Background A pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading over the world. However, the viral dynamics, host serologic responses, and their associations with clinical manifestations, have not been well described in prospective cohort. Methods We conducted a prospective cohort and enrolled 67 COVID-19 patients admitting between Jan 26 and Feb 5, 2020. Clinical specimens including nasopharyngeal swab, sputum, blood, urine and stool were tested periodically according to standardized case report form with final follow-up on February 27. The routes and duration of viral shedding, antibody response, and their associations with disease severity and clinical manifestations were systematically evaluated. Coronaviral particles in clinical specimens were observed by transmission electron microscopy (TEM). Results The median duration of SARS-CoV-2 RNA shedding were 12 (3-38), 19 (5-37), and 18 (7-26) days in nasopharyngeal swabs, sputum and stools, respectively. Only 13 urines (5.6%) and 12 plasmas (5.7%) were viral positive. Prolonged viral shedding was observed in severe patients than that of non-severe patients. Cough but not fever, aligned with viral shedding in clinical respiratory specimens, meanwhile the positive stool-RNA appeared to align with the proportion who concurrently had cough and sputum production, but not diarrhea. Typical coronaviral particles could be found directly in sputum by TEM. The anti-nucleocapsid-protein IgM started on day 7 and positive rate peaked on day 28, while that of IgG was on day 10 and day 49 after illness onset. IgM and IgG appear earlier, and their titers are significantly higher in severe patients than non-severe patients (p<0.05). The weak responders for IgG had a significantly higher viral clearance rate than that of strong responders (p= 0.011). Conclusions Nasopharyngeal, sputum and stools rather than blood and urine, were the major shedding routes for SARS-CoV-2, and meanwhile sputum had a prolonged viral shedding. Symptom cough seems to be aligned with viral shedding in clinical respiratory and fecal specimens. Stronger antibody response was associated with delayed viral clearance and disease severity.
BackgroundProtein Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) is an efficient biomarker specific for hepatocellular carcinoma (HCC). Some researchers have proved that levels of PIVKA-II reflect HCC oncogenesis and progression. However, the effectiveness of PIVKA-II based on real-world clnical data has barely been studied.MethodsA total of 14,861 samples were tested in Southwest Hospital in over 2 years’ time. Among them, 4073 samples were PIVKA-II positive. Finally, a total of 2070 patients with at least two image examinations were enrolled in this study. Levels of AFP and PIVKA-II were measured by chemiluminescence enzyme immunoassay (CLEIA) and chemiluminescent microparticle Immunoassay (CMIA), respectively.ResultsA total of 1016 patients with HCC were detected by PIVKA-II in a real-world application. In all these cases, 88.7% cases primarily occurred and patients with advanced HCC covered 61.3%. Levels of PIVKA-II were significantly higher in advanced group (4650.0 mAU/ml, 667.0–33,438.0 mAU/ml) than early-stage group (104.5 mAU/ml, 61.0–348.8 mAU/ml; P < 0.001). Levels of PIVKA-II elevated significantly in recurrence and residual group than recovery group (P < 0.001). A total of 1054 PIVKA-II positive patients were non-HCC cases. Among them, cirrhosis took the largest part (46.3%), followed by hepatitis (20.6%) and benign nodules (15.3%). High-levels of PIVKA-II in at-risk patients is an indicator of HCC development in two-year time.ConclusionsOur data showed that PIVKA-II effectively increases the detection rate of HCC was a valid complement to AFP and image examination in HCC surveillance.
Total knee replacement (TKR) is an effective method of treating end-stage arthritis of the knee. It is not, however, a procedure without risk due to a number of factors, one of which is diabetes mellitus. The purpose of this study was to estimate the general prevalence of diabetes in patients about to undergo primary TKR and to determine whether diabetes mellitus adversely affects the outcome. We conducted a systematic review and meta-analysis according to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. The Odds Ratio (OR) and mean difference (MD) were used to represent the estimate of risk of a specific outcome. Our results showed the prevalence of diabetes mellitus among patients undergoing TKR was 12.2%. Patients with diabetes mellitus had an increased risk of deep infection (OR = 1.61, 95% confidence interval (CI), 1.38 to 1.88), deep vein thrombosis (in Asia, OR = 2.57, 95% CI, 1.58 to 4.20), periprosthetic fracture (OR = 1.89, 95% CI, 1.04 to 3.45), aseptic loosening (OR = 9.36, 95% CI, 4.63 to 18.90), and a poorer Knee Society function subscore (MD = -5.86, 95% CI, -10.27 to -1.46). Surgeons should advise patients specifically about these increased risks when obtaining informed consent and be meticulous about their peri-operative care.
RNA virus population in a host does not consist of a consensus single haplotype but rather an ensemble of related sequences termed quasispecies. The dynamics of quasispecies afford SARS-CoV-2 a great ability on genetic fitness during intrahost evolution.
Background. Papillary thyroid carcinoma (PTC) is a form of thyroid cancer with high risk of cervical lymph node metastasis. Aim. The aim of this study was to investigate the incidence and the predictive factors for occult ipsilateral central lymph node (CLN) metastasis in the patients with papillary thyroid carcinoma. Methods. A total of 916 PTC patients (1017 lesions) undergoing central lymph node dissection in our hospital from 2005 to 2011 were enrolled. The relationship between CLN metastasis and clinical factors such as gender, age, tumor size, tumor number, capsule invasion, and tumor location was analyzed. Results. Occult CLN metastasis was observed in 52.41% (533/1017) of PTC lesions, respectively. Multivariate analysis showed that age ≤ 35 years, tumor size > 1.5 cm, present capsule invasion/extracapsular invasion, and tumor located in upper/middle pole/whole lobe were risk factors of CLN metastasis. Conclusions. Tumor located in upper/middle pole/whole lobe, less than 35 years old, tumor size > 1.5 cm, and present capsule invasion/extracapsular invasion were risk factors of CLN metastasis. We recommend performing ipsilateral prophylactic CLN dissection in cN0 PTC patients.
Capsular invasion is an independent risk factor of DLN metastasis and DLN metastasis could be used as a predictor of lateral node metastasis. The dissection of DLN in PTC patients is recommended and lateral lymph node should be evaluated for patients with DLN positive.
Papillary thyroid carcinoma (PTC) is the most common malignancy of the thyroid gland, with a relatively high cure rate. Distant metastasis (DM) of PTC is uncommon, but when it occurs, it significantly decreases the survival of PTC patients. The molecular mechanisms of DM in PTC have not been systematically studied. We performed whole exome sequencing and GeneseeqPrime (425 genes) panel sequencing of the primary tumor, plasma and matched white blood cell samples from 20 PTC with DM and 46 PTC without DM. We identified somatic mutations, gene fusions and copy number alterations and analyzed their relationships with DM of PTC. BRAF‐V600E was identified in 73% of PTC, followed by RET fusions (14%) in a mutually exclusive manner (P < 0.0001). We found that gene fusions (RET, ALK or NTRK1) (P < 0.01) and chromosome 22q loss (P < 0.01) were independently associated with DM in both univariate and multivariate analyses. A nomogram model consisting of chromosome 22q loss, gene fusions and three clinical variables was built for predicting DM in PTC (C‐index = 0.89). The plasma circulating tumor DNA (ctDNA) detection rate in PTC was only 38.9%; however, it was significantly associated with the metastatic status (P = 0.04), tumor size (P = 0.001) and invasiveness (P = 0.01). In conclusion, gene fusions and chromosome 22q loss were independently associated with DM in PTC and could serve as molecular biomarkers for predicting DM. The ctDNA detection rate was low in non–DM PTC but significantly higher in PTC with DM.
There are about half of papillary thyroid carcinoma (PTC) patients with the experience of central lymph node metastasis (CLNM), while the model to predict high-risk groups of CLNM from PTC patients is uncertain. The aim of this study was to evaluate candidate risk factors of CLNM and identify risk factors of recurrence to guide the postoperative therapeutic decision and follow-up for physicians and patients.A total of 4107 patients(4884 lesions) who underwent lymph node dissection in two hospitals from 2005 to 2014 were evaluated. CLNM risk was stratified and a risk-scoring model was developed on the basis of the identified independent risk factors for CLNM. Cox’s proportional hazards regression model was used to investigate the risk factors for recurrence.CLNM was proved in 37.96% (1559/4107) of patients and 33.96% (1659/4884) of lesions. In the multivariate analysis, Male, Age ≤35 years, Tumor size >0.5 cm,Lobe dissemination (+), Psammoma body (+), Multifocality and Capsule invasion (+) were independent risk predictors of CLNM (P < 0.01). A 14-point risk-scoring model was built to predict the stratified CLNM in PTC patients and the area under receiver operating characteristic curve of the model for the prediction of CLNM was 0.672 (95% CI: 0.656–0.688) (P < 0.01). COX regression model showed that Tumor size >0.5 cm, Lobe dissemination (+), Multifocality and CLNM were significant risk factors associated with poor outcomes. The research suggested that prophylactic CLN dissection could be performed in patients with total score ≥4 according to the risk-scoring model, and more aggressive treatment and more frequent follow-up should be considered for patients with Tumor size >0.5 cm, Lobe dissemination (+), Multifocality and CLNM.
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