Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Scleroderma renal crisis is characterized by malignant hypertension and oligo-anuric acute renal failure. Scleroderma renal crisis occurs in 2 to 5% of patients with systemic sclerosis, particularly those with diffuse cutaneous systemic sclerosis in the first years of disease evolution. High-dose corticosteroid therapy (> 15 mg/d) is associated with an increased risk of scleroderma renal crisis. Patients present with prominent left heart failure and hypertensive encephalopathy. Renal failure can be associated with moderate proteinuria, without hematuria. Thrombotic microangiopathy is detected in 43% of the cases. Anti-RNA polymerase III antibodies are present in one third of patients with scleroderma renal crisis. In case of renal failure, iatrogenic or functional origin must be investigated, as well as crescentic glomerulonephritis associated with antineutrophil cytoplasm antibodies (ANCA) or thrombotic microangiopathy. Renal biopsy is not necessary to establish the diagnosis in typical forms of scleroderma renal crisis. However, it can help to evaluate the prognosis and it is recommended when clinical presentation of scleroderma renal crisis is unusual. The prognosis of scleroderma renal crisis dramatically improved with the use of angiotensin-converting enzyme (ACE) inhibitors. However, 5-year survival of patients who developed a scleroderma renal crisis is only 65%. The treatment relies on the early control of blood pressure with increasing doses of ACE inhibitors, in association with calcium channel blockers if necessary. In case of severe renal failure and/or hypertension, dialysis can help to quickly control the vascular overload and the blood pressure. Dialysis can be stopped in about half of cases. After 2 years on dialysis, eligible patients should be considered for renal transplantation. The prevention of scleroderma renal crisis lacks consensus. Corticosteroids and/or nephrotoxic drugs should be avoided in patients with diffuse cutaneous systemic sclerosis.
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PMID:[Renal involvement in patients with systemic sclerosis]. 2152 52

Background: Zinc impairs replication of RNA viruses such as SARS-CoV-1, and may be effective against SARS-CoV-2. However, to achieve adequate intracellular zinc levels, administration with an ionophore, which increases intracellular zinc levels, may be necessary. We evaluated the impact of zinc with an ionophore (Zn+ionophore) on COVID-19 in-hospital mortality rates. Methods: A multicenter cohort study was conducted of 3,473 adult hospitalized patients with reverse-transcriptase-polymerase-chain-reaction (RT-PCR) positive SARS-CoV-2 infection admitted to four New York City hospitals between March 10 through May 20, 2020. Exclusion criteria were: death or discharge within 24h, comfort-care status, clinical trial enrollment, treatment with an IL-6 inhibitor or remdesivir. Patients who received Zn+ionophore were compared to patients who did not using multivariable time-dependent cox proportional hazards models for time to in-hospital death adjusting for confounders including age, sex, race, BMI, diabetes, week of admission, hospital location, sequential organ failure assessment (SOFA) score, intubation, acute renal failure, neurological events, treatment with corticosteroids, azithromycin or lopinavir/ritonavir and the propensity score of receiving Zn+ionophore. A sensitivity analysis was performed using a propensity score-matched cohort of patients who did or did not receive Zn+ionophore matched by age, sex and ventilator status. Results: Among 3,473 patients (median age 64, 1947 [56%] male, 522 [15%] ventilated, 545[16%] died), 1,006 (29%) received Zn+ionophore. Zn+ionophore was associated with a 24% reduced risk of in-hospital mortality (12% of those who received Zn+ionophore died versus 17% who did not; adjusted Hazard Ratio [aHR] 0.76, 95% CI 0.60-0.96, P=0.023). More patients who received Zn+ionophore were discharged home (72% Zn+ionophore vs 67% no Zn+ionophore, P=0.003) Neither Zn nor the ionophore alone were associated with decreased mortality rates. Propensity score-matched sensitivity analysis (N=1356) validated these results (Zn+ionophore aHR for mortality 0.63, 95%CI 0.44-0.91, P=0.015). There were no significant interactions for Zn+ionophore with other COVID-19 specific medications. Conclusions: Zinc with an ionophore was associated with increased rates of discharge home and a 24% reduced risk of in-hospital mortality among COVID-19 patients, while neither zinc alone nor the ionophore alone reduced mortality. Further randomized trials are warranted.
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PMID:Treatment with Zinc is Associated with Reduced In-Hospital Mortality Among COVID-19 Patients: A Multi-Center Cohort Study. 3314 42


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