Colchicine reduces the activation of NLRP3 inflammasome in COVID-19 patients.

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.

Is the variation in monocyte to high-density lipoprotein cholesterol ratio a predictor of major cardiovascular events after acute coronary syndrome?

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.

Is the variation in monocyte to high-density lipoprotein cholesterol ratio a predictor of major cardiovascular events after acute coronary syndrome?

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.

Trastuzumab-induced myocardiotoxicity mimicking acute coronary syndrome.

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.

Once-daily, low-cost, highly effective Helicobacter pylori treatment to family members of gastric cancer patients.

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.

Perioperative care of the adult with congenital heart disease in a free-standing tertiary pediatric facility.

Adult patients with congenital heart disease are presenting more frequently for cardiac surgery. Frequently, pediatric congenital heart surgeons perform these procedures at pediatric hospitals. Between July 1995 and June 2000, a retrospective review of adult patients (> or = 18 years old) who had undergone cardiothoracic operations was performed. A total of 112 operations were performed and divided into two groups--81 cardiac operations in 79 patients and 31 noncardiac operations in 23 patients. One patient had a cardiac and noncardiac operation performed. The overall early operative mortality was 6% (6/101). There were 3 late deaths. New-onset cardiac arrhythmias requiring treatment were diagnosed after 5/81 (6%) cardiac operations. Six of 79 (7%) patients were diagnosed with postoperative clinical depression. An acceptable mortality can be achieved when adult patients undergo cardiothoracic operations at a pediatric facility. New-onset arrhythmias necessitating treatment are relatively common, and postoperative clinical depression should be anticipated.

Behçet's-like syndrome associated with idiopathic CD4+ T-lymphocytopenia, opportunistic infections, and a large population of TCR alpha beta+ CD4- CD8- T cells.

Herein we report a patient with Behçet's like syndrome, idiopathic CD4+ T-lymphocytopenia, opportunistic infections, and a large polyclonal population of TCR alpha beta + CD4- CD8- T cells. Microfluorimetric analysis of peripheral blood mononuclear cells revealed CD4+ T-cell counts of 10 +/- 5/mm3. The CD3+ T cells were 99% TCR alpha beta +, of which 74 +/- 5% were CD4- CD8-. No clonal populations were detected by southern analysis for T-cell receptor V beta gene rearrangements. No evidence of human immunodeficiency virus infection was present, although nocardia, candida, pneumocystis, cytomegalovirus, and herpes infections were documented. The concomitant presence of opportunistic infections and a large population of TCR alpha beta + CD4- CD8- T cells suggests a pathogenic association and an intense immune response to microbial lipid or lipoglycan antigens presented in the context of CD1 molecules. This case demonstrates the potential for idiopathic CD4+ T-lymphocytopenia to occur in Behçet's-like syndrome with lethal consequences.