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OBJECTIVE: To evaluate whether colchicine treatment was associated with the inhibition of NLRP3 inflammasome activation in patients with COVID-19. METHODS: We present a post hoc analysis from a double-blinded placebo-controlled randomized clinical trial (RCT) on the effect of colchicine for the treatment of COVID-19. Serum levels of NOD-like receptor protein 3 (NLRP3) inflammasome products-active caspase-1 (Casp1p20), IL-1ß, and IL-18-were assessed at enrollment and after 48-72 h of treatment in patients receiving standard-of-care (SOC) plus placebo vs. those receiving SOC plus colchicine. The colchicine regimen was 0.5 mg tid for 5 days, followed by 0.5 mg bid for another 5 days. RESULTS: Thirty-six patients received SOC plus colchicine, and thirty-six received SOC plus placebo. Colchicine reduced the need for supplemental oxygen and the length of hospitalization. On Days 2-3, colchicine lowered the serum levels of Casp1p20 and IL-18, but not IL-1ß. CONCLUSION: Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the 'cytokine storm' in COVID-19. TRIAL REGISTRATION NUMBERS: RBR-8jyhxh.
Assuntos
COVID-19 , Inflamassomos , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-18 , Proteínas NLR , Colchicina/uso terapêutico , Interleucina-1beta/metabolismoRESUMO
In clinical practice, we need to develop new tools to identify the residual cardiovascular risk after acute coronary syndrome (ACS). This study aimed to evaluate whether the monocyte to high-density lipoprotein cholesterol ratio (MHR) variation (ΔMHR) obtained during hospital admission (MHR1) and repeated in the first outpatient evaluation (MHR2) is a predictor of major adverse cardiovascular events (MACE) after ACS. One hundred ninety-one patients admitted for ACS were prospectively included. The ΔMHR was calculated by subtracting MHR1 from MHR2. Patients were followed for 166±38 days in which the occurrence of MACE was observed. The best cutoff for ΔMHR was zero (0), and individuals were divided into two groups: ΔMHR<0 (n=113) and ΔMHR≥0 (n=78). The presence of MACE was higher in the ΔMHR≥0 (22%) than in the ΔMHR<0 (7%), with a hazard ratio (HR) of 3.96 (95% confidence interval [CI]: 1.74-8.99; P=0.0004). After adjusting for confounders, ΔMHR≥0 remained an independent MACE predictor with an adjusted HR of 3.13 (95%CI: 1.35-7.26, P=0.008). In conclusion, our study showed that ΔMHR was an independent MACE predictor after ACS. Thus, ΔMHR is a potential marker of residual cardiovascular risk after ACS.
Assuntos
Síndrome Coronariana Aguda , Humanos , HDL-Colesterol , Monócitos , Modelos de Riscos Proporcionais , Fatores de RiscoRESUMO
In clinical practice, we need to develop new tools to identify the residual cardiovascular risk after acute coronary syndrome (ACS). This study aimed to evaluate whether the monocyte to high-density lipoprotein cholesterol ratio (MHR) variation (ΔMHR) obtained during hospital admission (MHR1) and repeated in the first outpatient evaluation (MHR2) is a predictor of major adverse cardiovascular events (MACE) after ACS. One hundred ninety-one patients admitted for ACS were prospectively included. The ΔMHR was calculated by subtracting MHR1 from MHR2. Patients were followed for 166±38 days in which the occurrence of MACE was observed. The best cutoff for ΔMHR was zero (0), and individuals were divided into two groups: ΔMHR<0 (n=113) and ΔMHR≥0 (n=78). The presence of MACE was higher in the ΔMHR≥0 (22%) than in the ΔMHR<0 (7%), with a hazard ratio (HR) of 3.96 (95% confidence interval [CI]: 1.74-8.99; P=0.0004). After adjusting for confounders, ΔMHR≥0 remained an independent MACE predictor with an adjusted HR of 3.13 (95%CI: 1.35-7.26, P=0.008). In conclusion, our study showed that ΔMHR was an independent MACE predictor after ACS. Thus, ΔMHR is a potential marker of residual cardiovascular risk after ACS.
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Trastuzumab is an important biological agent in the treatment of HER2-positive breast cancer, with effects on response rates, progression-free survival, overall survival and quality of life. Although this drug is well tolerated in terms of adverse effects, trastuzumab-associated myocardiotoxicity has been described to have an incidence of 0.6-4.5% and in rare cases, the drug can trigger severe congestive heart failure with progression to death or even mimic acute coronary syndrome with complete left bundle branch blockade. In this paper is reported a case of trastuzumab-associated myocardiotoxicity manifesting as acute coronary syndrome in a 69-year-old female. The patient is currently undergoing a conservative clinical treatment that restricts overexertion.The majority of clinical studies report trastuzumab-induced cardiotoxicity as a rare event, and, when present, characterized by mild to moderate clinical signs, the ease of reversibility with pharmacological measures and the temporary discontinuation of the medication. Conversely, it is vital for the oncologist/cardiologist to consider the possibility that trastuzumab-induced cardiotoxicity may manifest itself as a severe clinical case, mimicking acute coronary syndrome, justifying careful risk stratification and adequate cardiac monitoring, especially in high-risk patients.
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BACKGROUND: Helicobacter pylori eradication in family members of gastric cancer patients is now widely accepted, although problems related to costs and compliance persist. AIM: To compare the efficacy, tolerability and long-term re-infection rates of two once-daily regimens for the eradication of H. pylori in family members of gastric cancer patients. METHODS: 106 first-degree family members of gastric cancer patients were recruited and submitted to the 13C-urea breath test (UBT) to detect H. pylori. If positive, they were randomly allocated to receive a combination of lanzoprazole 30 mg, clarithromycin OD (extended-release formulation) 500 mg and furazolidone 400 mg, once daily, in the morning, for 7 days (Group A) or the same regimen with only 200 mg furazolidone (Group B). Eradication was confirmed by urea breath test performed 6 weeks after treatment. 13C-urea breath test was repeated at 944 (784-1258) days after treatment in successfully treated participants to look for re-infection. RESULTS: Twenty-five participants were H. pylori negative and two H. pylori-positive individuals refused to sign the informed consent and were excluded. Therefore, 79 participants were studied. Forty participants were allocated to Group A and 39 to Group B. All participants completed treatment. Adverse effects, mostly mild, were observed in 18% of Group A and 18% of Group B (N.S.). The intention-to-treat eradication rate was 87.5% in Group A and 61.5% in Group B (P = 0.006). The mean annual re-infection rate was 3%. CONCLUSIONS: The combination of lanzoprazole 30 mg, one tablet of clarithromycin OD (extended release formulation) 500 mg and furazolidone 400 mg, once daily for 7 days, constitutes an inexpensive, safe and effective alternative for anti-H. pylori therapy in family members of gastric cancer patients.