The impact of cancer metastases on COVID-19 outcomes: A COVID-19 and Cancer Consortium registry-based retrospective cohort study.

BACKGROUND: COVID-19 can have a particularly detrimental effect on patients with cancer, but no studies to date have examined if the presence, or site, of metastatic cancer is related to COVID-19 outcomes. METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, the authors identified 10,065 patients with COVID-19 and cancer (2325 with and 7740 without metastasis at the time of COVID-19 diagnosis). The primary ordinal outcome was COVID-19 severity: not hospitalized, hospitalized but did not receive supplemental O2, hospitalized and received supplemental O2, admitted to an intensive care unit, received mechanical ventilation, or died from any cause. The authors used ordinal logistic regression models to compare COVID-19 severity by presence and specific site of metastatic cancer. They used logistic regression models to assess 30-day all-cause mortality. RESULTS: Compared to patients without metastasis, patients with metastases have increased hospitalization rates (59% vs. 49%) and higher 30 day mortality (18% vs. 9%). Patients with metastasis to bone, lung, liver, lymph nodes, and brain have significantly higher COVID-19 severity (adjusted odds ratios [ORs], 1.38, 1.59, 1.38, 1.00, and 2.21) compared to patients without metastases at those sites. Patients with metastasis to the lung have significantly higher odds of 30-day mortality (adjusted OR, 1.53; 95% confidence interval, 1.17-2.00) when adjusting for COVID-19 severity. CONCLUSIONS: Patients with metastatic cancer, especially with metastasis to the brain, are more likely to have severe outcomes after COVID-19 whereas patients with metastasis to the lung, compared to patients with cancer metastasis to other sites, have the highest 30-day mortality after COVID-19.

Burden of AML, 1990-2019: Estimates From the Global Burden of Disease Study.

PURPOSE: AML accounts for 80% of acute leukemia in adults. While progress has been made in treating younger patients in the past 2 decades, there has been limited improvement for older patients until recently. This study examines the global and European Union (EU) 15+ trends in AML between 1990 and 2019. METHODS: We extracted age-standardized incidence rates (ASIRs), age-standardized death rates (ASMRs), and disability-adjusted life years, stratified by sex from the Global Burden of Disease Study database, and mortality-to-incidence ratio (MIR) were computed. Trends were compared using Joinpoint regression. RESULTS: The findings show a global increase in AML incidence for both sexes from 1990 to 2019. In the EU15+ countries, most countries exhibited an increase in ASIR for both sexes. Joinpoint revealed that globally for male patients, ASIR steadily increased until 2010, remained stable until 2015 followed by a decline till 2019. Similar trends were observed in female patients. For ASMR, although there was an increase globally and in most EU15+ countries, there was a statistically significant decrease in mortality rates globally and in the majority of EU15+ countries in recent years. MIR improved in both sexes globally. On age stratification, AML burden was highest among older groups (55 years and older), while the lowest rates were observed in younger than 20 years. CONCLUSION: The findings from our study indicate a global rise in AML incidence and mortality in both sexes and decrease in MIR from 1990 to 2019 suggesting a better survival. However, on Joinpoint analysis, there is no change in MIR in women in the past decade and past 4 years in men indicating plateau in survival trends despite recent advances.

The relevance of cortisol co-secretion from aldosterone-producing adenomas.

AIMS AND OBJECTIVES: Adrenal adenomas are usually non-functioning, but can secrete aldosterone or cortisol. It has recently been suggested that many more adenomas than previously thought secrete more than one hormone. This has important implications for their clinical management. Our aim was to determine the frequency of cortisol co-secretion in primary hyperaldosteronism at our institution and investigate the difference in metabolic profiles and clinical outcomes between co-secreting and non-co-secreting patients. DESIGN AND PATIENTS: A retrospective study of 25 patients with primary hyperaldosteronism who also underwent formal dexamethasone suppression tests to determine cortisol co-secretion. MEASUREMENTS: Post-dexamethasone suppression test cortisol, serum ALT, total cholesterol, HDL-cholesterol, LDL-cholesterol, HbA1C (were recorded) and mean arterial pressure are reported in this cohort of patients with primary hyperaldosteronism. RESULTS: Four out of 25 patients with primary hyperaldosteronism failed dexamethasone suppression tests. This suggests a frequency of co-secretion ranging between 4 and 16%. No significant difference was found in serum ALT, total cholesterol, serum HDL-cholesterol, LDL-cholesterol and mean arterial blood pressure at presentation between co-secretors and non-co-secretors. CONCLUSION: A frequency range of 4-16% suggests that a significant proportion of patients with primary hyperaldosteronism co-secrete cortisol. Co-secretors did not have a worse metabolic profile than non-secretors. The impact of co-secretion on metabolic profile and surgical management remains unclear and warrants further study.

Mitochondrial DNA depletion in sporadic inclusion body myositis.

Sporadic inclusion body myositis (sIBM) is a late onset disorder of unkown aetiology. Mitochondrial changes such as cytochrome oxidase deficient fibres are a well recognised feature and mitochondrial DNA (mtDNA) deletions have also been reported, but not consistently. Since mtDNA deletions are not present in all cases, we investigated whether other types of mtDNA abnormality were responsible for the mitochondrial changes. We studied 9 patients with sIBM. To control for fibre loss or replacement with inflammatory cells, we compared sIBM patients with necrotising myopathy (n = 4) as well as with healthy controls. Qualitative anlysis for mtDNA deletions and quantitative measurement of mtDNA copy number showed that muscle from patients with sIBM contained on average 67% less mtDNA than healthy controls (P = 0.001). The level of mtDNA was also significantly depleted in sIBM when compared to necrotising myopathy. No significant difference in copy number was seen in patients with necrotising myopathy compared to controls. Deletions of mtDNA were present in 4 patients with sIBM, but not all. Our findings suggest that mtDNA depletion is a more consistent finding in sIBM, and one that may be implicated in the pathogenesis of the disease.