Epidemiology and Outcomes of Hospitalized Chimeric Antigen Receptor T-Cell (CAR-T) Therapy Patients Who Developed Acute Respiratory Failure.

Objectives:The aim of the study was to examine the incidence, baseline characteristics, and outcomes of Chimeric Antigen Receptor T-cell (CAR-T) therapy admissions in individuals who developed acute respiratory failure (ARF). The study utilized the National Inpatient Sample (NIS) database for the years 2017 to 2020. Methods: The study identified CAR-T cell therapy hospitalizations through the International Classification of Diseases, Tenth Revision, Procedure Coding System (ICD-10-PCS) codes. Patients with acute respiratory failure (ARF) were further classified using specific International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM) codes. Descriptive statistics were performed to analyze baseline characteristics, comorbidities, complications, and outcomes. Results: Analysis of the NIS Database identified 5545 CAR-T therapy admissions between 2017 and 2020, revealing a rising trend over time. In our study, we found that hypertension (39%), dyslipidemia (21.7%), and venous thromboembolism (13%) were the most frequently observed comorbidities in CAR-T cell therapy admissions. Acute respiratory failure (ARF) was reported in 7.1% of admissions, and they had higher all-cause in-hospital mortality than CAR-T cell therapy admissions without ARF (32.9% vs 1.3%, P < 0.001). ARF admissions that required invasive mechanical ventilation (IMV) also had higher all-cause in-hospital mortality compared to admissions not requiring IMV (48.9% vs 11.8%, P = 0.001). There was no difference in the mortality rate among admissions with non-Hodgkin's Lymphoma, Multiple Myeloma, and Leukemia that utilized CAR-T therapy. Conclusions: In this largest study to date, we illuminate the incidence and outcomes of CAR-T cell therapy admissions with ARF. Higher mortality rates were observed in CAR-T cell therapy admissions with ARF. The study emphasizes the crucial role of interdisciplinary collaboration in CAR-T patient management and calls for additional research to clarify ARF's etiology and inform effective management strategies.

Trends and complications associated with acute new-onset heart failure: a National Readmissions Database-based cohort study.

Literature regarding recent trends and outcomes of acute new-onset heart failure (AHF) with preserved ejection fraction (AHFpEF) and reduced ejection fraction (AHFrEF) is limited. The objective of this study is to study the outcomes of AHFpEF and AHFrEF in the USA. Data from the National Readmissions Database (NRD) sample that constitutes 49.1% of the stratified sample of all hospitals in the USA, representing more than 95% of the national population, were analyzed for hospitalization visits for acute heart failure. ICD-9 and ICD-10 codes were used to identify AHF. A total of 2,559,102 adult index AHF patients (mean age 70.79 ± 14.58 years, 49.4% females), 1,028,970 (40.2%) AHFpEF and 1,330,999 (52%) AHFrEF, were recorded in the National Readmissions Database for the years 2016-2018. A total of 152,465 (5.96%) acute heart failure, 47,271 (4.6%) AHFpEF and 91,973 (6.91%) AHFrEF, died during hospitalization, and 45,810 (1.9%) were readmitted in 30 days among alive discharges. Higher complication rates which included ventricular arrhythmias, acute coronary, and cerebrovascular events were observed among AHFrEF than AHFpEF. Higher proportion of patients with AHFrEF needed intensive care unit and ventilatory support during the hospitalization. The trend of incidence of AHFrEF, mortality among AHFrEF, and overall mortality worsened while AHFpEF improved over the study years 2012-2018 (p-trend < 0.05). Coronary procedures improved mortality rates among AHFpEF and AHFrEF. AHF is very common and is associated with significant mortality. The incidence of AHFrEF and mortality among AHFrEF had worsened, which calls for urgent intervention. Improved recognition of AHF is needed, and guideline-directed treatment of underlying risk factors including coronary artery disease can improve mortality. Graphic abstract of the analysis presented (created with BioRender.com).

ST-Elevation Myocardial Infarction Among Septic Shock and Coronary Interventions: A National Emergency Database Study.

OBJECTIVE: To study coronary interventions and mortality among patients with ST-elevated myocardial infarction (STEMI) who were admitted with septic shock. METHODS: Data from the national emergency department sample (NEDS) that constitutes 20% sample of hospital-owned emergency departments in the United States was analyzed for the septic shock related visits from 2016 to 2018. Septic shock was defined by the ICD codes. RESULTS: Out of 1 375 507 adult septic shock patients, 521 300 had a primary diagnosis of septic shock (mean age 67.41±15.67 years, 51.1% females) in the national emergency database for the years 2016 to 2018. Of these patients, 2768 (0.53%) had STEMI recorded during the hospitalization. Mortality rates for STEMI patients were higher than patients without STEMI (52.3% vs 23.5%). Mortality rates improved with PCI among STEMI patients (43.8% vs 56.2%). Coronary angiography was performed among 16% of patients of which percutaneous coronary intervention (PCI) rates were 7.7% among patients with STEMI septic shock. PCI numerically improved mortality, however, had no significant difference than patients without PCI on multivariate logistic regression and univariate logistic regression post coarsened exact matching of baseline characteristics among STEMI patients. Among the predictors, STEMI was a significant predictor of mortality in septic shock patients (OR 2.87, 95% CI 2.37-3.49; P<.001). Age, peripheral vascular disease, were predominant predictors of mortality in STEMI with septic shock subgroup (P <.001). Pneumonia was the predominant underlying infection among STEMI (36.4%) and without STEMI group (29.5%). CONCLUSION: STEMI complicating septic shock worsens mortality. PCI and coronary angiography numerically improved mortality, however, had no significant difference from patients without PCI. More research will be needed to improve mortality in such a critically ill subgroup of patients.

Thrombotic superior vena cava syndrome: a national emergency department database study.

Literature regarding etiology and trends of incidence of major thoracic vein thrombosis in the United States is limited. To study the causes, complications, in-hospital mortality rate, and trend in the incidence of major thoracic vein thrombosis which could have led to superior vena cava syndrome (SVCS) between 2010 and 2018. Data from the nationwide emergency department sample (NEDS) that constitutes 20% sample of hospital-owned emergency departments (ED) and in-patient sample in the United States were analyzed using diagnostic codes. A linear p-trend was used to assess the trends. Of the total 1082 million ED visits, 37,807 (3.5/100,000) (mean age 53.81 ± 18.07 years, 55% females) patients were recorded with major thoracic vein thrombosis in the ED encounters. Among these patients, 4070 (10.6%) patients had one or more cancers associated with thrombosis. Pacemaker/defibrillator-related thrombosis was recorded in 2820 (7.5%) patients, while intravascular catheter-induced thrombosis was recorded in 1755 (4.55%) patients. Half of the patients had associated complication of pulmonary embolism. A total of 59 (0.15%) patients died during these hospital encounters. The yearly trend for the thrombosis for every 100,000 ED encounters in the United States increased from 2.17/100,000 in 2010 to 5.98/100,000 in 2018 (liner p-trend < 0.001). Yearly trend for catheter/lead associated thrombosis was also up-trending (p-trend 0.015). SVCS is an uncommon medical emergency related to malignancy and indwelling venous devices. The increasing trend in SVCS incidence, predominantly catheter/lead induced, and the high rate of associated pulmonary embolism should prompt physicians to remain vigilant for appropriate evaluation.

Survival in Immunocompromised Patients Ultimately Requiring Invasive Mechanical Ventilation: A Pooled Individual Patient Data Analysis.

Rationale: Acute respiratory failure (ARF) is associated with high mortality in immunocompromised patients, particularly when invasive mechanical ventilation is needed. Therefore, noninvasive oxygenation/ventilation strategies have been developed to avoid intubation, with uncertain impact on mortality, especially when intubation is delayed. Objectives: We sought to report trends of survival over time in immunocompromised patients receiving invasive mechanical ventilation. The impact of delayed intubation after failure of noninvasive strategies was also assessed. Methods: Systematic review and meta-analysis using individual patient data of studies that focused on immunocompromised adult patients with ARF requiring invasive mechanical ventilation. Studies published in English were identified through PubMed, Web of Science, and Cochrane Central (2008-2018). Individual patient data were requested from corresponding authors for all identified studies. We used mixed-effect models to estimate the effect of delayed intubation on hospital mortality and described mortality rates over time. Measurements and Main Results: A total of 11,087 patients were included (24 studies, three controlled trials, and 21 cohorts), of whom 7,736 (74%) were intubated within 24 hours of ICU admission (early intubation). The crude mortality rate was 53.2%. Adjusted survivals improved over time (from 1995 to 2017, odds ratio [OR] for hospital mortality per year, 0.96 [0.95-0.97]). For each elapsed day between ICU admission and intubation, mortality was higher (OR, 1.38 [1.26-1.52]; P < 0.001). Early intubation was significantly associated with lower mortality (OR, 0.83 [0.72-0.96]), regardless of initial oxygenation strategy. These results persisted after propensity score analysis (matched OR associated with delayed intubation, 1.56 [1.44-1.70]). Conclusions: In immunocompromised intubated patients, survival has improved over time. Time between ICU admission and intubation is a strong predictor of mortality, suggesting a detrimental effect of late initial oxygenation failure.

ST-Elevation Myocardial Infarction Outcomes: A United States Nationwide Emergency Departments Cohort Study.

BACKGROUND: Literature regarding trends in incidence and mortality of ST-elevation myocardial infarction (STEMI) in emergency departments (EDs) is limited. OBJECTIVE: To study the trends of incidence and mortality of STEMI. METHODS: Using the National Emergency Department Sample database in the United States, we identified all ED encounters for patients presenting with STEMI using International Classification of Diseases codes. A linear p-trend was used to assess the trends. RESULTS: Out of the 973 million ED encounters represented, 641,762 (65/100,000; mean age 69 [59-81] years, 35.8% female) adult patients were recorded with STEMI. Among the major complications associated with STEMI, a total of 49,401 (7.7%) had cardiac complications, which included acute heart failure (n = 9361, 1.6%), ventricular tachycardia or fibrillation (n = 12,267, 1.91%), conduction block (n = 20,165, 3.1%), and cardiogenic shock (n = 7608, 1.2%). There were 5675 (0.9%) patients recorded with cerebrovascular events, which included acute ischemic stroke among 5205 (0.8%) patients and 470 (0.1%) with transient ischemic attack. Acute kidney injury was recorded for 10,082 (1.6%) patients. The trend for incidence of STEMI in the ED had decreased from 7.76/10,000 in 2011 to 4.07/10,000 in 2018 (linear p-trend 0.0006). However, the yearly mortality of STEMI related to ED encounters had remained relatively steady: 7.56% in 2011 to 7.50% in 2018 (linear p-trend 0.2364). CONCLUSION: Despite the fact that the number of patients presenting to the ED with STEMI has been decreasing, the mortality trends have remained steady. Further research of in-hospital STEMI may yield opportunities to reduce the risk of complications, improve patient outcomes and decrease health care burden.

Trends in Incidence, and Mortality of Acute Exacerbation of Chronic Obstructive Pulmonary Disease in the United States Emergency Department (2010-2018).

Literature regarding trends of incidence, mortality, and complications of acute exacerbation of chronic obstructive pulmonary disease (COPD) in the emergency departments (ED) is limited. What are trends of COPD exacerbation in ED? Data were obtained from the Nationwide Emergency Department Sample (NEDS) that constitutes a 20% sample of hospital-owned EDs and inpatient sample in the US. All ED encounters were included in the analysis. Complications of AECOPD were obtained by using ICD codes. Out of 1.082 billion ED encounters, 5,295,408 (mean age 63.31 ± 12.63 years, females 55%) presented with COPD exacerbation. Among these patients, 353,563(6.7%) had AECOPD-plus (features of pulmonary embolism, acute heart failure and/or pneumonia) while 4,941,845 (93.3%) had exacerbation without associated features or precipitating factors which we grouped as AECOPD. The AECOPD-plus group was associated with statistically significantly higher proportion of cardiovascular complications including AF (5.6% vs 3.5%; p < 0.001), VT/VF (0.14% vs 0.06%; p < 0.001), STEMI (0.22% vs 0.11%; p < 0.001) and NSTEMI (0.65% vs 0.2%; p < 0.001). The in-hospital mortality rates were greater in the AECOPD-plus population (0.7% vs 0.1%; p < 0.001). The incidence of both AECOPD and AECOPD-plus had worsened (p-trend 0.004 and 0.0003) and the trend of mortality had improved (p-trend 0.0055 and 0.003, respectively). The prevalence of smoking for among all COPD patients had increased (p-value 0.004), however, the prevalence trend of smoking among AECOPD groups was static over the years 2010-2018. There was an increasing trend of COPD exacerbation in conjunction with smoking; however, mortality trends improved significantly. Moreover, the rising burden of AECOPD would suggest improvement in diagnostics and policy making regarding management.

COPD-dependent effects of genetic variation in key inflammation pathway genes on lung cancer risk.

Genome-wide association studies (GWAS) have identified several loci contributing to lung cancer and COPD risk independently; however, inflammation-related pathways likely harbor additional lung cancer risk-associated variants in biologically relevant immune genes that differ dependent on COPD. We selected single nucleotide polymorphisms (SNPs) proximal to 2,069 genes within 48 immune pathways. We modeled the contribution of these variants to lung cancer risk in a discovery sample of 1,932 lung cancer cases and controls stratified by COPD status and validation sample of 953 cases and controls also stratified by COPD. There were 43 validated SNPs in those with COPD and 60 SNPs in those without COPD associated with lung cancer risk. Furthermore, 29 of 43 and 28 of 60 SNPs demonstrated a statistically significant interaction with COPD in the pooled sample. These variants demonstrated tissue-dependent effects on proximal gene expression, enhanced network connectivity and resided together in specific immune pathways. These results reveal that key inflammatory related genes and pathways, not found in prior GWAS, impact lung cancer risk in a COPD-dependent manner. Genetic variation identified in our study supplements prior lung cancer GWAS and serves as a foundation to further interrogate risk relationships in smoking and COPD populations.

Influenza and Pneumocystis jirovecii pneumonia in an allogeneic hematopoietic stem cell transplantation recipient: Coinfection or superinfection?

Influenza infection and Pneumocystis jirovecii pneumonia (PJP) in hematopoietic stem cell transplant (HSCT) patients are well characterized; however, no dual infections have been reported in this patient population and little evidence of mechanisms of interaction between the two infections exists. We present a 53-year-old male allogeneic HSCT patient on immunosuppressive therapy for the treatment of graft versus host disease initially diagnosed with influenza A H3 and later PJP. Despite the development of acute respiratory distress syndrome, the patient was successfully treated with appropriate antimicrobial therapy and aggressive supportive care. This case demonstrates the necessity of maintaining a high index of suspicion for fungal (including PJP) coinfection or superinfection in the setting of worsening influenza infection.

Tenofovir alafenamide associated fatal lactic acidosis in an autologous hematopoietic stem cell transplant recipient.

Fatal lactic acidosis has been reported while on the treatment with Nucleoside/nucleotide analogues (NA) for the treatment of hepatitis B, C and HIV. No cases of such a complication have been reported in hematopoietic stem cell transplant (HSCT) recipients. We present a 65-year male who underwent autologous HSCT for the treatment of multiple myeloma. Prior to transplant he was started on single agent tenofovir alafenamide (TAF) for treatment of resolved hepatitis B infection. He presented few weeks later with severe lactic acidosis. Other causes of lactic acidosis were excluded. The patient died of multi-organ failure despite stopping TAF and aggressive supportive care. The case demonstrates the need for increased awareness of this potential complication of NA treatment in the course of transplantation.

Trends in Outcomes, Financial Burden, and Mortality for Acute Exacerbation of Chronic Obstructive Pulmonary Disease (COPD) in the United States from 2002 to 2010.

Chronic obstructive pulmonary disease (COPD) is the cause of substantial economic and social burden. We evaluated the temporal trends of hospitalizations from acute exacerbation of COPD and determined its outcome and financial impact using the National (Nationwide) Inpatient Sample (NIS) databases (2002-2010). Individuals aged ≥ 18 years were included. Subjects who were hospitalized with primary diagnosis of COPD exacerbation and those who were admitted for other causes but had underlying acute exacerbation of COPD (secondary diagnosis) were captured by International Classification of Diseases-Ninth Revision (ICD-9) codes. The hospital outcomes and length of stay were determined. Multivariate logistic regression was used to identify the independent predictors of inpatient mortality. Overall acute exacerbation of COPD-related hospitalizations accounted for nearly 3.31% of all hospitalizations in the year 2002. This did not change significantly to year 2010 (3.43%, p = 0.608). However, there was an increase in hospitalization with secondary diagnosis of COPD. Elderly white patients accounted for most of the hospitalizations. Medicare was the primary payer source for most of the hospitalizations (73-75%). There was a significant decrease in inpatient mortality from 4.8% in 2002 to 3.9% in 2010 (slope -0.096, p < 0.001). Similarly, there was a significant decrease in average length of stay from 6.4 days in 2002 to 6.0 days in 2010 (slope -0.042, p < 0.001). Despite this, the hospitalization cost was increased substantially from $22,187 in 2002 to $38,455 in 2010. However, financial burden has increased over the years.

Whole-exome sequencing reveals genetic variability among lung cancer cases subphenotyped for emphysema.

Lung cancer continues to be a major public health challenge in the United States despite efforts to decrease the prevalence of smoking; outcomes are especially poor for African-American patients compared to other races/ethnicities. Chronic obstructive pulmonary disease (COPD) co-occurs with lung cancer frequently, but not always, suggesting both shared and distinct risk factors for these two diseases. To identify germline genetic variation that distinguishes between lung cancer in the presence and absence of emphysema, we performed whole-exome sequencing on 46 African-American lung cancer cases (23 with and 23 without emphysema frequency matched on age, sex, histology and pack years). Using conditional logistic regression, we found 6305 variants (of 168 150 varying sites) significantly associated with lung cancer subphenotype (P ≤ 0.05). Next, we validated 10 of these variants in an independent set of 612 lung cancer cases (267 with emphysema and 345 without emphysema) from the same population of inference as the sequenced cases. We found one variant that was significantly associated with lung cancer subphenotype in the validation sample. These findings contribute to teasing apart shared genetic factors from independent genetic factors for lung cancer and COPD.

Bronchoscopy can be done safely in patients with thrombocytopenia.

BACKGROUND: Prophylactic platelet (PLT) transfusions are often administered to patients before bronchoscopy or bronchoalveolar lavage (BAL) to prevent bleeding. There is a paucity of data to validate this approach, with a commonly suggested PLT transfusion threshold of fewer than 50 × 10(9) /L, largely based on expert opinion. We conducted a retrospective study on the incidence of bleeding complications in patients with thrombocytopenia undergoing bronchoscopy. STUDY DESIGN AND METHODS: We identified 150 consecutive patients with PLT counts of not more than 100 × 10(9) /L who underwent bronchoscopy and/or BAL from January 2009 to May 2014 at our institution. The British Thoracic Society (BTS) guidelines were used to categorize bleeding associated with bronchoscopy. RESULTS: Infection (40%) was the primary indication for bronchoscopy with BAL. Fifty-eight of 89 (65%) patients with baseline PLT counts of not more than 50 × 10(9) /L received prophylactic transfusions compared to 8% of those with PLT counts of more than 50 × 10(9) /L. The PLT count did not increase to more than 50 × 10(9) /L in many patients who received transfusions. Seventy-two patients had counts of less than 50 × 10(9) /L at the time of bronchoscopy, with 15 patients having counts of less than 20 × 10(9) /L. Only one patient with a PLT count of 61 × 10(9) /L had bleeding that required continuous suctioning but then resolved spontaneously (termed "mild bleeding" by BTS criteria). Bloody lavage that resolved spontaneously without continuous suctioning (termed "no bleeding" by the BTS criteria) was observed in nine (6%) patients. CONCLUSION: The very low incidence of bleeding complications from bronchoscopy with or without BAL even in patients with PLT counts of not more than 30 × 10(9) /L (no episodes of clinically significant bleeding in 35 patients) demonstrates that bronchoscopy can be done safely in patients with severe thrombocytopenia.

Azithromycin improves lung function in patients with post-lung transplant bronchiolitis obliterans syndrome: a meta-analysis.

INTRODUCTION: Azithromycin has been shown to reverse or halt the decline of forced expiratory volume in one s (FEV1) in patients with bronchiolitis obliterans (BOS) syndrome following lung transplant. The overall effect of azithromycin on the absolute values of FEV1 has not been compared between reported studies. We studied the effects of azithromycin on lung function in patients with post-lung transplant BOS syndrome. METHODS: A meta-analysis was performed using studies identified following an extensive database search. To be included, studies were published in English or French and explicitly reported percentage change in FEV1 or hazard ratios. RESULTS: A total of 10 studies were included in this review. One hundred and forty patients were evaluated after treatment with azithromycin for an average follow-up period of seven months. The mean percentage increase in FEV1 was 8.8 (CI 5.1-12.47) p < 0.001. The pooled hazard ratio was 0.25 (CI 0.06-0.56) p = 0.041 for a mean follow-up period of 2.9 yr. CONCLUSION: This study demonstrated a significant improvement in lung function in patients with BOS syndrome following lung transplant after seven months of treatment. It remains uncertain whether this improvement stays after seven months. We also found that patients on azithromycin were less likely to die from BOS syndrome compared with patients who were not on azithromycin.

Lung transplantation following hematopoietic stem cell transplantation: report of two cases and systematic review of literature.

BACKGROUND: Non-infectious pulmonary complications following hematopoietic stem cell transplantation (HSCT) are major cause of morbidity and mortality with limited treatment options. Lung transplantation (LT) has been rarely reported as a treatment option for selected HSCT recipients with these problems. OBJECTIVE: Describe the outcome of HSCT recipients who underwent LT. METHODS: Two cases of LT following HSCT from our institution are presented. Cases reported in literature were identified using English language PubMed/MEDLINE with keywords hematopoietic stem cell transplantation, bone marrow transplantation, or bronchiolitis obliterans cross-referenced with lung transplantation. We extracted data on baseline characteristics and survival data following LT. RESULTS: Total of 84 patients are analyzed. Age at time of LT was median of 22 yr (range 1-66). Seventy-nine patients were recipients of allogeneic HSCT. The indications for LT were bronchiolitis obliterans syndrome (BOS; 63 patients), pulmonary fibrosis (13 patients), BOS/pulmonary fibrosis (five patients), and graft-versus-host-disease (GVHD) of lung (three patients). The median time between HSCT and LT was 52.3 months (range 6-240). The median follow-up after LT was 36 months (range 0-168). During this time, BOS was documented in 25 patients. Relapse of hematological malignancy was reported in two patients, and new malignancy developed in four patients. At the end of follow-up, 60 patients were alive and 24 patients died. The probability of survival following LT at 24 and 36 months was 0.88 (95% CI 0.78-0.93) and 0.79 (95% CI 0.67-0.87), respectively. CONCLUSION: LT is a potential therapeutic option in selected patients with severe chronic pulmonary disease following HSCT. Further studies are needed to determine the appropriate timing and the outcome of this approach.

A Study on the Epidemiology of COVID-19-Related Guillain-Barré Syndrome in the United States.

INTRODUCTION: Several neurological complications have been reported with COVID-19, including Guillain-Barré syndrome (GBS). We looked at incidence, baseline characteristics, and in-hospital outcomes of COVID-19-associated GBS in the United States. STUDY DESIGN AND METHODS: We conducted a retrospective analysis using the US National Inpatient Sample database to identify hospitalizations for COVID-19 and GBS, using International Classification of Disease, 10th Revision, codes G610 and G650 for GBS and U071 for COVID-19. The codes used in this study are listed in Supplemental Digital Content 1 (see e Appendix, http://links.lww.com/JCND/A69). RESULTS: In total, 13,705 GBS admissions were recorded nationwide in 2020; of these, 1155 (8.43%) were associated with COVID-19. The frequency of GBS in COVID-19 admissions was 0.07%, compared with 0.08% in non-COVID-19 admissions (P = 0.8166). COVID-19 cohort with GBS had higher utilization of invasive mechanical ventilation (20.8% vs. 11.8%, P < 0.001) in comparison with COVID-19 cohort without GBS. GBS admissions with COVID-19 exhibited significantly higher inpatient mortality (12.2% vs. 3%, P < 0.001) compared with GBS admissions without COVID-19. INTERPRETATION: Our findings underscore GBS as a rare yet severe complication of COVID-19, highlighting a significant difference in mortality when compared with GBS not associated with COVID-19.

Incidence and inhospital outcomes of coronavirus disease 2019-associated pulmonary aspergillosis in the United States.

OBJECTIVE: The aim of this study was to estimate the predictors, associations, and outcomes of COVID-19-associated pulmonary disease (CAPA) in the United States. STUDY DESIGN AND METHODS: This retrospective cohort study was performed by using the National Inpatient Sample Database 2020 to identify coronavirus disease 2019 (COVID-19) and CAPA hospitalizations. Baseline variables and outcomes were compared between COVID-19 hospitalizations without aspergillosis and those with aspergillosis. These variables were then used to perform an adjusted analysis for obtaining predictors and factors associated with CAPA and its inhospital mortality. RESULTS: Of the 1,020,880 hospitalizations identified with the principal diagnosis of COVID-19, CAPA was identified in 1510 (0.1%) hospitalizations. The CAPA cohort consisted of a higher proportion of males (58%) as well as racial and ethnic minorities (Hispanics, Blacks, and others [including Asian or Pacific islanders, native Americans]). Inhospital mortality was significantly higher (47.35% vs. 10.87%, P < 0.001), the average length of stay was longer (27.61 vs. 7.29 days, P < 0.001), and the mean cost per hospitalization was higher ($121,560 vs. $18,423, P < 0.001) in the CAPA group compared to COVID-19 without aspergillosis. History of solid organ transplant, chronic obstructive pulmonary disease, and venous thromboembolism were associated with higher odds of CAPA among other factors. The use of invasive mechanical ventilation (adjusted odds ratio [aOR] 6.24, P < 0.001), acute kidney injury (aOR 2.02, P = 0.028), and septic shock (aOR 2.07, P = 0.018) were associated with higher inhospital mortality in the CAPA cohort. CONCLUSION: While CAPA is an infrequent complication during hospitalizations for COVID-19, it significantly increases all-cause mortality, prolongs hospital stays, and leads to higher hospital expenses compared to COVID-19 cases without aspergillosis.

Outcomes and Long-Term Survival of Adolescent and Young Adult Patients Admitted to the Intensive Care Unit Following Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Experience of 152 Patients.

BACKGROUND AND OBJECTIVES: Prognostic factors reliably predicting outcomes for critically ill adolescent and young adult (AYA) patients undergoing allogeneic hematopoietic cell transplantation (allo-HSCT) are lacking. We assessed transplant and intensive care unit (ICU)-related factors impacting patient outcomes. PATIENTS AND METHODS: AYA patients who underwent allo-HSCT and required ICU admission at a Tertiary care Centre, during the period of 2003-2013, were included in this retrospective review. This was a non-interventional study. Only outcomes after the first allo-HSCT and index ICU admissions were analyzed. Disease-, transplant-, and ICU-related variables were analyzed to identify risk factors predictive of survival. RESULTS: Overall, 152 patients were included (males, 60.5%); median age at transplantation was 24 years (interquartile range [IQR] 18-32.5); median age at admission to the ICU was 25.8 years (IQR 19-34). Eighty-four percent underwent transplantation for a hematological malignancy; 129 (85%) received myeloablative conditioning. Seventy-one percent of ICU admissions occurred within the first year after allo-HSCT. ICU admission was primarily due to respiratory failure (47.3%) and sepsis (43.4%). One hundred and three patients (68%) died within 28 days of ICU admission. The 1- and 5-year overall survival rates were 19% and 17%, respectively. Main causes for ICU-related death were refractory septic shock with multiorgan failure (n = 49, 32%) and acute respiratory distress syndrome (ARDS) (n = 39, 26%). Univariate analysis showed that ICU mortality was associated with an Acute Physiology and Chronic Health Evaluation (APACHE) II score >20, a sequential organ failure assessment (SOFA score) > 12, a high lactate level, anemia, thrombocytopenia, leukopenia, hyperbilirubinemia, a high international normalized ratio (INR) and acute graft-versus-host disease (GVHD). Multivariate analysis identified thrombocytopenia, high INR, and acute GVHD as independent predictors of mortality. CONCLUSIONS: In AYA allo-HSCT patients admitted to the ICU, mortality remains high. Higher SOFA and APACHE scores, the need for organ support, thrombocytopenia, coagulopathy, and acute GVHD predict poor outcomes.