Background

Obesity and several obesity-related co-morbidities are risk factors for severe COVID-19 disease. Because bariatric surgery successfully treats obesity-related conditions, we hypothesized that prior bariatric surgery may be associated with less severe COVID-19 disease.

Objectives

To examine the association between prior bariatric surgery and outcomes in patients with obesity admitted with COVID-19.

Setting

United States METHODS: The Vizient database was used to obtain demographic and outcomes data for adults with obesity admitted with COVID-19 from May 2020 to January 2021. Patients were divided into 2 groups: those with and those without prior bariatric surgery. The primary outcome was in-hospital mortality. Secondary outcomes were mortality by age, sex, race/ethnicity, and co-morbidity; intubation rate; hemodialysis rate; and length of stay. Because the database only provides aggregate data and not patient-level data, multivariate analysis could not be performed.

Results

Among the 124,699 patients with obesity admitted with COVID-19, 2,607 had previous bariatric surgery and 122,092 did not. The proportion of patients ≥65 years of age was higher in the non-bariatric surgery group (36.0% versus 27.6%, P < .0001). Compared with patients without prior bariatric surgery, patients with prior bariatric surgery had lower in-hospital mortality (7.8 versus 11.2%, P < .0001) and intubation rates (18.5% versus 23.6%, P = .0009). Hemodialysis rate (7.2% versus 6.9%, P = .5) and length of stay (8.8 versus 9.6 days, P = .8) were similar between groups. Mortality was significantly lower in the bariatric surgery group for patients 18-64 years of age (5.9% versus 7.4%, P = .01) and ≥65 years of age (12.9% versus 17.9%, P = .0006).

Conclusions

This retrospective cohort study found that inpatients with obesity and COVID-19 who had prior bariatric surgery had improved outcomes compared with a similar cohort without prior bariatric surgery. Further studies should examine mechanisms for the association between bariatric surgery and less severe COVID-19.

BACKGROUND AND PURPOSE The endocannabinoid 2-arachidonoylglycerol (2-AG) is degraded primarily by monoacylglycerol lipase (MGL). We compared peripheral antinociceptive effects of JZL184, a novel irreversible MGL inhibitor, with the reversible MGL-preferring inhibitor URB602 and exogenous 2-AG in rats. EXPERIMENTAL APPROACH Nociception in the formalin test was assessed in groups receiving dorsal paw injections of vehicle, JZL184 (0.001-300 µg), URB602 (0.001-600 µg), 2-AG (ED(50)), 2-AG + JZL184 (at their ED(50)), 2-AG + URB602 (at their ED(50)), AM251 (80 µg), AM251 + JZL184 (10 µg), AM630 (25 µg) or AM630 + JZL184 (10 µg). Effects of MGL inhibitors on endocannabinoid accumulation and on activities of endocannabinoid-metabolizing enzymes were assessed. KEY RESULTS Intra-paw administration of JZL184, URB602 and 2-AG suppressed early and late phases of formalin pain. JZL184 and URB602 acted through a common mechanism. JZL184 (ED(50) Phase 1: 0.06 ± 0.028; Phase 2: 0.03 ± 0.011 µg) produced greater antinociception than URB602 (ED(50) Phase 1: 120 ± 51.3; Phase 2: 66 ± 23.9 µg) or 2-AG. Both MGL inhibitors produced additive antinociceptive effects when combined with 2-AG. Antinociceptive effects of JZL184, like those of URB602, were blocked by cannabinoid receptor 1 (CB(1)) and cannabinoid receptor 2 (CB(2)) antagonists. JZL184 suppressed MGL but not fatty-acid amide hydrolase or N-arachidonoyl-phosphatidylethanolamine phospholipase D activities ex vivo. URB602 increased hind paw 2-AG without altering anandamide levels. CONCLUSIONS AND IMPLICATIONS MGL inhibitors suppressed formalin-induced pain through peripheral CB(1) and CB(2) receptor mechanisms. MGL inhibition increased paw skin 2-AG accumulation to mediate these effects. MGL represents a target for the treatment of inflammatory pain.

We report a 41-year-old woman presented with a 4-year history of an exuberant, erythematous tumor, with necrotic appearance of the right distal toe. The histopathology examination showed a nodular-ulcerative melanoma, with bone infiltration. Widespread metastases including the right ovary, peritoneum, and right breast were present. The patient was misdiagnosed for almost 4 years as having onychomycosis, ingrown nail and pyogenic granuloma.

Cells in injured and inflamed tissues produce a number of proalgesic lipid-derived mediators, which excite nociceptive neurons by activating selective G-protein-coupled receptors or ligand-gated ion channels. Recent work has shown that these proalgesic factors are counteracted by a distinct group of lipid molecules that lower nociceptor excitability and attenuate nociception in peripheral tissues. Analgesic lipid mediators include endogenous agonists of cannabinoid receptors (endocannabinoids), lipid-amide agonists of peroxisome proliferator-activated receptor-α, and products of oxidative metabolism of polyunsaturated fatty acids via cytochrome P450 and other enzyme pathways. Evidence indicates that these lipid messengers are produced and act at different stages of inflammation and the response to tissue injury, and may be part of a peripheral gating mechanism that regulates the access of nociceptive information to the spinal cord and the brain. Growing knowledge about this peripheral control system may be used to discover safer medicines for pain.

Bilateral olfactory bulbectomy (OBX) in rodents produces behavioral and neurochemical changes associated clinically with depression and schizophrenia. Most notably, OBX induces hyperlocomotion in response to the stress of exposure to a novel environment. We examined the role of the endocannabinoid system in regulating this locomotor response in OBX and sham-operated rats. In our study, OBX-induced hyperactivity was restricted to the first 3 min of the open field test, demonstrating the presence of novelty (0-3 min) and habituation (3-30 min) phases of the open field locomotor response. Levels of the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide were decreased in the ventral striatum, a brain region deafferented by OBX, whereas cannabinoid receptor densities were unaltered. In sham-operated rats, 2-AG levels in the ventral striatum were negatively correlated with distance traveled during the novelty phase. Thus, low levels of 2-AG are reflected in a hyperactive open field response. This correlation was not observed in OBX rats. Conversely, 2-AG levels in endocannabinoid-compromised OBX rats correlated with distance traveled during the habituation phase. In OBX rats, pharmacological blockade of cannabinoid CB(1) receptors with either AM251 (1 mg kg(-1) i.p.) or rimonabant (1 mg kg(-1) i.p.) increased distance traveled during the habituation phase. Thus, blockade of endocannabinoid signaling impairs habituation of the hyperlocomotor response in OBX, but not sham-operated, rats. By contrast, in sham-operated rats, effects of CB(1) antagonism were restricted to the novelty phase. These findings suggest that dysregulation in the endocannabinoid system, and 2-AG in particular, is implicated in the hyperactive locomotor response induced by OBX. Our studies suggest that drugs that enhance 2-AG signaling, such as 2-AG degradation inhibitors, might be useful in human brain disorders modeled by OBX.

As the coronavirus disease 2019 pandemic continues to impact hospital systems both in the United States and throughout the world, it is important to understand how the pandemic has impacted the volume of hospital admissions. Using the Vizient Inc (Chicago, IL) clinical databases, we analyzed inpatient hospital discharges from the general medicine service and its subspecialty services including cardiology, neonatology, pulmonary/critical care, oncology, psychiatry, and neurology between December 2019 and July 2020. We compared baseline discharge data to that of the first six months of the pandemic, from February to July 2020. We set the baseline as discharges by specialty from February 2019 through January 2020, averaged over the 12 months. Compared to baseline, by April 2020 the volume of general medicine hospital discharge was reduced by -20.2%, from 235,581 to 188,027 discharges. We found that while overall the number of discharges decreased from baseline, with a nadir in April 2020, pulmonary/critical care services had an increase in hospital discharge volume throughout the pandemic, from 7534 at baseline to 15,792 discharges in April. These findings are important for understanding health care use during the pandemic and ensuring proper allocation of resources and funding throughout the coronavirus disease 2019 pandemic.

Background

In March 2020, the Surgeon General recommended limiting elective procedures to prepare for the COVID-19 surge. We hypothesize a consequence of COVID-19 is reduced operative volume across the country. We aim to examine changes in volume of common gastrointestinal operations during COVID-19, including elective, urgent/emergent, and cancer operations. We also evaluate if hospitals with more COVID-19 admissions were most impacted.

Methods

The Vizient database was used to determine monthly operative volume from November 2019 to June 2020 for elective operations (hiatal hernia repairs, bariatric surgery), urgent operations (cholecystectomies, appendectomies, inguinal hernia repairs), and cancer operations (colectomies, gastrectomies, esophagectomies). COVID-19 admissions per hospital were also determined. November 2019-January 2020 was defined as "pre-COVID." The monthly reduction in volume from pre-COVID was calculated for each operation. The top quartile (25%) of hospitals with the most COVID admissions were also evaluated separately from hospitals with fewer COVID cases. Data were analyzed using analysis of variance.

Results

Data from 559 hospitals were analyzed. The volumes of all operations evaluated were significantly reduced during the pandemic except gastrectomies and esophagectomies for cancer. The greatest reduction in all operations was in April. In April, the volume of bariatric surgery reduced by 98% (P < 0.001), hiatal hernia repairs by 96% (P < 0.001), urgent cholecystectomies by 42% (P < 0.001), urgent inguinal hernia repairs by 40% (P < 0.001), urgent appendectomies by 24% (P < 0.001), and colectomies for cancer by 39% (P < 0.001). Hospitals with the most COVID-19 admissions had greater reductions in all operations than hospitals with fewer COVID cases.

Conclusions

The coronavirus pandemic led to a significant reduction in volume of all gastrointestinal operations evaluated except gastrectomies and esophagectomies. While elective, non-cancer operations were most affected, urgent and some cancer operations also declined significantly. As COVID-19 continues to surge, Americans may suffer continued limited access to surgical care and a significant operative backlog may be forthcoming.

Rationale

An endocannabinoid signaling system has not been identified in hamsters.

Objective

We examined the existence of an endocannabinoid signaling system in Syrian hamsters using neuroanatomical, biochemical, and behavioral pharmacological approaches.

Materials and methods

The distribution of cannabinoid receptors was mapped, and membrane fatty-acid amide hydrolase (FAAH) activity and levels of fatty-acid amides were measured in hamster brain. The impact of cannabinoid CB1 receptor blockade and inhibition of FAAH was evaluated in the elevated plus maze, rota-rod test, and models of unconditioned and conditioned social defeat.

Results

A characteristic heterogeneous distribution of cannabinoid receptors was detected in hamster brain using [3H]CP55,940 binding and autoradiography. The FAAH inhibitor URB597 inhibited FAAH activity (IC50 = 12.8 nM) and elevated levels of fatty-acid amides (N-palmitoyl ethanolamine and N-oleoyl ethanolamine) in hamster brain. Anandamide levels were not reliably altered. The cannabinoid agonist WIN55,212-2 (1- 10 mg/kg i.p.) induced CB1-mediated motor ataxia. Blockade of CB1 with rimonabant (5 mg/kg i.p.) induced anxiogenic-like behavior in the elevated plus maze. URB597 (0.1-0.3 mg/kg i.p.) induced CB1-mediated anxiolytic-like effects in the elevated plus maze, similar to the benzodiazepine diazepam (2 mg/kg i.p.). Diazepam (2-6 mg/kg i.p.) suppressed the expression, but not the acquisition, of conditioned defeat. By contrast, neither URB597 (0.3-3.0 mg/kg i.p.) nor rimonabant (5 mg/kg i.p.) altered unconditioned or conditioned social defeat or rota-rod performance.

Conclusions

Endocannabinoids engage functional CB1 receptors in hamster brain to suppress anxiety-like behavior and undergo enzymatic hydrolysis catalyzed by FAAH. Our results further suggest that neither unconditioned nor conditioned social defeat in the Syrian hamster is dependent upon cannabinoid CB1 receptor activation.

Introduction

The coronavirus disease 2019 (COVID-19) pandemic continues to spread globally and as of February 4, 2021, there are more than 26 million confirmed cases and more than 440,000 deaths in the United States (US). A top priority of the Centers for Disease Control and Prevention (CDC) is to identify risk factors for severe COVID-19 illness. The objective of this study was to analyze the characteristics and outcomes of COVID-19 adults who were managed in an outpatient setting compared to patients who required hospitalization at US academic centers.

Methods

Using the Vizient clinical database, Discharge records of adults with a diagnosis of COVID-19 between March 1, 2020 and January 31, 2021 were reviewed. Outcome measures included demographics, characteristics, rate of hospitalization, and mortality, and data were analyzed based on inpatient versus outpatient management.

Results

Among COVID-19 adults, 1,360,078 patients were managed in an outpatient setting while 545,635 patients required hospitalization. Compared to hospitalized COVID-19 adults, COVID-19 adults who were managed in an outpatient setting were more likely to be female (56.1% vs 47.5%, p <0.001), white (57.7% vs 54.8%, p <0.001), within younger age group of 18-50 years (p<0.001) and have lower rate of comorbidities. Mortality was significantly lower in outpatient group compared to hospitalized group (0.2% vs 12.2%, respectively, p <0.01%). For outpatient group, mortality increased with increasing age group: 0.02% (52 of 295,112) for patients 18-30 years and 1.2% (1,373 of 117,866) for patients >75 years. The rate of hospitalization was lowest for age group 18-30 years at 10.6% (35,607 of 330,719) and highest for age group >75 years at 56.1% (150,381 of 268,247).

Conclusion

This analysis of US academic centers showed that 28.6% of COVID-19 adults who sought care at one of the hospitals reporting data to the Vizient clinical database required in-patient treatment. The rate of hospitalization in our study was lowest for the youngest age group of 18-30 years and highest for age group >75 years. Beside older age, other factors associated with outpatient management included female gender, white race, and having commercial insurance.