A More Important Role of Diabetes Mellitus in Mortality in Elderly Critical COVID-19 Patients: a Single-center Retrospective Study

BackgroundCOVID-19 has been circulating worldwide since December 2019. However, its independent risk factors of mortality need further insights in elderly critical COVID-19 patients.MethodsTotally 48 elderly and critically ill COVID-19 patients with clear end point were enrolled when the data were collected, with 16 discharged and 32 died. Kaplan-Meier analysis and Cox regression were performed to identify the risk factors of mortality in elderly critical COVID-19 patients. Survival curve was conducted to present the impact of Diabetes Mellitus on mortality. Mann-Whitney U and t tests were used to 39 clinical variates between the survivor and non-survivor groups.ResultsAs Kaplan-Meier analysis confirmed, only three variates Diabetes Mellitus, chronic obstructive pulmonary disease and family aggregation showed significant difference between the survivor and non-survivor groups. However, only variate Diabetes Mellitus presented significance in Cox regression. Higher C-reaction protein, interleukin-2 (IL-2), IL-8 and creatinine were detected in survivor group than non-survivor group, which was reverse to estimated glomerular filtration rate. The other laboratory finding showed no significant difference between survivor and non-survivor groups.ConclusionsDiabetes Mellitus, chronic obstructive pulmonary disease and family aggregation can contribute to mortality by COVID-19 while Diabetes Mellitus also reduces the survival time of elderly and critically ill COVID-19 patients, highlighting the more important role of Diabetes Mellitus. Laboratory findings could not serve as good predictors of death for elderly and critically ill COVID-19 patients.

New Therapies for Primary Hyperlipidaemia

Primary hyperlipidemias include a heterogeneous set of monogenic and polygenic conditions characterized by a strong family aggregation, severe forms of hypercholesterolemia and/or hypertriglyceridemia, appearance early on life and a high risk of cardiovascular events and/or recurrent pancreatitis. In real life, a small proportion of the primary hyperlipidemia cases is recognized and treated properly. Our goal is to present an update of current and upcoming therapies for patients with primary hyperlipidemia. Recently, new lipid lowering medications have obtained FDA and/or EMA authorization. These drugs target metabolic pathways, including (ATP)-citrate lyase (bempedoic acid), PCSK9 (inclisiran), apo CIII (volanesorsen) and ANGPTL3 (volanesorsen), that have additive effects with the actions of the currently available therapies (i.e. statins, ezetimibe or fibrates). We discuss the potential clinical indications for the novel medications. To conclude, the addition of these new medications to the therapeutic options for primary hyperlipidemia patients may increase the likelihood to achieve the treatment targets. Also, it could be a safer alternative for subjects with side effects for the currently available drugs.

Familial Aggregation and Heritability of Myopia: A Local Population Survey in Shanxi, China

Purpose. To further determine the roles of environmental and genetic factors in the development of myopia, a comprehensive survey was performed. The guidance for myopia-susceptible people is established which might help prevent or delay the onset and development of myopia. Methods. 1,852 students were recruited using the multistage sampling approach from the Gaoping county in Shanxi. The refractive status of students was examined using an autorefractometer, and the refractive status of students’ first-degree relatives was collected using a well-designed questionnaire. Family aggregation of myopia was analyzed according to the myopic status of the students (nonmyopic or myopic group). The prevalence and heritability of myopia in students and their first-degree relatives were further explored by subdividing into mild, moderate, and high myopia groups. Significance analysis among each group was performed by the χ2 test using SPSS 25.0 software. Falconer’s method was used to calculate the inheritability of myopia. Results. A total of 1,852 subjects were recruited in this study, and 1,813 subjects were finally included. The family aggregation of myopia in the myopic student group (34.7%) was significantly higher than that in the nonmyopic group (8.5%). The prevalence of mild, moderate, and high myopia in children (students and siblings) was higher than that in their parents. The rate of high myopia (6.33%) was significantly higher among students with one or both myopic parents than those without myopic parents (3.85%). The heritability of mild, moderate, and high myopia among parents-offspring was 3.72%, 20.47%, and 48.00%, respectively. The heritability of mild, moderate, and high myopia among siblings was 17.50%, 86.09%, and 78.75%, which is significantly higher than that among parents-offspring. In addition to genetic factors, extensive near-work time, higher education pressure, and minimal outdoor activities contribute significantly to mild and moderate myopia. Conclusions. Myopia is of high risk due to familial aggregation. Students with a family history of myopia are more likely to have high myopia than those without family history. The occurrence and development of high myopia are affected by both the genetic and environmental factors, which could either weaken or strengthen myopia. Therefore, students with a family history of myopia should pay close attention to their eye health to avoid the occurrence of myopia and the deepening of diopter, which may lead to high myopia and its related complications.

Pedigree Investigation, Clinical Characteristics and Prognosis Analysis of Hematological Disease Patients with Germline TET2 Mutation

Background: More and more germline gene mutations have been discovered in hematological malignances with the development of next gene sequencing (NGS). Tet methylcytosine dioxygenase 2 (TET2) is one of the most common mutation genes in hematological neoplasms. We aimed to analyzed whether germline TET2 mutation has a family aggregation or is a tumor predisposition gene. Further we compared its impact with somatic TET2 mutation in hematological diseases.Methods: A total cohort of 103 hematological patients with TET2 mutation were included from December 2016 to December 2019. Data were extracted from hematology department of West China Hospital of Sichuan University. Bone marrow (BM) or peripheral blood (PB) as somatic DNA origin to be detected by next-generation sequencing (NGS), and nails and hairs as germline DNA origin to be detected by Sanger sequencing, respectively. Further, we compared the clinical characteristics between the patients with germline and somatic TET2 mutation.Results: 103 patients were included, including 33 (32.03%) patients with germline TET2 mutation and 70 (67.97%) patients with somatic TET2 mutation. Variant allele frequency (VAF) of germline TET2 mutation was more stable in our study, ranging from 40% to 55% and mutation sites were more concentrated. Patients with germline TET2 mutation were younger with median age 48 (range, 16-82) (P=0.0078). Further, patients with germline TET2 mutation were mainly myelodysplastic syndromes (MDS) (n=13, 39.4%), while patients with somatic TET2 mutation were acute myeloid leukemia (AML) (n=28, 40.0%) (P=0.0003). Germline TET2 mutation affected the distribution of peripheral blood cell count and the proportion in bone marrow (P<0.05). Germline TET2 mutation was a poor prognosis factor in MDS patients via univariate analysis (HR=5.3, 95%CI: 0.89-32.2, P=0.0209), but not in multivariate analysis by Cox regression model (P=0.062).Conclusions: Some family members were asymptomatic carriers, which indicated germline TET2 mutation might have a family aggregation. More importantly, TET2 gene may be a predisposition gene of hematological malignant when the other gene mutations as the second hit. The VAF of germline TET2 mutation is more stable. At the same time, the germline TET2 mutation may be an adverse factor for the MDS patients.

Comparison of Clinical Features in HLA-B27 Positive and Negative Patients With Axial Spondyloarthritis: Results From a Cohort of 4,131 Patients

Objective: The aim of our study was to assess the influence of the HLA-B27 status on axial spondyloarthritis (axSpA) in the largest cohort in China.Methods: An observational, cross-sectional, and analytic study of axSpA patients from the China axSpA database was performed. Demographic and clinical data were compared in terms of the HLA-B27 status. Univariate and multivariate analyses were performed to identify variables related to HLA-B27 presence.Results: We enrolled 4,131 patients in this study; of those, 36,95 (89.4%) were HLA-B27 positive. In the multivariate analysis, male gender (p &lt; 0.001), younger age (p &lt; 0.001), a disease duration of more than 3 years (p &lt; 0.001), a family history of SpA (p &lt; 0.001), uveitis (p &lt; 0.001), ASDAS-CRP (p &lt; 0.001), and biologic treatment (p &lt; 0.001) were the main variables that were independently related to HLA-B27 presence, whereas a diagnosis delay time &gt;36 months (p &lt; 0.001) and psoriasis (p &lt; 0.001) were independently related to HLA-B27 absence.Conclusion: In Chinese axial SpA patients, presence of HLA-B27 is associated with the male sex, younger age, longer disease duration, greater family aggregation, and higher frequency of uveitis; absence of HLA-B27 is associated with longer diagnosis delay time and higher frequency of psoriasis.

Family aggregation analysis shows a possible heritable background of equine grass sickness (dysautonomia) in a Hungarian stud population

Equine grass sickness (also known as dysautonomia) is a life-threatening polyneuropathic disease affecting horses with approx. 80% mortality. Since its first description over a century ago, several factors, such as the phenotype, intestinal microbiome, environment, management and climate, have been supposed to be associated with the increased risk of dysautonomia. In this retrospective study, we examined the possible involvement of genetic factors. Medical and pedigree datasets regarding 1,233 horses with 49 affected animals born during a 23-year period were used in the analysis. Among the descendants of some stallions, the proportion of animals diagnosed with dysautonomia was unexpectedly high. Among males, the odds of dysautonomia were found to be higher, albeit not significantly, than among females. Significant familial clustering (genealogical index of familiality, P = 0.001) was observed among the affected animals. Further subgroups were identified with significant (P < 0.001) aggregation among close relatives using kinship-based methods. Our analysis, along with the slightly higher disease frequency in males, suggests that dysautonomia may have a genetic causal factor with an X-linked recessive inheritance pattern. This is the first study providing ancestry data and suggesting a heritable component in the likely multifactorial aetiology of the disease.

Two Variants in the NOTCH4 and HLA-C Genes Contribute to Familial Clustering of Psoriasis

Psoriasis is a multifactorial immune-mediated skin disease with a strong genetic background. Previous studies reported that psoriasis with a family history (PFH) and sporadic psoriasis (SP) have a distinct manifestation and genetic predisposition. However, the genetic heterogeneity of PFH and SP in the major histocompatibility complex (MHC) region has not been fully elucidated. To explore genetic variants in the MHC region that drive family aggregation of psoriasis, we included a total of 8,127 psoriasis cases and 9,906 healthy controls from Han Chinese and divided psoriasis into two subtypes, PFH ( n = 1,538 ) and SP ( n = 5,262 ). Then, we calculated the heritability of PFH and SP and performed a large-scale stratified association analysis. We confirmed that variants in the MHC region collectively explained a higher heritability of PFH (16.8%) than SP (13.3%). Further stratified association analysis illustrated that HLA-C ∗ 06:02 and NOTCH4:G511S contribute to the family aggregation of psoriasis, and BTNL2:R281K specifically confers risk for SP. HLA-C ∗ 06:02 and NOTCH4:G511S could partially explain why patients with PFH have a stronger genetic predisposition, more complex phenotypes, and more frequent other autoimmune diseases. The identification of the SP-specific variant BTNL2:R281K revealed that the genetic architecture of SP is not just a subset of PFH.

Two case reports of COVID-19: A 6-year-old boy and his 66-year-old grandmother

Background: Currently, COVID-19 is a global pandemic disease that has caused a large number of infections worldwide. Reports of COVID-19 cases are not uncommon, but there is no report that SAMS-CoV-2 RNA test results for grandma and grandchildren in family aggregation infections are completely different.Case presentation: A 6-year-old boy's chest CT indicated lung infection, but SAMS-CoV-2 RNA test was negative. His grandmother's imaging showed lung inflammation absorption, and nucleic acid test was positive. Conclusions: Children and the elderly people have different clinical manifestations during the course of SAMS-CoV-2 infection, it is challenging to identify whether they are infectious. Therefore, the diagnosis of COVID-19 requires a combination of multiple detection measures, including clinical features, imaging features, and SAMS-CoV-2 RNA test results.Keywords: COVID-19; SAMS-CoV-2 RNA test; Imaging diagnosis; Case report