Seroprevalence of hepatitis B and C viruses in moderate and severe COVID-19 inpatients: A cross-sectional study at a referral center in Mexico

Introduction and ObjectivesThe emergence of SARS-CoV-2, which causes the coronavirus disease (COVID-19) has caused a great impact on healthcare systems worldwide, including hepatitis B and C viruses screening and elimination programs. The high number of COVID-19 hospitalizations represent a great opportunity to screen patients for hepatitis B virus (HBV) and hepatitis C virus (HCV), which was the aim of this study.Material and MethodsCross-sectional, retrospective study performed between April 2020 and 20201 at a referral center in Mexico dedicated to the care of adults with severe/critical COVID-19. We retrieved clinical, demographic, and laboratory results from each patient´s medical records, including antibodies against HCV (anti-HCV), HBV surface antigen (HBsAg), antibodies against the HBV core antigen (anti-HBcAg), and antibodies against HBsAg (anti-HBsAg).ResultsOut of 3620 patients that were admitted to the hospital, 24 (0.66%), 4 (0.11%), and 72 (1.99%) tested positive for anti-HCV, HBsAg, and anti-HBcAg, respectively. Of all seronegative patients, 954 (27%) had undetectable anti-HBsAg and 401 (12%) had anti-HBsAg at protective levels. Blood transfusion was the most relevant risk factor. Only 9.7% of the anti-HBc positive, 25% of the HBsAg positive, and 52% of the anti-HCV positive were aware of their serological status.ConclusionsIn this study we found a prevalence of anti-HCV of 0.66%, HBsAg in 0.11%, and isolated anti-HBcAg in 1.99%. We also found that HBV vaccination coverage has been suboptimal and needs to be reinforced. This study gave us a trustworthy insight of the actual seroprevalence in Mexico, which can help provide feedback to the Hepatitis National Elimination Plan.     

Loss of circulating CD27+ memory B cells and CCR4+ T cells occurring in association with elevated EBV loads in XLP patients surviving primary EBV infection

Detailed longitudinal studies of patients with X-linked lymphoproliferative disease (XLP) may increase our understanding of the immunologic defects that contribute to the development of lymphoma and hypogammaglobulinemia in XLP. We describe progressive changes observed in immunoglobulin concentrations, lymphocyte subsets, and Epstein-Barr virus (EBV) loads occurring in a 2-year period in a newly infected, but otherwise healthy, carrier (patient 9). We compare these findings with those observed in the patient's brother, who had hypogammaglobulinemia and XLP (patient 4). Immunoglobulin G (IgG), IgM, and IgA concentrations increased in patient 9 during acute EBV infection, but thereafter they decreased steadily to concentrations consistent with hypogammaglobulinemia, reaching a plateau 5 months after infection. In both patients, CD19+ B-lymphocyte rates remained lower than 3%, with a contraction of the B-cell memory compartment (CD27+ CD19+/CD19+) to 20% (normal range, 32%-56%). T-lymphocyte subpopulations showed a reduction in CD4+ T-cell counts and a permanent CD8+ T-cell expansion. Interestingly, CXCR3 memory TH1 cells were expanded and CCR4+ TH2 lymphocytes were reduced, suggesting that abnormal skewing of memory T-cell subsets might contribute to reduced antibody synthesis. Despite an expanded number of CD3+CD8+ lymphocytes, increased EBV loads occurred in both patients without overt clinical symptoms of mononucleosis, lymphoproliferative disease, or lymphoma.     

"Stem cell" origin of the hematopoietic defect in dyskeratosis congenita

We have used the long-term bone marrow culture (LTBMC) system to analyze hematopoiesis in three patients with dyskeratosis congenita (DC), two of whom had aplastic anemia, and the third had a normal blood count (apart from mild macrocytosis) and normal BM cellularity. Hematopoiesis was severely defective in all three patients, as measured by a low incidence of colony-forming cells and a low level of hematopoiesis in LTBMC. The function of the marrow stroma was normal in its ability to support the growth of hematopoietic progenitors from normal marrows seeded onto them in all three cases, but the generation of hematopoietic progenitors from patients marrow cells inoculated onto normal stromas was reduced, thus suggesting the defect to be of stem cell origin. The parents and unaffected brother of one of the families have also been studied in LTBMC and all showed normal hematopoietic and stromal cell function. From this study we speculate that there are some similarities between DC and the defect in the W/Wv mouse.     

Thallium-201 scintigraphy for diagnosis of old myocardial infarction: comparison with electrocardiographic, ventriculographic, and coronary arteriographic findings.

Myocardial scintigraphy with 201Tl was performed at rest in a selected group of 36 patients with unequivocal clinical and electrocardiographic evidence of old myocardial infarction. The scintigraphic findings were correlated with electrocardiographic pattern, and with regional left ventricular wall motion and the severity of coronary artery disease defined by contrast angiography. Detection was dependent on the extent of the infarct but was independent of QRS morphology and of the severity of coronary disease. When positive, 201Tl scintigraphy was often a more precise method than the electrocardiogram for localising and delineating the extent of the infarct. Furthermore, the perfusion defect corresponded in location and extent to abnormalities of left ventricular wall motion. The site or severity of coronary artery disease could not be determined from the 201Tl scintigram.     

Global risk stratification in primary hypertension: the role of the kidney

OBJECTIVE: Microalbuminuria and a reduction in creatinine clearance are well known, independent predictors of unfavourable cardiovascular prognosis. Our aim was to evaluate the impact of renal damage on global risk stratification in 459 non-diabetic, untreated hypertensive patients (64% men, mean age 47.3 years). METHODS: Renal damage was defined as creatinine clearance < 60 ml/min per 1.73 m2 (Cockcroft-Gault formula) or the presence of microalbuminuria (albumin to creatinine ratio). Cardiac and vascular organ damage was assessed by ultrasound scan. We evaluated the impact of renal damage, left ventricular hypertrophy and carotid atherosclerosis on risk stratification as recommended by the 2007 European Society of Hypertension-European Society of Cardiology Guidelines. RESULTS: The prevalence of renal damage, microalbuminuria and creatinine clearance < 60 ml/min per 1.73 m2 was 24, 12 and 13%, respectively. There was no correlation between albuminuria and estimated creatinine clearance, and only 0.9% of patients showed microalbuminuria and reduced creatinine clearance simultaneously. The presence of renal damage entailed a 3.3 times higher risk of having cardiovascular abnormalities. Based on routine work-up, 58% of our study patients were classified as high-very high risk. The simultaneous evaluation of albuminuria and creatinine clearance resulted in a significant change in risk stratification, since 68% of patients were classified in the high-very high risk class. The search for left ventricular hypertrophy or carotid atherosclerosis by ultrasonography did not improve risk stratification significantly as compared to the assessment of renal damage. CONCLUSIONS: Our findings support the assessment of renal abnormalities as the first step when evaluating target organ damage for cardiovascular risk assessment in hypertensive patients.     

Etoposide causes illegitimate V(D)J recombination in human lymphoid leukemic cells

Etoposide is one of the most widely used antineoplastics. Unfortunately, the same treatment schedules associated with impressive efficacy are associated with an increased risk of secondary acute myeloid leukemia (AML), which has prompted its withdrawal from some treatment regimens, thereby potentially compromising efficacy against the original tumor. Because etoposide-associated AML is characterized by site-specific illegitimate DNA recombination, we studied whether etoposide could directly cause site-specific deletions of exons 2 and 3 in the hprt gene. Human lymphoid CCRF-CEM cells were treated with etoposide for 4 hours, and DNA was isolated after subculturing. The deletion of exons 2 and 3 from hprt was assayed by a quantitative polymerase chain reaction (PCR) method. In the absence of etoposide treatment, the frequency of deletions of exons 2 and 3 was very low (5.05 x 10(-8)). After exposure to 10 mumol/ L etoposide, the frequency of the exon 2 + 3 deletion was increased immediately after and at 24 hours after etoposide treatment (65 to 89 x 10(-8)) and increased to higher levels (128 to 173 x 10(-8)) after 2 and 6 days of subculture (P < .001 overall). The frequency of the exon 2 + 3 deletion assessed at 6 days of subculture after 4 hours of 0, 0.25, 1, 2.5, 5, and 10 mumol/L etoposide treatment increased with etoposide concentration, ie, 5.05 x 10(-8), 89.2 x 10(-8), 108 x 10(-8), 142 x 10(-8), 163 x 10(-8), and 173 x 10(-8), respectively (P < .0001). Sequencing of a subset of amplified products confirmed the presence of DNA sequences at the breakpoints consistent with V(D)J recombination. By contrast, exon 2 + 3 deletions after etoposide treatment in the myeloid cell lines KG-1A and K562 showed no evidence of V(D)J recombinase in their genesis. We conclude that etoposide can induce the illegitimate site-specific action of V(D)J recombinase on an unnatural DNA substrate after a single treatment in human lymphoid cells.     

Switching from high-dose clopidogrel to prasugrel in ACS patients undergoing PCI: a single-center experience

Prasugrel has been shown to be superior to clopidogrel in the setting of ACS patients undergoing coronary angioplasty. However, few data have been reported so far on those patients who switch from clopidogrel to prasugrel after coronary angioplasty. Aim of the current study was to evaluate the safety of prasugrel loading dose administration in ACS patients undergoing PCI and preatreated with high-dose clopidogrel. From May 2010 to December 2011 150 ACS patients undergoing coronary angioplasty and pretreated with high-dose clopidogrel, were switched to prasugrel loading dose soon after the procedure. They were matched (ratio 1:2) according to sex and age with a group of 300 ACS patients undergoing angioplasty and treated with high-dose clopidogrel only from May 2010 to December 2011. All demographic clinical and angiographic were collected. Primary endpoint was the rate of major bleeding complications (according to ACUITY trial definition) at 30-day follow-up. Secondary endpoints were: TIMI major and minor bleeding, definite stent thrombosis, major adverse cardiac events (MACE) and Net adverse cardiac events (NACE) at 30-day follow-up. The two groups of patients showed similar baseline demographic, and clinical characteristics. Most of the patients had unstable angina or non-ST segment elevation myocardial infarction. Almost (about 95 %) all patients underwent radial approach. No difference was observed in major bleeding complications according to both ACUITY (2.0 vs 2.0 %) and TIMI Major (0.7 vs 1.3 %) definition. No difference between the two groups was observed in terms of in-stent thrombosis, MACE and NACE at 30-day follow-up. Our observational study showed that switching to prasugrel with loading dose soon after angioplasty among ACS patients who were pretreated with clopidogrel seems to be well tolerated without overt evidence of heightened major bleeding. Future large randomized trials are certainly needed to confirm these findings.     

Impact of multivessel disease on infarct size among STEMI patients undergoing primary angioplasty

Background

Although primary angioplasty achieves Thrombolysis In Myocardial Infarction (TIMI) 3 flow in most patients with ST-elevation myocardial infarction, epicardial recanalization does not guarantee optimal perfusion in a large proportion of patients. Multivessel disease has been demonstrated to be associated with impaired survival, however its impact on infarct size has not been largely investigated, that therefore is the aim of the current study.

Methods

Our population is represented by 827 STEMI patients undergoing primary PCI. Infarct size was evaluated at 30 days by technetium-99m-sestamibi.

Results

Multivessel disease was observed in 343 patients (41.5%). It was associated with older age (65 [57–74] vs 63 [53–71], p < 0.001), higher rate of previous MI (6.4% vs 2.5%, p = 0.005), longer ischemia time evaluated as continuous variable (210 [155–280] min vs 196 [145–270] min, p = 0.065) or percentage of patients with ischemia time >3 h (63.7% vs 56.4%, p = 0.038), and a trend in more cardiogenic shock (5.5% vs 2.9%, p = 0.055). Patients with multivessel disease received more often Abciximab (92.1% vs 88.4%, p < 0.001), Intra-aortic balloon pump (6.4% vs 1.9%, p < 0.001). No differences were observed in other clinical or angiographic characteristics. In particular, multivessel disease did not affect the rate of postprocedural TIMI 3 flow (90.9% vs 93.4%, p = 0.18) and ST-segment resolution (52.4% vs 54.9%, p = 0.48). Multivessel disease did not affect infarct size (12.7% [4.5%–24.9%] vs 12.3% [4%–24.1%], p = 0.58). Similar results were observed in subanalyses without any significant interaction for each variable (anterior infarct location (p int = 0.23), gender (p int = 0.9), age (p int = 0.7), diabetes (p int = 0.15)). The absence of any impact of multivessel disease on infarct size was confirmed when the analysis was conducted according to the percentage of patients with infarct size above the median, even after correction for baseline characteristics, such as age, previous MI, ischemia time, use of Gp IIb–IIIa inhibitors, cardiogenic shock, ischemia time (OR [95% CI] = 1.09 [0.82–1.45], p = 0.58).

Conclusions

This study shows that among STEMI patients undergoing primary PCI multivessel disease does not affect infarct size.     

Relationship between changes in platelet reactivity and ischemic events following percutaneous coronary intervention: A meta-regression analysis of 30 randomized trials

Objective

High on-treatment platelet reactivity (HPR) is a well-known risk factor for adverse events in patients undergoing percutaneous coronary intervention (PCI). However, whether reducing platelet reactivity can lead to a lower incidence of ischemic events after PCI is still controversial. Therefore, we sought to investigate this issue by a meta-regression analysis of randomized trials.

Methods

We collected randomized trials reporting HPR rates in patients receiving different antiplatelet therapies. ΔHPR was defined as the difference between HPR rates achieved in control vs. experimental arms, and the relationship between ΔHPR and clinical outcomes was evaluated.

Results

Thirty trials totalling 6683 patients with a mean follow-up of 3-month were included. Reducing platelet reactivity was associated to a decreased risk of major adverse cardiac events (MACE), with a linear relationship between ΔHPR and MACE (change in tau² = −2.50; p = 0.023). Particularly, achieving a 10% difference in HPR rates resulted in a parallel risk reduction in MACE of about 11% (Exp^(b) = 0.98; 95% CI, 0.97–0.99).Changes in HPR predict the risk of ischemic events in patients with acute coronary syndrome (change in tau² = −2.52; Exp^(b) = 0.98; 95% CI, 0.97–0.99; p = 0.03), but not in patients with poor response to clopidogrel (change in tau² = −1.44; Exp^(b) = 0.98; 95% CI, 0.96–1.01; p = 0.19) or stable coronary artery disease (change in tau² = −0.14; Exp^(b) = 0.99; 95% CI, 0.94–1.05; p = 0.89).

Conclusion

Reducing HPR occurrence decreases the risk of ischemic events in patients with acute coronary syndrome undergoing PCI, whereas a strategy of reducing platelet reactivity does not improve clinical outcomes in patients with poor response to clopidogrel or stable coronary artery disease.