Noroviral diarrhea in solid organ transplant recipients: An analysis of interventions and outcomes.

INTRODUCTION: Noroviral infection can lead to chronic diarrhea in solid organ transplant (SOT) recipients with significant morbidity and mortality. Existing literature has described a wide spectrum of illness and has not come to a consensus on the optimal management of this condition. METHODS: We undertook a retrospective review of all adult SOT recipients between 1/1/2018 and 12/31/2020 who were diagnosed with their first episode of noroviral diarrhea (NVD). Demographic, clinical interventions, and outcomes within 6 months of diagnosis were recorded. Patients' outcomes were classified as either resolved, improved or persistent at 6 months. RESULTS: Seventy-nine SOT recipients were included. Thirty-eight patients (48%) had chronic diarrhea at baseline (CDB). Thirty-two patients (40%) received nitazoxanide, 28 patients (35%) had their immunosuppression adjusted and seven patients (9%) received intravenous immunoglobulin. Diarrhea improved or resolved in 68 patients (85%). Improvement or resolution of diarrhea was observed in 98% of those who did not have history of chronic diarrhea versus 74% in those who did (p = .002). NVD improved in all 12 patients who had mycophenolate discontinued, although this was not statistically significant (p = .131). CONCLUSION: CDB was associated with worse outcomes regardless of intervention. A low threshold to test for NVD in SOT recipients with chronic diarrhea is prudent to prevent delayed diagnosis.

Viral kinetics and outcomes of adenovirus viremia following allogeneic hematopoietic cell transplantation.

BACKGROUND: Adenovirus (AdV) is a serious infection following hematopoietic cell transplantation (HCT). Little is known about AdV viral kinetics and optimal threshold for initiation of pre-emptive therapy. METHODS: Single-center retrospective study of 16 consecutive adult HCT recipients with detectable AdV identified over a 5-year period. RESULTS: Median time to AdV reactivation after HCT was 176 days (IQR 86-408). Nine patients received cidofovir, although 14/16 had no tissue-invasive disease. Among treated patients, median duration of viremia was shorter when initiating treatment at viral loads < 10,000 copies/ml (28 vs. 52 days). All-cause mortality in this cohort was 44%. All six patients (five of which were untreated) with peak viral loads < 10,000 copies/ml survived; whereas only 30% (3/10) of patients with peak viral loads greater than this threshold survived, despite most (n = 8; 80%) of them receiving cidofovir (P = .01). Three-month survival following diagnosis of AdV viremia was significantly lower with peak viremia > 10,000 copies/ml (100 vs. 17%; P = .005). CONCLUSION: AdV is associated with high all-cause mortality, especially for viremia > 10,000 copies/ml. Delaying therapy until viremia reaches AdV levels ≥10,000 copies/ml was associated with more protracted infection and poor outcomes. Larger studies are needed.

Correction to: Clinical experience with a novel assay measuring cytomegalovirus (CMV)-specific CD4+ and CD8+ T-cell immunity by flow cytometry and intracellular cytokine staining to predict clinically significant CMV events.

After publication of the original article [1], we were notified that an author's family name has been erroneously spelled. Aditya Chandrokar should be replaced with Aditya Chandorkar.

Clinical experience with a novel assay measuring cytomegalovirus (CMV)-specific CD4+ and CD8+ T-cell immunity by flow cytometry and intracellular cytokine staining to predict clinically significant CMV events.

BACKGROUND: Cytomegalovirus (CMV) infection is one of the most common opportunistic infections following organ transplantation, despite administration of CMV prophylaxis. CMV-specific T-cell immunity (TCI) has been associated with reduced rates of CMV infection. We describe for the first time clinical experience using the CMV T-Cell Immunity Panel (CMV-TCIP), a commercially available assay which measures CMV-specific CD4+ and CD8+ T-cell responses, to predict clinically significant CMV events. METHODS: Adult (> 18-year-old) patients with CMV-TCIP results and ≥ 1 subsequent assessment for CMV DNAemia were included at Brown University and the University of Maryland Medical Center-affiliated hospitals between 4/2017 and 5/2019. A clinically significant CMV event was defined as CMV DNAemia prompting initiation of treatment. We excluded indeterminate results, mostly due to background positivity, allogeneic hematopoetic cell transplant (HCT) recipients, or patients who were continued on antiviral therapy against CMV irrespective of the CMV-TCIP result, because ongoing antiviral therapy could prevent a CMV event. RESULTS: We analyzed 44 samples from 37 patients: 31 were solid organ transplant recipients, 4 had hematologic malignancies, 2 had autoimmune disorders. The CMV-protection receiver operating characteristic (ROC) area under the curve (AUC) was significant for %CMV-specific CD4+ (AUC: 0.78, P < 0.001) and borderline for CD8+ (AUC: 0.66, P = 0.064) T-cells. At a cut-off value of 0.22% CMV-specific CD4+ T-cells, positive predictive value (PPV) for protection against CMV was 85% (95%CI 65-96%), and negative predictive value (NPV) was 67% (95%CI 41-87%). CONCLUSIONS: The CMV-TCIP, in particular %CMV-specific CD4+ T-cells, showed good diagnostic performance to predict CMV events. The CMV-TCIP may be a useful test in clinical practice, and merits further validation in larger prospective studies.

Kidney transplantation during coronavirus 2019 pandemic at a large hospital in Miami.

BACKGROUND: Coronavirus 2019 (COVID-19) pandemic has resulted in more than 350 000 deaths worldwide. The number of kidney transplants has declined during the pandemic. We describe our deceased donor kidney transplantation (DDKT) experience during the pandemic. METHODS: A retrospective study was conducted to evaluate the safety of DDKT during the COVID-19 pandemic. Multiple preventive measures were implemented. Adult patients that underwent DDKT from 3/1/20 to 4/30/20 were included. COVID-19 clinical manifestations from donors and recipients, and post-transplant outcomes (COVID-19 infections, readmissions, allograft rejection, and mortality) were obtained. The kidney transplant (KT) recipients were followed until 5/31/20. RESULTS: Seventy-six patients received kidneys from 57 donors. Fever, dyspnea, and cough were reported in 1, 2, and 1 donor, respectively. Thirty-eight (66.6%) donors were tested for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) prior to donation (mainly by nasopharyngeal or bronchoalveolar lavage polymerase chain reaction [PCR]) and 36 (47.3%) KT recipients were tested at the time of DDKT by nasopharyngeal PCR; all of these were negative. Our recipients were followed for a median of 63 (range: 33-91) days. A total of 42 (55.3%) recipients were tested post-transplant for SARS-CoV2 by nasopharyngeal PCR including 12 patients that became symptomatic; all tests were negative except for one that was inconclusive, but it was repeated and came back negative. Forty (52.6%) KT recipients were readmitted, and 7 (9.2%) had biopsy-proven rejection during the follow-up. None of the KT recipients transplanted during this period died. CONCLUSIONS: Our cohort demonstrated that DDKT can be safely performed during the COVID-19 pandemic when preventive measures are implemented.

Recurrent right ventricular takotsubo cardiomyopathy in a patient with recurrent aspiration.

Takotsubo cardiomyopathy is described as transient hypokinesis of the apical and mid-segments of the left ventricle with hypercontractile basal segments triggered by emotional or physical stress. Variants with basal hypokinesis and apical hyperkinesis have been described, as well as simultaneous involvement of the right ventricle (RV). Proposed mechanisms include myocardial "stunning" due to excessive catecholamine release. The echocardiographic presentation of Takotsubo cardiomyopathy may be related to differences in regional sympathetic innervation and catecholamine receptor density in the myocardium in the setting of high levels of circulating catecholamines. We describe the first case of isolated, recurrent RV Takotsubo cardiomyopathy reported in the literature.

Utility of CMV-Specific Immune Monitoring for the Management of CMV in Solid Organ Transplant Recipients: A Clinical Update.

Cytomegalovirus (CMV) is one of the most important opportunistic infections in solid organ transplant (SOT) recipients. However, current techniques used to predict risk for CMV infection fall short. CMV-specific cell mediated immunity (CMI) plays an important role in protecting against CMV infection. There is evidence that assays measuring CMV-CMI might better identify SOT recipients at risk of complications from CMV compared to anti-CMV IgG, which is our current standard of care. Here, we review recently published studies that utilize CMV-CMI, at various points before and after transplantation, to help predict risk and guide the management of CMV infection following organ transplantation. The evidence supports the use of these novel assays to help identify SOT recipients at increased risk and highlights the need for larger prospective trials evaluating these modalities in this high-risk population.

Discordance Between Radiologic Findings and Molecular Testing in Patients With Underlying Hematologic Malignancy and Coronavirus Disease 2019.

Severe acute respiratory syndrome coronavirus 2 is associated with severe disease in patients with hematologic malignancy. We report a series of patients with underlying hematologic malignancy and coronavirus disease of 2019 with discrepancy between radiographic findings and molecular testing. Initial chest x-ray findings should raise suspicion in immunosuppressed patients with typical clinical presentation even with negative initial testing.

Dosing Cefepime for Renal Function Does Not Completely Prevent Neurotoxicity in a Patient With Kidney Transplant.

Dosing cefepime for renal function does not completely prevent neurotoxicity in a kidney transplant patient. Cefepime neurotoxicity has been reported primarily among patients with renal insufficiency who received standard doses of the antibiotic. We report a case of nonconvulsive status epilepticus from dose-adjusted cefepime in a kidney transplant patient. The timing of symptoms along with clinical and electroencephalographic improvement after discontinuation of cefepime was critical to the diagnosis. Whether we should adjust the dose of cefepime differently in a patient with transplanted kidney to prevent neurotoxicity is unknown.

When Epidemiology Is the Clue to a Positive Outcome: A Case of Malaria During Pregnancy.

BACKGROUND Malaria infection during pregnancy is associated with increased perinatal and maternal morbidity and mortality. CASE REPORT A 29-year-old primigravida at 37 weeks of gestation, with no significant medical history, presented complaining of fever, chills, and generalized body aches. She had been living in Malawi for 1 year and was on atovaquone/proguanil prophylaxis until she was found to be pregnant. Prophylaxis was changed to mefloquine and discontinued upon her return to the US. Six weeks prior to presentation, she traveled to Malawi for 1 month when she was off prophylaxis. On admission, vital signs and physical exam results were normal. Given epidemiologic findings, a malaria smear was performed and showed 4% parasitemia. She was treated with mefloquine and discharged. Two days after discharge, she again presented with fever, chills, and body aches. A malaria smear showed <0.01% parasitemia, with 2 ring forms. Serologies for dengue, chikungunya, leptospira, and blood cultures were negative. These symptoms were deemed secondary to early recrudescence. The species was later identified as P. falciparum. The patient was treated with quinine sulfate and clindamycin. She delivered at full term without complication. CONCLUSIONS Pregnant women are more susceptible to severe forms of malaria, such as P. falciparum. A high index of suspicion and early identification of malaria are vital to prevent deleterious outcomes.

IVC filters-Trends in placement and indications, a study of 2 populations.

Inferior vena cava filter (IVCF) placement appears to be expanding over time despite absence of clear directing evidence.Two populations were studied. The first population included patients who received an IVCF between January 2005 and August 2013 at our community hospital center. Demographic information, indications for placement, and retrieval rate was recorded among other variables. The second population comprised of patients receiving an IVCF from 2005 to 2012 according to the Nationwide Inpatient Sample (NIS) using ICD-9CM coding. Patients were divided into 2 groups based on the year of admission for comparison, that is, first group from 2005 to 2008 and the second from 2009 to 2012. In addition, we analyzed annual trends in filter placement, acute venothromboembolic events (VTE) and several underlying comorbidities within this population.At our center, 802 IVCFs were placed (55.2% retrievable); 34% for absolute, 61% for relative, and 5% for prophylactic indications. Major bleeding (27.5%), minor self-limited bleeding (13.7%), and fall history (11.2%) were the commonest indications. Periprocedural complication rate was 0.7%, and filter retrieval rate was 7%. The NIS population (811,487 filters) saw a decline in IVCF placement after year 2009, following an initial uptrend (Ptrend < 0.01). IVCF use among patients with neither acute VTE nor bleeding among prior VTE saw a 3-fold absolute reduction from 2005 to 2012 (33,075-11,655; Ptrend < 0.01). Patients from 2009 to 2012 were more likely to be male and had higher rates of acute VTE, thrombolytic use, cancer, bleeding, hypotension, acute cardiorespiratory failure, shock, prior falls, blood product transfusion, hospital mortality including higher Charlson comorbidity scores. The patients were younger, had shorter length of stay, and were less likely to be associated with strokes including hemorrhagic or require ventilator support. Prior falls (adjusted odds ratio-aOR 2.8), thrombolytic use (aOR 1.76), and shock (aOR 1.45) were most predictive of IVCF placement between 2009 and 2012 on regression analysis.Recent trends suggest that a higher proportion of patients receive temporary IVCF, for predominantly relative indications. Nationally, the number of filters being placed is decreasing, especially among those who did not experience acute VTE or bleeding events. Prior falls, thrombolytic therapy, and shock were most predictive of IVCF placement in latter half of the study period.