Antibody Response to the SARS-CoV-2 Vaccine and COVID-19 Vulnerability during the Omicron Pandemic in Patients with CLL: Two-Year Follow-Up of a Multicenter Study.

High morbidity and mortality due to COVID-19 were described in the pre-vaccination era in patients with chronic lymphocytic leukemia (CLL). To evaluate COVID-19 morbidity after the SARS-CoV-2 vaccine, we carried out a prospective study in 200 CLL patients. The median age of patients was 70 years; 35% showed IgG levels ≤ 550 mg/dL, 61% unmutated IGHV, and 34% showed TP53 disruption. Most patients, 83.5%, were previously treated, including 36% with ibrutinib and 37.5% with venetoclax. The serologic response rates to the second and third dose of the vaccine were 39% and 53%, respectively. With a median follow-up of 23.4 months, 41% of patients experienced COVID-19, 36.5% during the Omicron pandemic, and 10% had subsequent COVID-19 events. Severe COVID-19 requiring hospitalization was recorded in 26% of patients, and 4% died. Significant and independent factors associated with the response to the vaccine and vulnerability to COVID-19 were age (OR: 0.93; HR: 0.97) and less than 18 months between the start of targeted agents and vaccine (OR: 0.17; HR: 0.31). TP53 mutation and ≥two prior treatments also emerged as significant and independent factors associated with an increased risk of developing COVID-19 (HR: 1.85; HR: 2.08). No statistical difference in COVID-19 morbidity was found in patients with or without antibody response to the vaccine (47.5% vs. 52.5%; p = 0.21). Given the persistent risk of infection due to the continuous emergence of SARS-CoV-2 variants, our results support the importance of new vaccines and protective measures to prevent and mitigate COVID-19 in CLL patients.

Optimal management of patients after acute coronary syndrome.

Patients with clinically established atherosclerotic cardiovascular disease are at a very high risk of recurrent cardiovascular events. An adequate management of risk factors and the implementation of healthy behaviours significantly decrease the risk of unfavourable clinical outcomes and future cardiovascular events, including death. Patients discharged after an acute coronary syndrome should be managed according to their individual risk level in order to ensure the appropriate treatment. Nevertheless, care pathways should also take into consideration the available resources and the logistical/structural aspects. In this setting, cardiac rehabilitation is prosed as a multidisciplinary approach to improving daily function and reducing cardiovascular risk factors. The organization of a network with the involvement of different medical and non-medical figures is essential to ensure successful outcomes and expected cost-effectiveness.

ICH in primary or metastatic brain cancer patients with or without anticoagulant treatment: a systematic review and meta-analysis.

Anticoagulant treatment in patients with primary and metastatic brain cancer is a concern due to risk of intracranial hemorrhage (ICH). We performed a systematic review and meta-analysis to evaluate the risk of ICH in patients with primary or metastatic brain cancer treated with or without anticoagulants. Articles on ICH in patients with primary or metastatic brain cancer treated with or without anticoagulants published up to September 2021 were identified by searching PubMed, EMBASE, and Cochrane Library databases. The primary outcome of this analysis was ICH. Thirty studies were included. Rate of ICH was 13.0% in 1009 patients with metastatic brain cancer and 6.4% in 2353 patients with primary brain cancer (relative risk [RR], 3.26; 95% confidence interval [CI], 2.69-3.94; I2 = 92.8%). In patients with primary brain cancer, ICH occurred in 12.5% and 4.4% of patients treated with or without anticoagulants, respectively (11 studies, 659 treated and 1346 not treated patients; RR, 2.63; 95% CI, 1.48-4.67; I2 = 49.6%). In patients with metastatic brain cancer, ICH occurred in 14.7% and 15.4% (5 studies, 265 treated and 301 not treated patients; RR, 0.92; 95% CI, 0.43-1.93; I2 = 0%). ICH occurred in 8.3% of 172 treated with direct oral anticoagulants (DOACs) and in 11.7% of 278 treated with low-molecular weight heparin (LMWH) (5 studies; RR, 0.44; 95% CI, 0.25-0.79; I2 = 0%). Patients with metastatic brain cancer have a particularly high risk of ICH. Patients with primary brain cancer have an increased risk of ICH during anticoagulation. DOACs are associated with a lower risk of ICH than LMWH.

A Retrospective Study on the Efficacy of Subcutaneous Immunoglobulin as Compared to Intravenous Formulation in Patients with Chronic Lymphocytic Leukemia and Secondary Antibody Deficiency.

Secondary antibody deficiency (SAD) is a common complication in chronic lymphocytic leukemia (CLL) which favors the development of life-threatening infections. Subcutaneous immunoglobulins (IG) (SCIG) have been proven to be as effective as intravenous immunoglobulin (IVIG) in primary immunodeficiencies. Since only a few studies investigated SCIG in secondary antibody deficiency, the aim of this study was to assess the efficacy and safety of SCIG or IVIG in CLL patients with secondary antibody deficiency. One hundred and sixteen CLL patients were recruited, 63% were males, and the median age was 68 years; 44% had bronchiectasis and 76% never smoked. Forty-nine patients received IVIG and 88 SCIG, including 28 patients who shifted from IVIG to SCIG. Despite similar baseline IgG levels, patients receiving SCIG achieved higher IgG after at least +6 months (p = 0.0009). We observed that SCIG can decrease the cumulative incidence of first (HR 0.39 p < 0.0001) and second (HR 0.56 p = 0.0411) infection more than IVIG. The effect was remarkable in that patients were able to reach at least 6 g/L of IgG after 6 months of treatments (p < 0.0001). Replacement therapies were well tolerated with less adverse events and a lower discontinuation rate in patients was managed with SCIG than IVIG. In this study we describe the clinical features of a large cohort of CLL with secondary antibody deficiency receiving IG. We demonstrated that SCIG are active and well tolerated drugs that allows to reach higher IgG levels and decrease the rate of infections better than IVIG, in particular when IgG levels reach 6 g/L.

Specific miRNA and Gene Deregulation Characterize the Increased Angiogenic Remodeling of Thoracic Aneurysmatic Aortopathy in Marfan Syndrome.

Marfan syndrome (MFS) is a connective tissue disease caused by mutations in the FBN1 gene, leading to alterations in the extracellular matrix microfibril assembly and the early formation of thoracic aorta aneurysms (TAAs). Non-genetic TAAs share many clinico-pathological aspects with MFS and deregulation of some microRNAs (miRNAs) has been demonstrated to be involved in the progression of TAA. In this study, 40 patients undergoing elective ascending aorta surgery were enrolled to compare TAA histomorphological features, miRNA profile and related target genes in order to find specific alterations that may explain the earlier and more severe clinical outcomes in MFS patients. Histomorphological, ultrastructural and in vitro studies were performed in order to compare aortic wall features of MFS and non-MFS TAA. MFS displayed greater glycosaminoglycan accumulation and loss/fragmentation of elastic fibers compared to non-MFS TAA. Immunohistochemistry revealed increased CD133+ angiogenic remodeling, greater MMP-2 expression, inflammation and smooth muscle cell (SMC) turnover in MFS TAA. Cultured SMCs from MFS confirmed higher turnover and α-smooth muscle actin expression compared with non-MFS TAA. Moreover, twenty-five miRNAs, including miR-26a, miR-29, miR-143 and miR-145, were found to be downregulated and only miR-632 was upregulated in MFS TAA in vivo. Bioinformatics analysis revealed that some deregulated miRNAs in MFS TAA are implicated in cell proliferation, extracellular matrix structure/function and TGFß signaling. Finally, gene analysis showed 28 upregulated and seven downregulated genes in MFS TAA, some of them belonging to the CDH1/APC and CCNA2/TP53 signaling pathways. Specific miRNA and gene deregulation characterized the aortopathy of MFS and this was associated with increased angiogenic remodeling, likely favoring the early and more severe clinical outcomes, compared to non-MFS TAA. Our findings provide new insights concerning the pathogenetic mechanisms of MFS TAA; further investigation is needed to confirm if these newly identified specific deregulated miRNAs may represent potential therapeutic targets to counteract the rapid progression of MFS aortopathy.

Long-Term Outcome of Acute Coronary Syndromes in Young Patients.

INTRODUCTION: Acute coronary syndromes (ACS) in young patients are uncommon and their influence on morbidity and mortality in this population is still debated. AIM: We investigated clinical and angiographic characteristics, risk factors and outcome in young patients diagnosed with ACS, compared with those of older patients, evaluating survival free from death and/or nonfatal myocardial infarction (MI) and/or coronary revascularization (primary endpoint), and then with respect to each component of the primary endpoint. METHODS: We retrospectively analyzed 1696 patients diagnosed with ACS between 2007 and 2013. 116 were aged ≤45 years (young adults), 1116 were >45 and <75 years (older adults) and 464 were ≥75 years. RESULTS: Young adults were mostly male, with a prevalent diagnosis of STEMI, had less frequently typical cardiovascular risk factors and lower prevalence of extensive coronary artery disease. Over a median 3 years follow up, survival free from composite endpoint was better in young than in older adult patients (11.2 vs. 24.2%; p = 0.001), mainly due to a lower rate of death while the occurrence of non fatal MI and of coronary revascularization was similar (7.8 vs. 8.7%, p = 0.86; 8.7 vs. 12.9%, p = 0.23 respectively). Diabetes was the strongest independent risk factor of worse prognosis in the young cohort (OR 3.47; 95% CI 1.01-11.9; p = 0.04). CONCLUSIONS: Young adults showed peculiar clinical features and lower mortality compared with older adults. Morbidity was not different between the two populations, with diabetes independently associated with a worse prognosis.

Clinical impact of nonsustained ventricular tachycardia recorded by the implantable cardioverter-defibrillator in patients with hypertrophic cardiomyopathy.

BACKGROUND: Nonsustained ventricular tachycardia (NSVT) is a risk factor for sudden death (SD) in hypertrophic cardiomyopathy (HCM). Implantable cardioverter-defibrillators (ICDs) enable accurate assessment of NSVT burden and characteristics. In a cohort of HCM patients with ICD, we characterized Holter- and ICD-retrieved NSVT and evaluated their relationship with prognosis. METHODS AND RESULTS: We studied a cohort of consecutive HCM patients who underwent Holter ECG before receiving a primary prevention ICD. Patients were followed from ICD implantation to the first appropriate ICD therapy. We evaluated the association of NSVT characteristics with ICD interventions. Study cohort included 51 HCM patients (28 males, mean age: 48 ± 15 years). Thirty-four patients (66%) had NSVT at pre-ICD Holter ECG. Out of 17 patients with negative baseline Holter, 7 (41%) showed ICD-NSVT. In patients with both Holter- and ICD-NSVT, these latter were faster (199 ± 27 bpm vs. 146 ± 24 bpm; P < 0.001) and longer (16 ± 8 beats vs. 10 ± 11 beats; P = 0.008) than Holter-NSVT. During follow-up (38 ± 24 months), 11 patients (22%) experienced appropriate ICD therapy. NSVT length in beats (hazard ratio [HR]: 1.05; 95% CI: 1.00-1.10; P = 0.02) but not heart rate (HR: 1.00; 95% CI: 0.98-1.02; P = 0.86) predicted ICD intervention. A simple index of NSVT severity (heart rate × length in beats/100 >28) predicted ICD intervention (HR: 5.45; 95% CI: 1.10-27.32; P = 0.03). CONCLUSIONS: Long-lasting and rapid NSVT recorded during continuous rhythm monitoring predict appropriate ICD intervention in high-risk HCM patients. Further studies should assess whether prolonged rhythm monitoring may assist in evaluating patients at intermediate risk of SD, in which the decision to implant an ICD needs to be individualized.

Determinants of peak oxygen uptake in patients with hypertrophic cardiomyopathy: a single-center study.

Most patients with hypertrophic cardiomyopathy (HCM) usually complain of a reduced exercise capacity, and several factors have been advocated as possible causes of this clinical feature. The present single-center study was designed to investigate exercise capacity and its main clinical determinants in HCM patients. One hundred ninety seven patients of 223 evaluated underwent a complete clinical assessment, including Doppler echocardiography, cardiopulmonary exercise test (CPET) and, in most cases, cardiac magnetic resonance. The HCM population (male 75 %; age 47 ± 16 years; NYHA class I or II 95 %; left ventricular ejection fraction 61 ± 3 %; resting left ventricular outflow tract gradient ≥30 mmHg 22 %; late gadolinium enhancement presence 58 %) showed slightly reduced mean peak oxygen uptake values (pVO2 75 ± 15 %, 23.2 ± 6.7 ml/kg/min) with a significant reduction of the achieved percentage of peak heart rate reserve (%pHRR 65 ± 20 %). Adopting a pVO2 <80 % cut-off value, 59 % of HCM patients showed a reduced exercise capacity. Age, male gender, left atrial size, chronotropic and systolic blood pressure response, ventilatory efficiency, late gadolinium enhancement presence and ß-blocker therapy were independently associated with pVO2 (R (2)-adjusted index 0.738). A %pHRR cut-off value of 74 % appeared to most accurately predict an impaired exercise capacity (area under curve 0.90). A great prevalence of reduced exercise capacity is present in NYHA class I-II HCM patients. Notwithstanding its multifactorial genesis, few parameters might be adopted in identifying this feature. In this context, %pHRR value might represent a reliable and easy-to-obtain tool for the clinical evaluation of HCM patients.