Clinical utility of a cytomegalovirus-specific T cell assay in assessing the risk of post-prophylaxis cytomegalovirus infection and post-treatment relapse.

INTRODUCTION: Cytomegalovirus (CMV) causes significant morbidity in solid organ transplant recipients (SOTR). Measuring cell-mediated immunity (CMI) may inform the risk of CMV infection after antiviral prophylaxis and predict relapse after CMV treatment. METHODS: We serially assessed CMV CMI using the QuantiFERON-CMV assay (QF-CMV; Qiagen, Germantown, MD) in two cohorts of SOTRs: during valganciclovir prophylaxis and during treatment of CMV viremia. Results of CMI were correlated with post-prophylaxis CMV infection and post-treatment relapse, respectively. RESULTS: Only one (4.2%) of 24 CMV D+/R- patients demonstrated positive QF-CMV by the end of valganciclovir prophylaxis. Four (16.6%) patients developed post-prophylaxis CMV infection; all four had undetectable QF-CMV at end of prophylaxis. Among 20 patients treated for CMV infection, 18 (90%) developed QF-CMV levels >.2 IU/mL by end of antiviral treatment and none developed CMV relapse. In contrast, the single patient who relapsed after completing treatment had a CMV CMI <.2 IU/ml (p = .0036). CONCLUSION: Since CMV D+/R- SOTRs are unlikely to develop adequate CMV CMI while receiving valganciclovir prophylaxis, the utility of CMV CMI monitoring for risk stratification during time of prophylaxis had limited value. Conversely, CMV CMI testing may be a useful marker of the risk of CMV relapse after antiviral treatment.

Interleukin-18 and tumor necrosis factor-α are elevated in solid organ transplant recipients with possible cytomegalovirus end-organ disease.

End-organ cytomegalovirus (CMV) disease can be life threatening to solid organ transplant recipients. Diagnosis is often complicated by variation in amount of CMV DNA in plasma and the need for an invasive procedure to obtain a biopsy of the suspected affected organ, which can delay recognition and treatment. Several inflammatory cytokines are elevated in CMV disease, and the purpose of this study was to determine if they could be used to distinguish solid organ transplant recipients with CMV DNAemia alone from those with possible end-organ CMV disease. We found that regardless of pre-transplant CMV serostatus, plasma interleukin (IL)-18, tumor necrosis factor-α (TNF-α), and amount of CMV DNA in plasma were increased in possible end-organ CMV disease, with elevated IL-18 associated with increased odds of possible end-organ CMV disease even after adjusting for amount of CMV DNA. These findings highlight IL-18 and TNF-α as potential non-invasive markers of possible end-organ CMV disease regardless of transplanted organ or serostatus in solid organ transplant recipients.

Clinical utility of cytomegalovirus viral load in solid organ transplant recipients.

PURPOSE OF REVIEW: Quantitative nucleic acid testing (QNAT) to measure viral load has become a mainstay in the management of cytomegalovirus (CMV) infection and disease in solid organ transplant recipients. In this article, we review the clinical applications of CMV QNAT in the management of solid organ transplant recipients. RECENT FINDINGS: Because several platforms were available for CMV QNAT, there was a wide inter-assay variability in the viral load reporting, and this limited the generation of widely applicable viral load thresholds that can be used for various clinical applications. With the recent availability of international standard and certified reference materials, there is now opportunity to standardize viral load reporting, with the goal of deriving viral load thresholds for various clinical applications, such as rapid diagnosis of CMV infection and disease, predicting the risk of disease and assessing the severity of illness, monitoring efficacy of antiviral therapies and assessing the risk of viral relapse and drug resistance. SUMMARY: Recent advances in the field such as CMV QNAT standardization, as discussed in this review, are anticipated to optimize the management of CMV infection and disease in solid organ transplant recipients.

Disseminated Tuberculosis With an Atypical Cutaneous Manifestation in a Hematopoietic Cell Transplant Patient in the Early Posttransplant Period: Case Report and Review of the Literature.

We describe an unusual case of posttransplant tuberculosis reactivation in a man who underwent allogeneic hematopoietic cell transplant. Concomitant with disseminated adenovirus infection, reactivation of tuberculosis manifested as disseminated, nonfollicular pustules on day +49. Skin biopsy was obtained on day +50. Initial histopathologic evaluation did not suggest mycobacterial infection, but tissue stain showed acid-fast organisms, which were subsequently identified as Mycobacterium tuberculosis. Shortly after the cutaneous presentation of tuberculosis, the patient died on day +52. Our case is among a paucity of reports describing tuberculosis reactivation in hematopoietic cell transplant patients in the early posttransplant period. It highlights the difficulty of diagnosing contemporaneous systemic infections, and it presents a rare and atypical cutaneous manifestation of tuberculosis in a hematopoietic cell transplant patient. Our case and review of the literature emphasize the need for further research to elucidate risk factors associated with early posttransplant reactivation of tuberculosis, and the importance of remaining vigilant for active tuberculosis in hematopoietic cell transplant patients with epidemiologic risk factors.

Dipyridamole-associated shock and pulmonary edema.

OBJECTIVE: To report a case of fulminant shock and noncardiogenic pulmonary edema induced by intravenously administered dipyridamole. CASE SUMMARY: A 73-year-old woman presented to the office of her cardiologist for dipyridamole myocardial scintigraphy. Several minutes after administration of intravenous dipyridamole 0.57 mg/kg over 4 minutes she developed wheezing, followed by cardiovascular collapse and pulmonary edema requiring 100% oxygen and endotracheal intubation. She had never received dipyridamole before this, and no other medications or exposures were documented proximate to the collapse. On transfer to the hospital, she developed shock refractory to multiple vasopressors, which responded to continuous infusions of epinephrine. She also had severe pulmonary edema requiring invasive ventilation, 100% inspired oxygen, and 24 cm H2O positive end-expiratory pressure. An echocardiogram did not show new left-ventricular dysfunction and there were signs of right-heart underfilling, supporting a diagnosis of noncardiogenic pulmonary edema. Both shock and pulmonary edema resolved within 12 hours. DISCUSSION: Dipyridamole-associated hypotension has been reported in a number of case series and registries. Detailed case descriptions, however, are not available in the literature to permit understanding of the mechanism of shock following hypotension resulting from dipyridamole myocardial scintigraphy. Our case is exceptional in that echocardiography results support a diagnosis of hypovolemic (rather than cardiogenic) shock. To our knowledge, this is the first case of severe (most likely noncardiogenic) pulmonary edema associated with intravenous infusion of dipyridamole. An objective causality assessment suggested that this patient's cardiopulmonary collapse was probably related to dipyridamole. CONCLUSIONS: While hypotension has been previously associated with intravenous use of dipyridamole, ours is the first report to suggest a noncardiogenic mechanism for shock. To our knowledge, this is the first reported case of noncardiogenic pulmonary edema following dipyridamole infusion.

High-value laboratory testing for hospitalized COVID-19 patients: a review.

We present here an evidence-based review of the utility, timing, and indications for laboratory test use in the domains of inflammation, cardiology, hematology, nephrology and co-infection for clinicians managing the care of hospitalized COVID-19 patients. Levels of IL-6, CRP, absolute lymphocyte count, neutrophils and neutrophil-to-lymphocyte ratio obtained upon admission may help predict the severity of COVID-19. Elevated LDH, ferritin, AST, and d-dimer are associated with severe illness and mortality. Elevated cardiac troponin at hospital admission can alert clinicians to patients at risk for cardiac complications. Elevated proBNP may help distinguish a cardiac complication from noncardiac etiologies. Evaluation for co-infection is typically unnecessary in nonsevere cases but is essential in severe COVID-19, intensive care unit patients, and immunocompromised patients.

Cryptococcus neoformans infections in patients with lymphoproliferative neoplasms.

Cryptococcosis is a rare opportunistic infection increasingly associated with lymphoproliferative disorders. The clinical course and outcomes in these patients have not been extensively studied. We retrospectively reviewed charts of adult patients with lymphoproliferative disorders diagnosed with cryptococcal infections. A total of 34 patients were identified; 31 (91%) had a B-cell neoplasm and 3 (9%) had a T-cell neoplasm. The most frequent clinical syndrome was disseminated cryptococcal infection (38%), followed by pneumonia (29%). 74% received prior chemotherapy and the overall mortality in this group was nearly six-fold higher than chemotherapy naïve patients; 26% were chemotherapy naïve. After a median follow-up of nine months from the date of infection, 24 patients had died (71%). The overall mortality at 30-days and one year was 18% and 46%, respectively. The high mortality warrants future studies to identify those at highest risk. Clinicians should remain vigilant as early diagnosis and treatment are of utmost importance.

Infectious complications in patients on treatment with Ruxolitinib: case report and review of the literature.

BACKGROUND: Primary myelofibrosis is a chronic myeloproliferative neoplasm that may cause debilitating symptoms, which can be improved with the use of Ruxolitinib, a Janus kinase 2 inhibitor. However, this agent has significant immunomodulatory effects which may increase the risk for infections. METHODS: We searched the literature and our institutional electronic medical record for reported cases of infections in adult patients on ruxolitinib treatment. RESULTS: We found 28 cases in our literature search and 4 cases from our Institution for a total of 32 cases. The most common infection was tuberculosis in 11/32 cases (34%), followed by cryptococcal infection in 3/32 (9%) and hepatitis B virus reactivation in 3/32 (9%). CONCLUSION: Opportunistic infections associated with ruxolitinib use are increasingly reported in the literature; further studies should investigate the role of systematic screening and prophylaxis against infections in this subset of patients.