Oncolytic HSV-1 G207 Immunovirotherapy for Pediatric High-Grade Gliomas.

BACKGROUND: Outcomes in children and adolescents with recurrent or progressive high-grade glioma are poor, with a historical median overall survival of 5.6 months. Pediatric high-grade gliomas are largely immunologically silent or "cold," with few tumor-infiltrating lymphocytes. Preclinically, pediatric brain tumors are highly sensitive to oncolytic virotherapy with genetically engineered herpes simplex virus type 1 (HSV-1) G207, which lacks genes essential for replication in normal brain tissue. METHODS: We conducted a phase 1 trial of G207, which used a 3+3 design with four dose cohorts of children and adolescents with biopsy-confirmed recurrent or progressive supratentorial brain tumors. Patients underwent stereotactic placement of up to four intratumoral catheters. The following day, they received G207 (107 or 108 plaque-forming units) by controlled-rate infusion over a period of 6 hours. Cohorts 3 and 4 received radiation (5 Gy) to the gross tumor volume within 24 hours after G207 administration. Viral shedding from saliva, conjunctiva, and blood was assessed by culture and polymerase-chain-reaction assay. Matched pre- and post-treatment tissue samples were examined for tumor-infiltrating lymphocytes by immunohistologic analysis. RESULTS: Twelve patients 7 to 18 years of age with high-grade glioma received G207. No dose-limiting toxic effects or serious adverse events were attributed to G207 by the investigators. Twenty grade 1 adverse events were possibly related to G207. No virus shedding was detected. Radiographic, neuropathological, or clinical responses were seen in 11 patients. The median overall survival was 12.2 months (95% confidence interval, 8.0 to 16.4); as of June 5, 2020, a total of 4 of 11 patients were still alive 18 months after G207 treatment. G207 markedly increased the number of tumor-infiltrating lymphocytes. CONCLUSIONS: Intratumoral G207 alone and with radiation had an acceptable adverse-event profile with evidence of responses in patients with recurrent or progressive pediatric high-grade glioma. G207 converted immunologically "cold" tumors to "hot." (Supported by the Food and Drug Administration and others; ClinicalTrials.gov number, NCT02457845.).

Computed Tomography-Measured Psoas Muscle Density as a Predictive Factor for Hypophosphatemia Associated With Refeeding.

BACKGROUND: Initiation of parenteral nutrition (PN) after a period of starvation can be complicated by refeeding syndrome (RFS). RFS is associated with electrolyte abnormalities including hypomagnesemia, hyponatremia, and hypophosphatemia. Risk factors include recent weight loss, low body mass index, and electrolyte deficiencies; however, these associations are not strong. We hypothesized that a validated measure of nutrition risk, computed tomography (CT)-measured psoas muscle density, can be used to predict the development of hypophosphatemia associated with RFS. METHODS: A retrospective analysis of surgical patients initiated on PN with an abdominal CT scan within the past 3 months was conducted. CT-measured psoas muscle density was assessed as a predictive variable for the development of electrolyte abnormalities. Daily electrolyte and clinical outcome measures were recorded. RESULTS: One hundred nine patients were stratified based on Hounsfield unit average calculation (HUAC). The lowest 25th percentile of patients had HUAC <25. Low HUAC was associated with a significant percent decrease in phosphate levels from baseline to PN day 3 (P < .01) and significant difference in serum phosphate value on PN day 3 (P < .01). The low muscle density quartile also experienced longer days on the mechanical ventilator (P = .01) compared with patients with a higher psoas muscle density. CONCLUSION: Psoas muscle density predicted the development of hypophosphatemia in patients initiated on PN. This measurement may aid in identifying patients at highest risk of experiencing RFS. A mean psoas HU <25 may prompt additional precautions, including additional phosphate replacement and slower initiation of PN.

Continuous glucose monitoring identifies relationship between optimized glycemic control and post-discharge acute care facility needs.

OBJECTIVE: Hyperglycemia is an independent risk factor in hospitalized patients for adverse outcomes, even if patients are not diabetic. We used continuous glucose monitoring to evaluate whether glycemic control (hyperglycemia) in the first 72 h after an intensive care admission was associated with the need for admission to a post discharge long-term medical facility. RESULTS: We enrolled 59 coronary artery bypass grafting patients. Poor glycemic control was defined as greater than 33% of continuous glucose monitoring values < 70 and > 180 mg/dL (group 1); and then these patients were reevaluated with a less strict definition of poor glycemic control with greater than 25% of continuous glucose values < 70 and > 180 mg/dL (group 2). In group 1 4/10 (40.0%) whose glucose was not well controlled went to an extended care post discharge facility as opposed to 6/49 (12.2%) that were well controlled. In reevaluation as group 2, 5/14 (35.7%) whose glucose was not well controlled went to an extended care post discharge facility as opposed to 5/45 (11.1%) who were well controlled. Admission to a post discharge facility was increased in patients with poor glycemic control p = 0.045 and p = 0.042 for group 1 and group 2, and with odds ratios of 4.8 (95% CI 1.0-22.5) and 4.4 (95% CI 1.0-19.4), respectively.

Management outcomes of diverticulitis and colitis in patients with active cancer.

BACKGROUND: Little is reported in the literature on management strategies and outcomes in patients with an active cancer diagnosis who undergo emergent general surgery. The purpose of this study is to evaluate preoperative risk factors in both operative and non-operative management, as well as to describe the outcomes of colonic emergencies within a cancer patient population. METHODS: A single institution cancer database was reviewed retrospectively to identify patients with an active cancer diagnosis who had an emergency general surgery consult placed for an acute colonic pathology. RESULTS: A total of 87 patients were included. Among these, 38 patients underwent operative and 49 underwent nonoperative management. There was a 71% rate of postoperative complications in the operative group; these patients were also more likely to require intensive care unit admission (P < .001), die during their hospitalization (P = .003), have a greater 30-day mortality (P = .001) and were less likely to be discharged to home (P < .001). No patients in the nonoperative group required admission to the intensive care unit, 3 of the 49 (6%) died during their hospitalization, and 75% of nonoperative patients were discharged to home. CONCLUSION: When clinically appropriate, patients with active cancer who present with an acute colonic emergency can undergo nonoperative management safely. In contrast, patients undergoing operative management have a substantial risk of morbidity and mortality.

A retrospective analysis on patients at high-risk for obstructive sleep apnea undergoing ear, nose, and throat surgeries.

Background: Obstructive sleep apnea (OSA) may be related to episodes of oxygen de-saturation, hypercapnia, cardiovascular dysfunction, cor-pulmonale, and pulmonary hypertension. STOP-BANG is an acronym for eight specific questions used to assess the likelihood of OSA. If the individual exhibits three or more of these indicators, he/she should be considered to be at high risk for OSA complications. Therefore, the decision of proceeding with inpatient versus outpatient ENT surgery still remains controversial. The primary objective of the study was to identify and correlate desaturation (SPO2 <90%) episodes and risk factors. Methods: We conducted a single-center retrospective study between October 1, 2011 and August 31, 2014 in order to identify postoperative complications during the first 24 hours that justify postoperative monitoring and hospital admission. A total of 292 subjects were included for data analysis. Patients were divided into two groups based on the number of OSA risk factors: group A with 3-4 risk factors (n = 166), and group B with ≥5 risk factors (n = 126). The following information was collected: demographics, ASA, preoperative STOP-BANG score, length of surgery, intraoperative complications, opioid consumption, post anesthesia care unit (PACU) and overall length of stay, supplemental oxygen requirement, oxygen desaturation, and postoperative opioid consumption. Results: No statistically significant difference was found when comparing demographic variables between both groups. All STOP-BANG variables showed statistical significance. PACU and inpatient variables were similar among both groups, with the exception of length of hospital stay (longer stay in group B when compared to group A [p = 0.003]). Desaturation differences between both groups during PACU were statistically significant (p = 0.008). A post-hoc analysis showed a 0% incidence of overall desaturation in the group with three STOP-BANG indicators. Conclusions: Our retrospective analysis concluded that patients diagnosed with three STOP-BANG risk factors did not experience postoperative complications and hospital admission was not justified. Level of Evidence: 4.