Risk Factors and Multidimensional Assessment of Long Coronavirus Disease Fatigue: A Nested Case-Control Study.

BACKGROUND: Fatigue is the most prevalent and debilitating long-COVID (coronavirus disease) symptom; however, risk factors and pathophysiology of this condition remain unknown. We assessed risk factors for long-COVID fatigue and explored its possible pathophysiology. METHODS: This was a nested case-control study in a COVID recovery clinic. Individuals with (cases) and without (controls) significant fatigue were included. We performed a multidimensional assessment evaluating various parameters, including pulmonary function tests and cardiopulmonary exercise testing, and implemented multivariable logistic regression to assess risk factors for significant long-COVID fatigue. RESULTS: A total of 141 individuals were included. The mean age was 47 (SD: 13) years; 115 (82%) were recovering from mild coronavirus disease 2019 (COVID-19). Mean time for evaluation was 8 months following COVID-19. Sixty-six (47%) individuals were classified with significant long-COVID fatigue. They had a significantly higher number of children, lower proportion of hypothyroidism, higher proportion of sore throat during acute illness, higher proportions of long-COVID symptoms, and of physical limitation in daily activities. Individuals with long-COVID fatigue also had poorer sleep quality and higher degree of depression. They had significantly lower heart rate [153.52 (22.64) vs 163.52 (18.53); P = .038] and oxygen consumption per kilogram [27.69 (7.52) vs 30.71 (7.52); P = .036] at peak exercise. The 2 independent risk factors for fatigue identified in multivariable analysis were peak exercise heart rate (OR: .79 per 10 beats/minute; 95% CI: .65-.96; P = .019) and long-COVID memory impairment (OR: 3.76; 95% CI: 1.57-9.01; P = .003). CONCLUSIONS: Long-COVID fatigue may be related to autonomic dysfunction, impaired cognition, and decreased mood. This may suggest a limbic-vagal pathophysiology. CLINICAL TRIALS REGISTRATION: NCT04851561.

T-Lymphoblastic Leukemia/Lymphoma and Thymoma: A Case Report and Review of the Literature of a Rare Association.

The co-occurrence of thymoma and T-lymphoblastic lymphoma/leukemia is an extremely rare but previously reported association that poses a diagnostic and therapeutic challenge. We describe a 67-year-old patient with long-standing untreated B1 thymoma that presented with constitutional symptoms and a painless soft tissue mass on the right chest wall. Pathological analysis of the biopsy from the mass demonstrated T-lymphoblastic leukemia/lymphoma. The patient went through a complicated course, was refractory to several lines of therapy, and eventually underwent allogeneic hematopoietic stem cell transplantation in complete remission from a matched related donor. The association between thymoma and malignant neoplasms has been described in the literature, most notably with colorectal adenocarcinoma and thyroid cancer. Thymoma-associated leukemia is, however, extremely unusual, with limited reports in the literature. Distinguishing between thymoma and leukemia can be challenging and often requires meticulous diagnostic efforts. For patients with a past history of thymoma, awareness of this particular association should be bared in mind to allow earlier diagnosis and therapy.

Post-transplant diabetes mellitus: incidence, predicting factors and outcomes.

PURPOSE: To identify predictors and evaluate outcomes of posttransplant diabetes mellitus (PTDM) and to investigate the effect of treatment modalities on outcomes. METHODS: The database of a tertiary medical center was searched for all adult patients without prior diabetes who underwent lung, liver, or heart transplantation between January 1, 2012 and June 30, 2018. Patients in whom PTDM (defined as HbA1C ≥ 6.5% at least 3 months post transplantation) developed during follow-up (mean 3.32 years) were identified. Risk factors for PTDM, determined by regression analysis and clinical outcomes [all-cause mortality, severe infections, graft loss, and major adverse cardiovascular events (MACE)], were compared between those who developed PTDM and those who did not; in the former, insulin-based therapy was compared with non-insulin regimen. RESULTS: The cohort included 281 transplant recipients: 158 lung, 109 liver, and 14 heart. PTDM was diagnosed in 60 (21.35%) patients at a mean of 11.3 ± 12.89 months post transplantation. The only significant independent risk factor for PTDM was age (HR 1.028, 95% CI = 1.002-1.054, P = 0.0314). PTDM was associated with higher rates of severe infections (HR 2.565, 95% CI = 1.626-4.050, P < 0.0001), MACE (HR 1.856, 95% CI = 1.013-3.401, P = 0.0454) and death (HR 1.840, 95% CI = 1.024-3.304, P = 0.0413). Recipients treated with insulin-based regimens had a higher risk of severe infections (HR 2.579, 95% CI = 1.640-4.055, P < 0.0001), MACE (1.925, 95% CI = 1.074-3.451, P = 0.0278) and death (HR 1.960, 95% CI = 1.071-3.586, P = 0.0291). CONCLUSIONS: PTDM is associated with increased mortality and poor outcomes in lung, liver, and heart transplant recipients. Early identification and aggressive treatment of PTDM and its associated cardiometabolic risk factors may improve outcomes.

Infections associated with bendamustine containing regimens in hematological patients: a retrospective multi-center study.

A multi-center retrospective analysis of a cohort of patients in Israel treated with any bendamustine containing regimen between 2010-2014 was performed in order to determine the incidence and predictors for infection. The Kaplan Meier Model, employing log rank analysis, was used to assess time-to-infection. The Cox Proportional Hazards model was used to analyze multivariate effects of risk and 234 patients were included in the analysis. One hundred and nine (46.6%) developed at least one infection and 33.76% had severe infections. Seventy-six (41.5%) developed bacterial infection, nine (3.8%) fungal infection and 26 (11.5%) had viral infections. Factors significantly associated with time to infection on multivariable analysis were: bendamustine-combinations [hazard ratio (HR) = 0.589 (95% CI = 0.374-0.926), p = 0.022], Hb level [HR = 0.791 (95% CI = 0.716-0.875), p < 0.0001] and ischemic heart disease [HR = 1.828 (95% CI = 1.165-2.868), p = 0.009]. Infections were associated with a higher mortality and hospitalization rate.