Early posthospitalization recovery after extracorporeal membrane oxygenation in survivors of COVID-19.

OBJECTIVE: We sought to determine the influence of venovenous extracorporeal membrane oxygenation (ECMO) on outcomes of mechanically ventilated patients with COVID-19 during the first 120 days after hospital discharge. METHODS: Five academic centers conducted a retrospective analysis of mechanically ventilated patients with COVID-19 admitted during March through May 2020. Survivors had access to a multidisciplinary postintensive care recovery clinic. Physical, psychological, and cognitive deficits were measured using validated instruments and compared based on ECMO status. RESULTS: Two hundred sixty two mechanically ventilated patients were compared with 46 patients cannulated for venovenous ECMO. Patients receiving ECMO were younger and traveled farther but there was no significant difference in gender, race, or body mass index. ECMO patients were mechanically ventilated for longer durations (median, 26 days [interquartile range, 19.5-41 days] vs 13 days [interquartile range, 7-20 days]) and were more likely to receive inhaled pulmonary vasodilators, neuromuscular blockade, investigational COVID-19 therapies, blood transfusions, and inotropes. Patients receiving ECMO experienced greater bleeding and clotting events (P < .01). However, survival at discharge was similar (69.6% vs 70.6%). Of the 217 survivors, 65.0% had documented follow-up within 120 days. Overall, 95.5% were residing at home, 25.7% had returned to work or usual activity, and 23.1% were still using supplemental oxygen; these rates did not differ significantly based on ECMO status. Rates of physical, psychological, and cognitive deficits were similar. CONCLUSIONS: Our data suggest that COVID-19 survivors experience significant physical, psychological, and cognitive deficits following intensive care unit admission. Despite a more complex critical illness course, longer average duration of mechanical ventilation, and longer average length of stay, patients treated with venovenous ECMO had similar survival at discharge and outcomes within 120 days of discharge.

Worse survival in patients with right ventricular dysfunction and COVID-19-associated acute respiratory distress requiring extracorporeal membrane oxygenation: A multicenter study from the ORACLE Group.

OBJECTIVE: We sought to determine the impact of right ventricular dysfunction on the outcomes of mechanically ventilated patients with COVID-19 requiring veno-venous extracorporeal membrane oxygenation. METHODS: Six academic centers conducted a retrospective analysis of mechanically ventilated patients with COVID-19 stratified by support with veno-venous extracorporeal membrane oxygenation during the first wave of the pandemic (March to August 2020). Echocardiograms performed for clinical indications were reviewed for right and left ventricular function. Baseline characteristics, hospitalization characteristics, and survival were compared. RESULTS: The cohort included 424 mechanically ventilated patients with COVID-19, 126 of whom were cannulated for veno-venous extracorporeal membrane oxygenation. Right ventricular dysfunction was observed in 38.1% of patients who received extracorporeal membrane oxygenation and 27.4% of patients who did not receive extracorporeal membrane oxygenation with an echocardiogram. Biventricular dysfunction was observed in 5.5% of patients who received extracorporeal membrane oxygenation. Baseline patient characteristics were similar in both the extracorporeal membrane oxygenation and non-extracorporeal membrane oxygenation cohorts stratified by the presence of right ventricular dysfunction. In the extracorporeal membrane oxygenation cohort, right ventricular dysfunction was associated with increased inotrope use (66.7% vs 24.4%, P < .001), bleeding complications (77.1% vs 53.8%, P = .015), and worse survival independent of left ventricular dysfunction (39.6% vs 64.1%, P = .012). There was no significant difference in days ventilated before extracorporeal membrane oxygenation, length of hospital stay, hours on extracorporeal membrane oxygenation, duration of mechanical ventilation, vasopressor use, inhaled pulmonary vasodilator use, infectious complications, clotting complications, or stroke. The cohort without extracorporeal membrane oxygenation cohort demonstrated no statistically significant differences in in-hospital outcomes. CONCLUSIONS: The presence of right ventricular dysfunction in patients with COVID-19-related acute respiratory distress syndrome supported with veno-venous extracorporeal membrane oxygenation was associated with increased in-hospital mortality. Additional studies are required to determine if mitigating right ventricular dysfunction in patients requiring veno-venous extracorporeal membrane oxygenation improves mortality.

Palliative Care and Moral Distress: An Institutional Survey of Critical Care Nurses.

BACKGROUND: The need for palliative care in the intensive care unit is increasing. Whether gaps and variations in palliative care education and use are associated with moral distress among critical care nurses is unknown. OBJECTIVES: To examine critical care nurses' perceived knowledge of palliative care, their recent experiences of moral distress, and possible relationships between these variables. METHODS: In this quantitative, descriptive study, survey questionnaires were distributed to 517 critical care nurses across 7 intensive care units at an academic health center in Virginia. Validated instruments were used to measure participants' perceptions of palliative care in their practice setting and their recent experiences of moral distress. RESULTS: A total of 167 completed questionnaires were analyzed. Fewer than 40% of respondents reported being highly competent in any palliative care domain. Most respondents had little palliative care education, with 38% reporting none in the past 2 years. Most respondents reported moral distress during the study period, and moral distress levels differed significantly on the basis of perceived use of palliative care (P = .03). Respondents who perceived less frequent use of palliative care tended to experience higher levels of moral distress. CONCLUSIONS: Many critical care nurses do not feel prepared to provide palliative care. When palliative care access is perceived as inadequate, nurses may be more apt to experience moral distress. Health system leaders should prioritize palliative care training for critical care nurses and their colleagues and empower them to reduce barriers to palliative care.

A Randomized Controlled Trial Comparing Two Lung Expansion Therapies After Upper Abdominal Surgery.

BACKGROUND: Lung expansion therapy is often ordered after surgery to improve alveolar ventilation and reduce risks of postoperative pulmonary complications. The impact of lung expansion therapy at altering ventilation in patients who are not intubated has not been described. The primary purpose of this study was to determine if there is a difference in dorsal redistribution of ventilation and incidences of postoperative pulmonary complications when comparing incentive spirometry (IS) with EzPAP lung expansion therapy after upper abdominal surgery. Our a priori null hypothesis was that there are no differences. METHODS: This randomized controlled trial enrolled adult human subjects after upper- abdominal surgery from January 2017 to November 2018. The subjects were allocated to receive IS or EzPAP 3 times a day on postoperative days 1-5. An electrical impedance tomography device was connected to the subjects for a single lung expansion therapy session on postoperative days 1, 3, and 5 to measure the change in post-lung expansion therapy dorsal end-expiratory lung impedance (ΔEELI%). Lung expansion therapy sessions with electrical impedance tomography included 2 min of normal breathing, 3 cycles of 10 breaths, and 2 min of normal breathing after cycle 3. Postoperative pulmonary complications were screened until hospital discharge. Mann-Whitney, chi-square, and Fisher exact tests were applied. Data were reported as count (n), percentage, and median (interquartile range) for primary and secondary outcomes. Alpha (2-tailed) was < 0.05. RESULTS: A total of 112 subjects were enrolled to receive IS (n = 56) or EzPAP (n = 56). Baseline characteristics were equal. Post-lung expansion therapy dorsal ΔEELI% increased for both groups, but the dorsal ΔEELI% for IS versus EzPAP on postoperative day 1 (16% versus 12%, P = .39), postoperative day 3 (6% versus 6%, P = .68), and postoperative day 5 (9% versus 6%, P = .46) was not significantly different. Hospital length of stay (4 d; P = .30) and incidence of postoperative pulmonary complications (3.6% versus 7.1%, P = .19) were similar. CONCLUSIONS: There was no significant post-lung expansion therapy dorsal ΔEELI% or postoperative pulmonary complications among the adults who received IS or EzPAP 3 times a day after upper abdominal surgery. (ClinicalTrials.gov registration NCT02892773.).

Effect of Ganciclovir on IL-6 Levels Among Cytomegalovirus-Seropositive Adults With Critical Illness: A Randomized Clinical Trial.

Importance: The role of cytomegalovirus (CMV) reactivation in mediating adverse clinical outcomes in nonimmunosuppressed adults with critical illness is unknown. Objective: To determine whether ganciclovir prophylaxis reduces plasma interleukin 6 (IL-6) levels in CMV-seropositive adults who are critically ill. Design, Setting, and Participants: Double-blind, placebo-controlled, randomized clinical trial (conducted March 10, 2011-April 29, 2016) with a follow-up of 180 days (November 10, 2016) that included 160 CMV-seropositive adults with either sepsis or trauma and respiratory failure at 14 university intensive care units (ICUs) across the United States. Interventions: Patients were randomized (1:1) to receive either intravenous ganciclovir (5 mg/kg twice daily for 5 days), followed by either intravenous ganciclovir or oral valganciclovir once daily until hospital discharge (n = 84) or to receive matching placebo (n = 76). Main Outcomes and Measures: The primary outcome was change in IL-6 level from day 1 to 14. Secondary outcomes were incidence of CMV reactivation in plasma, mechanical ventilation days, incidence of secondary bacteremia or fungemia, ICU length of stay, mortality, and ventilator-free days (VFDs) at 28 days. Results: Among 160 randomized patients (mean age, 57 years; women, 43%), 156 patients received 1or more dose(s) of study medication, and 132 patients (85%) completed the study. The mean change in plasma IL-6 levels between groups was -0.79 log10 units (-2.06 to 0.48) in the ganciclovir group and -0.79 log10 units (-2.14 to 0.56) in the placebo group (point estimate of difference, 0 [95% CI, -0.3 to 0.3]; P > .99). Among secondary outcomes, CMV reactivation in plasma was significantly lower in the ganciclovir group (12% [10 of 84 patients] vs 39% [28 of 72 patients]); absolute risk difference, -27 (95% CI, -40 to -14), P < .001. The ganciclovir group had more median VFDs in both the intention-to-treat (ITT) group and in the prespecified sepsis subgroup (ITT group: 23 days in ganciclovir group vs 20 days in the placebo group, P = .05; sepsis subgroup, 23 days in the ganciclovir group vs 20 days in the placebo group, P = .03). There were no significant differences between the ganciclovir and placebo groups in duration of mechanical ventilation (5 days for the ganciclovir group vs 6 days for the placebo group, P = .16), incidence of secondary bacteremia or fungemia (15% for the ganciclovir group vs 15% for the placebo group, P = .67), ICU length of stay (8 days for the ganciclovir group vs 8 days for the placebo group, P = .76), or mortality (12% for the ganciclovir group vs 15% for the placebo group, P = .54). Conclusions and Relevance: Among CMV-seropositive adults with critical illness due to sepsis or trauma, ganciclovir did not reduce IL-6 levels and the current study does not support routine clinical use of ganciclovir as a prophylactic agent in patients with sepsis. Additional research is necessary to determine the clinical efficacy and safety of CMV suppression in this setting. Trial Registration: clinicaltrials.gov Identifier: NCT01335932.

Hidden Reservoir: An Outbreak of Tuberculosis in Hospital Employees with No Patient Contact.

We describe an outbreak of tuberculosis (TB) in the food preparation area of a hospital, which demonstrates that employees in healthcare settings may serve as potential risks for spread of TB even if they have no direct patient contact. Infect Control Hosp Epidemiol 2016;37:1111-1113.

Disabled homolog 2 controls macrophage phenotypic polarization and adipose tissue inflammation.

Acute and chronic tissue injury results in the generation of a myriad of environmental cues that macrophages respond to by changing their phenotype and function. This phenotypic regulation is critical for controlling tissue inflammation and resolution. Here, we have identified the adaptor protein disabled homolog 2 (DAB2) as a regulator of phenotypic switching in macrophages. Dab2 expression was upregulated in M2 macrophages and suppressed in M1 macrophages isolated from both mice and humans, and genetic deletion of Dab2 predisposed macrophages to adopt a proinflammatory M1 phenotype. In mice with myeloid cell-specific deletion of Dab2 (Dab2fl/fl Lysm-Cre), treatment with sublethal doses of LPS resulted in increased proinflammatory gene expression and macrophage activation. Moreover, chronic high-fat feeding exacerbated adipose tissue inflammation, M1 polarization of adipose tissue macrophages, and the development of insulin resistance in DAB2-deficient animals compared with controls. Mutational analyses revealed that DAB2 interacts with TNF receptor-associated factor 6 (TRAF6) and attenuates IκB kinase ß-dependent (IKKß-dependent) phosphorylation of Ser536 in the transactivation domain of NF-κB p65. Together, these findings reveal that DAB2 is critical for controlling inflammatory signaling during phenotypic polarization of macrophages and suggest that manipulation of DAB2 expression and function may hold therapeutic potential for the treatment of acute and chronic inflammatory disorders.

Hepatitis B in healthcare workers: Transmission events and guidance for management.

Hepatitis B virus (HBV) is the most efficiently transmissible of the bloodborne viruses that are important in healthcare settings. Healthcare workers (HCWs) are at risk for exposure to HBV from infected patients and, if infected, are similarly at risk of transmitting HBV to patients. Published cases of HBV transmission from HCW to patient are relatively rare, having decreased in frequency following the introduction of standard (universal) precautions, adoption of enhanced percutaneous injury precautions such as double-gloving in surgery, and routine HBV vaccination of HCWs. Here we review published cases of HCW-to-patient transmission of HBV, details of which have helped to guide the creation of formal guidelines for the management of HBV-infected HCWs. We also compare the published guidelines for the management of HBV-infected HCWs from various governing bodies, focusing on their differences with regard to vaccination requirements, viral load limits, frequency of monitoring, and restrictions on practice. Importantly, while there are differences among the recommendations from governing bodies, no guidelines uniformly restrict HBV-infected HCWs from performing invasive or exposure-prone procedures.

Transmission of hepatitis B virus from an orthopedic surgeon with a high viral load.

BACKGROUND: During the evaluation of a needle-stick injury, an orthopedic surgeon was found to be unknowingly infected with hepatitis B virus (HBV) (viral load >17.9 million IU/mL). He had previously completed two 3-dose series of hepatitis B vaccine without achieving a protective level of surface antibody. We investigated whether any surgical patients had acquired HBV infection while under his care. METHODS: A retrospective cohort study of all patients who underwent surgery by the surgeon was conducted. Patients were notified of their potential exposure and need for testing, and samples with positive HBV loads underwent DNA sequencing. Characteristics of the surgical procedures for the cohort were evaluated. RESULTS: A total of 232 (70.7%) of potentially exposed patients consented to testing; 2 were found to have acute infection and 6 had possible transmission (evidence of past exposure without risk factors). Genome sequence analysis of HBV DNA from the infected surgeon and patients with acute infection revealed genetically related virus (>99.9% nucleotide identity). Only age was found to be statistically different between those with confirmed or possible HBV transmission and those who remained susceptible to HBV. CONCLUSIONS: We documented HBV transmission during orthopedic surgery to 2 patients from a surgeon with HBV. This investigation highlights the importance of evaluating individuals who do not respond to 2 series of HBV vaccination, the increased risk of HBV transmission from providers with high viral loads, and the need to evaluate the clinical practice of providers with HBV and implement appropriate procedure-based practice restrictions.

The purpose, composition, and function of an institutional review board: balancing priorities.

The institutional review board (IRB) is one part of the research enterprise designated to protect human subjects. At times the IRB can feel like an oppressive oversight body bound by regulations and designed to inhibit research. However, in reality the IRB was an attempt by the federal government to streamline a variety of processes to ensure the protection of human subjects. Growing out of a history of unethical scientific research, the principle goal of the IRB is to protect human subjects. At some institutions the IRB has an additional role, to take a second look at proposed scientific methods to ensure the highest quality research. The legal basis, purpose, composition, and function of an IRB, and potential challenges in human-subjects research are reviewed here.

A case of vanishing bile duct syndrome and IBD secondary to Hodgkin's lymphoma.

BACKGROUND: A 39-year-old man presented with a 2-month history of abdominal pain, jaundice, non-bloody diarrhea, weakness, and weight loss. Initial evaluation revealed intrahepatic ductopenia consistent with vanishing bile duct syndrome and IBD, type unclassified. Although treatment with budesonide improved his symptoms, they worsened several months later. On repeat evaluation, he was found to have extensive lymphadenopathy and an elevated white blood cell count. INVESTIGATIONS: Physical examination, laboratory investigations, abdominal ultrasound, CT scans, magnetic resonance cholangiopancreatography, endoscopic retrograde cholangiopancreatography, colonoscopies with biopsies, hepatic biopsy, axillary lymph node biopsy. DIAGNOSIS: Hodgkin's lymphoma with secondary vanishing bile duct syndrome and IBD, type unclassified. MANAGEMENT: The initial symptoms were managed with budesonide, but following recurrence, the patient's underlying lymphoma was treated with nitrogen mustard and dexamethasone.