Altered somatic hypermutation patterns in COVID-19 patients classifies disease severity

IntroductionThe success of the human body in fighting SARS-CoV2 infection relies on lymphocytes and their antigen receptors. Identifying and characterizing clinically relevant receptors is of utmost importance.MethodsWe report here the application of a machine learning approach, utilizing B cell receptor repertoire sequencing data from severely and mildly infected individuals with SARS-CoV2 compared with uninfected controls.ResultsIn contrast to previous studies, our approach successfully stratifies non-infected from infected individuals, as well as disease level of severity. The features that drive this classification are based on somatic hypermutation patterns, and point to alterations in the somatic hypermutation process in COVID-19 patients.DiscussionThese features may be used to build and adapt therapeutic strategies to COVID-19, in particular to quantitatively assess potential diagnostic and therapeutic antibodies. These results constitute a proof of concept for future epidemiological challenges

Urgent Transcatheter Edge-to-Edge Repair for Severe Mitral Regurgitation in Patients with Refractory Cardiogenic Shock

Introduction Patients suffering from cardiogenic shock (CS) and mitral regurgitation (MR) demonstrate worse prognosis, with higher mortality rates. We sought to evaluate the effectiveness of urgent valve intervention of the mitral valve, using transcatheter edge-to-edge repair (TEER) procedures in patients presenting with CS in a tertiary Intensive Coronary Care Unit (ICCU). Methods and Results Patients with unremitting CS and severe MR were selected for urgent TEER. Baseline clinical and echocardiographic characteristics were recorded, as well as procedural success (MR severity and hemodynamics), and 30-days and 6-month mortality. Urgent TEER was done in 13 patients, whose average age was 70 years; 12 (92%) of the patients were male. All 13 patients had suffered previous ischemic heart disease—12 (92%) with either acute severe MR or worsening of previously known MR by an acute ischemic event. Using the SCAI criteria, 8 patients (61%) were classified as ‘E’ (Extreme) category; 4 (31%) were classified as ‘C’. At 30 days, 12 out of the 13 patients survived (corresponding to an 8% mortality rate); all of those 12 patients remained alive at 6 months post-admission/procedure. Conclusions The use of TEER was associated with greater 30-day and 6-month survival rates, compared to the worldwide mortality rates of patients admitted with CS. This finding may change the previous paradigm that CS and MR are associated with the worst outcome, and we might be able to offer these patients a safe and effective therapeutic option

Outcomes of Patients Treated with Blood Transfusion in a Contemporary Tertiary Care Medical Center Intensive Cardiac Care Unit

Background: Acutely ill patients treated with blood transfusion (BT) have unfavorable prognoses. Nevertheless, data regarding outcomes in patients treated with BT admitted into a contemporary tertiary care medical center intensive cardiac care unit (ICCU) are limited. The current study aimed to assess the mortality rate and outcomes of patients treated with BT in a modern ICCU. Methods: Prospective single center study where we evaluated mortality, in the short and long term, of patients treated with BT between the period of January 2020 and December 2021 in an ICCU. Outcomes: A total of 2132 consecutive patients were admitted to the ICCU during the study period and were followed-up for up to 2 years. In total, 108 (5%) patients were treated with BT (BT-group) during their admission, with 305 packed cell units. The mean age was 73.8 ± 14 years in the BT-group vs. 66.6 ± 16 years in the non-BT (NBT) group, p < 0.0001. Females were more likely to receive BT as compared with males (48.1% vs. 29.5%, respectively, p < 0.0001). The crude mortality rate was 29.6% in the BT-group and 9.2% in the NBT-group, p < 0.0001. Multivariate Cox analysis found that even one unit of BT was independently associated with more than two-fold the mortality rate [HR = 2.19 95% CI (1.47–3.62)] as compared with the NBT-group, p < 0.0001]. Receiver operating characteristic (ROC) curve was plotted for multivariable analysis and showed area under curve (AUC) of 0.8 [95% CI (0.760–0.852)]. Conclusions: BT continues to be a potent and independent predictor for both short- and long-term mortality even in a contemporary ICCU, despite the advanced technology, equipment and delivery of care. Further considerations for refining the strategy of BT administration in ICCU patients and guidelines for different subsets of high-risk patients may be warranted

Outcomes of Patients Treated with Blood Transfusion in a Contemporary Tertiary Care Medical Center Intensive Cardiac Care Unit

Background: Acutely ill patients treated with blood transfusion (BT) have unfavorable prognoses. Nevertheless, data regarding outcomes in patients treated with BT admitted into a contemporary tertiary care medical center intensive cardiac care unit (ICCU) are limited. The current study aimed to assess the mortality rate and outcomes of patients treated with BT in a modern ICCU. Methods: Prospective single center study where we evaluated mortality, in the short and long term, of patients treated with BT between the period of January 2020 and December 2021 in an ICCU. Outcomes: A total of 2132 consecutive patients were admitted to the ICCU during the study period and were followed-up for up to 2 years. In total, 108 (5%) patients were treated with BT (BT-group) during their admission, with 305 packed cell units. The mean age was 73.8 ± 14 years in the BT-group vs. 66.6 ± 16 years in the non-BT (NBT) group, p p p p < 0.0001]. Receiver operating characteristic (ROC) curve was plotted for multivariable analysis and showed area under curve (AUC) of 0.8 [95% CI (0.760–0.852)]. Conclusions: BT continues to be a potent and independent predictor for both short- and long-term mortality even in a contemporary ICCU, despite the advanced technology, equipment and delivery of care. Further considerations for refining the strategy of BT administration in ICCU patients and guidelines for different subsets of high-risk patients may be warranted

D-Dimer as a Prognostic Factor in a Tertiary Center Intensive Coronary Care Unit

Introduction D-dimer is a small protein fragment produced during fibrinolysis. High D-dimer levels were shown to have prognostic impact in critically ill patients. Nevertheless, data regarding D-dimer's prognostic impact among tertiary care intensive coronary care unit (ICCU) patients is scarce. Material and method All patients admitted to the ICCU between 1-12/2020 were prospectively included. Based on admission D-dimer level, patients were categorized into low and high D-dimer groups (50 years old). Results and discussion A total of 959 consecutive patients were included, including 296 (27.4%) and 663 (61.3%) patients with low and high D-Dimer levels, respectively. Patients with high D-dimer level were older compared with patients with low D-dimer level (age 70.4 ± 15 and 59 ± 13 years, p = 0.004) and had more comorbidities. The most common primary diagnosis on admission among the low D-dimer group was acute coronary syndrome (ACS) (74.3%), while in the high D-dimer group it was a combination of ACS (33.6%), cardiac structural interventions (26.7%) and various arrhythmias (21.1%). High D-dimer levels were associated with increased mortality rate, even after adjustment for age, gender, comorbidities and left ventricular ejection fraction (LVEF). High D-dimer levels were independently associated with increased overall 1-year mortality rate (HR = 5.8; 95% CI; 1.7-19.1; p = 0.004). Conclusion Elevated D-dimer levels on admission in ICCU patients is an independently poor prognostic factor for in-hospital morbidity and 1-year overall mortality rate following hospitalization

Mean Platelet Volume as a Predictor of Coronary Artery Disease Severity and its Association With Coronary Artery Calcification

Coronary calcium score (CCS) is a highly sensitive marker for estimating coronary artery calcification (CAC) and detecting coronary artery disease (CAD). Mean platelet volume (MPV (is a platelet indicator that represent platelet stimulation and production. The aim of the current study was to examine the association between MPV values and CAC. We examined 290 patients who underwent coronary computerized tomography (CT) exam between the years 2017 and 2020 in a tertiary care medical center. Only patients evaluated for chest pain were included. The Multi-Ethnic Study of Atherosclerosis (MESA) CAC calculator was used to categorize patients CCS by age, gender, and ethnicity to CAC severity percentiles (<50, 50-74, 75-89, ≥90). Thereafter, the association between CAC percentile and MPV on admission was evaluated. Out of 290 patients, 251 (87%) met the inclusion and exclusion criteria. There was a strong association between higher MPV and higher CAC percentile ( P  = .009). The 90th CAC percentile was associated with the highest prevalence of diabetes mellitus (DM), hypertension, dyslipidemia, and statin therapy ( P  = .002, .003, .001, and .001, respectively). In a multivariate analysis (including age, gender, DM, hypertension, statin therapy, and low-density lipoprotein level) MPV was found to be an independent predictor of CAC percentile (OR 1.55-2.65, P  < .001). Higher MPV was found to be an independent predictor for CAC severity. These findings could further help clinicians detect patients at risk for CAD using a simple and routine blood test