Epigenetic memory of coronavirus infection in innate immune cells and their progenitors.

Inflammation can trigger lasting phenotypes in immune and non-immune cells. Whether and how human infections and associated inflammation can form innate immune memory in hematopoietic stem and progenitor cells (HSPC) has remained unclear. We found that circulating HSPC, enriched from peripheral blood, captured the diversity of bone marrow HSPC, enabling investigation of their epigenomic reprogramming following coronavirus disease 2019 (COVID-19). Alterations in innate immune phenotypes and epigenetic programs of HSPC persisted for months to 1 year following severe COVID-19 and were associated with distinct transcription factor (TF) activities, altered regulation of inflammatory programs, and durable increases in myelopoiesis. HSPC epigenomic alterations were conveyed, through differentiation, to progeny innate immune cells. Early activity of IL-6 contributed to these persistent phenotypes in human COVID-19 and a mouse coronavirus infection model. Epigenetic reprogramming of HSPC may underlie altered immune function following infection and be broadly relevant, especially for millions of COVID-19 survivors.

Evolution of antibody immunity to SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected 78 million individuals and is responsible for over 1.7 million deaths to date. Infection is associated with the development of variable levels of antibodies with neutralizing activity, which can protect against infection in animal models1,2. Antibody levels decrease with time, but, to our knowledge, the nature and quality of the memory B cells that would be required to produce antibodies upon reinfection has not been examined. Here we report on the humoral memory response in a cohort of 87 individuals assessed at 1.3 and 6.2 months after infection with SARS-CoV-2. We find that titres of IgM and IgG antibodies against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 decrease significantly over this time period, with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by fivefold in pseudotype virus assays. By contrast, the number of RBD-specific memory B cells remains unchanged at 6.2 months after infection. Memory B cells display clonal turnover after 6.2 months, and the antibodies that they express have greater somatic hypermutation, resistance to RBD mutations and increased potency, indicative of continued evolution of the humoral response. Immunofluorescence and PCR analyses of intestinal biopsies obtained from asymptomatic individuals at 4 months after the onset of coronavirus disease 2019 (COVID-19) revealed the persistence of SARS-CoV-2 nucleic acids and immunoreactivity in the small bowel of 7 out of 14 individuals. We conclude that the memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence.

Readiness for Hospital Discharge, Stress, and Coping in Mothers of Children Undergoing Cardiac Surgeries: A Single-Center Prospective Study.

OBJECTIVES: To examine the relationship between stress, coping, and discharge readiness in mothers of children undergoing congenital heart surgeries. DESIGN: Quantitative descriptive study at three time points: pre surgery (time point I), day of hospital discharge (time point II) and 2 weeks following discharge (time point III). SETTING: Tertiary care pediatric hospital in Singapore. PARTICIPANTS: One hundred mothers whose children had undergone congenital heart surgeries. MEASUREMENTS AND MAIN RESULTS: Data collection included self-reported questionnaires of the Pediatric Inventory for Parents and the Coping Health Inventory for Parents across three time points. Readiness for Hospital Discharge Scale was administered at hospital discharge (time point II). The utilization of health services and support was reported at post discharge (time point III). One-hundred mothers participated in this study between May 2016 and July 2017. Their mean age was 35.8 years (SD = 7.0), and the mean age of their children was 3.7 years (SD = 4.6). There was significant reduction in mean stress difficulty (Pediatric Inventory for Parents) of mothers (F = 4.58; p = 0.013) from time point I to III. No significant changes were found in the overall mean coping score (Coping Health Inventory for Parents) of mothers across time. The mean overall score for the readiness for discharge (Readiness for Hospital Discharge Scale) of mothers at hospital discharge was 207.34 (SD = 29.22). Coping through family integration subscale and communication stress predicted discharge readiness of mothers (adjusted R = 0.11; p = 0.034). Mothers who reported higher overall stress (Pediatric Inventory for Parents) 2 weeks post discharge were more likely to call a friend or family member, visit the emergency department, or have their child readmitted to hospital following hospital discharge. CONCLUSIONS: We identified coping by family integration and communication-related stress as predictors of readiness for discharge. Strategies targeted at communication and family integration for discharge preparation may improve caregivers' readiness for hospital discharge.

The Impact of Time to Rate Control of Junctional Ectopic Tachycardia After Congenital Heart Surgery.

BACKGROUND: Junctional ectopic tachycardia (JET) after congenital heart disease (CHD) surgery is often self-limiting but is associated with increased risk of morbidity and mortality. Contributing factors and impact of time to achieve rate control of JET are poorly described. METHODS: From January 2010 to June 2015, a retrospective, single-center cohort study was performed of children who developed JET after CHD surgery . We classified the cohort into two groups: patients who achieved rate control of JET in ≤24 hours and in >24 hours. We examined factors associated with time to rate control and compared clinical outcomes (mortality, duration of mechanical ventilation, length of intensive care unit [ICU], and hospital stay) between the two groups. RESULTS: Our cohort included 27 children, with a median age of 3 (interquartile range: 0.7-38] months. The most common CHD lesions were ventricular septal defect (n = 10, 37%), tetralogy of Fallot (n = 7, 25.9%), and transposition of the great arteries (n = 4, 14.8%). In all, 15 (55.6%) and 12 (44.4%) patients achieved rate control of JET in ≤24 hours and >24 hours, respectively. There was a difference in median mechanical ventilation time (97 [21-145) vs 311 [100-676] hours; P = .013) and ICU stay (5.0 [2.0-8.0] vs 15.5 [5.5-32.8] days, P = .023) between the patients who achieved faster rate control than those who didn't. There was no difference in length of hospital stay and mortality between the groups. CONCLUSION: Our study demonstrated that time to achieve rate control of JET was associated with increased duration of mechanical ventilation and ICU stay.

The safe volume threshold for chest drain removal following pulmonary resection.

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'In patients undergoing pulmonary resection, is there a safe drainage volume threshold for chest drain removal?' Altogether 1054 papers were found, of which 5 papers represented the best evidence. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Chest drainage threshold, where used, ranged from 250 to 500 ml/day. Both randomized controlled trials showed no significant difference in reintervention rates with a higher chest drainage volume threshold. Four studies that performed analysis on other complications showed no statistical significant difference with a higher chest drainage volume threshold. Four studies evaluating length of hospital stay showed reduced or no difference in the length of stay with a higher chest drainage volume threshold. Two cohort studies reported the mortality rate of 0-0.01% with a higher chest drainage volume threshold. We conclude that early chest drain removal after pulmonary resection, accepting a higher chest drainage volume threshold of 250-500 ml/day is safe, and may result in shorter hospital stay without increasing reintervention, morbidity or mortality.

Intramyocardial Hematoma After Ebstein Anomaly Repair.

Intramyocardial hematoma is a rare condition and is an incomplete form of myocardial rupture, which may occur after myocardial infarction, cardiac surgery, trauma, percutaneous coronary intervention, or spontaneously. We describe a case of a 16-year-old girl with intramyocardial hematoma mimicking an intracavitary thrombus following repair of Ebstein anomaly. The intramyocardial hematoma was incorrectly diagnosed on echocardiography as a right ventricular thrombus, and the true nature of the lesion was only realized during repeat surgical intervention for severe tricuspid regurgitation. The hematoma was managed conservatively and spontaneously resolved.

Therapeutic hypothermia in adult patients receiving extracorporeal life support: early results of a randomized controlled study.

Cardiac arrest with cerebral ischaemia frequently leads to severe neurological impairment. Extracorporeal life support (ECLS) has emerged as a valuable adjunct in resuscitation of cardiac arrest. Despite ECLS, the incidence of permanent neurological injury remains high. We hypothesize that patients receiving ECLS for cardiac arrest treated with therapeutic hypothermia at 34 °C have lower neurological complication rates compared to standard ECLS therapy at normothermia. Early results of this randomized study suggest that therapeutic hypothermia is safe in adult patients receiving ECLS, with similar complication rates as ECLS without hypothermia. Further studies are warranted to measure the efficacy of this therapy.

Surgical correction of persistent truncus arteriosus on a 33-year-old male with unilateral pulmonary hypertension from migration of pulmonary artery band.

BACKGROUND: Persistent truncus arteriosus is a rare congenital condition with which survival into adulthood is dismal without surgery. This is the oldest patient reported to our knowledge demonstrating the feasibility of assessing operability in persistent truncus arteriosus with unilateral pulmonary stenosis, and performing full corrective surgery in adulthood. CASE PRESENTATION: We report a Chinese male with successful correction of Type I persistent truncus arteriosus at 33 years of age. He had unilateral pulmonary hypertension from migration of pulmonary artery band from the main to the right pulmonary artery, severe truncal valve regurgitation from previous infective endocarditis, and progressive congestive heart failure. Improvement of lung perfusion was demonstrated 21 months post operation. CONCLUSION: This case demonstrated that in patients with persistent truncus arteriosus and two pulmonary arteries, pulmonary vascular disease or underdevelopment of one lung does not preclude a full corrective surgery so long as the other vascular bed is normal. It is important to emphasize the importance of assessing patient's operability in totality.

Ventricular septal rupture following acute myocardial infarction.

OBJECTIVE: Ventricular septal rupture (VSR) is a complication of acute myocardial infarction (AMI) that is associated with significant mortality. We aim to review the clinical outcome in the current era. METHODS AND RESULTS: Patients admitted to a single tertiary centre from 1997 to 2008 with VSR post-AMI were identified from the local cardiac registry. We performed a retrospective review on 25 patients. Mean age (15 women) was 71 years. Most patients had cardiovascular risk factors (84%); the commonest was hypertension (72%). Anterior AMI (80%) and apical VSR (84%) formed the majority of the cases. Eleven patients (44%) received prior coronary reperfusion therapy either via thrombolysis or PCI. Median time to rupture was 1 day from diagnosis of infarction. More than half (60%) of the patients were in Killip class 3 or 4 at diagnosis of rupture. Mean left ventricular ejection fraction (LVEF) was 33 +/- 10%. Most patients (80%) required IABP for haemodynamic support. All patients who underwent surgery had ventricular septal repair; amongst them 47% had concomitant CABG. Those managed conservatively were older (P = 0.01). Overall mortality rate was 44%. Most died within the first four days (82%). Surgical and non-surgical survival rates were 68% and 17%, respectively (P= 0.039). Patient demographics, prior coronary reperfusion techniques, Killip class status and LVEF were not significant predictors of mortality. However, non-anterior wall AMI and non-apical VSR were significantly associated with poorer survival (P = 0.009, P = 0.026 respectively). CONCLUSIONS: While the occurrence ofVSR post-AMI appears to be low compared to earlier studies, it continues to be associated with significant mortality. Non-anterior wall AMI and non-apical VSR were associated with poorer survival and surgical repair conferred survival advantage over conservative management.

Factors influencing radial artery size.

Size matching of radial artery conduits to coronary arteries is important as it affects the long-term patency. However, factors affecting radial artery size have not been adequately investigated. We retrospectively reviewed 327 consecutive patients who had duplex ultrasonography of their radial arteries over a 2-year period. There were 225 men and 102 women. The mean radial artery size was 2.45 +/- 0.54 mm. The factors found to positively affect the size of the radial artery were sex, hypertension, and hyperlipidemia. Diabetes mellitus and age were found to negatively affect radial artery size. Renal disease, race, and smoking did not significantly influence the size of the radial artery. However, as the R squared of this model was insignificant, further studies need to be undertaken to determine other factors that may influence radial artery size.