Morenokold4713
To explore the contagiousness and new SARS-CoV-2 mutations in pediatric COVID-19.
This cohort study enrolled all pediatric patients admitted to 8 hospitals in Zhejiang Province of China between 21 January and 29 February 2020, their family members and close-contact classmates. Epidemiological, demographic, clinical and laboratory data were collected. Bioinformatics was used to analyze the features of SARS-CoV-2. Individuals were divided into 3 groups by the first-generation case Groups 1 (unclear), 2 (adult), and 3 (child). The secondary attack rate (SAR) and R
were compared among the groups.
The infection rate among 211 individuals was 64%(135/211). The SAR in Groups 2 and 3 was 71%(73/103) and 3%(1/30), respectively; the median R
in Groups 2 and 3 was 2 (range 1-8) and 0 (range 0-1), respectively. Compared with adult cases, the SAR and R
of pediatric cases were significantly lower (p<0.05). We obtained SARS-CoV-2 sequences from the same infant's throat and fecal samples at a two-month interval and found that the new spike protein A958D mutation detected in the stool improved thermostability theoretically.
Children have lower ability to spread SARS-CoV-2. The new A958D mutation is a potential reason for its long residence in the intestine.
Children have lower ability to spread SARS-CoV-2. The new A958D mutation is a potential reason for its long residence in the intestine.
Multidrug-resistant tuberculosis (MDR-TB) patients have been suffering long, ineffective, and toxic treatment until short-course injectable-free regimens emerged. However, the new WHO-recommended regimens might be less feasible in the real-world setting. Here, we evaluated two optimized all-oral short-course regimens in China.
From April 2019 to August 2020, we conducted a prospective nonrandomized controlled trial and consecutively included 103 MDR-TB patients diagnosed with pulmonary MDR-TB in Shenzhen, China. A 4-5 drug regimen of 9-12 months was tailored to the strain's resistance patterns, patients' affordability, and tolerance to drugs. This was an interim analysis, focusing on the early treatment period.
53.4% (55/103) of patients were prescribed linezolid, fluoroquinolone (FQ), clofazimine, cycloserine, and pyrazinamide, followed by a regimen in which clofazimine was replaced by bedaquiline (35/103, 34.0%). The culture conversion rate was 83.1% and 94.4% at two and four months, respectively, with no significant difference between bedaquiline-free and bedaquiline-containing cases and between FQ-susceptible and FQ-resistant cases. Among 41 patients who completed treatment, 40 (97.6%) patients had a favorable outcome and no relapse was observed. Peripheral neuropathy and arthralgia/myalgia were the most frequent AEs (56.3%, 58/103). 18 AEs caused permanent discontinuation of drugs, mostly due to pyrazinamide and linezolid.
Optimized all-oral short-course regimens showed satisfactory efficacy and safety in early treatment stage. Further research is needed to confirm these results.
Optimized all-oral short-course regimens showed satisfactory efficacy and safety in early treatment stage. Further research is needed to confirm these results.
The relationship between immunity and trace elements levels is well known. We aimed to estimate the association of serum trace elements with severity and outcomes in the Coronavirus Disease-2019 (COVID-19) patients.
In this single-centered, prospective, observational study, we enrolled 114 patients admitted to severe intensive care units (ICUs) and corresponding 112 sex and aged-matched non-ICU ward patients. Demographic data, clinical characteristics, and outcomes were all collected. We analyzed serum levels of zinc (Zn), copper (Cu), selenium (Se), and manganese (Mn) in both severity groups.
The serum levels of Cu, Se, and Mn in both groups were within the normal range while Zn serum levels were lower than normal values. Based on these findings, Zn, Cu, Se, and Mn serum levels were not associated with disease severity (P > 0.05), while we found Zn serum levels were strongly associated with patient outcomes (P=0.005). Our results indicated lower Mn serum levels were associated with age more than 55 years (P= 0.006). Our results were not in favor of a causal relationship between serum trace elements levels and disease severity.
We found Zn level to be a strong indicator for patients' outcomes that can be considered for monitoring patient prognosis. Nutritional measures or supplementation can help reduce poor outcomes caused by low Zn levels in Iranian COVID-19 patients.
We found Zn level to be a strong indicator for patients' outcomes that can be considered for monitoring patient prognosis. Nutritional measures or supplementation can help reduce poor outcomes caused by low Zn levels in Iranian COVID-19 patients.Although each autoimmune disease is associated with specific tissue or organ damage, rheumatic diseases share a pro-inflammatory pattern that might increase cardiovascular risk. Retrospective and prospective studies on patients affected by systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) highlighted the concept of "accelerated atherosclerosis". Therefore, the purpose of this systematic review and meta-analysis is the assessment of symptomatic or asymptomatic cardiovascular events among patients with rheumatic diseases as RA and SLE. find more The literature research obtained all manuscripts published in the English language between 2015 and 2019 for a total of 2355 manuscripts. After selection through inclusion and exclusion criteria, four articles examined cardiovascular risk in RA patients, 8 in SLE patients, and 2 in RA and SLE patients. Patients with SLE had a RR of 1.98 (95% CI 1.18-3.31) of symptomatic cardiovascular events compared to the unexposed cohort. The meta-regression analysis showed that younger patient (age per year increase β = -0.12 95%CI -0.20, -0.4), belonging to studies conducted in continent different from America (β = -0.89; -95% CI 1.67, -0.10), after 2000 (β = 0.87; 95% CI 0.09, 1.65) and with a higher quality score 0.80 (95% CI 0.31, 1.29) had a higher risk of cardiovascular events. In patients with RA, the RR of cardiovascular events was 1.55 (95% CI 1.18-2.02). These data are helpful to implement cardiovascular preventive strategies among people suffering from rheumatologic diseases to decrease the incidence of cardiovascular events. However, these implementation needs to build a higher network between rheumatologists and primary care healthcare workers to furnish the same information to patients and monitor their preventive practice compliance.Circulating cell-free DNA (ccfDNA) is used increasingly as a cancer biomarker for prognostication, as a correlate for tumor volume, or as input for downstream molecular analysis. Determining optimal blood processing and ccfDNA quantification are crucial for ccfDNA to serve as an accurate biomarker as it moves into the clinical realm. Whole blood was collected from 50 subjects, processed to plasma, and used immediately or frozen at -80°C. Plasma ccfDNA was extracted and concentration was assessed by real-time quantitative PCR (qPCR), Qubit, and droplet digital PCR (ddPCR). For the 24 plasma samples from metastatic pancreatic cancer patients, the variant allele fractions (VAF) of KRAS G12/13 pathogenic variants in circulating tumor DNA (ctDNA) were measured by ddPCR. Using a high-speed (16,000 × g) or slower-speed (4100 × g) second centrifugation step showed no difference in ccfDNA yield (qPCR P = 0.208, Qubit P = 0.468, and ddPCR P = 0.509) or ctDNA VAF (P = 0.438). A two- versus three-spin centrifugation protocol also showed no difference in ccfDNA yield (qPCR P = 0.317, Qubit P = 0.439, and ddPCR P = 0.160) or ctDNA VAF (P = 0.496). A higher yield was observed from fresh versus frozen plasma by qPCR (P = 0.001) and Qubit (P less then 0.001), whereas a higher yield was observed for frozen versus fresh plasma by ddPCR (P = 0.010), however, no difference was observed in ctDNA VAF (P = 0.219). Overall, our findings suggest factors to consider when implementing a ccfDNA extraction and quantification workflow in a research or clinical setting.Somatic copy number alterations (SCNAs) can be detected in cell-free DNA (cfDNA) by shallow whole genome sequencing (sWGS). Polymerase chain reaction (PCR) is typically included in library preparations but a PCR-free method could serve as a high throughput alternative. To evaluate a PCR-free method for research and diagnostics, archival peripheral blood or bone marrow plasma samples collected in EDTA- or lithium heparin-containing tubes were collected from patients with non-small cell lung cancer (n=10 longitudinal samples; 4 patients), B-cell lymphoma (n=31), acute myeloid leukemia (n=15) or from healthy donors (n=14). sWGS was performed on PCR-free and PCR library preparations and the mapping quality, percentage of unique reads, genome coverage, fragment lengths and copy number profiles were compared. The percentage of unique reads was significantly higher for PCR-free compared to PCR, independent of the type of collection tube; EDTA PCR-free 96.4%, n=35; EDTA PCR 85.1%, n=32; heparin PCR-free 94.5%, n=25; heparin PCR 89.4%, n=10. All other evaluated metrics were highly comparable for PCR-free and PCR library preparations. These results demonstrate the feasibility of SCNA detection by PCR-free sWGS using cfDNA from plasma collected in EDTA- or lithium heparin-containing tubes and pave the way for an automated cfDNA analysis workflow for samples from cancer patients.Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome responsible for 1% of colorectal cancers (CRCs). Up to 90% of classic FAPs are caused by inactivating mutations in APC, and mosaicism has been previously reported in 20% of de novo cases, usually linked to milder phenotypic manifestations. This study aimed to explore the prevalence of mosaicism in 11 unsolved cases of classic FAP and to evaluate the diagnostic yield of somatic testing. Paired samples of colorectal polyps, tumors, and/or mucosa were analyzed using a custom next-generation sequencing panel targeting 15 polyposis and CRC-predisposing genes. Whenever possible, the extension of mosaicism to blood or sperm was also examined. Of 11 patients with classic adenomatous polyposis, a mosaic pathogenic variant in APC was identified in 7 (64%). No other altered genes were identified. In two of seven patients (29%), mosaicism was found restricted to colonic tissues, whereas in five of seven patients (71%), it was extended to the blood. Germline affectation was confirmed in one patient. We report the first analysis at a somatic level of 15 genes associated with CRC susceptibility, which highlights the role of APC mosaicism in classic FAP etiology. The results further reinforce the importance of testing target tissues when blood test results are negative.Despite widespread use in targeted tumor testing, multiplex PCR/semiconductor (Ion Torrent) sequencing-based assessment of all comprehensive genomic profiling (CGP) variant classes has been limited. Herein, we describe the development and validation of StrataNGS, a 429-gene, multiplex PCR/semiconductor sequencing-based CGP laboratory-developed test performed on co-isolated DNA and RNA from formalin-fixed, paraffin-embedded tumor specimens with ≥2 mm2 tumor surface area. Validation was performed in accordance with MolDX CGP validation guidelines using 1986 clinical formalin-fixed, paraffin-embedded samples and an in-house developed optimized bioinformatics pipeline. Across CGP variant classes, accuracy ranged from 0.945 for tumor mutational burden (TMB) status to >0.999 for mutations and gene fusions, positive predictive value ranged from 0.915 for TMB status to 1.00 for gene fusions, and reproducibility ranged from 0.998 for copy number alterations to 1.00 for splice variants and insertions/deletions. StrataNGS TMB estimates were highly correlated to those from whole exome- or FoundationOne CDx-determined TMB (Pearson r = 0.
