Pneumocystis jirovecii in solid organ transplant recipients: updates in epidemiology, diagnosis, treatment, and prevention.

PURPOSE OF REVIEW: This review highlights the epidemiology of Pneumocystis jirovecii pneumonia in solid organ transplant recipients, advancements in the diagnostic landscape, and updates in treatment and prevention. RECENT FINDINGS: The increasing use of immune-depleting agents in the context of solid organ transplantation has given rise to P. jirovecii pneumonia in this population. The use of prophylaxis has dramatically reduced risk of infection; however, late-onset infections occur after cessation of prophylaxis and in the setting of lymphopenia, advancing patient age, acute allograft rejection, and cytomegalovirus infection. Diagnosis requires respiratory specimens, with PCR detection of Pneumocystis replacing traditional staining methods. Quantitative PCR may be a useful adjunct to differentiate between infection and colonization. Metagenomic next-generation sequencing is gaining attention as a noninvasive diagnostic tool. Trimethoprim-sulfamethoxazole remains the drug of choice for treatment and prevention of Pneumocystis pneumonia. Novel antifungal agents are under investigation. SUMMARY: P. jirovecii is a fungal opportunistic pathogen that remains a cause of significant morbidity and mortality in solid organ transplant recipients. Early detection and timely treatment remain the pillars of management.

Improving Emergency Access to Human Immunodeficiency Virus Prophylaxis for Patients Evaluated After Sexual Assault.

INTRODUCTION: Patients evaluated after sexual assault may benefit from nonoccupational postexposure prophylaxis (nPEP) to prevent infection with HIV, yet multiple barriers may prohibit nPEP delivery. The IN-STEP (Integrating nPEP after Sexual Trauma in Emergency Practice) project was designed to improve access to HIV screening and prevention for patients evaluated in the emergency department (ED) of our academic hospital after a sexual assault. METHODS: The IN-STEP team identified and addressed four key areas for improvement: (1) training of ED providers to perform nPEP assessments; (2) access to HIV testing in the ED; (3) provision of nPEP medications, using a patient-centered approach; and (4) continuity of care between the ED and follow-up sites in the community. Improvements were implemented using parallel plan-do-study-act cycles corresponding to these four key areas. RESULTS: IN-STEP resulted in significant systems improvements in HIV screening, prevention, and continuity of care. This program not only improved the care of patients affected by sexual assault but also those evaluated for HIV due to other indications. CONCLUSIONS: Involvement of a multidisciplinary leadership team, clear delineation of a patient-centered project focus, and coordination across four parallel areas for improvement were useful for completing this complex effort.

Genetic disruption of the scaffolding protein, Kinase Suppressor of Ras 1 (KSR1), differentially regulates GM-CSF-stimulated hyperproliferation in hematopoietic progenitors expressing activating PTPN11 mutants D61Y and E76K.

Activating PTPN11 mutants promote hematopoietic progenitor hyperactivation of Erk and hypersensitivity to GM-CSF. We hypothesized that Kinase Suppressor of Ras 1 (KSR1) contributes to activating PTPN11-induced GM-CSF hypersensitivity. Bone marrow progenitors from WT and KSR1-/- mice expressing WT Shp2, Shp2E76K, or Shp2D61Y were evaluated functionally and biochemically. KSR1 activation and interaction with phospho-Erk was enhanced in Shp2D61Y- and ShpE76K-expressing cells. Genetic disruption of KSR1 partially normalized Shp2E76K-induced GM-CSF hypersensitivity, but failed to correct Shp2D61Y-induced GM-CSF hypersensitivity. Collectively, these studies suggest that cells expressing Shp2E76K have a greater dependence on KSR1 for GM-CSF hypersensitivity than cells expressing Shp2D61Y.