Design and rationale of the CHILL phase II trial of hypothermia and neuromuscular blockade for acute respiratory distress syndrome.

The Cooling to Help Injured Lungs (CHILL) trial is an open label, two group, parallel design multicenter, randomized phase IIB clinical trial assessing the efficacy and safety of targeted temperature management with combined external cooling and neuromuscular blockade to block shivering in patients with early moderate-severe acute respiratory distress syndrome (ARDS). This report provides the background and rationale for the clinical trial and outlines the methods using the Consolidated Standards of Reporting Trials guidelines. Key design challenges include: [1] protocolizing important co-interventions; [2] incorporation of patients with COVID-19 as the cause of ARDS; [3] inability to blind the investigators; and [4] ability to obtain timely informed consent from patients or legally authorized representatives early in the disease process. Results of the Reevaluation of Systemic Early Neuromuscular Blockade (ROSE) trial informed the decision to mandate sedation and neuromuscular blockade only in the group assigned to therapeutic hypothermia and proceed without this mandate in the control group assigned to a usual temperature management protocol. Previous trials conducted in National Heart, Lung, and Blood Institute ARDS Clinical Trials (ARDSNet) and Prevention and Early Treatment of Acute Lung Injury (PETAL) Networks informed ventilator management, ventilation liberation and fluid management protocols. Since ARDS due to COVID-19 is a common cause of ARDS during pandemic surges and shares many features with ARDS from other causes, patients with ARDS due to COVID-19 are included. Finally, a stepwise approach to obtaining informed consent prior to documenting critical hypoxemia was adopted to facilitate enrollment and reduce the number of candidates excluded because eligibility time window expiration.

Remote patient monitoring to facilitate same-day discharge after laparoscopic sleeve gastrectomy: a pilot evaluation.

BACKGROUND: Limited hospital inpatient capacity, exacerbated by SARS-CoV-2 (COVID-19) and associated staffing shortages, has driven interest in converting surgeries historically done as inpatient procedures to same-day surgeries (SDS). Remote patient monitoring (RPM) has the potential to increase safety and confidence in SDS but has had mixed success in a bariatric population. OBJECTIVES: Assess the feasibility of and adherence to a protocol offering patients same-day laparoscopic sleeve gastrectomy (SG) supported by RPM with an updated wearable device. Secondary outcomes were readmissions, costs, adherence, and clinical alarm rates. SETTING: Academic, military tertiary referral center (United States). METHODS: A single-center, retrospective case control study of patients undergoing SG, comparing SDS with RPM to patients admitted to the hospital for SG during this time. Patients for SDS were selected by set inclusion/exclusion criteria and patient/surgeon preference, and perioperative management was standardized. RESULTS: Twenty patients were enrolled in the SDS group, then compared with 53 inpatients. Inpatients were older (46 versus 39, P = .006), but with no significant differences in sex, preoperative body mass index, or co-morbidities. RPM wearable and blood pressure adherence was found to be 97% and 80%, respectively. Readmission rates were similar (10% versus 7.5%, P > .05). RPM alarm rates were .5 (0-1.3) per patient for each 24-hour home monitoring period. SDS patients also demonstrated the potential for cost savings over inpatient SG, depending on the number of patients monitored per day as well as the healthcare setting. CONCLUSIONS: SG as SDS with RPM was a feasible approach. It should be evaluated in other surgical procedures and higher-risk patient populations.

Remote patient monitoring to facilitate same-day discharge following laparoscopic sleeve gastrectomy: a pilot evaluation

Background Limited hospital inpatient capacity, exacerbated by SARS-CoV-2 (COVID-19) and associated staffing shortages, has driven interest in converting surgeries historically done as inpatient procedures to same-day surgeries (SDS). Remote patient monitoring (RPM) has the potential increase safety and confidence in SDS but has had mixed success in a bariatric population. Objective Assess the feasibility of, and adherence to, a protocol offering patients same-day laparoscopic sleeve gastrectomy (SG) supported by RPM with an updated wearable device. Secondary outcomes were readmissions, costs, adherence, and clinical alarm rates. Setting Academic, military tertiary referral center (United States) Methods A single center, retrospective case control study of patients undergoing laparoscopic sleeve gastrectomy, comparing SDS with RPM to patients admitted to the hospital for SG during this time. Patients for SDS were selected by set inclusion/exclusion criteria and patient/surgeon preference, and perioperative management was standardized. Results Twenty patients were enrolled into the SDS group, then compared to 53 inpatients. Inpatients were older (46 vs 39, p=0.006), but with no significant differences in sex, pre-operative BMI or comorbidities. RPM wearable and blood pressure adherence was found to be 97 and 80 %, respectively. Readmission rates were similar (10 vs 7.5 %, p > 0.05). RPM alarm rates were 0.5 (0 – 1.3) per patient for each 24-hour home monitoring period. SDS patients also demonstrated the potential for cost savings over inpatient SG, depending on the number of patients monitored per day, as well as the healthcare setting. Conclusion SG as SDS with RPM was a feasible approach. It should be evaluated in other surgical procedures and higher risk patient populations.

Single-Center Experience With the Seraph-100® Microbind® Affinity Blood Filter in Patients With SARS-CoV-2 Infection and Septic Shock at a Military Treatment Facility.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) infection is characterized by a dysregulated inflammatory response, which may result in severe hemodynamic instability and septic shock. The Seraph-100® Microbind® Affinity Blood Filter is a commercially available extracorporeal pathogen absorbent device with the ability to bind pathogens and cytokines present within the blood. Our study aimed to evaluate the efficacy of the Seraph-100® for patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and septic shock. MATERIALS AND METHODS: A retrospective review was performed to evaluate the use of the Seraph-100® blood filter at a Single Center tertiary-care facility at Brooke Army Medical Center from 2020 to 2021. Nine patients (11 treatments) were completed with the Seraph-100® blood filter in patients with SARS-CoV-2 infection and septic shock. The Seraph-100® blood filter was used in combination with continuous renal replacement therapy and slow low-efficiency dialysis or directly in parallel with the extracorporeal membrane oxygenation circuit. RESULTS: Within this cohort, there was a statistically significant improvement in the following clinical parameters comparing values to before and after treatment with the Seraph-100® blood filter: Mean arterial pressure (mmHg) (64.2 ± 2.36 vs. 76.2 ± 2.68; P < .001), heart rate (beats per minute) (128 ± 6.6 vs. 100.3 ± 6.07; P < .001), administered fraction of oxygen (%) (74.4 ± 10.58 vs. 60.3 ± 10.35; P < .001), serum lactate (mmol/L) (6.14 ± 1.25 vs. 2.8 ± 1.14; P = .0095), and pH (7.29 ± 0.03 vs. 7.39 ± 0.04; P = .0203). There were statistically significant improvements in vasopressor requirements: norepinephrine (mcg/min) (36.3 ± 4.74 vs. 8.3 ± 3.92; P < .001), vasopressin (units/min) (0.04 ± 0.004 vs. 0.02 ± 0.003; P < .001), dobutamine (mcg/kg/min) (2.3 ± 1.00 vs. 0.2 ± 0.75; P = .006) and angiotensin II (ng/kg/min) (34.5 ± 6.4 vs. 3.3 ± 5.26; P < .001). CONCLUSIONS: The use of the Seraph-100® blood filter was associated with statistically and clinically significant improvements in hemodynamic parameters and decreased vasopressor requirements in patients with septic shock and SARS-CoV-2 infection.

Financial and Clinical Impact of Virtual Care During the COVID-19 Pandemic: Difference-in-Differences Analysis.

BACKGROUND: Virtual care (VC) and remote patient monitoring programs were deployed widely during the COVID-19 pandemic. Deployments were heterogeneous and evolved as the pandemic progressed, complicating subsequent attempts to quantify their impact. The unique arrangement of the US Military Health System (MHS) enabled direct comparison between facilities that did and did not implement a standardized VC program. The VC program enrolled patients symptomatic for COVID-19 or at risk for severe disease. Patients' vital signs were continuously monitored at home with a wearable device (Current Health). A central team monitored vital signs and conducted daily or twice-daily reviews (the nurse-to-patient ratio was 1:30). OBJECTIVE: Our goal was to describe the operational model of a VC program for COVID-19, evaluate its financial impact, and detail its clinical outcomes. METHODS: This was a retrospective difference-in-differences (DiD) evaluation that compared 8 military treatment facilities (MTFs) with and 39 MTFs without a VC program. Tricare Prime beneficiaries diagnosed with COVID-19 (Medicare Severity Diagnosis Related Group 177 or International Classification of Diseases-10 codes U07.1/07.2) who were eligible for care within the MHS and aged 21 years and or older between December 2020 and December 2021 were included. Primary outcomes were length of stay and associated cost savings; secondary outcomes were escalation to physical care from home, 30-day readmissions after VC discharge, adherence to the wearable, and alarms per patient-day. RESULTS: A total of 1838 patients with COVID-19 were admitted to an MTF with a VC program of 3988 admitted to the MHS. Of these patients, 237 (13%) were enrolled in the VC program. The DiD analysis indicated that centers with the program had a 12% lower length of stay averaged across all COVID-19 patients, saving US $2047 per patient. The total cost of equipping, establishing, and staffing the VC program was estimated at US $3816 per day. Total net savings were estimated at US $2.3 million in the first year of the program across the MHS. The wearables were activated by 231 patients (97.5%) and were monitored through the Current Health platform for a total of 3474 (median 7.9, range 3.2-16.5) days. Wearable adherence was 85% (IQR 63%-94%). Patients triggered a median of 1.6 (IQR 0.7-5.2) vital sign alarms per patient per day; 203 (85.7%) were monitored at home and then directly discharged from VC; 27 (11.4%) were escalated to a physical hospital bed as part of their initial admission. There were no increases in 30-day readmissions or emergency department visits. CONCLUSIONS: Monitored patients were adherent to the wearable device and triggered a manageable number of alarms/day for the monitoring-team-to-patient ratio. Despite only enrolling 13% of COVID-19 patients at centers where it was available, the program offered substantial savings averaged across all patients in those centers without adversely affecting clinical outcomes.

Risk of strong antibody decline in dialysis and transplant patients after SARS-CoV-2mRNA vaccination: Six months data from the observational Dia-Vacc study.

Background: Vulnerable dialysis and kidney transplant patients show impaired seroconversion rates compared to medical personnel eight weeks after SARS-CoV-2mRNA vaccination. Methods: We evaluated six months follow up data in our observational Dia-Vacc study exploring specific cellular (interferon-γ release assay) or/and humoral immune responses after 2x SARS-CoV-2mRNA vaccination in 1205 participants including medical personnel (125 MP), dialysis patients (970 DP) and kidney transplant recipients (110 KTR) with seroconversion (de novo IgA or IgG antibody positivity by ELISA) after eight weeks. Findings: Six months after vaccination, seroconversion remained positive in 98% of MP, but 91%/87% of DP/KTR (p = 0·005), respectively. Receptor binding domain-IgG (RBD-IgG) antibodies were positive in 98% of MP, but only 68%/57% of DP/KTR (p < 0·001), respectively. Compared to MP, DP and KTR were at risk for a strong IgG or RBD-IgG decline (p < 0·001). Within the DP but not KTR group male gender, peritoneal dialysis, short time on dialysis, BNT162b2mRNA vaccine, immunosuppressive drug use and diabetes mellitus were independent risk factors for a strong decline of IgG or RBD antibodies. The percentage of cellular immunity decline was similar in all groups. Interpretation: Both vulnerable DP and KTR groups are at risk for a strong decline for IgG and RBD antibodies. In KTR, antibody titres peak at a markedly lower level and accelerated antibody decline is mixed with a delayed/increasing IgG, RBD-IgG, or cellular immune response in a 16% fraction of patients. In both populations, immune monitoring should be used for early timing of additional booster vaccinations. Funding: This study was funded by the Else Kröner Fresenius Stiftung, Bad Homburg v. d. H., grant number Fördervertrag EKFS 2021_EKSE.27.

RISK FACTORS ASSOCIATED WITH DEVELOPING PERSISTENT SYMPTOMS AFTER COVID-19: A RETROSPECTIVE STUDY

B Introduction: b COVID-19 has been associated with significant morbidity and mortality and results in severe hypoxemic respiratory failure, often requiring admission to the Intensive Care Unit. However, recently persistent symptoms lasting more than 4-12 weeks after diagnosis have been described, referred to as post-acute COVID or long-COVID. [Extracted from the article] Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Argatroban for Anticoagulation in Patients Requiring Venovenous Extracorporeal Membrane Oxygenation in Coronavirus Disease 2019.

A significant proportion of patients with coronavirus disease 2019 requiring venovenous extracorporeal membrane oxygenation at our institution demonstrated heparin resistance, which in combination with a heparin shortage resulted in the transition to argatroban with or without aspirin as an alternative anticoagulation strategy. The optimal anticoagulation strategy for coronavirus disease 2019 patients requiring venovenous extracorporeal membrane oxygenation is unknown, and therefore, we sought to evaluate the efficacy and safety of argatroban with or without aspirin as an alternative anticoagulation strategy in this patient population. DESIGN: Retrospective cohort. SETTING: Single-center tertiary-care facility in Fort Sam Houston, TX, from 2020 to 2021. PATIENTS: Twenty-four patients who were cannulated for venovenous extracorporeal membrane oxygenation due to respiratory failure secondary to coronavirus disease 2019. INTERVENTIONS: Argatroban, with or without aspirin, was substituted for heparin in coronavirus disease 2019 patients requiring venovenous extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: Eighty percent of our coronavirus disease 2019 patients requiring venovenous extracorporeal membrane oxygenation demonstrated heparin resistance, and patients who were initially started on heparin were significantly more likely to require a change to argatroban than vice versa due to difficulty achieving or maintaining therapeutic anticoagulation goals (93.4% vs 11.1%; p < 0.0001). The time to reach the therapeutic anticoagulation goal was significantly longer for patients who were initially started on heparin in comparison with argatroban (24 vs 6 hr; p = 0.0173). Bleeding and thrombotic complications were not significantly different between the two cohorts. CONCLUSIONS: Argatroban, with or without aspirin, is an effective anticoagulation strategy for patients who require venovenous extracorporeal membrane oxygenation support secondary to coronavirus disease 2019. In comparison with heparin, this anticoagulation strategy was not associated with a significant difference in bleeding or thrombotic complications, and was associated with a significantly decreased time to therapeutic anticoagulation goal, likely as a result of high rates of heparin resistance observed in this patient population.

Humoral and cellular immunity to SARS-CoV-2 vaccination in renal transplant versus dialysis patients: A prospective, multicenter observational study using mRNA-1273 or BNT162b2 mRNA vaccine.

BACKGROUND: Dialysis and kidney transplant patients are vulnerable populations for COVID-19 related disease and mortality. METHODS: We conducted a prospective study exploring the eight week time course of specific cellular (interferon-γ release assay and flow cytometry) or/and humoral immune responses (ELISA) to SARS-CoV-2 boost vaccination in more than 3100 participants including medical personnel, dialysis patients and kidney transplant recipients using mRNA vaccines BNT162b2 or mRNA-1273. RESULTS: SARS-CoV-2-vaccination induced seroconversion efficacy in dialysis patients was similar to medical personnel (> 95%), but markedly impaired in kidney transplant recipients (42%). T-cellular immunity largely mimicked humoral results. Major risk factors of seroconversion failure were immunosuppressive drug number and type (belatacept, MMF-MPA, calcineurin-inhibitors) as well as vaccine type (BNT162b2 mRNA). Seroconversion rates induced by mRNA-1273 compared to BNT162b2 vaccine were 97% to 88% (p < 0.001) in dialysis and 49% to 26% in transplant patients, respectively. Specific IgG directed against the new binding domain of the spike protein (RDB) were significantly higher in dialysis patients vaccinated by mRNA-1273 (95%) compared to BNT162b2 (85%, p < 0.001). Vaccination appeared safe and highly effective demonstrating an almost complete lack of symptomatic COVID-19 disease after boost vaccination as well as ceased disease incidences during third pandemic wave in dialysis patients. CONCLUSION: Dialysis patients exhibit a remarkably high seroconversion rate of 95% after boost vaccination, while humoral response is impaired in the majority of transplant recipients. Immunosuppressive drug number and type as well as vaccine type (BNT162b2) are major determinants of seroconversion failure in both dialysis and transplant patients suggesting immune monitoring and adaption of vaccination protocols.