Carl Shanholtz - Academia.edu (original) (raw)

Papers by Carl Shanholtz

BMJ (Clinical research ed.), Jan 5, 2012

To evaluate the association of volume limited and pressure limited (lung protective) mechanical v... more To evaluate the association of volume limited and pressure limited (lung protective) mechanical ventilation with two year survival in patients with acute lung injury. Prospective cohort study. 13 intensive care units at four hospitals in Baltimore, Maryland, USA. 485 consecutive mechanically ventilated patients with acute lung injury. Two year survival after onset of acute lung injury. 485 patients contributed data for 6240 eligible ventilator settings, as measured twice daily (median of eight eligible ventilator settings per patient; 41% of which adhered to lung protective ventilation). Of these patients, 311 (64%) died within two years. After adjusting for the total duration of ventilation and other relevant covariates, each additional ventilator setting adherent to lung protective ventilation was associated with a 3% decrease in the risk of mortality over two years (hazard ratio 0.97, 95% confidence interval 0.95 to 0.99, P=0.002). Compared with no adherence, the estimated absolu...

Trials

Background Convalescent plasma is being used widely as a treatment for coronavirus disease 2019 (... more Background Convalescent plasma is being used widely as a treatment for coronavirus disease 2019 (COVID-19). However, the clinical efficacy of COVID-19 convalescent plasma is unclear. Methods The Passive Immunity Trial for Our Nation (PassITON) is a multicenter, placebo-controlled, blinded, randomized clinical trial being conducted in the USA to provide high-quality evidence on the efficacy of COVID-19 convalescent plasma as a treatment for adults hospitalized with symptomatic disease. Adults hospitalized with COVID-19 with respiratory symptoms for less than 14 days are eligible. Enrolled patients are randomized in a 1:1 ratio to 1 unit (200–399 mL) of COVID-19 convalescent plasma that has demonstrated neutralizing function using a SARS-CoV-2 chimeric virus neutralization assay. Study treatments are administered in a blinded fashion and patients are followed for 28 days. The primary outcome is clinical status 14 days after study treatment as measured on a 7-category ordinal scale ass...

Introduction Sepsis-induced acute lung injury (ALI) has been reported to have a higher case fatal... more Introduction Sepsis-induced acute lung injury (ALI) has been reported to have a higher case fatality rate than other causes of ALI. However, differences in the severity of illness in septic vs. non-septic ALI patients might explain this finding. Methods 520 patients enrolled in the Improving Care of ALI Patients Study (ICAP) were prospectively characterized as having sepsis or non sepsis-induced ALI. Biologically plausible risk factors for in-hospital death were considered in multiple logistic regression models to evaluate the independent association of sepsis vs. non-sepsis ALI risk factors with mortality. Results Patients with sepsis-induced ALI had greater illness severity and organ dysfunction (APACHE II and SOFA scores) at ALI diagnosis and higher crude in-hospital mortality rates compared with non-sepsis ALI patients. Patients with sepsis

Infection Control & Hospital Epidemiology

Background: Prompt diagnosis and intervention for ventilator-associated pneumonia (VAP) is critic... more Background: Prompt diagnosis and intervention for ventilator-associated pneumonia (VAP) is critical but can lead to overdiagnosis and overtreatment. Objectives: We investigated healthcare provider (HCP) perceptions and challenges associated with VAP diagnosis, and we sought to identify opportunities for diagnostic stewardship. Methods: We conducted a qualitative study of 30 HCPs at a tertiary-care hospital. Participants included attending physicians, residents and fellows (trainees), advanced practice providers (APPs), and pharmacists. Interviews were composed of open-ended questions in 4 sections: (1) clinical suspicion and thresholds for respiratory culture ordering, (2) preferences for respiratory sample collection, (3) culture report interpretation, and (4) VAP diagnosis and treatment. Interviews transcripts were analyzed using Nvivo 12 software, and responses were organized into themes. Results: Overall, 10 attending physicians (75%) and 16 trainees (75%) trainees and APPs beli...

Blood

Introduction : With increased use of CAR-T for relapsed/refractory (R/R) large B-cell lymphoma (L... more Introduction : With increased use of CAR-T for relapsed/refractory (R/R) large B-cell lymphoma (LBCL), CAR-T related complications including cytokine release syndrome (CRS) and ICANS pose a significant clinical challenge. While CAR-T mediated inflammation leading to endothelial activation and blood-brain barrier disruption may play a key role in ICANS, the exact mechanism remains unclear. Prognostic or predictive biomarkers for ICANS are not well established. Recent reports (Karschnia et al, Blood 2019) suggested an association between ICANS and inferior overall survival (OS). To better understand ICANS, we herein report a single-center analysis of LBCL patients treated with CD19-directed CAR-T, exploring the associated clinical features, predictive biomarkers, and its prognostic significance. Methods: Patients (pts) with R/R LBCL treated with axicabtagene ciloleucel (Axi-cel) between 4/2018-5/2019 were identified. Data regarding patient and disease characteristics, treatment course...

Chest

extubation failures occurred within 48 hours. In the univariate model extubation failure was sign... more extubation failures occurred within 48 hours. In the univariate model extubation failure was significantly associated with lower serum albumin (albumin < 2.5 g/dL, odds ratio [OR] 1⁄4 6.1; 95% [CI], 3.04-14.66), lower hemoglobin (hemoglobin < 9.0 g/dL, OR 1⁄4 10.2; 95% CI, 6.00-28.04), positive cumulative fluid balance (+1.5 L, OR 1⁄4 7.2; 95 % CI 1.20 53.0) and lower GCS scores (GCS score # 9, OR 1⁄4 6.1; 95% CI 1⁄4 1.15-32.34). Further multivariate logistic regression analysis revealed an association of delta

American Journal of Hematology

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the care of patients with rel... more Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the care of patients with relapsed or refractory (R/R) large B cell lymphoma (LBCL). Tisagenlecleucel and Axicabtagene Ciloleucel, two anti-CD19 CART therapies, are approved by the United States Food and Drug Administration for the treatment of R/R LBCL after two or more lines of systemic therapy. Despite unprecedented efficacy of CART therapy in this multiply R/R setting with overall responses up to 83% and 58% complete responses 1 , relapses post CART therapy remain challenging to treat. In patients with B-acute lymphoblastic leukemia (ALL), resistance to CART therapy is thought to be due in part to emergence of CD19 negative escape variants 2 ; however, this mechanism of relapse is not well-established after CART therapy for r/r LBCL. Herein, we report two patients with R/R LBCL who experienced a CD19-negative disease relapse following anti-CD19 CART therapy. Two patients with CD19-negative disease relapse were identified from the University of Maryland Cellular Therapy database. The study and analysis was approved by the local institutional review board. Patient 1: A previously healthy 60-year-old woman was diagnosed with LBCL, treated with R-CHOP, and subsequently achieved durable complete remission (CR). Fourteen years later, she developed new adenopathy, and a lymph node biopsy showed small lymphocytic lymphoma (SLL) without peripheral blood lymphocytosis. Two years later, her lymphadenopathy worsened, and a positron emission tomography/computed tomography (PET/CT) showed dif

Critical care medicine, 2018

High fractions of inspired oxygen may augment lung damage to exacerbate lung injury in patients w... more High fractions of inspired oxygen may augment lung damage to exacerbate lung injury in patients with acute respiratory distress syndrome. Participants enrolled in Acute Respiratory Distress Syndrome Network trials had a goal partial pressure of oxygen in arterial blood range of 55-80 mm Hg, yet the effect of oxygen exposure above this arterial oxygen tension range on clinical outcomes is unknown. We sought to determine if oxygen exposure that resulted in a partial pressure of oxygen in arterial blood above goal (> 80 mm Hg) was associated with worse outcomes in patients with acute respiratory distress syndrome. Longitudinal analysis of data collected in these trials. Ten clinical trials conducted at Acute Respiratory Distress Syndrome Network hospitals between 1996 and 2013. Critically ill patients with acute respiratory distress syndrome. None. We defined above goal oxygen exposure as the difference between the fraction of inspired oxygen and 0.5 whenever the fraction of inspire...

Critical care (London, England), Jan 2, 2018

Thorax

BackgroundDelayed return to work is common after acute respiratory distress syndrome (ARDS), but ... more BackgroundDelayed return to work is common after acute respiratory distress syndrome (ARDS), but has undergone little detailed evaluation. We examined factors associated with the timing of return to work after ARDS, along with lost earnings and shifts in healthcare coverage.MethodsFive-year, multisite prospective, longitudinal cohort study of 138 2-year ARDS survivors hospitalised between 2004 and 2007. Employment and healthcare coverage were collected via structured interview. Predictors of time to return to work were evaluated using Fine and Grey regression analysis. Lost earnings were estimated using Bureau of Labor Statistics data.ResultsSixty-seven (49%) of the 138 2-year survivors were employed prior to ARDS. Among 64 5-year survivors, 20 (31%) never returned to work across 5-year follow-up. Predictors of delayed return to work (HR (95% CI)) included baseline Charlson Comorbidity Index (0.77 (0.59 to 0.99) per point; p=0.04), mechanical ventilation duration (0.67 (0.55 to 0.82...

Journal of Critical Care, 2017

Pandemic influenza A pdm09 (pH1N1) virus was the predominant isolate identified during the 2009-1... more Pandemic influenza A pdm09 (pH1N1) virus was the predominant isolate identified during the 2009-10 and 2013-14 influenza outbreaks, causing significant morbidity and mortality. We describe clinical characteristics of critically ill patients during 2 pH1N1 outbreaks. Single-center, retrospective cohort study of patients admitted to the intensive care unit receiving oseltamivir for suspected influenza during 2 outbreak periods. Demographics and comorbidities were collected from the medical record. Outcomes included use of adjunct oxygenation therapies and oseltamivir dosing. One hundred twenty-four patients were included (2009, n=53; 2013, n=71). Demographics were as follows: mean (SD) age, 52.3 (14.2) years; mean (SD) Acute Physiology and Chronic Health Evaluation II score, 19.4 (9.2); 71% had greater than or equal to 2 comorbidities; and mortality was 27%. Inhaled nitric oxide was administered more commonly in 2009 (P=.01), whereas neuromuscular blockade (P=.02) and epoprostenol were administered more commonly in 2013 (P=.01). Patients in 2009 were more likely to receive high-dose oseltamivir (P=.02; odds ratio, 1.8; 95% confidence interval, 1.18-6.62). No differences in clinical outcomes were observed between 2009 and 2013. Use of adjunct oxygenation therapies and nontraditional antiviral dosing has changed significantly since the 2009 pandemic, although this has not resulted in a measurable impact on clinical outcomes.

Thorax, Oct 20, 2017

To inform selection of physical measures for studies of acute respiratory distress syndrome (ARDS... more To inform selection of physical measures for studies of acute respiratory distress syndrome (ARDS) survivors within 12 months of ARDS. Secondary analysis of data from 6-month survivors participating in a US multicentre prospective study (ARDSNet Long-Term Outcome Study, N=134) or a multisite prospective study in Baltimore, Maryland, USA (Improving Care of Acute Lung Injury Patients, N=99). Physical measures, assessed at 6-month follow-up, were categorised according to the WHO's International Classification of Disability and Health: body functions and structures, activity and participation. Patient-centred outcomes were evaluated at 6 and 12 months: survival, hospitalisation, alive at home status and health-related quality of life. Pearson correlation, linear and logistic regression models were used to quantify associations of physical measures with patient-centred outcomes. No 6-month body functions and structures measure demonstrated consistent association with 6-month or 12-mo...

Intensive Care Medicine, 2016

Survivors of acute respiratory distress syndrome (ARDS) are at high risk for new or ongoing physi... more Survivors of acute respiratory distress syndrome (ARDS) are at high risk for new or ongoing physical declines after hospital discharge. The objective of our study was to evaluate the epidemiology of physical declines over 5-year follow-up and identify patients at risk for decline. This multi-site prospective cohort study evaluated ARDS survivors who completed a physical status assessment at 3 or 6 months post-discharge. Three measures were evaluated: muscle strength (Medical Resource Council sumscore); exercise capacity [6-min walk test (6MWT)]; physical functioning [36-Item Short Form Health Survey (SF-36 survey)]. Patients were defined as &amp;amp;amp;quot;declined&amp;amp;amp;quot; if a comparison of their current and prior score showed a decrease that was greater than the Reliable Change Index-or if the patient died. Risk factors [pre-ARDS baseline status, intensive care unit (ICU) illness severity, and other intensive care variables] were evaluated using longitudinal, generalized linear regression models for each measure. During the follow-up of 193 ARDS survivors (55 % male; median age 49 years), 166 (86 %) experienced decline in ≥1 physical measure (including death) and 133 (69 %) experienced a physical decline (excluding death). For all measures, age was a significant risk factor [odds ratios (OR) 1.34-1.69 per decade; p &amp;amp;amp;lt; 0.001]. Pre-ARDS comorbidity (Charlson Index) was independently associated with declines in strength and exercise capacity (OR 1.10 and 1.18, respectively; p &amp;amp;amp;lt; 0.02), and organ failure [maximum daily Sequential Organ Failure Assessment (SOFA) score in ICU] was associated with declines in strength (OR 1.06 per 1 point of SOFA score; p = 0.02). Over the follow-up period, the majority of ARDS survivors experienced a physical decline, with older age and pre-ICU comorbidity being important risk factors for this decline.

Critical care clinics, 2016

Acute and chronic liver failure are associated with numerous alterations in different features of... more Acute and chronic liver failure are associated with numerous alterations in different features of the coagulation system. Consequently, there is widespread confusion regarding the potential for both bleeding and thrombosis in patients with liver disease. The risk of bleeding is related to the hemodynamic changes in portal pressures and venous congestion whereas the thrombotic risk stems from changes in the coagulation system. Antithrombotic prophylaxis and treatment of patients with hemorrhage and thrombosis requires careful assessment, interpretation of laboratory workup, and attention to coexistent morbidities. A framework for the management of these conditions is presented for clinicians.

Critical Care Medicine, Aug 1, 1999

From the Division of Pulmonary and Critical Care Medicine of the Department of Medicine (Drs. Bro... more From the Division of Pulmonary and Critical Care Medicine of the Department of Medicine (Drs. Brower, Fessler, Shade, White, and Wiener), the Department of Anesthesiology and Critical Care Medicine (Drs. Dodd-o and Almog), and the Department of Oncology-Biostatistics ...

Clinical Pulmonary Medicine, 1999

BMJ case reports, Jan 4, 2016