Faculty Bibliography

Liver dysfunction manifesting as elevated aminotransferase levels has been a common feature of coronavirus disease-2019 (COVID-19) infection. The mechanism of liver injury in COVID-19 infection is unclear. However, it has been hypothesized to be a result of direct cytopathic effects of the virus, immune dysfunction and cytokine storm-related multiorgan damage, hypoxia-reperfusion injury and idiosyncratic drug-induced liver injury due to medications used in the management of COVID-19. The favored hypothesis regarding the pathophysiology of liver injury in the setting of COVID-19 is cytokine storm, an aberrant and unabated inflammatory response leading to hyperproduction of cytokines. In the current review, we have summarized the potential pathophysiologic mechanisms of cytokine-induced liver injury based on the reported literature.

BACKGROUND:While specific interventions have previously demonstrated benefit in patients with the Acute Respiratory Distress Syndrome (ARDS), use of these interventions is inconsistent, and patient mortality remains high. The impact of variability in center management practices on ARDS mortality rates remains unknown. RESEARCH QUESTION/OBJECTIVE:What is the impact of treatment variability on mortality in patients with moderate-to-severe ARDS in the United States (US)? STUDY DESIGN AND METHODS/METHODS:O, who were admitted to 29 US centers between October 1, 2016 and April 30, 2017. The primary outcome was 28-day in-hospital mortality. Center variation in ventilator management, adjunctive therapy use, and mortality were also assessed. RESULTS:O) was 31.4% and varied between centers (0%-65%), as did rates of adjunctive therapy use (27.1%-96.4%), types of modalities used (neuromuscular blockade, prone positioning, systemic steroids, pulmonary vasodilators, and extracorporeal support), and mortality (16.7-73.3%). Center standardized mortality ratios (SMRs), calculated using baseline patient-level characteristics to derive expected mortality rate, ranged from 0.33 to 1.98. Of the treatment-level factors explored, only center adherence to early lung protective ventilation (LPV) was correlated with SMR. INTERPRETATION/CONCLUSIONS:Substantial center-to-center variability exists in ARDS management, suggesting that further opportunities for improving ARDS outcomes exist. Early adherence to LPV was associated with lower center mortality and may be a surrogate for overall quality of care processes. Future collaboration is needed to identify additional treatment-level factors influencing center-level outcomes. CLINICAL TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov Identifier: NCT03021824.

Objectives/UNASSIGNED:To understand how patients and family members experience dehumanizing or humanizing treatment when in the ICU. Design/UNASSIGNED:Qualitative study included web-based focus groups and open-ended surveys posted to ICU patient/family social media boards. Focus groups were audio recorded and transcribed. Social media responses were collected and organized by stakeholder group. Data underwent qualitative analysis. Setting/UNASSIGNED:Remote focus groups and online surveys. Patients/UNASSIGNED:ICU patient survivors, family members, and ICU teams. Interventions/UNASSIGNED:Not available. Measurements and Main Results/UNASSIGNED:Semi-structured questions and open-ended survey responses. We enrolled 40 patients/family members and 31 ICU team members. Focus groups and surveys revealed three primary themes orienting humanizing/dehumanizing ICU experiences: 1) communication, 2) outcomes, and 3) causes of dehumanization. Dehumanization occurred during "communication" exchanges when ICU team members talked "over" patients, made distressing remarks when patients were present, or failed to inform patients about ICU-related care. "Outcomes" of dehumanization were associated with patient loss of trust in the medical team, loss of motivation to participate in ICU recovery, feeling of distress, guilt, depression, and anxiety. Humanizing behaviors were associated with improved recovery, well-being, and trust. "Perceived causes" of dehumanizing behaviors were linked to patient, ICU team, and healthcare system factors. CONCLUSIONS:Behaviors of ICU clinicians may cause patients and families to feel dehumanized when in the ICU. Negative behaviors are noticed by patients and families, possibly contributing to poor outcomes including mental health, recovery, and lack of trust in ICU teams. Supporting ICU clinicians may enable a more empathic environment and in turn more humanizing clinician-patient encounters.

BACKGROUND:For people with advanced stage cystic fibrosis (CF), tailored survival estimates could facilitate preparation for decision-making in the event of acutely deteriorating respiratory function. METHODS:We used the US CF Foundation national database (2008-2013) to identify adult people with incident advanced stage CF (forced expiratory volume in 1 s (FEV1) ≤45% predicted). Using the lasso method for variable selection, we divided the dataset into training and validation samples (2:1), and developed two multivariable Cox proportional hazards models to calculate probabilities of survival from baseline (T0 model), and from 1 year after (T12 model). We also performed Kaplan-Meier survival analyses. RESULTS:colonisation; cirrhosis; depression; dialysis; current smoking; unclassifiable mutation class and cumulative CF exacerbations predicted increased mortality. Baseline transplant evaluation status of 'accepted, on waiting list' predicted decreased mortality. For the T12 model, interim decrease in FEV1 >10%, and pulmonary exacerbations additionally increased predicted mortality. Lung transplantation was associated with lower mortality. Of the 4752, 93.5%, 86.4%, 79.7% and 73.9% survived to 1, 2, 3 and 4 years, respectively, without considering any confounding variables. The models had moderate predictive ability indicated by the area under the time-dependent receiver operating characteristic curve (0.787, 95% CI 0.769 to 0.794 for T0 model; and 0.779, 95% CI 0.767 to 0.797 for T12 model). CONCLUSION/CONCLUSIONS:We have developed models predicting survival in people with incident advanced stage CF, which can be reapplied over time to support shared decision-making about end-of-life treatment choices and lung transplantation. These estimates must be updated as data become available regarding long-term outcomes for people treated with CF transmembrane conductance regulator modulators.

BACKGROUND:Cystic fibrosis (CF) is a life-limiting genetic disease that causes chronic lung infections. We developed an internet-based decision aid (DA) to help patients with CF make better informed decisions regarding treatments and advance care planning. We built the DA around two major treatment decisions: whether to have a lung transplant and whether to agree to invasive mechanical ventilation (intubation). OBJECTIVE:This study aims to conduct usability testing of the InformedChoices CF DA among key stakeholder groups. METHODS:We performed a patient needs assessment using think-aloud usability testing with patients with CF, their surrogates, and CF clinicians. Think-aloud participants provided feedback while navigating the DA, and after viewing, they answered surveys. Transcripts from the think-aloud sessions and survey results were categorized into common, generalizable themes and optimizations for improving content, comprehension, and navigation. We assessed the ease of use of the DA (System Usability Scale) and also assessed the participants' perceptions regarding the overall tone, with an emphasis on emotional reactions to the DA content, level of detail, and usefulness of the information for making decisions about either intubation or lung transplantation, including how well they understood the information and were able to apply it to their own decision-making process. We also assessed the DA's ease of navigation, esthetics, and whether participants were able to complete a series of usability tasks (eg, locating specific information in the DA or using the interactive survival estimates calculator) to ensure that the website was easy to navigate during the clinic-based advance care planning discussions. RESULTS:A total of 12 participants from 3 sites were enrolled from March 9 to August 30, 2018, for the usability testing: 5 CF clinicians (mean age 48.2, SD 12.0 years), 5 adults with CF, and 2 family and surrogate caregivers of people with CF (mean age of CF adults and family and surrogate caregivers 38.8, SD 10.8 years). Among the 12 participants, the average System Usability Scale score for the DA was 88.33 (excellent). Think-aloud analysis identified 3 themes: functionality, visibility and navigation, and content and usefulness. Areas for improvement included reducing repetition, enhancing comprehension, and changing the flow. Several changes to improve the content and usefulness of the DA were recommended, including adding information about alternatives to childbearing, such as adoption and surrogacy. On the basis of survey responses, we found that the navigation of the site was easy for clinicians, patients, and surrogates who participated in usability testing. CONCLUSIONS:Usability testing revealed areas of potential improvement. Testing also yielded positive feedback, suggesting the DA's future success. Integrating changes before implementation should improve the DA's comprehension, navigation, and usefulness and lead to greater adoption.

BACKGROUND:Cytokine storm is a marker of COVID-19 illness severity and increased mortality. Immunomodulatory treatments have been repurposed to improve mortality outcomes. RESEARCH QUESTION/OBJECTIVE:To identify if immunomodulatory therapies improve survival in patients with COVID-19 cytokine storm. STUDY DESIGN AND METHODS/METHODS:We conducted a retrospective analysis of electronic health records across the Northwell Health system. COVID-19 patients hospitalized between March 1, 2020 and April 24, 2020 were included. Cytokine storm was defined by inflammatory markers: ferritin >700ng/mL, C-reactive protein >30mg/dL or lactate dehydrogenase >300U/L. Patients were subdivided into six groups-no immunomodulatory treatment (standard of care) and five groups that received either corticosteroids, anti-interleukin 6 antibody (tocilizumab) or anti-interleukin-1 therapy (anakinra) alone or in combination with corticosteroids. The primary outcome was hospital mortality. RESULTS:5,776 patients met the inclusion criteria. The most common comorbidities were hypertension (44-59%), diabetes (32-46%) and cardiovascular disease (5-14%). Patients most frequently met criteria with high lactate dehydrogenase (76.2%) alone or in combination, followed by ferritin (63.2%) and C-reactive protein (8.4%). More than 80% of patients had an elevated D-dimer. Patients treated with corticosteroids and tocilizumab combination had lower mortality compared to standard of care (Hazard Ratio (HR):0.44, 95% confidence interval (CI): 0.35-0.55; p<0.0001) and when compared to corticosteroids alone (HR:0.66, 95%CI: 0.53-0.83; p-value=0.004), or in combination with anakinra (HR:0.64, 95%CI:0.50-0.81; p-value=0.003) . Corticosteroids when administered alone (HR:0.66, 95%CI:0.57-0.76; p<0.0001) or in combination with tocilizumab (HR:0.43, 95%CI:0.35-0.55; p<0.0001) or anakinra (HR:0.68, 95%CI:0.57-0.81; p<0.0001) improved hospital survival compared to standard of care. INTERPRETATION/CONCLUSIONS:The combination of corticosteroids with tocilizumab had superior survival outcome when compared to standard of care and corticosteroids alone or in combination with anakinra. Furthermore, corticosteroid use either alone or in combination with tocilizumab or anakinra was associated with reduced hospital mortality for patients with COVID-19 cytokine storm compared to standard of care.

Objective/UNASSIGNED:To optimize the ability of hospitalized patients isolated due to COVID-19 to participate in physical therapy. Design/UNASSIGNED:This was a prospective, quality improvement trial of the feasibility and acceptability of a "hybrid" in-person and telerehabilitation platform to deliver physical therapy to hospitalized adults. Setting/UNASSIGNED:Inpatient wards of a tertiary care, multi-specialty academic medical center in the greater New York City metropolitan area. Participants/UNASSIGNED:A convenience sample of 39 COVID-19+ adults, mean age 57.3 years, 69% male, all previously community dwelling agreed to participate in a combination of in-person and telerehabilitation sessions (TR). Intervention/UNASSIGNED:Initial in-person evaluation by physical therapist followed by twice daily PT sessions, one in-person and one via a telehealth platform meeting Health Insurance Portability and Accountability Act (HIPAA) confidentiality requirements. The communication platform was downloaded to each participant's personal smart device to establish audiovisual contact with the Physical Therapist. Measures/UNASSIGNED:The 6-clicks Activity Measure for Post-Acute Care (AM-PAC) was used to score self-reported functional status pre-morbidly by, and by the therapist at baseline and discharge. Results/UNASSIGNED:Functional status measured by AM-PAC 6-clicks demonstrated improvement from admission to discharge. Barriers to participation were identified and strategies are planned to facilitate use of the platform in future. Conclusions/UNASSIGNED:A consistent and structured protocol for engaging patient participation in PT delivered via a telehealth platform was successfully developed. A process was put in place to allow for further development, recruitment and testing in a randomized trial.

The clinical progression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) to critical illness is associated with an exaggerated immune response, leading to magnified inflammation termed the "cytokine storm." This response is thought to contribute to the pathogenicity of severe COVID-19. There is an initial weak interferon response and macrophage activation that results in delayed neutrophil recruitment leading to impeded viral clearance. This causes prolonged immune stimulation and the release of proinflammatory cytokines. Elevated inflammatory markers in COVID-19 (i.e., D-dimer, C-reactive protein, lactate dehydrogenase, ferritin, and interleukin-6) are reminiscent of "cytokine storm" seen in severe hyperinflammatory macrophage disorders. The dysfunctional immune response in COVID-19 also includes lymphopenia, reduced T-cells, reduced natural killer cell maturation, and unmitigated plasmablast proliferation causing aberrant immunoglobulin G levels. The progression to severe disease is accompanied by endotheliopathy, immunothrombosis, and hypercoagulability. Thus, both parts of the immune system-innate and adaptive-play a significant role in the cytokine storm, multiorgan dysfunction, and coagulopathy. This review highlights the importance of understanding the immunological mechanisms of COVID-19 as they inform the clinical presentation and advise potential therapeutic targets.

BACKGROUND:Telehealth-delivered pulmonary rehabilitation (telePR) has been shown to be as effective as standard pulmonary rehabilitation (PR) at improving the quality of life in patients living with chronic obstructive pulmonary disease (COPD). However, it is not known how effective telePR may prove to be among low-income, urban Hispanic American and African American patient populations. To address this question, a collaborative team at Northwell Health developed a telePR intervention and assessed its efficacy among low-income Hispanic American and African American patient populations. The telePR intervention system components included an ergonomic recumbent bike, a tablet with a built-in camera, and wireless monitoring devices. OBJECTIVE:The objective of the study was to assess patient adoption and diminish barriers to use by initiating a user-centered design approach, which included usability testing to refine the telePR intervention prior to enrolling patients with COPD into a larger telePR study. METHODS:Usability testing was conducted in two phases to identify opportunities to streamline and improve the patient experience. The first phase included a prefield usability testing phase to evaluate technical, patient safety, and environmental factors comprising the system architecture. This was followed by an ergonomic evaluation of user interactions with the bicycle, telehealth tablets, and connected wearable devices to ensure optimal placement and practical support for all components of the intervention. The second phase of research included feasibility testing to observe and further optimize the system based on iterative rounds of telePR sessions. RESULTS:During usability and feasibility research, we identified and addressed multiple opportunities for system improvements. These included physical and environmental changes, modifications to accommodate individual patient factors, safety improvements, and technology upgrades. Each enrolled patient was subsequently identified and classified into one of the following 3 categories: (1) independent, (2) intermediate, or (3) dependent. This categorization was used to predict the level of training and support needed for successful participation in the telePR sessions. Feasibility results revealed that patients in the dependent category were unable to perform the rehab sessions without in-person support due to low technical acumen and difficulty with certain features of the system, even after modifications had been made. Intermediate and independent users, however, did exhibit increased independent utilization of telePR due to iterative improvements. CONCLUSIONS:Usability testing helped reduce barriers to use for two subsets of our population, the intermediate and independent users. In addition, it identified a third subset, dependent users, for whom the telePR solution was deemed unsuitable without in-person support. The study established the need for the development of standard operating procedures, and guides were created for both patients and remote respiratory therapists to facilitate the appropriate use of the telePR system intervention. Observational research also led to the development of standard protocols for the first and all subsequent telePR sessions. The primary goals in developing standardization protocols were to establish trust, ensure a positive experience, and encourage future patient engagement with telePR sessions.