A Retrospective Study: Quick Scoring of Symptoms to Estimate the Risk of Cardiac Arrest in the Emergency Department.

Purpose: At present, not enough is known about the symptoms before cardiac arrest. The purpose of this study is to describe the precursor symptoms of cardiac arrest, focusing on the relationship between symptoms and cardiac arrest, and to establish a quick scoring model of symptoms for predicting cardiac arrest. Patients and Methods. A retrospective case-control study was carried out on cardiac arrest patients who visited the emergency department of Peking University Third Hospital from January 2018 to June 2019. Symptoms that occurred or were obviously aggravated within the 14 days before CA were defined as warning symptoms. Results: More than half the cardiac arrest patients experienced warning symptoms within 14 days before cardiac arrest. Dyspnea (p < 0.001) was found to be associated with cardiac arrest; syncope and cold sweat are other symptoms that may have particular clinical significance. Gender (p < 0.001), age (p < 0.001), history of heart failure (p=0.006), chronic kidney disease (p=0.011), and hyperlipidemia (p=0.004) were other factors contributing to our model. Conclusions: Warning symptoms during the 14 days prior to cardiac arrest are common for CA patients. The Quick Scoring Model for Cardiac Arrest (QSM-CA) was developed to help emergency physicians and emergency medical services (EMS) personnel quickly identify patients with a high risk of cardiac arrest.

Identification of Novel FBN2 Variants in a Cohort of Congenital Contractural Arachnodactyly.

Congenital contractural arachnodactyly (CCA) is a rare autosomal dominant disorder of connective tissue characterized by crumpled ears, arachnodactyly, camptodactyly, large joint contracture, and kyphoscoliosis. The nature course of CCA has not been well-described. We aim to decipher the genetic and phenotypic spectrum of CCA. The cohort was enrolled in Beijing Jishuitan Hospital and Peking Union Medical College Hospital, Beijing, China, based on Deciphering disorders Involving Scoliosis and COmorbidities (DISCO) study (http://www.discostudy.org/). Exome sequencing was performed on patients' blood DNA. A recent published CCA scoring system was validated in our cohort. Seven novel variants and three previously reported FBN2 variants were identified through exome sequencing. Two variants outside of the neonatal region of FBN2 gene were found. The phenotypes were comparable between patients in our cohort and previous literature, with arachnodactyly, camptodactyly and large joints contractures found in almost all patients. All patients eligible for analysis were successfully classified into likely CCA based on the CCA scoring system. Furthermore, we found a double disease-causing heterozygous variant of FBN2 and ANKRD11 in a patient with blended phenotypes consisting of CCA and KBG syndrome. The identification of seven novel variants broadens the mutational and phenotypic spectrum of CCA and may provide implications for genetic counseling and clinical management.

Activating PIK3CA postzygotic mutations in segmental overgrowth of muscles with bone involvement in the body extremities.

Segmental overgrowth of the skeletal muscles with bone involvement in body extremities, predominantly affecting the upper limb, is an extremely rare condition with only 40-50 affected children described clinically. The molecular pathogenesis of this disorder remains largely unclear except for the identification of a somatic PIK3CA mutation in each of the six patients genetically tested, all restricted to upper limbs in the literature. This study aimed to further characterize the molecular defects for patients affected with segmental overgrowth of the skeletal muscles by analyzing a 9-gene panel selected from the PI3K/AKT/mTOR pathway and genes associated with other related conditions. Nineteen unrelated patients were chosen for this study, comprising ten upper limb (nine unilateral and one bilateral) and nine lower limb (eight unilateral and one bilateral) cases with variable bone involvement. In each case, an activating PIK3CA mutation (p.E110del, p.N345K, p.E542K, p.E545K, p.H1047R, or p.H1047L) was identified in the affected muscle tissue with variant allele frequencies ranging from 13.88 to 30.43%, while no mutation was detected in the paired peripheral blood sample, indicating somatic mosaicism. All detected mutations were limited to PIK3CA and were previously reported in other overgrowth syndromes currently categorized under the PIK3CA-Related Overgrowth Spectrum (PROS). Our study provides strong molecular evidence that isolated segmental overgrowth of the skeletal muscle with bone involvement is a subtype of PROS. Our findings expand the PROS clinical presentations with a newly molecularly classified condition and can provide guidance in clinical and molecular diagnosis and treatment for patients with this condition.

Deciphering the mutational signature of congenital limb malformations.

Congenital limb malformations (CLMs) affect 1 in 500 live births. However, the value of exome sequencing (ES) for CLM is lacking. The purpose of this study was to decipher the mutational signature of CLM on an exome level. We enrolled a cohort of 66 unrelated probands (including 47 families) with CLM requiring surgical correction. ES was performed for all patients and available parental samples. A definite molecular diagnosis was achieved in 21 out of 66 (32%) patients. We identified 19 pathogenic or likely pathogenic single-nucleotide variants and three copy number variants, of which 11 variants were novel. We identified four variants of uncertain significance. Additionally, we identified RPL9 and UBA2 as novel candidate genes for CLM. By comparing the detailed phenotypic features, we expand the phenotypic spectrum of diastrophic dysplasia and chromosome 6q terminal deletion syndrome. We also found that the diagnostic rate was significantly higher in patients with a family history of CLM (p = 0.012) or more than one limb affected (p = 0.034). Our study expands our understanding of the mutational and phenotypic spectrum of CLM and provides novel insights into the genetic basis of these syndromes.

Thrombo-inflammatory features predicting mortality in patients with COVID-19: The FAD-85 score.

BACKGROUND: The roles of inflammation and hypercoagulation in predicting outcomes of coronavirus disease 2019 (COVID-19) are unclear. METHODS: Adult patients diagnosed with COVID-19 from 28 January 2020 to 4 March 2020 in Tongji Hospital, Wuhan were recruited. Data on related parameters were collected. Univariate analysis and multivariable binary logistic regression were used to explore predictors of critical illness and mortality. RESULTS: In total, 199 and 44 patients were enrolled in the training and testing sets, respectively. Elevated ferritin, tumor necrosis factor-α and D-dimer and decreased albumin concentration were associated with disease severity. Older age, elevated ferritin and elevated interleukin-6 were associated with 28-day mortality. The FAD-85 score, defined as age + 0.01 * ferritin +D-dimer, was used to predict risk of mortality. The sensitivity, specificity and accuracy of FAD-85 were 86.4%, 81.8% and 86.4%, respectively. A nomogram was established using age, ferritin and D-dimer to predict the risk of 28-day mortality. CONCLUSIONS: Thrombo-inflammatory parameters provide key information on the severity and prognosis of COVID-19 and can be used as references for clinical treatment to correct inflammatory and coagulation abnormalities.

Impact of Dispatcher-Assisted Bystander Cardiopulmonary Resuscitation with Out-of-Hospital Cardiac Arrest: A Systemic Review and Meta-Analysis.

OBJECTIVE: This systemic review and meta-analysis was conducted to explore the impact of dispatcher-assisted bystander cardiopulmonary resuscitation (DA-BCPR) on bystander cardiopulmonary resuscitation (BCPR) probability, survival, and neurological outcomes with out-of-hospital cardiac arrest (OHCA). METHODS: Electronically searching of PubMed, Embase, and Cochrane Library, along with manual retrieval, were done for clinical trials about the impact of DA-BCPR which were published from the date of inception to December 2018. The literature was screened according to inclusion and exclusion criteria, the baseline information, and interested outcomes were extracted. Two reviewers assessed the methodological quality of the included studies. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated by STATA version 13.1. RESULTS: In 13 studies, 235,550 patients were enrolled. Compared with no dispatcher instruction, DA-BCPR tended to be effective in improving BCPR rate (I2 = 98.2%; OR = 5.84; 95% CI, 4.58-7.46; P <.01), return of spontaneous circulation (ROSC) before admission (I2 = 36.0%; OR = 1.17; 95% CI, 1.06-1.29; P <.01), discharge or 30-day survival rate (I2 = 47.7%; OR = 1.25; 95% CI, 1.06-1.46; P <.01), and good neurological outcome (I2 = 30.9%; OR = 1.24; 95% CI, 1.04-1.48; P = .01). However, no significant difference in hospital admission was found (I2 = 29.0%; OR = 1.09; 95% CI, 0.91-1.30; P = .36). CONCLUSION: This review shows DA-BPCR plays a positive role for OHCA as a critical section in the life chain. It is effective in improving the probability of BCPR, survival, ROSC before admission, and neurological outcome.