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Laugesen Clancy posted an update 2 weeks, 1 day ago
Role of tumor markers in gall bladder carcinoma (GBC) is not well established. We evaluated the prognostic value of carbohydrate antigen 19-9 (CA19-9) and carcinoma embryonic antigen (CEA) in patients with GBC.
Of the 225 patients of GBC enrolled,176 patients were included in the study (excluded 49 patients with jaundice). Patients were divided into 3 groups; resectable n = 92, unresectable n = 17, metastatic n = 67. The clinico-pathological characteristics, tumor markers and survival data were analysed. The cutoff values of CA19-9 & CEA for predicting metastases were computed using receiver operating characteristic curve. Kaplan Meir survival and Cox regression analysis were done for factors predicting survival and recurrence.
The median value of Ca19-9 was significantly higher in metastatic group [resectable 21.3, unresectable 53.9 and metastatic 79; p < 0.001] but not for CEA [3.5, 7.8 and 5 ng/ml (p = 0.20)]. A cutoff value of 72 IU/ml for CA19-9, 5 ng/ml for CEA had a sensitivity and specificity of 52 and 80%, 51 and 72% respectively for detection of metastatic disease. Median, 3-year & 5-year survival were significantly lower in patients with CEA > 4 (p = 0.041), Ca19.9 > 37 (p = 0.019), T3/T4 (p = 0.001), node positive (p = 0.001) and presence of perineural invasion (p = 0.001). However, on multivariate analysis, only Ca19.9 > 37 predicted recurrence (p = 0.002, HR 5.8).
Raised CA19.9 and CEA predict metastatic disease in patients with GBC without jaundice with a high specificity and may help in prognostication of the patient. CA19-9 was better than CEA in prediction of tumor burden and in predicting recurrence.
Raised CA19.9 and CEA predict metastatic disease in patients with GBC without jaundice with a high specificity and may help in prognostication of the patient. CA19-9 was better than CEA in prediction of tumor burden and in predicting recurrence.
Because ofunknown features of the COVID-19 and thecomplexity of the populationaffected, standard clinical trial designs on treatments may not be optimal in such patients. We propose two independent clinical trials designs based on careful grouping of patient and outcome measures.
Using the World Health Organization ordinal scale on patient status, we classify treatable patients (Stages 3-7) into two risk groups. Patients in Stages 3, 4 and 5 are categorized as the intermediate-risk group, while patients in Stages 6 and 7 are categorized as the high-risk group. To ensure that an intervention, if deemed efficacious, is promptly made available to vulnerable patients, we propose a group sequential design incorporating four factors stratification, two interim analyses, and a toxicity monitoring rule for the intermediate-risk group. The primary response variable (binary variable) is based on the proportion of patients discharged from hospital by the 15
day. The goal is to detect a significantimprovement in th interim analyses for efficacy evaluation along with toxicity monitoring are encouraged. For the high-risk group, two interim analyses without toxicity monitoring is advised.
We recommend using a binary outcome with composite endpoints for patients in Stage 3, 4 or 5 with a power of 90% to detect an improvement of 20% in the response rate, and a 30 day mortality rate outcome for those in Stage 6 or 7 with a power of 90% to detect 15% (effect size) reduction in mortality rate. For the intermediate-risk group, two interim analyses for efficacy evaluation along with toxicity monitoring are encouraged. For the high-risk group, two interim analyses without toxicity monitoring is advised.
We describe the clinical benefit of immune checkpoint inhibitors using the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) and ASCO VF.
We identify all approved indications of immune checkpoint inhibitors based on RCTs between January 1, 2011 and September 30, 2018 by FDA. Information including medians and HR of OS (PFS or DFS) and 95% CI, grade 3 or 4 toxicities in each arm, QOL data, survival probability at fixed time were extracted.
Immune checkpoint inhibitors were approved for 18 indications based on RCTs. All the indications meet the ESMO-MCBS 1.1 threshold for meaningful benefit. By the updated ASCO-VF, the median Net Health Benefit (NHB) of these agents was 55.3 (range 17.4-77.1). Two third of the indication gained the bonus points for durable survival benefits by updated ASCO VF. When updated results were incorporated in the assessment, clinical benefit of most approved immune checkpoint inhibitors increased with a median improvement of NHB of 10 (range 2-20).
Approved immune checkpoint inhibitors provided clinical meaningful benefit by ESMO-MCBS 1.1, and most of these agents reach the threshold for bonus points for durable survival in the updated ASCO VF.
Approved immune checkpoint inhibitors provided clinical meaningful benefit by ESMO-MCBS 1.1, and most of these agents reach the threshold for bonus points for durable survival in the updated ASCO VF.
The COVID-19 pandemic has affected the world deeply, with more than 14,000,000 people infected and nearly 600,000 deaths. This review aimed to summarize the epidemiologic traits, clinical spectrum, CT results and laboratory findings of the COVID-19 pandemic.
We scoped for relevant literatures published during 1st December 2019 to 16th July 2020 based on three databases using English and Chinese languages. We reviewed and analyzed the relevant outcomes.
The COVID-19 pandemic was found to have a higher transmission rate compared to SARS and MERS and involved 4 stages of evolution. The basic reproduction number (R
) is 3.32 (95% CI3.24-3.39), the incubation period was 5.24 days (95% CI3.97-6.50, 5 studies) on average, and the average time for symptoms onset varied by countries. Common clinical spectrums identified included fever (38.1-39.0 °C), cough and fatigue, with Acute Respiratory Distress Syndrome (ARDS) being the most common complication reported. Body temperatures above 39.0 °C, dyspnea, and anorexia were more common symptoms in severe patients. Aged over 65 years old, having co-morbidities, and developing complications were the commonest high-risk factors associated with severe conditions. Leucopenia and lymphopenia were the most common signs of infection while liver and kidney damage were rare but may cause bad outcomes for patients. The bilateral, multifocal Ground-Glass Opacification (GGO) on peripheral, and the consolidative pulmonary opacity were the most frequent CT results and the tendency of mortality rates differed by region.
We provided a bird’s-eye view of the COVID-19 during the current pandemic, which will help better understanding the key traits of the disease. The findings could be used for disease’s future research, control and prevention.
We provided a bird’s-eye view of the COVID-19 during the current pandemic, which will help better understanding the key traits of the disease. The findings could be used for disease’s future research, control and prevention.
Uricemia dramatically rises with the stage of chronic kidney disease (CKD) and correlates with its mortality. Hemodialysis (HD) being the most used treatment at the end stage in sub-Saharan Africa, we sought to evaluate its efficacy on the clearance of uric acid (UAc) when used alone and twice per week.
A cross-sectional study of all consenting patients with CKD stage 5 recruited at random during HD sessions in a reference Centre in Cameroon from January to April 2017. We collected socio-demographic data, relevant clinical information, HD related variables, and measured serum uric acid (SUA) levels before and after the dialysis to assess the uric acid clearance. A clearance between 65 and 80% and above 80% was considered as low and good efficacy of HD respectively. Statistical analysis was performed using SPSS version 21.0. Factors associated with HD efficacy were assessed using Fisher’s exact test and are presented with their odds ratios (OR) and 95% confidence levels.
One hundred four patients (53 females) were included. The mean age was 49.9 ± 13.3 years. Hypertension (25%) and chronic glomerulonephritis (16%) were the main suspected etiologies of CKD. The median time on renal replacement therapy by HD was 3 years [1; 6]. The prevalence of hyperuricemia was 81.9%. The means of SUA levels were 78.8 ± 13.8 mg/L and 26.4 ± 6.6 mg/L respectively before and after dialysis. Mean SUA clearance was 66% ± 10%. The efficacy of HD on UAc was moderate in 92 (63.9%) and good in 2 (1.4%) patients. Excess weight (OR 0.4 [0.2; 0.9]) and Kt/Vurea < 1.2 (OR 0.1 [0.04; 0.2]) significantly reduces the efficacy of HD.
HD used alone for 2 sessions per week has a moderate efficacy on uric acid clearance in CKD. Therefore, we should improve the Kt/V (> 1.2), and combine HD to uric acid lowering drugs and diet modifications to increase its efficacy.
1.2), and combine HD to uric acid lowering drugs and diet modifications to increase its efficacy.
Herpes simplex virus type 1 (HSV-1) keratitis is a major cause of corneal blindness in the world, and an in-depth understanding of its pathogenesis may help improve existing diagnosis and treatment. The purpose of this study is to compare and analysis the total tear protein profile of HSV-1 epithelial keratitis patients, and to quantify the potential candidate biomarkers of HSV-1 epithelial keratitis.
We investigated the proteome in tear fluid from three HSV-1 epithelial keratitis patients and three healthy control subjects using nano-scale liquid chromatography-tandem mass spectrometry (nLC-MS/MS) analysis. Functional annotation of differentially expressed proteins was done with the Gene Ontology (GO) analysis. ELISA was done to quantify the potential candidate biomarkers in 26 clinical cases.
Tear fluid from three HSV-1 epithelial keratitis patients and three healthy control subjects contained a total of 1275 proteins and 326 proteins were unique to tear fluid of HSV-1 epithelial keratitis patients. Bioinformatics analysis revealed that tear proteins from HSV-1 epithelial keratitis patients may be involved in metabolic processes, antigen presentation, inflammatory response, and in the TNF-mediated and T cell receptor pathways. Furthermore, IL1A, IL12B, DEFB4A, and CAMP, which are associated with the inflammatory response and inhibition of viral infection, were significantly more abundant in the HSV-1 epithelial keratitis patients than in the healthy control subjects.
This study reports the proteomic profile of tears in HSV-1 epithelial keratitis for the first time and identifies a number of unique differentially expressed proteins.
This study reports the proteomic profile of tears in HSV-1 epithelial keratitis for the first time and identifies a number of unique differentially expressed proteins.
Sialidosis is a rare genetic lysosomal storage disorder caused by a deficit of neuraminidase enzyme activity. Patients with sialidosis present various neurological disorders such as myoclonic epilepsy and hypotonia, often associated with visual impairment. A typical aspect of sialidosis is the finding of a macular cherry-red spot on ocular fundus examination. In this paper we describe a unilateral case of Bergmeister’s papilla (BP) in a young female patient suffering from type 1 sialidosis.
A 28-year-old young woman suffering from type 1 sialidosis, confirmed by previously described compound heterozigosity Leu91Arg and Gly328Ser on N-acetyl-alpha-neuraminidase - 1 (NEU1) gene, underwent an opthalmological examination at the Eye Clinic of the University of Campania L. Vanvitelli, for bilateral visual deterioration. The patient was suffering from myoclonic epilepsy with hypotonia and severe motor disability. Blasticidin S in vivo Fundoscopic examination showed a typical macular cherry-red spot with retinal pigment epithelium dystrophy in the middle periphery, in both eyes.