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Introduction Prone positioning in mechanically ventilated patients with severe acute respiratory distress syndrome (ARDS) is associated with improved mortality. More data is needed to fully understand its utility in those with ARDS due to COVID-19. Methods We conducted a single center prospective observational study inclusive of 100 consecutive patients intubated for ARDS from COVID-19 admitted to the ICU from September 2020 to December 2020. Data was collected daily from time of intubation for 7 days along with 30-day outcomes. Results The study included a total of 53 patients proned and 47 non-proned during their hospitalization. Proned patients were 61.8 years old, and 56.6% men compared to 66.3 years old and 57.4% male in the non-proned group. Other baseline characteristics and treatments were similar between both groups other than proned patients having a higher BMI than non-proned patients (34.1 ± 7.5 vs 30.5 ± 7.4, p = 0.02), and lower initial P/F ratios (119.1 ± 54.5 vs 154.0 ± 92.7, p = 0.047). Proned patients required more neuromuscular blockade (OR 6.63, 95% CI 3.25–13.12, p

Objective: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a relatively safe and minimally invasive procedure frequently used to investigate mediastinal lymphadenopathy of unknown etiology. Due to its safety in comparison to mediastinoscopy, which is the diagnostic gold standard, EBUS-TBNA can be used as the first-line diagnostic modality for approaching mediastinal lymphadenopathy in suspected sarcoidosis. In this study, we evaluated the diagnostic yield and safety of EBUS-TBNA for sarcoidosis at our institution. Methods: A retrospective review was performed for all patients who presented with mediastinal lymphadenopathy and underwent EBUS-TBNA for presumed sarcoidosis for a three-year period and subsequently diagnosed with sarcoidosis. Twenty-five patients were included, and parameters such as nodal station sampled, radiographic stage, adverse events, alternative diagnosis method, and symptoms were recorded. Results: Thirteen of 25 patients had non-caseating granulomas on EBUS-TBNA with a diagnostic yield of 52%. Of 12 patients not diagnosed via EBUS-TBNA, a diagnosis was made in four patients (33%) via transbronchial lung biopsy, in three (25%) via mediastinoscopy, in one (8%) via video-assisted thoracoscopic surgery, in three (25%) with an elevated bronchoalveolar lavage (BAL) CD4/CD8 ratio and response to therapy, and in one (8%) via muscle biopsy. The average BAL CD4/CD8 ratio was 5.4 for all patients with sarcoidosis. All patients tolerated the procedure without major complications. Conclusion: EBUS-TBNA is a useful and minimally invasive tool for the diagnosis of sarcoidosis. It should be used as the first-line diagnostic study in suspected sarcoidosis if mediastinal lymphadenopathy is present.

Organizing pneumonia (OP) is a poorly understood complication of hematopoietic stem cell transplant (HSCT). We identified 15 patients diagnosed with OP following HSCT and described their clinical course. CT chest findings were remarkable for multifocal infiltrates that were predominantly consolidating or ground glass opacities. Bronchoalveolar lavage (BAL) was performed on 14 patients with five having lymphocytosis (> 25% lymphocytes), three with eosinophilia (> 5% eosinophils), three with neutrophilia (> 30% neutrophils), and three with normal cell counts. Flow cytometry was analyzed on BAL fluid in 13 patients with 11 having a CD4/CD8 of

Extracorporeal photopheresis (ECP) is a commonly used treatment for severe graft-versus-host-disease (GVHD). We sought to evaluate the effects of ECP over a prolonged period on forced expiratory volume in 1 s (FEV1) in patients with pulmonary GVHD. We identified eight patients who developed new airflow obstruction following allogeneic stem cell transplantation and a substantial decline in FEV1 despite receiving corticosteroids and standard therapy for pulmonary GVHD. Those eight patients were treated with ECP for a period of 1 year, with a primary endpoint of FEV1 change during this treatment period. Over the first 3 months of ECP, there was no further decline in FEV1 in seven of the eight patients. However, over the 1 year period, only two of the eight patients had stability in FEV1. The rate of FEV1 decline was substantially less once ECP was initiated, though the median FEV1 continued to decline over 1 year of therapy. All patients survived through the first year of ECP therapy. There was a significant decrease in the median dose of prednisone per patient throughout the 12 months of ECP treatment. ECP shows promise in slowing rate of decline of FEV1 in pulmonary GVHD, though the effects may not be long lived. J. Clin. Apheresis 31:347-352, 2016. © 2015 Wiley Periodicals, Inc.

Rituximab is an anti-CD20 monoclonal antibody that is used to suppress B-cell function in graft-versus-host-disease (GVHD). We sought to determine the effects of rituximab treatment on lung function in those patients with bronchiolitis obliterans syndrome (BOS) as a manifestation of GVHD. Thirteen patients were treated with rituximab with a diagnosis of BOS and a significant reduction in the forced expiratory volume in 1 s (FEV1) after hematopoietic stem cell transplantation (HSCT). The changes in their pulmonary function for 12 months following treatment with rituximab were followed, along with other intervention performed and daily average dosing of prednisone. Following rituximab administration, there was an improvement in the slope of decline in lung function from −5.12 ml/month prior to rituximab infusion to −0.31 ml/month after 3 months and to +2.27 ml/month 12 months later. Seven of the 13 patients had an increase in their FEV1 after treatment with rituximab. Additionally, the mean daily dose of prednisone decreased from 27 mg prior to rituximab treatment to 11 mg 12 months after treatment. Nine out of 13 patients survived 12 months after rituximab treatment. All of the patients with improvement in FEV1 following rituximab treatment were receiving concomitant extracorporeal photopheresis. Rituximab is safe with the potential to stabilize or improve lung function in patients with BOS after HSCT and should be considered as a treatment option in those patients.

Pre-engraftment syndrome (PES) is a condition occurring after umbilical cord blood transplantation (UCBT) characterized by fever and erythematous skin rash prior to neutrophil engraftment. We sought to determine the incidence and characterize the pulmonary manifestations of PES. A retrospective review of patients who underwent UCBT at the University of Kansas Medical Center over a 5-year period was performed. Data collected included patient baseline characteristics, presence of PES, pulmonary findings, treatments, and survival. Forty-four patients underwent UCBT with 22 of those patients developing PES. Full-intensity myeloablative conditioning regimen was found to be a risk factor for development of PES. Of those 22 patients, 13 had resting hypoxemia. The most common radiographic findings included diffuse ground glass opacities with pleural effusions. Fifteen patients with PES received corticosteroids, of which 12 had improvement in fevers and rash. These patients had a trend toward worse mortality than those not receiving corticosteroids. There was a nonsignificant trend toward worse survival in patients with PES and hypoxemia compared to those without hypoxemia. PES is a common complication following cord blood transplantation, with hypoxemia being present in over half of patients with PES. Hypoxemia with PES and treatment with corticosteroids may portend a worse prognosis.

Introduction: Fiber-optic bronchoscopy (FOB) with bronchoalveolar lavage (BAL) is a common procedure performed in immunocompromised patients with undiagnosed pulmonary pathology. Identifying patients with the highest potential diagnostic yield may help to avoid morbidity in patients unlikely to benefit from the procedure. We sought to determine which patient factors, specifically chest computed tomography (CT) findings, affected diagnostic yield of BAL. Methods: Retrospective chart review of immunocompromised patients who underwent FOB with BAL from 01/01/2010 to 12/31/2011 at an academic medical center was performed. The lung lobe lavaged, characteristics of pulmonary infiltrate on radiograph, patient symptoms, and diagnostic yield were collected. A positive diagnostic yield was defined as a positive microbiological culture, finding on cytopathologic staining, diffuse alveolar hemorrhage, alveolar eosinophilia or a positive immunologic or nucleic acid assay. Results: The overall diagnostic yield was 52.6%. Infiltrates that were predominantly reticular or nodular by CT had a lower diagnostic yield than predominantly consolidated, ground-glass, or tree-in-bud infiltrates (36.5% vs. 61.2%, P = 0.0058). The diagnostic yield was significantly improved in patients with both fever and chest symptoms compared to patients without symptoms (61.3% vs. 29.6%, P = 0.0066). Conclusion: CT findings of reticular and nodular infiltrates portend a worse diagnostic yield from BAL than those that are alveolar in nature. Symptomatic patients are more likely to have diagnostic FOB with BAL than asymptomatic patients.

Case Presentation A 19-year-old previously healthy man presented, minimally responsive, in respiratory distress to an ED after a 2-week history of headache, photophobia, and neck stiffness. Associated symptoms included low-grade fevers, malaise, and dark urine. He had no recent travel, ill contacts, consumption of undercooked meat, new sexual contacts, or illicit drug use. The patient resided in a campus dormitory and did not consume alcohol or tobacco.

A 53-year-old male with a past medical history of type I diabetes mellitus presented to our emergency department after being found obtunded at home following ingestion of a large amount of the caffeinated alcoholic beverage 4 Loko. The patient had profound hyperkalaemia, diabetic ketoacidosis and acute renal failure. He was admitted to the intensive care unit and was aggressively resuscitated with intravenous fluids. He was treated with insulin and sodium bicarbonate and had complete resolution of his acidosis and hyperkalaemia. Since their introduction, caffeinated alcoholic beverages have become increasingly popular, with expected sales of several billion dollars in 2011. The caffeine present in these beverages masks the depressant effect of alcohol and may thus lead to greater alcohol intake and make risk-taking behaviours more common. These beverages have not been studied in those with chronic medical conditions. As this case exemplifies, they may lead to excessive morbidity in those susceptible patients.

Extracorporeal photopheresis (ECP) is a commonly used treatment for severe graft-versus-host-disease (GVHD). We sought to evaluate the effects of ECP over a prolonged period on forced expiratory volume in 1 s (FEV1) in patients with pulmonary GVHD. We identified eight patients who developed new airflow obstruction following allogeneic stem cell transplantation and a substantial decline in FEV1 despite receiving corticosteroids and standard therapy for pulmonary GVHD. Those eight patients were treated with ECP for a period of 1 year, with a primary endpoint of FEV1 change during this treatment period. Over the first 3 months of ECP, there was no further decline in FEV1 in seven of the eight patients. However, over the 1 year period, only two of the eight patients had stability in FEV1. The rate of FEV1 decline was substantially less once ECP was initiated, though the median FEV1 continued to decline over 1 year of therapy. All patients survived through the first year of ECP therapy. There was a significant decrease in the median dose of prednisone per patient throughout the 12 months of ECP treatment. ECP shows promise in slowing rate of decline of FEV1 in pulmonary GVHD, though the effects may not be long lived. J. Clin. Apheresis 31:347-352, 2016. © 2015 Wiley Periodicals, Inc.

To describe the role of bronchoalveolar lavage (BAL) in the evaluation of pulmonary disease in immunocompromised patients.Recent discoveries in this field are largely in two areas: the array of diagnostic testing performed on BAL fluid and technical details that can enhance the yield from this procedure. Regarding diagnostic testing, the addition of new assays, including Aspergillus galactomannan antigen assay, respiratory viral panels, and Pneumocystis jirovecii PCR, has improved the diagnostic yield of BAL over conventional cultures and stains. To improve the diagnostic yield of the procedure itself, it should be done early in the clinical course, with the BAL in the anatomic area most affected, and with a preprocedural computed tomography of the chest to properly plan the procedure.Bronchoscopic evaluation with BAL can provide important diagnostic information in immunocompromised patients with pulmonary diseases and should be routinely performed when clinically indicated and able to be completed safely.

Purpose: To determine if the multiplex real-time polymerase chain reaction respiratory viral panel (RVP) provides the same results when performed on nasal wash versus bronchoalveolar lavage from the same patient within 5 days of each other. Methods: A retrospective chart review was performed on all adult immunocompromised patients who underwent bronchoalveolar lavage (BAL) with a respiratory viral panel (RVP) obtained from the BAL fluid from February 2011 to July 2012. All patients who also had a nasal wash RVP performed within 5 days of the BAL assay were included in this study. Results: There was exact concordance between BAL and NPW specimens in 45 of 58 patients: 26 cases in which both specimens were negative and 19 cases in which the exact same viruses were present in each specimen. In 8 cases, a virus was detected in BAL fluid that was not detected in NPW fluid; in 5 cases, a virus was found in NPW fluid but not BAL. Conclusions: There was good correlation between the two assays when performed within 5 days of each other from the 2 separate specimen sources. For optimal diagnostic detection, it may be useful to repeat the assay in both locations when clinically indicated.

Diagnosis of invasive pulmonary aspergillosis (IPA) is a challenging process in immunocompromised patients. Galactomannan (GM) antigen detection in bronchoalveolar lavage (BAL) fluid is a method to detect IPA with improved sensitivity over conventional studies. We sought to determine the diagnostic yield of BAL GM assay in a diverse population of immunocompromised patients. A retrospective review of 150 fiberoptic bronchoscopy (FOB) with BAL for newly diagnosed pulmonary infiltrate in immunocompromised patients was performed. Patient information, procedural details and laboratory studies were collected. BAL and serum samples were evaluated for GM using enzyme-linked immunoassay. Of 150 separate FOB with BAL, BAL GM was obtained in 143 samples. There were 31 positive BAL GM assays. In those 31 positive tests, 13 were confirmed as IPA, giving a positive predictive value of 41.9%. There was one false negative BAL GM. Of the 18 false positive BAL GM, 4 were receiving piperacillin-tazobactam and 11 were receiving an alternative beta-lactam antibiotic. BAL GM assay shows excellent sensitivity for diagnosing IPA. There was a significant number of false positive BAL GM assays and several of those patients were receiving beta-lactam antibiotics at the time of bronchoscopy.

Background The diagnosis of pulmonary lesions that are not bronchoscopically visible is a challenging process. Electromagnetic navigation bronchoscopy (ENB) is a new technology designed to diagnose peripheral pulmonary lesions. We sought to determine whether diagnostic yield from ENB was affected by bronchus sign, lesion location, or size. Methods Data were obtained retrospectively from all patients undergoing ENB at our institution since 2008. ENB was performed by 3 separate proceduralists at our institution from November 2008 until July 2011 using the superDimension/InReach system. Patient selection and modalities of specimen collection were at the discretion of the proceduralist. All procedures were performed using general anesthesia and fluoroscopy. Lesion size, location, diagnosis from ENB, and eventual diagnosis were recorded. Results Fifty-five individuals underwent ENB between 2008 and 2011. The average lesion size was 3.0 cm and the majority of lesions were located in the upper lobes (34/55 lesions). Of the 55 patients, in 41, a diagnosis was established from ENB, a diagnostic yield of 74.5%. Thirty-six patients were eventually diagnosed with a malignancy, of whom 25 were diagnosed by ENB, yielding a sensitivity for malignancy of 69.4%. The negative predictive value for malignancy with an ENB procedure was 54.2%. There were 2 cases of postprocedure respiratory failure, but there were no cases of pneumothorax. Bronchus sign, lesion size, and location did not affect the diagnostic yield. Conclusions ENB shows an acceptable diagnostic yield with an excellent safety profile in the diagnosis of pulmonary lesions. The use of fluoroscopy and general anesthesia may improve the diagnostic yield.

Duchenne muscular dystrophy is a fatal childhood disease caused by mutations that abolish the expression of dystrophin in muscle. Utrophin is a paralogue of dystrophin and can functionally replace it in skeletal muscle. A potential therapeutic approach is to increase utrophin levels in muscle. One way to achieve this aim is to increase the expression of the utrophin gene at a transcriptional level via promoter activation. In this study, we have shown that utrophin A mRNA levels can be induced by okadaic acid in murine myogenic C2C12 cells. We have found that a utrophin A promoter reporter can be induced by Sp1 in C2C12 myoblasts, but not in myotubes. This activation can be enhanced by okadaic acid treatment. Our data suggest that this induction is due to Sp1 phosphorylation during myogenesis and thus, utrophin expression in muscle could be regulated by treatment with phosphatase inhibitors. Control of utrophin promoter activation could then be used to increase the expression of utrophin, and thus ameliorate the symptoms of Duchenne muscular dystrophy.

Portal-systemic encephalopathy in both cirrhosis and non-cirrhotic patients can occur when a large portal-systemic shunt forms within the venous system. Though most commonly found in patients with portal hypertension, after trauma, surgical intervention, and liver biopsy, one can also be idiopathic. A 78-year-old Latino male developed worsening confusion and lethargy during a hospitalization for bridging of his anticoagulation. An extensive laboratory and radiologic workup did not initially reveal the etiology of his delirium and decreased state of consciousness. On exam, he had tremulousness and fetor hepaticus without corresponding liver function abnormalities in his laboratory testing. An ultrasound of the liver demonstrated a large veno-venous shunt between the right portal vein and the right hepatic vein. After multiple episodes of encephalopathy and progressive heart failure from significant right ventricular overload, the shunt was closed by interventional radiology. This treatable cause of encephalopathy may not be evident without radiologic studies.