Group 5 Pulmonary Hypertension Associated With T-Cell Large Granular Lymphocytic Leukemia: Hemodynamics and Treatment.

Group 5 pulmonary hypertension (PH) encompasses diverse diseases, with a few cases linking it to T-cell large granular lymphocytic (LGL) leukemia. We report a case of a 76-year-old woman, diagnosed with LGL leukemia and concomitant PH, treated with oral triple pulmonary arterial hypertension (PAH) therapy. She initially presented with dyspnea on exertion; evaluation revealed severe precapillary PH. Implementing cyclophosphamide for leukemia along with tadalafil and macitentan for PH led to sustained symptomatic and hemodynamic improvement for over 3 years. At that time, deterioration in PH prompted the addition of selexipag, resulting in sustained clinical improvement for an additional 5 years. This case exemplifies the potential for sustained benefits of PAH therapy in leukemia-associated PH and highlights the need for continued research on the mechanistic relationship between LGL leukemia and PH, with the hope of identifying new management strategies.

Culture-independent identification of bloodstream infections from whole blood: prospective evaluation in specimens of known infection status.

Sepsis caused by bloodstream infection (BSI) is a major healthcare burden and a leading cause of morbidity and mortality worldwide. Timely diagnosis is critical to optimize clinical outcome, as mortality rates rise every hour treatment is delayed. Blood culture remains the "gold standard" for diagnosis but is limited by its long turnaround time (1-7 days depending on the organism) and its potential to provide false-negative results due to interference by antimicrobial therapy or the presence of mixed (i.e., polymicrobial) infections. In this paper, we evaluated the performance of resistance and pathogen ID/BSI, a direct-from-specimen molecular assay. To reduce the false-positivity rate common with molecular methods, this assay isolates and detects genomic material only from viable microorganisms in the blood by incorporating a novel precursor step to selectively lyse host and non-viable microbial cells and remove cell-free genomic material prior to lysis and analysis of microbial cells. Here, we demonstrate that the assay is free of interference from host immune cells and common antimicrobial agents at elevated concentrations. We also demonstrate the accuracy of this technology in a prospective cohort pilot study of individuals with known sepsis/BSI status, including samples from both positive and negative individuals. IMPORTANCE: Blood culture remains the "gold standard" for the diagnosis of sepsis/bloodstream infection (BSI) but has many limitations which may lead to a delay in appropriate and accurate treatment in patients. Molecular diagnostic methods have the potential for markedly improving the management of such patients through faster turnaround times and increased accuracy. But molecular diagnostic methods have not been widely adopted for the identification of BSIs. By incorporating a precursor step of selective lysis of host and non-viable microorganisms, our resistance and pathogen ID (RaPID)/BSI molecular assay addresses many limitations of blood culture and other molecular assay. The RaPID/BSI assay has an approximate turnaround time of 4 hours, thereby significantly reducing the time to appropriate and accurate diagnosis of causative microorganisms in such patients. The short turnaround time also allows for close to real-time tracking of pathogenic clearance of microorganisms from the blood of these patients or if a change of antimicrobial regimen is required. Thus, the RaPID/BSI molecular assay helps with optimization of antimicrobial stewardship; prompt and accurate diagnosis of sepsis/BSI could help target timely treatment and reduce mortality and morbidity in such patients.