during the Vietnam War as civilian centers transitioned to blood component therapies. Little evidence supported this shift, and recent conflicts in Iraq and Afghanistan have renewed interest in military and civilian applications of whole blood transfusion. Within the past two decades, civilian trauma centers have begun to study transfusion protocols based upon cold-stored, low anti-A/B titer type O whole blood for the treatment of severely injured civilian trauma patients. Early data suggests equivalent or improved resuscitation and hemostatic markers with whole blood transfusion when compared to balanced blood component therapy. Additional studies are taking place to define the optimal way to utilize low-titer type O whole blood in both prehospital and trauma center resuscitation of bleeding patients.

Proteomic Analysis of Infants Undergoing Cardiopulmonary Bypass Using Contemporary Ontological Tools.

BACKGROUND: Cardiopulmonary bypass (CPB) is essential for the repair of many congenital cardiac defects in infants but is associated with significant derangements in hemostasis and systemic inflammation. As a result, hemorrhagic complications and thrombosis are major challenges in the management of children requiring CPB or extracorporeal membrane oxygenation. Conventional clinical laboratory tests capture individual hemostatic derangements (low platelets, elevated fibrinogen) but fail to describe the complex, overlapping interactions among the various components of coagulation, including cellular interactions, contact activation, fibrinolysis, and inflammation. Given recent advances in analytic tools for identifying protein-protein interactions in the plasma proteome, we hypothesized that an unbiased proteomic analysis would help identify networks of interacting proteins for further investigation in pediatric CPB. MATERIALS AND METHODS: Infants up to 1 y of age were enrolled. Plasma samples were collected at 0, 1, 4, and 24 h after CPB. Mass spectrometry was used to identify proteins undergoing changes in concentration after CPB, and STRING and ToppGene tools were used to identify biological networks. Two-dimensional difference gel electrophoresis identified changes in protein concentrations. Inflammatory markers were assessed by enzyme-linked immunosorbent assay at the same time points. RESULTS: Ten infants with cardiac anomalies requiring surgery and CPB were enrolled; no major complications were recorded (median age, 127.5 d; interquartile range, 181.25 d). Using two-dimensional difference gel electrophoresis, >1400 individual protein spots were observed, and 89 proteins demonstrated change in concentration >30% with P < 0.02 when comparing 1, 4, or 24 h to baseline. Among protein spots with significant changes in concentration after CPB, 29 were identified with mass spectrometry (33%). In our interrogation of functional associations among these differentially expressed proteins, our results were dominated by the acute phase response, coagulation, and cell signaling functional categories. Among cytokines analyzed by enzyme-linked immunosorbent assay, IL-2, IL-8, and IL-10 were elevated at 4 h but normalized by 24 h, whereas IL-6 was persistently elevated. CONCLUSIONS: Infants manifest a robust response to CPB that includes overlapping, complex pathways. Further investigation of interactions among immune, coagulation, and cell signaling systems may lead to novel therapeutics or biomarkers useful in the management of infants requiring CPB.

Impact of specific postoperative complications on the outcomes of emergency general surgery patients.

BACKGROUND: The relative contribution of specific postoperative complications on mortality after emergency operations has not been previously described. Identifying specific contributors to postoperative mortality following acute care surgery will allow for significant improvement in the care of these patients. METHODS: Patients from the 2005 to 2011 American College of Surgeons' National Surgical Quality Improvement Program database who underwent emergency operation by a general surgeon for one of seven diagnoses (gallbladder disease, gastroduodenal ulcer disease, intestinal ischemia, intestinal obstruction, intestinal perforation, diverticulitis, and abdominal wall hernia) were analyzed. Postoperative complications (pneumonia, myocardial infarction, incisional surgical site infection, organ/space surgical site infection, thromboembolic process, urinary tract infection, stroke, or major bleeding) were chosen based on surgical outcome measures monitored by national quality improvement initiatives and regulatory bodies. Regression techniques were used to determine the independent association between these complications and 30-day mortality, after adjustment for an array of patient- and procedure-related variables. RESULTS: Emergency operations accounted for 14.6% of the approximately 1.2 million general surgery procedures that are included in American College of Surgeons' National Surgical Quality Improvement Program but for 53.5% of the 19,094 postoperative deaths. A total of 43,429 emergency general surgery patients were analyzed. Incisional surgical site infection had the highest incidence (6.7%). The second most common complication was pneumonia (5.7%). Stroke, major bleeding, myocardial infarction, and pneumonia exhibited the strongest associations with postoperative death. CONCLUSION: Given its disproportionate contribution to surgical mortality, emergency surgery represents an ideal focus for quality improvement. Of the potential postoperative targets for quality improvement, pneumonia, myocardial infarction, stroke, and major bleeding have the strongest associations with subsequent mortality. Since pneumonia is both relatively common after emergency surgery and strongly associated with postoperative death, it should receive priority as a target for surgical quality improvement initiatives. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III.

Trials of nonoperative management exceeding 3 days are associated with increased morbidity in patients undergoing surgery for uncomplicated adhesive small bowel obstruction.

BACKGROUND: Controversy exists over how long trials of nonoperative management should be pursued in patients with uncomplicated adhesive small bowel obstructions (ASBOs) before deciding to proceed with surgery. The purpose of this study was to determine the effect of incremental delays in surgery on the 30-day postoperative outcomes of patients undergoing surgery for uncomplicated ASBO. METHODS: American College of Surgeons National Surgical Quality Improvement Program 2005-2011 data were used to identify patients with uncomplicated ASBO in whom a trial of nonoperative management was attempted. Multivariate logistic or linear regression model was created to determine the independent association between the length of preoperative hospitalization and 30-day postoperative outcomes after adjustment for patient- and procedure-related factors. RESULTS: A total of 9,297 patients were included in the study. The 30-day postoperative mortality and overall morbidity rates of the entire cohort were 4.4% and 29.6%, respectively. The median postoperative length of hospitalization was 7 days (interquartile range, 5-11 days). After risk adjustment, there was no association between preoperative length of hospitalization and 30-day postoperative mortality. In contrast, increased 30-day overall morbidity was observed in patients who received their operation after a preoperative length of hospitalization of 3 days compared with earlier in their hospitalization. Furthermore, an increased postoperative length of hospitalization was found in patients who were operated on after a preoperative length of hospitalization of 4 days. CONCLUSION: Trials of nonoperative management for uncomplicated ASBO exceeding 3 days are associated with increased morbidity and postoperative length of hospitalization. These trials should therefore generally not extend beyond this time point. LEVEL OF EVIDENCE: Therapeutic study, level IV.