Valganciclovir Dosing for Cytomegalovirus Prophylaxis in Solid-organ Transplant Recipients on Continuous Veno-venous Hemodialysis.

BACKGROUND: Optimal valganciclovir dosing for cytomegalovirus (CMV) prophylaxis in solid-organ transplant (SOT) patients on continuous veno-venous hemodialysis (CVVHD) is not known. Ganciclovir trough concentrations ≥0.60 µg/mL have been suggested for CMV prophylaxis. This study was conducted to determine if valganciclovir 450 mg enterally every 24 hours achieves ganciclovir trough concentrations ≥0.60 µg/mL in patients on CVVHD. METHODS: This single-center, prospective, open-label, pharmacokinetic study included adult SOT patients admitted to an intensive care unit from March 2018 to June 2019 on CVVHD. All patients were receiving valganciclovir 450 mg enterally every 24 hours for CMV prophylaxis prior to enrollment. Each patient had a peak and trough sample drawn at steady state. RESULTS: Ten SOT patients were included in the study (6 liver, 1 simultaneous liver-kidney, 2 bilateral lung, 1 heart). The mean ± SD age was 51.8 ± 14.0 years, and average body mass index was 27 ± 6.9 kg/m2. Ganciclovir trough concentrations ranged from 0.31 to 3.16 µg/mL, and 80% of participants have trough concentrations ≥0.60 µg/mL. No patients had documented neutropenia while on valganciclovir and CVVHD; 60% of patients had significant thrombocytopenia. CONCLUSIONS: Valganciclovir 450 mg enterally every 24 hours achieved ganciclovir trough concentrations ≥0.60 µg/mL in most patients on CVVHD, similar to those reported with intravenous ganciclovir for prophylaxis in this population. Based on these data, valganciclovir may require dosing every 24 hours to achieve concentrations equivalent to ganciclovir. Neutropenia did not occur in the study period. Thrombocytopenia was common and likely multifactorial.

Clinical course of COVID-19 in a liver transplant recipient on hemodialysis and response to tocilizumab therapy: A case report.

The novel coronavirus disease 2019 (COVID-19) is a highly infectious and rapidly spreading disease. There are limited published data on the epidemiology and outcomes of COVID-19 infection among organ transplant recipients. After initial flulike symptoms, progression to an inflammatory phase may occur, characterized by cytokine release rapidly leading to respiratory and multiorgan failure. We report the clinical course and management of a liver transplant recipient on hemodialysis, who presented with COVID-19 pneumonia, and despite completing a 5-day course of hydroxychloroquine, later developed marked inflammatory manifestations with rapid improvement after administration of off-label, single-dose tocilizumab. We also highlight the role of lung ultrasonography in early diagnosis of the inflammatory phase of COVID-19. Future investigation of the effects of immunomodulators among transplant recipients with COVID-19 infection will be important.

Evaluation of anticoagulation and nonsurgical major bleeding in recipients of continuous-flow left ventricular assist devices.

Continuous-flow left ventricular assist device (LVAD) placement has become a standard of care in advanced heart failure treatment. Bleeding is the most frequently reported adverse event after LVAD implantation and may be increased by antithrombotic agents used for prevention of pump thrombosis. This retrospective cohort included 85 adult patients implanted with a Heartmate II LVAD. Major bleeding was defined as occurring >7 days after implant and included intracranial hemorrhage, events requiring 2 units of packed red blood cells within a 24-h period, and death from bleeding. Primary outcome was intensity of anticoagulation between patients with or without at least one incidence of nonsurgical major bleeding. Major bleeding occurred in 35 (41%) patients with 0.48 events per patient year and a median (IQR) time to first bleed of 134.5 (39.3, 368.5) days. The median (IQR) INR at time of bleed was 1.7 (1.4, 2.5). Median INR during follow-up did not differ between groups and patients with major bleeding were not more likely to have a supra-therapeutic INR. Patients who bled were more likely to have received LVAD for destination therapy, to have lower weight, worse renal function, and lower hemoglobin at baseline. Duration of LVAD support and survival were similar between groups with no difference in occurrence of thrombosis. Incidence of nonsurgical major bleeding was not significantly associated with degree of anticoagulation. Certain baseline characteristics may be more important than anticoagulation intensity to identify patients at risk for bleeding after LVAD implant. Modification of anticoagulation alone is not a sufficient management strategy and early intervention may be required to mitigate bleeding impact.

Anthropometric, biochemical, dietary, morbidity and well-being assessments in women and children in Indonesia, India and Senegal: a UKRI GCRF Action Against Stunting Hub protocol paper.

INTRODUCTION: Child stunting has a complex aetiology, especially in the first 1000 days of life. Nutrition interventions alone have not produced expected impacts in reducing/preventing child stunting, indicating the importance of understanding the complex interplay between environmental, physiological and psychological factors influencing child nutritional status. This study will investigate maternal and child nutrition, health and well-being status and associated factors through the assessment of: (1) anthropometry, (2) biomarkers of nutrition and health status, (3) dietary intakes, (4) fetal growth and development, (5) infant morbidity, (6) infant and young child feeding (IYCF) and (7) perinatal maternal stress, depression and social support. METHODS: This study will be conducted in a prospective pregnancy cohort in India, Indonesia and Senegal. Pregnant women will be recruited in the second (Indonesia, Senegal) and third (India) trimester of pregnancy, and the mother and infant dyads followed until the infant is 24 months of age. During pregnancy, anthropometric measures will be taken, venous blood samples will be collected for biochemical assessment of nutrition and health status, dietary intakes will be assessed using a 4-pass-24-hour dietary recall method (MP24HR), fetal ultrasound for assessment of fetal growth. After birth, anthropometry measurements will be taken, venous blood samples will be collected, MP24HR will be conducted, infant morbidity and IYCF practices will be assessed and a sample of breastmilk will be collected for nutrient composition analyses. Perinatal maternal stress, depression, social support and hair cortisol levels (stress) will be measured. The results from this study will be integrated in an interdisciplinary analysis to examine factors influencing infant growth and inform global efforts in reducing child stunting. ETHICS AND DISSEMINATION: Ethical approval was granted by the Ethics Committee of the London School of Hygiene and Tropical Medicine (17915/RR/17513); National Institute of Nutrition (ICMR)-Ministry of Health and Family Welfare, Government of India (CR/04/I/2021); Health Research Ethics Committee, University of Indonesia and Cipto Mangunkusumo Hospital (KET-887/UN2.F1/ETIK/PPM.00.02/2019); and the Comité National d'Ethique pour la Recherche en Santé, Senegal (Protocole SEN19/78); the Royal Veterinary College (URN SR2020-0197) and the International Livestock Research Institute Institutional Research Ethics Committee (ILRI-IREC2020-33). Results will be published in peer-reviewed journals and disseminated to policy-makers and participating communities.

Risks of paxlovid in a heart transplant recipient.

The burden of morbidity and mortality from SARS-CoV-2 infection is especially significant in heart transplant patients who are at higher risk for poor outcomes owing to immunosuppression, blunted response to vaccination, and multiple comorbid conditions. Over the last 3 years the therapeutic landscape for COVID-19 has evolved and our drug armamentaria continues to expand. With these advancements comes a time of great hope to mitigate significant illness from SARS - CoV - 2 infection. However, as with many emerging frontiers, the administration of novel therapeutics to a complex patient population remains challenging. We present a patient case encountered at our institution that highlights the need for increased awareness of nuances while managing COVID-19 infection in a heart transplant recipient.

The Impact on COVID-19 by Intravenous Bevacizumab Used for Hereditary Hemorrhagic Telangiectasia: A Case Report.

Coronavirus disease 2019 (COVID-19) continues as an infectious pandemic. With emphasis on mitigating its impact globally, strategies have been emphasized on prevention to treatment in severe cases. As for pharmacotherapies, many have been researched, with a few being recommended for patients with COVID-19 depending upon their severity. Bevacizumab, a recombinant monoclonal antibody often used for oncological disease and rare genetic disorders, has gained attention in combatting COVID-19 due to the pharmacotherapy's ability to inhibit vascular endothelial growth factor A (VEGF-A). VEGF has been identified as significantly upregulated in the lungs of persons who have died of COVID-19, raising interest for VEGF to be a potential target for patients with COVID-19. We present a case of a patient who was admitted due to complications of a rare genetic disorder, called hereditary hemorrhagic telangiectasia (HHT), warranting intravenous bevacizumab, who subsequently was diagnosed with COVID-19 pneumonia. We discuss the patient's outcome and contribute to the growing potential of bevacizumab in the treatment of COVID-19.

A lack of race and ethnicity data in the treatment of hereditary hemorrhagic telangiectasia: a systematic review of intravenous bevacizumab efficacy.

BACKGROUND: For extreme hereditary hemorrhagic telangiectasia (HHT) disease, treatments such as intravenous bevacizumab are often utilized. However, whether its efficacy is similar across diverse races and ethnicities is unclear. METHODS: In this systematic review, we performed a search for English-language articles identified through PubMed, Embase, and Scopus databases whose research occurred in the United States (US). Search terms related to HHT, epistaxis, and intravenous bevacizumab. We searched specifically for the intervention of intravenous bevacizumab because the term serves as a suitable surrogate to convey a patient who has both a diagnosis of HHT and established care. We focused on number of patients recruited in intravenous bevacizumab trials who were identified by race or ethnicity. RESULTS: Our search identified 79 studies, of which four were conducted in the US. These four were selected for our systematic review. In these studies, 58 total patients were evaluated (ranging from 5 to 34 participants), whereby, information on age and gender were included. However, none of the US-based studies shared race or ethnicity data. CONCLUSION: Inability to find studies regarding intravenous bevacizumab use in patients with HHT in which race and ethnicity are reported limits our ability to understand the therapy's efficacy in specific populations. Without emphasis on race and ethnicity in such trials, showing the potential of HHT-related diversity in individuals with this disease may reaffirm implicit bias around HHT diagnosis and treatment. Future work on HHT should emphasize sociodemographic data collection and reporting in an effort to understand this disease in diverse populations.

Morbid obesity and functional status as predictors of surgical complication after renal transplantation.

BACKGROUND: This study evaluated the impact of body mass index (BMI) and patient functional status on the risk for surgical complications after kidney transplant. METHODS: This retrospective cohort study of adult kidney transplant recipients grouped patients by baseline Karnofsky status (low function ≤ 70%) and further stratified by morbid obesity (BMI ≥ 35 kg/m2) to assess surgical complication risk. RESULTS: 736 patients were included with surgical complications occurring in 25%. Logistic regression analysis with interaction terms demonstrated that morbid obesity and low functional status conditionally impact risk with an OR of 2.8 [95% CI (1.1-7.3)]. Within the functional status cohort, BMI ≥35 kg/m2 was associated with increased risk of surgical complication, superficial wound infection, and DGF. Independent predictors for surgical complications included diabetes and morbid obesity with low functional status. There was no significant difference in graft loss or death across the cohorts. CONCLUSIONS: While neither morbid obesity nor poor functional status alone predicts increased complications, the combined presence is associated with significant increase in risk for surgical complications after renal transplantation.

Assessment of Bleeding and Thrombosis Based on Aspirin Responsiveness after Continuous-Flow Left Ventricular Assist Device Placement.

Pump thrombosis (PT) is a severe complication of left ventricular assist device (LVAD) support. This study evaluated PT and bleeding after LVAD placement in patients responsive to a standard aspirin dose of 81 mg using platelet inhibition monitoring compared with initial nonresponders who were then titrated upward to achieve therapeutic response. Patients ≥ 18 years of age with initial placement of HeartMate II LVAD at our institution and at least one VerifyNow Aspirin test performed during initial hospitalization were included. The primary endpoints were bleeding and PT compared between initial aspirin responders and nonresponders. Of 85 patients, 19 (22%) were nonresponsive to initial aspirin therapy. Responders and nonresponders showed similar survival (p = 0.082), freedom from suspected/confirmed PT (p = 0.941), confirmed PT (p = 0.273), bleeding (p = 0.401), and incidence rates in PT and bleeding. Among the initial responders (<500 vs. 500-549 aspirin reaction units), there were no significant differences in survival (p = 0.177), freedom from suspected/confirmed PT (p = 0.542), confirmed PT (p = 0.159), bleeding (p = 0.879), and incidence of PT and bleeding. Platelet function testing may detect resistance to standard aspirin regimens used in LVAD patients. Dose escalation in initially nonresponsive patients to achieve responsiveness may confer a similar PT risk to patients initially responsive to standard aspirin dosing without increased bleeding risk.