White Matter Hyperintensity and Cardiovascular Disease Outcomes in the SPRINT MIND Trial.

BACKGROUND: The Systolic Blood Pressure Intervention Trial (SPRINT) randomized patients to a goal systolic blood pressure (SBP) <120 mm Hg vs. <140 mm Hg. In a subset of participants, the SPRINT MIND ancillary study performed a baseline MRI and measured white matter hyperintensity volume (WMHv). In this secondary analysis, we evaluated the association between baseline WMHv and cardiovascular events during follow-up in the overall sample. METHODS: The primary outcome was the same as SPRINT, a composite of stroke, myocardial infarction, acute coronary syndrome, decompensated congestive heart failure, or cardiovascular death. We fit Cox models to the primary outcome and report adjusted hazard ratios (HR) for log-transformed WMHv and quartiles of WMHv. RESULTS: Among 717 participants, the median (IQR) baseline WMHv was 1.62 (0.66-3.98) mL. The primary outcome occurred in 51/719 (7.1%). The median WMHv was higher in patients with the primary outcome (3.40 mL versus 1.56 mL, p < 0.001). In adjusted models, WMHv as a log-transformed continuous variable was associated with the primary outcome (HR 1.44, 95% CI 1.15-1.80). The highest quartile of WMHv, compared to the lowest, was also independently associated with the primary outcome (HR 3.21, 95% CI 1.27-8.13). CONCLUSIONS: We found that the baseline volume of WMH was associated with future CVD risk in SPRINT MIND. Prospective clinical trials with larger sample sizes than the current study are needed to determine whether intensive BP lowering can reduce the high cardiovascular risk in patients with WMH.

Serial Imaging of Virus-Associated Necrotizing Disseminated Acute Leukoencephalopathy (VANDAL) in COVID-19.

BACKGROUND AND PURPOSE: Various patterns of leukoencephalopathy have been described in coronavirus disease 2019 (COVID-19). In this article, we aimed to describe the clinical and imaging features of acute disseminated leukoencephalopathy in critically ill patients with COVID-19 and the imaging evolution during a short-term follow-up. MATERIALS AND METHODS: We identified and reviewed the clinical data, laboratory results, imaging findings, and outcomes for 8 critically ill patients with COVID-19 with acute disseminated leukoencephalopathy. RESULTS: All patients demonstrated multiple areas of white matter changes in both cerebral hemispheres; 87.5% (7/8) of patients had a posterior predilection. Four patients (50%) had short-term follow-up imaging within a median of 17 days after the first MR imaging; they developed brain atrophy, and their white matter lesions evolved into necrotizing cystic cavitations. All (8/8) patients had inflammatory cytokine release syndrome as demonstrated by elevated interleukin-6, D-dimer, lactate dehydrogenase, erythrocyte sedimentation rate, C-reactive protein, and ferritin levels. Most (7/8; 87.5%) patients were on prolonged ventilator support (median, 44.5 days; interquartile range, 20.5 days). These patients had poor functional outcomes (6/8 [75%] patients were discharged with mRS 5) and high mortality (2/8, 25%). CONCLUSIONS: Critically ill patients with COVID-19 can develop acute disseminated leukoencephalopathy that evolves into cystic degeneration of white matter lesions with brain atrophy during a short period, which we dubbed virus-associated necrotizing disseminated acute leukoencephalopathy. This may be the result of COVID-19-related endothelial injury, cytokine storm, or thrombotic microangiopathy.

Causes of mortality and severe morbidity requiring euthanasia in captive Tasmanian devils (Sarcophilus harrisii) in Tasmania.

BACKGROUND: Devil facial tumour disease (DFTD) is a contagious cancer causing marked population declines in wild Tasmanian devils. In response to this threat, a captive insurance population has been established. This study investigated causes of death in captive Tasmanian devils. METHODS: Clinical and laboratory records of captive Tasmanian devils held in seven Tasmanian captive facilities were analysed for cause of death or severe morbidity requiring euthanasia. RESULTS: Neoplasia was found to be the most common cause of mortality/severe morbidity, accounting for 27/63 of deaths. Cutaneous lymphoma was the most frequently observed tumour (10/27), at a higher incidence than previously reported. The most common cause of severe morbidity, following neoplasia, was leucoencephalomyelopathy, which caused severe, progressive hindlimb paresis and ataxia. CONCLUSION: Neoplasia, specifically cutaneous lymphoma, and degenerative neurological conditions are the most frequent causes of death in captive Tasmanian devils in Tasmania. Further work to determine the aetiologies of these conditions, as well as effective treatments, would be valuable.

Impact of white matter changes on neurologic outcomes of total arch replacement using antegrade cerebral perfusion.

OBJECTIVE: To evaluate the impact of white matter changes on neurologic outcomes after total arch replacement using antegrade cerebral perfusion. METHODS: White matter changes were assessed using a visual Fazekas scale on preoperative magnetic resonance images. From October 1999 to December 2016, 359 patients who had demonstrated changes on preoperative magnetic resonance imaging underwent elective total arch replacement using antegrade cerebral perfusion. Patients were classified into 3 severity groups: mild (100 patients), moderate (158 patients), and severe (101 patients). Mean follow-up time was 4.8 ± 3.6 years. Multivariate logistic regression methods were used to evaluate for an independent association between white matter changes and postoperative neurological outcomes. RESULTS: Hospital mortality was 2.8% (10/359), and no significant differences were found across the 3 groups (P = .604). Multivariate analysis demonstrated that the severity of white matter change was significantly associated with both postoperative permanent neurologic deficit (odds ratio, 5.77; 95% confidence interval, 1.58-38.4, P = .005) and transient neurologic deficit (odds ratio, 2.46; 95% confidence interval, 1.45-4.37, P < .001). CONCLUSIONS: White matter changes, defined using the visual Fazekas scale on preoperative magnetic resonance imaging, were significantly associated with significant postoperative adverse neurologic outcomes after total arch replacement using antegrade cerebral perfusion.

Mortality Risk After AIDS-Defining Opportunistic Illness Among HIV-Infected Persons--San Francisco, 1981-2012.

OBJECTIVE: To examine whether improved human immunodeficiency virus (HIV) treatment was associated with better survival after diagnosis of AIDS-defining opportunistic illnesses (AIDS-OIs) and how survival differed by AIDS-OI. DESIGN: We used HIV surveillance data to conduct a survival analysis. METHODS: We estimated survival probabilities after first AIDS-OI diagnosis among adult patients with AIDS in San Francisco during 3 treatment eras: 1981-1986; 1987-1996; and 1997-2012. We used Cox proportional hazards models to determine adjusted mortality risk by AIDS-OI in the years 1997-2012. RESULTS: Among 20 858 patients with AIDS, the most frequently diagnosed AIDS-OIs were Pneumocystis pneumonia (39.1%) and Kaposi sarcoma (20.1%). Overall 5-year survival probability increased from 7% in 1981-1986 to 65% in 1997-2012. In 1997-2012, after adjustment for known confounders and using Pneumocystis pneumonia as the referent category, mortality rates after first AIDS-OI were highest for brain lymphoma (hazard ratio [HR], 5.14; 95% confidence interval [CI], 2.98-8.87) and progressive multifocal leukoencephalopathy (HR, 4.22; 95% CI, 2.49-7.17). CONCLUSIONS: Survival after first AIDS-OI diagnosis has improved markedly since 1981. Some AIDS-OIs remain associated with substantially higher mortality risk than others, even after adjustment for known confounders. Better prevention and treatment strategies are still needed for AIDS-OIs occurring in the current HIV treatment era.

Reduced mortality rates in a cohort of long-term underground iron-ore miners.

BACKGROUND: Historically, working in iron-ore mines has been associated with an increased risk of lung cancer and silicosis. However, studies on other causes of mortality are inconsistent and in the case of cancer incidence, sparse. The aim of this study was to examine the association between iron-ore mining, mortality and cancer incidence. METHODS: A 54-year cohort study on iron-ore miners from mines in northern Sweden was carried out comprising 13,000 workers. Standardized rate ratios were calculated comparing the disease frequency, mortality, and cancer incidence with that of the general population of northern Sweden. Poisson regression was used to evaluate the association between the durations of employment and underground work, and outcome. RESULTS: Underground mining was associated with a significant decrease in adjusted mortality rate ratios for cerebrovascular and digestive system diseases, and stroke. For several outcomes, elevated standardized rate ratios were observed among blue-collar workers relative to the reference population. However, only the incidence of lung cancer increased with employment time underground (P < 0.001). CONCLUSIONS: Long-term iron-ore mining underground was associated with lower rates regarding several health outcomes. This is possibly explained by factors related to actual job activities, environmental exposure, or the selection of healthier workers for long-term underground employment.