A Safety and Tolerability Study of Thin Film Freeze-Dried Tacrolimus for Local Pulmonary Drug Delivery in Human Subjects.

Due to the low and erratic bioavailability of oral tacrolimus (TAC), the long-term survival rate following lung transplantation remained low compared to other solid organs. TAC was reformulated and developed as inhaled formulations by thin film freezing (TFF). Previous studies reported that inhaled TAC combined with 50% w/w lactose (LAC) was safe and effective for the treatment of lung transplant rejection in rodent models. In this study, we aimed to investigate the safety and tolerability of TFF TAC-LAC in human subjects. The formulation can be delivered to the lung as colloidal dispersions after reconstitution and as a dry powder. Healthy subjects inhaled TAC-LAC colloidal dispersions at 3 mg TAC/dose via a vibrating mesh nebulizer in the first stage of this study and TAC-LAC dry powder at 3 mg TAC/dose via a single dose dry powder inhaler in the second stage. Our results demonstrated that oral inhalation of TAC-LAC colloidal dispersions and dry powder exhibited low systemic absorption. Additionally, they were well-tolerated with no changes in CBC, liver, kidney, and lung functions. Only mild adverse side effects (e.g., cough, throat irritation, distaste) were observed. In summary, pulmonary delivery of TFF TAC-LAC would be a safe and promising therapy for lung transplant recipients.

COVID-19 in a Hispanic Woman.

Since making its debut on the global stage in December 2019, coronavirus disease 2019 (COVID-19) has afflicted nearly 4 million people and caused hundreds of thousands of deaths. Case reports and case series depicting the clinical effects of the causative virus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-have been published, yet few demonstrate the cytopathologic alterations of this disease. We present a clinical-pathologic correlation report of a previously healthy Hispanic woman with laboratory-confirmed COVID-19 who had typical features of acute respiratory distress syndrome (ARDS) and also showed cardiac abnormalities thought to represent fulminant viral myocarditis. Congruent with the ARDS clinical impression, autopsy findings were remarkable for extensive and markedly severe acute lung injury consistent with viral pneumonia, characterized by diffuse alveolar damage, pulmonary infarction, severe pulmonary edema, desquamation of pneumocytes with intra-alveolar aggregation, and pneumocyte morphologic alterations suggestive of viral cytopathic effect. However, there was incongruence between the clinical impression and the cardiovascular pathology findings in that viral myocarditis was not detected on histopathologic evaluation. This case highlights the importance of pathologic corroboration of the clinical impression and, in addition, illuminates the key role autopsy plays during a pandemic by providing valuable insight into viral pathology in tissues.

Recurrent Chylothorax in Renal Cell Carcinoma.

Chylothorax is a type of pleural effusion that results from the build up of chyle in the pleural space. Trauma and malignancies are its leading causes. Among malignancies, lymphomas cause the majority of chylothoraces. A few cases of chylothorax resulting from various solid malignancies have been reported in the literature but renal cell carcinoma (RCC) has been rarely associated. Here, we report a rare case of a unilateral chylothorax associated with a newly diagnosed RCC.

Community-acquired Pneumonia Secondary to Legionella pneumophila and Streptococcus pneumoniae: A Rare Co-infection.

Community-acquired pneumonia (CAP) is a frequent cause of hospitalization in adults. Streptococcus pneumoniae is the most commonly identified pathogen in CAP whereas Legionella pneumophilia is infrequently identified in CAP. Although co-infections have been previously described, the presence of both pneumococcus and legionella together is rare. We present a patient with positive urinary antigens for both Streptococcus pneumoniae and Legionella pneumophilia serogroup 1, indicating an unusual co-infection.

Impact of Procalcitonin Guidance on Management of Adults Hospitalized with Chronic Obstructive Pulmonary Disease Exacerbations.

BACKGROUND: Antibiotics are often prescribed for hospitalized patients with chronic obstructive pulmonary disease (COPD) exacerbations. The use of procalcitonin (PCT) in the management of pneumonia has safely reduced antibiotic durations, but limited data on the impact of PCT guidance on the management of COPD exacerbations remain. OBJECTIVE: To determine the impact of PCT guidance on antibiotic utilization for hospitalized adults with exacerbations of COPD. DESIGN: A retrospective, pre-/post-intervention cohort study was conducted to compare the management of patients admitted with COPD exacerbations before and after implementation of PCT guidance. The pre-intervention period was March 1, 2014, through October 31, 2014, and the post-intervention period was March 1, 2015, through October 31, 2015. PARTICIPANTS: All patients with hospital admissions during the pre- and post-intervention period with COPD exacerbations were included. Patients with concomitant pneumonia were excluded. INTERVENTION: Availability of PCT laboratory values in tandem with a PCT guidance algorithm and education. MAIN MEASURES: The primary outcome was duration of antibiotic therapy for COPD. Secondary objectives included duration of inpatient length of stay (LOS) and 30-day readmission rates. KEY RESULTS: There were a total of 166 and 139 patients in the pre- and post-intervention cohorts, respectively. There were no differences in mean age (66.2 vs. 65.9; P = 0.82) or use of home oxygenation (34% vs. 39%; P = 0.42) in the pre- and post-intervention groups, respectively. PCT guidance was associated with a reduced number of antibiotic days (5.3 vs. 3.0; p = 0.01) and inpatient LOS (4.1 days vs. 2.9 days; P = 0.01). Respiratory-related 30-day readmission rates were unaffected (10.8% vs. 9.4%; P = 0.25). CONCLUSIONS: Utilizing PCT guidance in the management of COPD exacerbations was associated with a decreased total duration of antibiotic therapy and hospital LOS without negatively impacting hospital readmissions.

Unusual acute liver failure from small cell carcinoma of the lung.

A 75-year-old woman with a 50-pack-year history of tobacco abuse presented with abdominal pain, encephalopathy and elevated liver enzymes. Serologic evaluation for viral hepatitis, drug levels and chronic liver disease panel was negative. Computed tomography (CT) scan of the abdomen showed hepatomegaly and a large area of decreased attenuation in the lateral segment of the left lobe of the liver which was also demonstrated on the magnetic resonance cholangiopancreatography. CT of the chest was significant for a 1.4 cm left peripheral lingular nodule. Hepatic mass biopsy revealed small cell carcinoma (SCC), favoring lung primary. She had persistent liver failure with encephalopathy, coagulopathy and elevated liver enzymes during her hospital stay. Acute liver failure (ALF) is characterized by liver damage, encephalopathy and coagulopathy in patients without any prior history of liver disease. Although malignant infiltration has been described as a cause of ALF, SCC of the lung is an uncommon etiology.

Impact of Procalcitonin Guidance with an Educational Program on Management of Adults Hospitalized with Pneumonia.

BACKGROUND: Community-acquired pneumonia and healthcare-associated pneumonia are often treated with prolonged antibiotic therapy. Procalcitonin (PCT) has effectively and safely reduced antibiotic use for pneumonia in controlled studies. However, limited data exist regarding PCT guidance in real-world settings for management of pneumonia. METHODS: A retrospective, preintervention/postintervention study was conducted to compare management for patients admitted with pneumonia before and after implementation of PCT guidance at 2 teaching hospitals in Pittsburgh, Pennsylvania. The preintervention period was March 1, 2014 through October 31, 2014, and the postintervention period was March, 1 2015 through October 31, 2015. RESULTS: A total of 152 and 232 patients were included in the preintervention and postintervention cohorts, respectively. When compared with the preintervention group, mean duration of therapy decreased (9.9 vs 6.0 days; P < .001). More patients received an appropriate duration of 7 days or less (26.9% vs 66.4%; P < .001). Additionally, mean hospital length of stay decreased in the postintervention group (4.9 vs 3.5 days; P = .006). Pneumonia-related 30-day readmission rates (7.2% vs 4.3%; P = .26) were unaffected. In the postintervention group, patients with PCT levels <0.25 µg/L received shorter mean duration of therapy compared with patients with levels >0.25 µg/L (4.6 vs 8.0 days; P < .001), as well as reduced hospital length of stay (3.2 vs 3.9 days; P = .02). CONCLUSIONS: In this real-world study, PCT guidance led to shorter durations of total antibiotic therapy and abridged inpatient length of stay without affecting hospital readmissions.

Advanced Therapies in Venous Thromboembolism.

Advanced therapies are available for both deep venous thrombosis and pulmonary embolism when anticoagulation alone is not sufficient to improve clinical outcomes. In some cases, clinical deterioration ensues despite anticoagulation, and this requires unique techniques that can ameliorate the clinical course. Such advancements are described in this upcoming article.