Prolonged Prone Position Ventilation Is Associated With Reduced Mortality in Intubated COVID-19 Patients.

BACKGROUND: Prone position ventilation (PPV) is resource-intensive, yet the optimal strategy for PPV in intubated patients with COVID-19 is unclear. RESEARCH QUESTION: Does a prolonged (24 or more h) PPV strategy improve mortality in intubated COVID-19 patients compared with intermittent (∼16 h with daily supination) PPV? STUDY DESIGN AND METHODS: Multicenter, retrospective cohort study of consecutively admitted intubated COVID-19 patients treated with PPV between March 11 and May 31, 2020. The primary outcome was 30-day all-cause mortality. Secondary outcomes included 90-day all-cause mortality and prone-related complications. Inverse probability treatment weights (IPTW) were used to control for potential treatment selection bias. RESULTS: Of the COVID-19 patients who received PPV, 157 underwent prolonged and 110 underwent intermittent PPV. Patients undergoing prolonged PPV had reduced 30-day (adjusted hazard ratio [aHR], 0.475; 95% CI, 0.336-0.670; P < .001) and 90-day (aHR, 0.638; 95% CI, 0.461-0.883; P = .006) mortality compared with intermittent PPV. In patients with Pao2/Fio2 ≤ 150 at the time of pronation, prolonged PPV was associated with reduced 30-day (aHR, 0.357; 95% CI, 0.213-0.597; P < .001) and 90-day mortality (aHR, 0.562; 95% CI, 0.357-0.884; P = .008). Patients treated with prolonged PPV underwent fewer pronation and supination events (median, 1; 95% CI, 1-2 vs 3; 95% CI, 1-4; P < .001). PPV strategy was not associated with overall PPV-related complications, although patients receiving prolonged PPV had increased rates of facial edema and lower rates of peri-proning hypotension. INTERPRETATION: Among intubated COVID-19 patients who received PPV, prolonged PPV was associated with reduced mortality. Prolonged PPV was associated with fewer pronation and supination events and a small increase in rates of facial edema. These findings suggest that prolonged PPV is a safe, effective strategy for mortality reduction in intubated COVID-19 patients.

Preferred Language Mediates Association Between Race, Ethnicity, and Delayed Presentation in Critically Ill Patients With COVID-19.

Which social factors explain racial and ethnic disparities in COVID-19 access to care and outcomes remain unclear. OBJECTIVES: We hypothesized that preferred language mediates the association between race, ethnicity and delays to care. DESIGN SETTING AND PARTICIPANTS: Multicenter, retrospective cohort study of adults with COVID-19 consecutively admitted to the ICU in three Massachusetts hospitals in 2020. MAIN OUTCOME AND MEASURES: Causal mediation analysis was performed to evaluate potential mediators including preferred language, insurance status, and neighborhood characteristics. RESULTS: Non-Hispanic White (NHW) patients (157/442, 36%) were more likely to speak English as their preferred language (78% vs. 13%), were less likely to be un- or under-insured (1% vs. 28%), lived in neighborhoods with lower social vulnerability index (SVI) than patients from racial and ethnic minority groups (SVI percentile 59 [28] vs. 74 [21]) but had more comorbidities (Charlson comorbidity index 4.6 [2.5] vs. 3.0 [2.5]), and were older (70 [13.2] vs. 58 [15.1] years). From symptom onset, NHW patients were admitted 1.67 [0.71-2.63] days earlier than patients from racial and ethnic minority groups (p < 0.01). Non-English preferred language was associated with delay to admission of 1.29 [0.40-2.18] days (p < 0.01). Preferred language mediated 63% of the total effect (p = 0.02) between race, ethnicity and days from symptom onset to hospital admission. Insurance status, social vulnerability, and distance to the hospital were not on the causal pathway between race, ethnicity and delay to admission. CONCLUSIONS AND RELEVANCE: Preferred language mediates the association between race, ethnicity and delays to presentation for critically ill patients with COVID-19, although our results are limited by possible collider stratification bias. Effective COVID-19 treatments require early diagnosis, and delays are associated with increased mortality. Further research on the role preferred language plays in racial and ethnic disparities may identify effective solutions for equitable care.

Sigmoid Venous Thrombosis in JAK2 V617F Mutated Polycythemia Vera.

A 60-year-old female presented with headaches, blurry vision, diplopia, and dizziness for six weeks. Her workup revealed an elevated hematocrit, thrombocytosis, high ferritin, and normal erythropoietin. She was diagnosed with polycythemia vera with the JAK2 V617F mutation. The patient underwent magnetic resonance venography, which showed left-sided sigmoid venous thrombosis. She was placed on low-molecular-weight heparin, with a plan to transition to oral anticoagulation after four weeks and repeat imaging in three months to assess for resolution. Thrombotic events may occur in patients with polycythemia vera, and a JAK2 mutation further heightens that risk. Even so, intracranial venous thrombosis is not among the most common events, and it should be kept in the differential for any patient with myeloproliferative neoplasms presenting with new neurological symptoms.

Evaluating complete remission with partial hematologic recovery (CRh) as a response criterion in myelodysplastic syndromes (MDS).

Myelodysplastic syndromes (MDS) treated with DNMTI therapy have responses according to the 2006 IWG response criteria. CR responses have had the strongest association with OS. Recently, CR with partial hematologic recovery (CRh; i.e. blasts <5%, ANC > 500, platelets > 50) has been evaluated in AML, but its relevance is unknown in MDS. We identified adult patients with MDS treated with DNMTIs. We assessed best overall response to therapy according to IWG 2006 criteria, and subsequently identified patients meeting CRh criteria from the subgroup with SD or mCR. We evaluated duration of therapy and overall survival according to response. We identified 311 patients with MDS who received treatment between 2007 and 2018. The median age at the time of therapy was 69 years (range 23-91). Median follow up was 60 months. According to IWG 2006, responses included CR (n = 43, 14%), PR (n = 2, 1%), mCR (n = 57, 18%), SD (n = 149, 48%) and PD (n = 60, 19%). 79 patients (25%) achieved HI. A total of 62 patients (20%) met CRh criteria leading to reclassification of mCR (now n = 26, 8%) or SD (now n = 118, 38%). Patients achieving CR had similar time on therapy (median 8.1mo) compared to CRh (median 6mo, HR 1.4, 95% CI 0.9-2.0), and longer than other responses (p < 0.001). OS varied according to response; median OS was similar between CR (23.3mo) and CRh (25mo, HR 1.28 [0.79-2.08]), which was longer than those with mCR (17.2mo, HR 1.71 [0.96-3.05]), SD (16.3mo, HR 1.61 [1.04-2.48]), and PD (8.7mo, HR 3.04 [1.91-4.83]) (p < 0.001). OS associations with CR/CRh were confirmed in multivariable analysis accounting for allogeneic transplant. MDS patients who achieve a CRh response had similar survival and duration on therapy as patients who achieve CR response and superior to other IWG responses. These data support further evaluation of CRh into future response criteria and clinical trials.

Code status orders in patients admitted to the intensive care unit with COVID-19: A retrospective cohort study.

Purpose: Code status orders impact clinical outcomes as well as patients' and surrogates' experiences. This is the first multicenter cohort examining code status orders of ICU patients with COVID-19 reported to date. Materials and methods: This is a retrospective cohort study including adult patients who tested positive for SARS-CoV-2 and were admitted to the ICU at three hospitals in Massachusetts from March 11, 2020 - May 31, 2020. We examined differences in code status orders at multiple timepoints and performed multivariable regression analysis to identify variables associated with code status at admission. Results: Among 459 ICU patients with COVID-19, 421 (91.7%) were Full Code at hospital admission. Age and admission from a facility were positively associated with DNR status (adjusted OR 1.10, 95% CI 1.05-1.15, p < 0.001 and adjusted OR 2.68, CI 1.23-5.71, p = 0.011, respectively) while non-English preferred language was negatively associated with DNR status (adjusted OR 0.29, 95% CI 0.10-0.74, p = 0.012). Among 147 patients who died during hospitalization, 95.2% (140) died with DNR code status; most (86.4%) died within two days of final code status change. Conclusions: The association of non-English preferred language with Full Code status in critically ill COVID-19 patients highlights the importance of medical interpreters in the ICU. Patients who died were transitioned to DNR more than in previous studies, possibly reflecting changes in practice during a novel pandemic.

Immunogenicity and Reactogenicity of SARS-CoV-2 Vaccines in Patients With Cancer: The CANVAX Cohort Study.

PURPOSE: The immunogenicity and reactogenicity of SARS-CoV-2 vaccines in patients with cancer are poorly understood. METHODS: We performed a prospective cohort study of adults with solid-organ or hematologic cancers to evaluate anti-SARS-CoV-2 immunoglobulin A/M/G spike antibodies, neutralization, and reactogenicity ≥ 7 days following two doses of mRNA-1273, BNT162b2, or one dose of Ad26.COV2.S. We analyzed responses by multivariate regression and included data from 1,638 healthy controls, previously reported, for comparison. RESULTS: Between April and July 2021, we enrolled 1,001 patients; 762 were eligible for analysis (656 had neutralization measured). mRNA-1273 was the most immunogenic (log10 geometric mean concentration [GMC] 2.9, log10 geometric mean neutralization titer [GMT] 2.3), followed by BNT162b2 (GMC 2.4; GMT 1.9) and Ad26.COV2.S (GMC 1.5; GMT 1.4; P < .001). The proportion of low neutralization (< 20% of convalescent titers) among Ad26.COV2.S recipients was 69.9%. Prior COVID-19 infection (in 7.1% of the cohort) was associated with higher responses (P < .001). Antibody titers and neutralization were quantitatively lower in patients with cancer than in comparable healthy controls, regardless of vaccine type (P < .001). Receipt of chemotherapy in the prior year or current steroids were associated with lower antibody levels and immune checkpoint blockade with higher neutralization. Systemic reactogenicity varied by vaccine and correlated with immune responses (P = .002 for concentration, P = .016 for neutralization). In 32 patients who received an additional vaccine dose, side effects were similar to prior doses, and 30 of 32 demonstrated increased antibody titers (GMC 1.05 before additional dose, 3.17 after dose). CONCLUSION: Immune responses to SARS-CoV-2 vaccines are modestly impaired in patients with cancer. These data suggest utility of antibody testing to identify patients for whom additional vaccine doses may be effective and appropriate, although larger prospective studies are needed.

Coronavirus Disease 2019 Infection in a Patient Population with Lung Cancer: Incidence, Presentation, and Alternative Diagnostic Considerations.

INTRODUCTION: Lung cancer is associated with severe coronavirus disease 2019 (COVID-19) infections. Symptom overlap between COVID-19 and lung cancer may complicate diagnostic evaluation. We aimed to investigate the incidence, symptoms, differential diagnosis, and outcomes of COVID-19 in patients with lung cancer. METHODS: To determine an at-risk population for COVID-19, we retrospectively identified patients with lung cancer receiving longitudinal care within a single institution in the 12 months (April 1, 2019 to March 31, 2020) immediately preceding the COVID-19 pandemic, including an "active therapy population" treated within the last 60 days of this period. Among patients subsequently referred for COVID-19 testing, we compared symptoms, laboratory values, radiographic findings, and outcomes of positive versus negative patients. RESULTS: Between April 1, 2019 and March 31, 2020, a total of 696 patients received longitudinal care, including 406 (58%) in the active therapy population. Among 55 patients referred for COVID-19 testing, 24 (44%) were positive for COVID-19, representing a cumulative incidence of 3.4% (longitudinal population) and 1.5% (active therapy population). Compared with patients who were COVID-19 negative, those who were COVID-19 positive were more likely to have a supplemental oxygen requirement (11% versus 54%, p = 0.005) and to have typical COVID-19 pneumonia imaging findings (5 versus 56%, p = 0.001). Otherwise, there were no marked differences in presenting symptoms. Among patients who were COVID-19 negative, alternative etiologies included treatment-related toxicity (26%), atypical pneumonia (22%), and disease progression (22%). A total of 16 patients positive for COVID-19 (67%) required hospitalization, and seven (29%) died from COVID-related complications. CONCLUSIONS: COVID-19 was infrequent in this lung cancer population, but these patients experienced high rates of morbidity and mortality. Oncologists should maintain a low threshold for COVID-19 testing in patients with lung cancer presenting with acute symptoms.

Immunotherapy in EGFR-Mutant and ALK-Positive Lung Cancer: Implications for Oncogene-Driven Lung Cancer.

Non-small cell lung cancer (NSCLC) is a heterogeneous disease, commonly defined by genetic alterations in oncogenic drivers. Targeted therapies have transformed the management of oncogene-driven lung cancers, with targeted agents now approved in the United States for 7 distinct molecular alterations. Nonetheless, acquired resistance remains an ongoing challenge, underscoring the need for alternative therapeutic approaches. Immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1) axis have emerged as important therapies in the management of advanced NSCLC, but the role of these agents in patients with oncogenic driver mutations remains unclear. Here, we focus on epidermal growth factor receptor-mutant and anaplastic lymphoma kinase-rearranged NSCLC as paradigms to explore the role of immune checkpoint inhibitors in oncogene-driven NSCLC. We provide an overview of the clinical data examining programmed death ligand 1 (PD-L1) inhibitor monotherapy, PD-(L)1 inhibitors, and tyrosine kinase inhibitor combinations, as well as combinations of PD-(L)1 inhibitors and chemotherapy.

Novel Therapies in the Treatment of Adult Acute Lymphoblastic Leukemia.

PURPOSE OF REVIEW: Acute lymphoblastic leukemia (ALL) is a rare hematologic malignancy. Advances in multi-agent chemotherapy have resulted in dramatic improvements in the number of pediatric cases that result in a cure; however, until recently, treatment options for older adults or patients with relapsed and refractory disease were extremely limited. This review seeks to describe in greater detail a number of emerging novel treatment modalities recently approved for this cancer. RECENT FINDINGS: In this review, we discuss a number of recently approved novel therapies for ALL, including new approaches with targeted tyrosine kinase inhibitors, novel immune-based therapies including the bispecific antibody blinatumomab and the antibody-drug conjugate inotuzumab ozogamicin, and the role of cellular therapeutics such as chimeric antigen receptor (CAR) T cells. We also discuss the impact that advances in diagnostics and disease classification and monitoring have had on treatment. A number of advances in ALL have resulted in dramatic changes to the treatment landscape and therapeutic options both at the time of diagnosis and in salvage. These findings are reshaping our treatment paradigms throughout the course of disease.