Impact of body mass index on surgical case durations in an academic medical center.

STUDY OBJECTIVE: To investigate the association between patient body mass index (BMI) and operating room duration. DESIGN: Retrospective cohort analysis. SETTING: Demographic data and anesthesia/surgical times for adult surgical patients at University of Virginia Health between August 2017 and February 2019 were collected and analyzed. PATIENTS: A total of 31,548 cases were included in the final analysis. 55% of patients were female, and 51% were classified as ASA Physical Status 2. The mean operating room (OR) duration was 144.2 min ± 112.7 (median = 118, IQR = 121). Orthopedic surgery (32%) was the most common surgery. MEASUREMENTS: Linear mixed effects models were used to examine whether procedure intervals differed across three BMI categories (BMI < 30, 30 ≤ BMI < 40, BMI ≥ 40), considering within-surgeon correlations. Surgical times were log-transformed to correct for positive skewness. MAIN RESULTS: The average time in the operating room was longer for patients with higher BMI (mean ± SD [median, IQR] = 139.5 ± 111.2 [113.0, IQR = 114], 150.2 ± 115.4 [125, IQR = 127], and 153.1 ± 111.1 [130, IQR = 134] for BMI < 30, 30 ≤ BMI < 40, and BMI ≥ 40), respectively. We found a 2% [95% CI = 1-3%] and 3% [95% CI = 1-5%] increase in OR time for 30 ≤ BMI < 40 and BMI ≥ 40, respectively, compared to BMI < 30, after controlling for within-surgeon correlations and covariates. The excess time was primarily determined by anesthesia times. CONCLUSION: In an academic hospital, patients with BMI ≥ 30 required more time in the operating room than patients with BMI < 30, when controlling for confounders. This information can be incorporated into modern-day OR scheduling software, potentially resulting in more accurate case duration estimates that reduce waiting and improve OR efficiency.

Abdominal Aortic Aneurysms (Etiology, Epidemiology, and Natural History).

Abdominal aortic aneurysm is a potentially lethal condition that is decreasing in frequency as tobacco use declines. The exact etiology remains unknown, but smoking and other perturbations seem to trigger an inflammatory state in the tunica media. Male sex and advanced age are clear demographic risk factors for the development of abdominal aortic aneurysms. The natural history of this disease varies, but screening remains vital as it is rarely diagnosed on physical examination, and elective repair (most commonly done endovascularly) offers significant morbidity and mortality advantages over emergent intervention for aortic rupture.

Glucosylceramide synthase maintains influenza virus entry and infection.

Influenza virus is an enveloped virus wrapped in a lipid bilayer derived from the host cell plasma membrane. Infection by influenza virus is dependent on these host cell lipids, which include sphingolipids. Here we examined the role of the sphingolipid, glucosylceramide, in influenza virus infection by knocking out the enzyme responsible for its synthesis, glucosylceramide synthase (UGCG). We observed diminished influenza virus infection in HEK 293 and A549 UGCG knockout cells and demonstrated that this is attributed to impaired viral entry. We also observed that entry mediated by the glycoproteins of other enveloped viruses that enter cells by endocytosis is also impaired in UGCG knockout cells, suggesting a broader role for UGCG in viral entry by endocytosis.

Glucosylceramidase Maintains Influenza Virus Infection by Regulating Endocytosis.

Influenza virus is an RNA virus encapsulated in a lipid bilayer derived from the host cell plasma membrane. Previous studies showed that influenza virus infection depends on cellular lipids, including the sphingolipids sphingomyelin and sphingosine. Here we examined the role of a third sphingolipid, glucosylceramide, in influenza virus infection following clustered regularly interspaced short palindromic repeats with Cas9 (CRISPR-Cas9)-mediated knockout (KO) of its metabolizing enzyme glucosylceramidase (GBA). After confirming GBA knockout of HEK 293 and A549 cells by both Western blotting and lipid mass spectrometry, we observed diminished infection in both KO cell lines by a PR8 (H1N1) green fluorescent protein (GFP) reporter virus. We further showed that the reduction in infection correlated with impaired influenza virus trafficking to late endosomes and hence with fusion and entry. To examine whether GBA is required for other enveloped viruses, we compared the results seen with entry mediated by the glycoproteins of Ebola virus, influenza virus, vesicular stomatitis virus (VSV), and measles virus in GBA knockout cells. Entry inhibition was relatively robust for Ebola virus and influenza virus, modest for VSV, and mild for measles virus, suggesting a greater role for viruses that enter cells by fusing with late endosomes. As the virus studies suggested a general role for GBA along the endocytic pathway, we tested that hypothesis and found that trafficking of epidermal growth factor (EGF) to late endosomes and degradation of its receptor were impaired in GBA knockout cells. Collectively, our findings suggest that GBA is critically important for endocytic trafficking of viruses as well as of cellular cargos, including growth factor receptors. Modulation of glucosylceramide levels may therefore represent a novel accompaniment to strategies to antagonize "late-penetrating" viruses, including influenza virus.IMPORTANCE Influenza virus is the pathogen responsible for the second largest pandemic in human history. A better understanding of how influenza virus enters host cells may lead to the development of more-efficacious therapies against emerging strains of the virus. Here we show that the glycosphingolipid metabolizing enzyme glucosylceramidase is required for optimal influenza virus trafficking to late endosomes and for consequent fusion, entry, and infection. We also provide evidence that promotion of influenza virus entry by glucosylceramidase extends to other endosome-entering viruses and is due to a general requirement for this enzyme, and hence for optimal levels of glucosylceramide, for efficient trafficking of endogenous cargos, such as the epidermal growth factor (EGF) receptor, along the endocytic pathway. This work therefore has implications for the basic process of endocytosis as well as for pathogenic processes, including virus entry and Gaucher disease.