Delayed-onset cytomegalovirus infection is frequent after discontinuing letermovir in cord blood transplant recipients.

Cytomegalovirus (CMV)-seropositive umbilical cord blood transplantation (CBT) recipients have a high incidence of CMV-associated complications. There are limited data regarding the efficacy of letermovir for preventing clinically significant CMV infection (CS-CMVi), and the impact of letermovir prophylaxis on delayed-onset CMV reactivation after letermovir discontinuation, in CBT recipients. We compared the cumulative incidence of CS-CMVi and CMV detection in 21 CMV-seropositive CBT recipients receiving letermovir prophylaxis with a historical cohort of 40 CBT recipients receiving high-dose valacyclovir prophylaxis. Letermovir was administered on day +1 up to day +98. The cumulative incidence of CS-CMVi was significantly lower by day 98 in the letermovir cohort (19% vs 65%). This difference was lost by 1 year due to a higher incidence of delayed-onset CMV reactivation in the letermovir cohort. No patients developed CMV disease in the letermovir cohort within the first 98 days compared with 2 cases (2.4%) in the high-dose valacyclovir cohort; 2 patients developed CMV enteritis after discontinuing letermovir. Median viral loads were similar in both cohorts. Thus, letermovir is effective at preventing CS-CMVi after CBT, but frequent delayed-onset infections after letermovir discontinuation mandate close monitoring and consideration for extended prophylaxis.

Shared inflammatory pathways and therapeutic strategies in COVID-19 and cancer immunotherapy.

COVID-19, the syndrome caused by the infection with SARS-CoV-2 coronavirus, is characterized, in its severe form, by interstitial diffuse pneumonitis and acute respiratory distress syndrome (ARDS). ARDS and systemic manifestations of COVID-19 are mainly due to an exaggerated immune response triggered by the viral infection. Cytokine release syndrome (CRS), an inflammatory syndrome characterized by elevated levels of circulating cytokines, and endothelial dysfunction are systemic manifestations of COVID-19. CRS is also an adverse event of immunotherapy (IMTX), the treatment of diseases using drugs, cells, and antibodies to stimulate or suppress the immune system. Graft-versus-host disease complications after an allogeneic stem cell transplant, toxicity after the infusion of chimeric antigen receptor-T cell therapy and monoclonal antibodies can all lead to CRS. It is hypothesized that anti-inflammatory drugs used for treatment of CRS in IMTX may be useful in reducing the mortality in COVID-19, whereas IMTX itself may help in ameliorating effects of SARS-CoV-2 infection. In this paper, we focused on the potential shared mechanisms and differences between COVID-19 and IMTX-related toxicities. We performed a systematic review of the clinical trials testing anti-inflammatory therapies and of the data published from prospective trials. Preliminary evidence suggests there might be a benefit in targeting the cytokines involved in the pathogenesis of COVID-19, especially by inhibiting the interleukin-6 pathway. Many other approaches based on novel drugs and cell therapies are currently under investigation and may lead to a reduction in hospitalization and mortality due to COVID-19.

Cord blood maternal microchimerism following unrelated cord blood transplantation.

Cord blood transplantation (CBT) is associated with low risk of leukemia relapse. Mechanisms underlying antileukemia benefit of CBT are not well understood, however a previous study strongly but indirectly implicated cells from the mother of the cord blood (CB) donor. A fetus acquires a small number of maternal cells referred to as maternal microchimerism (MMc) and MMc is sometimes detectable in CB. From a series of 95 patients who underwent double or single CBT at our center, we obtained or generated HLA-genotyping of CB mothers in 68. We employed a technique of highly sensitive HLA-specific quantitative-PCR assays targeting polymorphisms unique to the CB mother to assay CB-MMc in patients post-CBT. After additional exclusion criteria, CB-MMc was evaluated at multiple timepoints in 36 patients (529 specimens). CB-MMc was present in seven (19.4%) patients in bone marrow, peripheral blood, innate and adaptive immune cell subsets, and was detected up to 1-year post-CBT. Statistical trends to lower relapse, mortality, and treatment failure were observed for patients with vs. without CB-MMc post-CBT. Our study provides proof-of-concept that maternal cells of the CB graft can be tracked in recipients post-CBT, and underscore the importance of further investigating CB-MMc in sustained remission from leukemia following CBT.

Pain Management in Childhood Leukemia: Diagnosis and Available Analgesic Treatments.

Pain is one of the most common symptoms in children suffering from leukemia, who are often misdiagnosed with other childhood painful diseases such as juvenile idiopathic arthritis. Corticosteroid-induced osteonecrosis (ON) and vincristine-induced peripheral neuropathy (VIPN) are the most common painful manifestations. Additionally, ongoing pain may continue to impact quality of life in survivorship. This narrative review focuses on the pathophysiological mechanisms of pain in childhood leukemia and current available indications for analgesic treatments. Pain management in children is often inadequate because of difficulties in pain assessment, different indications across countries, and the lack of specific pediatric trials. Analgesic drugs are often prescribed off-label to children by extrapolating information from adult guidelines, with possible increased risk of adverse events. Optimal pain management should involve a multidisciplinary team to ensure assessment and interventions tailored to the individual patient.

Effects of Alcohol on the Cardiovascular System in Women.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality for women. This review summarizes the relationship between alcohol consumption and common CVDs in women and highlights potential differences from men. Except for risk of hypertension, no sex-related effects of alcohol consumption on the risk for coronary heart disease and stroke have been reported, and data on the sex-related effects on risk for peripheral arterial disease are limited. For women, alcohol consumption has a J-shaped relationship with hypertension. About 1 to 2 standard drinks per day is associated with lower risk for the development of hypertension, whereas for men, the relationship is relatively linear. In the area of alcoholic cardiomyopathy, the prevalence is greater for men, but women may develop alcoholic cardiomyopathy at a lower lifetime level of alcohol consumption. Overall, data support that 1 to 2 standard drinks per day for women and men is associated with a lower risk of CVD, and higher daily amounts may increase the risk of CVD.

The effects of repeated binge drinking on arterial stiffness and urinary norepinephrine levels in young adults.

OBJECTIVES: The aim of this study was to investigate the effect of repeated binge drinking and moderate alcohol consumption in young adults on arterial stiffness and sympathetic activity. METHODS: We enrolled 49 healthy young adults, free of cardiovascular diseases (25 men; age: 23.5 ±â€Š0.4 years; BMI: 23.4 ±â€Š0.4 kg/m; mean ±â€ŠS.E). Individuals included were those with a history of repeated binge drinking (>2 years duration; n = 20), drank at moderate levels (MODs, >5 years duration; n = 16) and abstained from alcohol (last 2-3 years; n = 13). Arterial stiffness was assessed using carotid to femoral pulse wave velocity (cfPWV) and sympathetic activity was assessed using 24-h urinary norepinephrine levels. Also measured was aortic SBP and augmentation index (AIx), a measure of wave reflection. RESULTS: Binge drinkers and MODs had higher cfPWV than alcohol abstainers (0.6 and 0.5 m/s, respectively; P ≤ 0.04). In addition, binge drinkers had higher urinary norepinephrine levels than MODs and alcohol abstainers (P < 0.05). Higher cfPWV were correlated with higher norepinephrine levels (r = 0.35. P = 0.02). Aortic SBP (P = 0.2) and AIx (P = 0.96) were similar among binge drinkers, MODs and alcohol abstainers. CONCLUSION: Our findings suggest that repeated exposure to alcohol, regardless of drinking pattern, may increase aortic arterial stiffness in healthy young adults. In addition, sympathetic activation, reflected by increased 24-h urinary norepinephrine levels, may contribute to alcohol-induced arterial stiffening in young adults.

Tetrahydrobiopterin Restores Microvascular Dysfunction in Young Adult Binge Drinkers.

BACKGROUND: Repeated binge drinking is associated with reduced microvascular function. However, microvascular responses to pathophysiological stimulus such as high pressure as well as potential mechanisms that underlie binge-induced microvascular dysfunction are unknown. Therefore, using an ex vivo experimental model, we examined microvascular responses following a brief period of high intraluminal pressure in isolated arterioles from young adults who have a history of repeated binge drinking. In addition, we examined whether the application of the endothelial nitric oxide synthase cofactor, tetrahydrobiopterin, would restore microvascular function in response to flow and high intraluminal pressure in young adult binge drinkers. METHODS: Isolated subcutaneous adipose arterioles were obtained from young adult binge drinkers (BD; n = 14), moderate drinkers (MODs; n = 10), and alcohol abstainers (ABs; n = 12; mean age: 23.7 ± 0.5 years; and body mass index: 23.4 ± 0.4 kg/m2 ). Arteriolar flow-induced dilation (FID, pressure gradient: ∆10 to 100 cm H2 O) was measured before and after acute high intraluminal pressure with and without tetrahydrobiopterin. RESULTS: Before high pressure, FID at Δ60 and Δ100 cm H2 O pressure gradient in BDs was 14% lower and 18% lower, respectively, than ABs (p < 0.05), while MODs and ABs had similar FID across all pressure gradients (p ≥ 0.2). After high pressure, FID in BDs was further reduced by 10% (p < 0.0005) and this impairment was ameliorated by the treatment of tetrahydrobiopterin (4 to 26% higher, p < 0.005). In contrast, FID after high pressure did not change in MODs and ABs (p ≥ 0.5). CONCLUSIONS: Microvascular dysfunction in young adult binge drinkers may be exacerbated with acute pathophysiological stimulus. These binge-induced dysfunctions may be reversed by tetrahydrobiopterin, which suggests a role of oxidative stress and/or uncoupled endothelial nitric oxide synthase in binge drinking.

Patient and program characteristics of early outpatient cardiac rehabilitation programs in the United States.

PURPOSE: The purpose of this study was to perform a brief survey to determine the patient and program characteristics associated with early outpatient cardiac rehabilitation (EOCR) in the United States. METHODS: To assess these characteristics, a brief survey (13 items, some with multiple responses) was sent by the American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR) to all program administrators or directors on the AACVPR mailing list in 2009. RESULTS: Responses were received from 138 program administrators or directors in 44 states, accounting for 19 689 patients who completed at least 1 EOCR exercise session. More men (68%) were enrolled in EOCR programs, and the 3 most prevalent primary diagnoses were percutaneous coronary intervention or stent (31%), coronary artery bypass graft surgery (30%), and myocardial infarction (22%). Seventy-two percent of responding programs were AACVPR certified and had staff trained primarily (66%) in either nursing or exercise physiology. Eighty-four percent of the programs offered an outpatient maintenance cardiac rehabilitation program, and 62% were located in a rural setting. CONCLUSIONS: This study provides valuable information on use and patient demographics of EOCR programs in the United States. This information may be beneficial for health care professionals, health care institutions, third-party payers, and regulatory agencies that seek to quantify health care quality.