Cell-free junctional DNA fragment from hepatitis B virus integration in HCC for monitoring postresection recurrence and clonality.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4090-4090 ◽  
Author(s):  
Ya-Chun Wang ◽  
Chiao-Ling Li ◽  
Ming-Chih Ho ◽  
You-Yu Lin ◽  
Sheng-Tai Tzeng ◽  
...  
Keyword(s):  
De Novo ◽  
Residual Tumor ◽  
Digital Pcr ◽  
Early Recurrence ◽  
First Year ◽  
Therapeutic Trials ◽  
Integration Sites ◽  
One Year ◽  
Virus Integration ◽  
Hcc Recurrence

4090 Background: About one-third of patients suffer tumor recurrence within the first year after surgical resection of HCC. Early recurrence compromised their overall survival. Timing detection of HCC recurrence and its clonality is required to implement therapeutic trials appropriately. This study examined the virus-host chimera DNA (vh-chimera DNA), generated from junctions of HBV integration in HCC chromosome and released into blood, as a potential circulating biomarker for this clinical setting. Methods: We established a capture-next generation sequencing (NGS) platform to identify the HBV integrations in 50 resected HBV-related HCC. For individual HCC, the major clonal HBV integration sites were chosen to design specific primers for droplet digital PCR (ddPCR) to detect and quantify the vh-chimera DNA in plasma samples, collected either just before surgery or two months after surgery. Levels of vh-chimera DNA were then correlated with baseline HCC size or recurrence in one-year follow up. Results: We succeeded in detecting HBV integrations in the HCC from 44 out of 50 HBV-related HCC patients (88%). The copy number of vh-chimera DNA in plasma at surgery from 42 patients correlated with tumor sizes, with the detection limit at 1.5-2 cm. Among the plasma collected 2 months after surgery, 26.2% of samples contained the same HCC signature vh-chimera DNA as baseline plasma, indicating a possible residual tumor. Consistently, 81.8% of them suffered HCC recurrence within one year. The signature vh-DNA in the plasma suggested the majority of recurrences coming from the original HCC clones, whereas 2 from de novo ones. Conclusions: This study supported vh-chimera DNA as a new circulation marker for detecting the existence of most HBV-related HCC. This new biomarker may complement AFP to help detect residual or recurrent HCC and their clonality after curative therapies.

scholarly journals Message of the Department Chair

2021 ◽  
Vol 55 (5) ◽  
Author(s):  
Eileen Liesl A. Cubillan
Keyword(s):  
General Hospital ◽  
Department Chair ◽  
De Novo ◽  
Editorial Staff ◽  
The Philippines ◽  
First Year ◽  
The Creation ◽  
One Year ◽  
Special Editor ◽  
The Way

The creation of a department often happens ‘de novo’. For most institutions, they were born as a department while for Dermatology in the UP College of Medicine, Philippine General Hospital, it took almost two decades to become one. The Unit of Dermatology was established by Dr. Perpetuo Gutierrez under the Department of Medicine in 1922. He was the pioneer and known to be the Father of Philippine Dermatology as he paved the way for the development of the specialty in our country. Fast forward to February 2020 and five section and division chiefs later, the Division of Dermatology has finally become the Department of Dermatology - the 21st department of the UP College of Medicine. In essence, the Department is just one year old but UP Dermatology is 99 years old, turning 100 in 2022. For this first year as a department, we celebrate with our second Dermatology issue of the Acta Medica Philippina. Again, we showcase the original studies and interesting cases seen both in the outpatient and in-patient wards of the Philippine General Hospital. In behalf of the faculty and residents of the Department of Dermatology, I thank the editorial staff of the Acta Medica Philippina. I also congratulate Dr. Hanna Orillaza, Special editor for this issue, and most especially the authors for continuing the Department’s thrust for excellence in research; boosting further the Department’s strength in training as we continue to graduate dermatologists that are in the forefront both here and abroad; and, more importantly, continuing to broaden our reach in the service of Filipino patients in the various regions of the country.   Eileen Liesl A. Cubillan, MD, FPDS, FDSPFounding Chair Department of DermatologyCollege of Medicine and Philippine General HospitalUniversity of the Philippines Manila

scholarly journals Therapeutic clinical trials to combat COVID-19 pandemic in India: analysis from trial registry

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Angelika Batta ◽  
Raj Khirasaria ◽  
Vinod Kapoor ◽  
Deepansh Varshney
Keyword(s):  
Clinical Trials ◽  
De Novo ◽  
Treatment Options ◽  
Drug Repurposing ◽  
Trial Registry ◽  
Therapeutic Treatment ◽  
Clinical Trial Registry ◽  
Clear Cut ◽  
Therapeutic Trials ◽  
Microsoft Office

AbstractObjectivesWith the emergence of Novel corona virus, hunt for finding a preventive and therapeutic treatment options has already begun at a rapid pace with faster clinical development programs. The present study was carried out to give an insight of therapeutic interventional trials registered under clinical trial registry of India (CTRI) for COVID-19 pandemic.MethodsAll trials registered under CTRI were evaluated using keyword “COVID” from its inception till 9th June 2020. Out of which, therapeutic interventional studies were chosen for further analysis. Following information was collected for each trial: type of therapeutic intervention (preventive/therapeutic), treatment given, no. of centers (single center/multicentric), type of institution (government/private), study design (randomized/single-blinded/double-blinded) and sponsors (Government/private). Microsoft Office Excel 2007 was used for tabulation and analysis.ResultsThe search yielded total of 205 trials, out of which, 127 (62%) trials were interventional trials. Out of these, 71 (56%) were AYUSH interventions, 36 (28.3%) tested drugs, 9 (7%) tested a nondrug intervention, rest were nutraceuticals and vaccines. About 66 (56%) were therapeutic trials. Majority were single-centered trials, i.e. 87 (73.7%). Trials were government funded in 57 (48.3%) studies. Majority were randomized controlled trials, i.e. 67 (56.8%). AYUSH preparations included AYUSH-64, Arsenic Album, SamshamaniVati etc.ConclusionsThe number of therapeutic interventional clinical trials was fair in India. A clear-cut need exists for an increase in both quantity and quality of clinical trials for COVID-19. Drug repurposing approach in all systems of medicine can facilitate prompt clinical decisions at lower costs than de novo drug development.

scholarly journals Cardiovascular risk factors associated with acute myocardial infarction and stroke in the MADIABETES cohort

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
M. A. Salinero-Fort ◽  
F. J. San Andrés-Rebollo ◽  
J. Cárdenas-Valladolid ◽  
M. Méndez-Bailón ◽  
R. M. Chico-Moraleja ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Blood Pressure ◽  
Antihypertensive Drugs ◽  
Hdl Cholesterol ◽  
First Year ◽  
Backward Elimination ◽  
One Year ◽  
Time Varying Covariates

AbstractWe aimed to develop two models to estimate first AMI and stroke/TIA, respectively, in type 2 diabetes mellitus patients, by applying backward elimination to the following variables: age, sex, duration of diabetes, smoking, BMI, and use of antihyperglycemic drugs, statins, and aspirin. As time-varying covariates, we analyzed blood pressure, albuminuria, lipid profile, HbA1c, retinopathy, neuropathy, and atrial fibrillation (only in stroke/TIA model). Both models were stratified by antihypertensive drugs. We evaluated 2980 patients (52.8% women; 67.3 ± 11.2 years) with 24,159 person-years of follow-up. We recorded 114 cases of AMI and 185 cases of stroke/TIA. The factors that were independently associated with first AMI were age (≥ 75 years vs. < 75 years) (p = 0.019), higher HbA1c (> 64 mmol/mol vs. < 53 mmol/mol) (p = 0.003), HDL-cholesterol (0.90–1.81 mmol/L vs. < 0.90 mmol/L) (p = 0.002), and diastolic blood pressure (65–85 mmHg vs. < 65 mmHg) (p < 0.001). The factors that were independently associated with first stroke/TIA were age (≥ 75 years vs. < 60 years) (p < 0.001), atrial fibrillation (first year after the diagnosis vs. more than one year) (p = 0.001), glomerular filtration rate (per each 15 mL/min/1.73 m2 decrease) (p < 0.001), total cholesterol (3.88–6.46 mmol/L vs. < 3.88 mmol/L) (p < 0.001), triglycerides (per each increment of 1.13 mmol/L) (p = 0.031), albuminuria (p < 0.001), neuropathy (p = 0.01), and retinopathy (p = 0.023).

scholarly journals Mortality in older adults following a fragility fracture: real-world retrospective matched-cohort study in Ontario

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jacques P. Brown ◽  
Jonathan D. Adachi ◽  
Emil Schemitsch ◽  
Jean-Eric Tarride ◽  
Vivien Brown ◽  
...  
Keyword(s):  
Cohort Study ◽  
Hip Fracture ◽  
Fragility Fracture ◽  
Mortality Risk ◽  
Real World ◽  
First Year ◽  
Matched Cohort ◽  
Matched Cohort Study ◽  
Fracture Cohort ◽  
One Year

Abstract Background Recent studies are lacking reports on mortality after non-hip fractures in adults aged > 65. Methods This retrospective, matched-cohort study used de-identified health services data from the publicly funded healthcare system in Ontario, Canada, contained in the ICES Data Repository. Patients aged 66 years and older with an index fragility fracture occurring at any osteoporotic site between 2011 and 2015 were identified from acute hospital admissions, emergency and ambulatory care using International Classification of Diseases (ICD)-10 codes and data were analyzed until 2017. Thus, follow-up ranged from 2 years to 6 years. Patients were excluded if they presented with an index fracture occurring at a non-osteoporotic fracture site, their index fracture was associated with a trauma code, or they experienced a previous fracture within 5 years prior to their index fracture. This fracture cohort was matched 1:1 to controls within a non-fracture cohort by date, sex, age, geography and comorbidities. All-cause mortality risk was assessed. Results The survival probability for up to 6 years post-fracture was significantly reduced for the fracture cohort vs matched non-fracture controls (p < 0.0001; n = 101,773 per cohort), with the sharpest decline occurring within the first-year post-fracture. Crude relative risk of mortality (95% confidence interval) within 1-year post-fracture was 2.47 (2.38–2.56) in women and 3.22 (3.06–3.40) in men. In the fracture vs non-fracture cohort, the absolute mortality risk within one year after a fragility fracture occurring at any site was 12.5% vs 5.1% in women and 19.5% vs 6.0% in men. The absolute mortality risk within one year after a fragility fracture occurring at a non-hip vs hip site was 9.4% vs 21.5% in women and 14.4% vs 32.3% in men. Conclusions In this real-world cohort aged > 65 years, a fragility fracture occurring at any site was associated with reduced survival for up to 6 years post-fracture. The greatest reduction in survival occurred within the first-year post-fracture, where mortality risk more than doubled and deaths were observed in 1 in 11 women and 1 in 7 men following a non-hip fracture and in 1 in 5 women and 1 in 3 men following a hip fracture.

scholarly journals Across the COVID-19 Waves; Assessing Temporal Fluctuations in Perceived Stress, Post-Traumatic Symptoms, Worry, Anxiety and Civic Moral Disengagement over One Year of Pandemic

2021 ◽  
Vol 18 (11) ◽  
pp. 5651
Author(s):  
Alessio Gori ◽  
Eleonora Topino
Keyword(s):  
Perceived Stress ◽  
State Anxiety ◽  
Moral Disengagement ◽  
Online Survey ◽  
Well Being ◽  
First Year ◽  
Effective Interventions ◽  
Post Traumatic ◽  
One Year ◽  
Traumatic Symptoms

This study aimed at investigating the psychological effect of the COVID-19 pandemic in Italy by analysing the trends of perceived stress, post-traumatic symptoms, state anxiety, worry, and civic moral disengagement in four different moments from March 2020 to March 2021. The study involved a total of 1827 Italian participants (30% men and 70% women; Mage = 34.72; SD = 12.40) divided into four groups to which an online survey was administered. The first group completed the survey in March 2020, the second one in August 2020, the third one in November 2020, and the fourth one in March 2021. Results highlighted significant decreases in post-traumatic symptoms and a significant increase in civic moral disengagement over the first year of the COVID-19 pandemic. The levels of perceived stress, worry, and state anxiety remained constant. The correlations between the variables at different times were also explored, as well as gender differences over the year. The COVID-19 emergency has had significant effects on the mental state of the population, with important repercussions for individual and collective well-being during but probably also after the pandemic. This study offers a clear snapshot of the psychological outcomes over one COVID-19 pandemic year, providing important information that may contribute to tailor more effective interventions for mental health.

scholarly journals Dravet syndrome associated mutations in GABRA1, GABRB2 and GABRG2 define the genetic landscape of defects of GABAA receptors

2021 ◽  
Author(s):  
Ciria C Hernandez ◽  
XiaoJuan Tian ◽  
Ningning Hu ◽  
Wangzhen Shen ◽  
Mackenzie A Catron ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
De Novo ◽  
Epileptic Encephalopathy ◽  
Dravet Syndrome ◽  
First Year ◽  
Genes Encoding ◽  
Genetic Landscape ◽  
Clonic Seizures ◽  
Trafficking Defects ◽  
First Year Of Life

Abstract Dravet syndrome is a rare, catastrophic epileptic encephalopathy that begins in the first year of life, usually with febrile or afebrile hemiclonic or generalized tonic-clonic seizures followed by status epilepticus. De novo variants in genes that mediate synaptic transmission such as SCN1A and PCDH19 are often associated with Dravet syndrome. Recently, GABAA receptor subunit genes (GABRs) encoding α1 (GABRA1), β3 (GABRB3) and γ2 (GABRG2), but not β2 (GABRB2) or β1 (GABRB1), subunits are frequently associated with Dravet syndrome or Dravet syndrome-like phenotype. We performed next generation sequencing on 870 patients with Dravet syndrome and identified nine variants in three different GABRs. Interestingly, the variants were all in genes encoding the most common GABAA receptor, the α1β2γ2 receptor. Mutations in GABRA1 (c.644T&gt;C, p.L215P; c.640C&gt;T, p.R214C; c.859G&gt;A; V287I; c.641G&gt;A, p.R214H) and GABRG2 (c.269C&gt;G, p.T90R; c.1025C&gt;T, p.P342L) presented as de novo cases, while in GABRB2 two variants were de novo (c.992T&gt;C, p.F331S; c.542A&gt;T, p.Y181F) and one was autosomal dominant and inherited from the maternal side (c.990_992del, p.330_331del). We characterized the effects of these GABR variants on GABAA receptor biogenesis and channel function. We found that defects in receptor gating were the common deficiency of GABRA1 and GABRB2 Dravet syndrome variants, while mainly trafficking defects were found with the GABRG2 (c.269C&gt;G, p.T90R) variant. It seems that variants in α1 and β2 subunits are less tolerated than in γ2 subunits, since variant α1 and β2 subunits express well but were functionally deficient. This suggests that all of these GABR variants are all targeting GABR genes that encode the assembled α1β2γ2 receptor, and regardless of which of the three subunits are mutated, variants in genes coding for α1, β2 and γ2 receptor subunits make them candidate causative genes in the pathogenesis of Dravet syndrome.

scholarly journals AFP and eGFR are related to early and late recurrence of HCC following antiviral therapy

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Takao Watanabe ◽  
Yoshio Tokumoto ◽  
Kouji Joko ◽  
Kojiro Michitaka ◽  
Norio Horiike ◽  
...  
Keyword(s):  
Risk Factors ◽  
Confidence Interval ◽  
Early Phase ◽  
Late Phase ◽  
Previous History ◽  
Late Recurrence ◽  
Early Recurrence ◽  
Hazard Ratio ◽  
Post Treatment ◽  
Hcc Recurrence

Abstract Background An unexpected recurrence of hepatocellular carcinoma (HCC) sometimes occurs in patients with hepatitis C virus (HCV) after treatment with direct-acting antivirals (DAAs). However, the characteristics of patients with HCC recurrence may differ depending on time after DAA treatment. We aimed to identify risk factors related to HCC recurrence according to time after DAA treatment. Methods Of 1663 patients with HCV treated with a DAA, 199 patients had a previous history of HCC. We defined HCC recurrence within 1 year after DAA treatment as ‘early recurrence’, and recurrence more than 1 year after as ‘late recurrence’. The different risk factors between the early and late phases of HCC recurrence after the end of DAA therapy were investigated. Results Ninety-seven patients experienced HCC recurrence during the study period. Incidences of recurrence were 29.8, 41.0, and 53.4% at 1, 2, and 3 years, respectively, after the end of DAA therapy. Multivariate analysis identified post-treatment α-fetoprotein (AFP) as an independent factor contributing to HCC recurrence in the early phase (hazard ratio, 1.056; 95% confidence interval, 1.026–1.087, p < 0.001) and post-treatment estimated glomerular filtration rate (eGFR) (hazard ratio, 0.98; 95% confidence interval, 0.96–0.99, p = 0.032) as a predictor of HCC recurrence in the late phase. Conclusion Patients with higher post-treatment AFP in the early phase and those with lower post-treatment eGFR in the late phase had a high risk of HCC recurrence. The risk factors associated with HCC recurrence after DAA treatment were different between the early and late phases.

scholarly journals Selection for avian leukosis virus integration sites determines the clonal progression of B-cell lymphomas

2017 ◽  
Vol 13 (11) ◽  
pp. e1006708 ◽  
Author(s):  
Sanandan Malhotra ◽  
Shelby Winans ◽  
Gary Lam ◽  
James Justice ◽  
Robin Morgan ◽  
...  
Keyword(s):  
B Cell ◽  
Avian Leukosis Virus ◽  
B Cell Lymphomas ◽  
Integration Sites ◽  
Selection For ◽  
Virus Integration ◽  
Clonal Progression

scholarly journals Standard induction with basiliximab versus no induction in low immunological risk kidney transplant recipients: study protocol for a randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Aziza Ajlan ◽  
Hassan Aleid ◽  
Tariq Zulfiquar Ali ◽  
Hala Joharji ◽  
Khalid Almeshari ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
De Novo ◽  
Controlled Trial ◽  
Controlled Clinical Trial ◽  
First Year ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Double Blind ◽  
Donor Specific Antibodies

Abstract Background Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent in low immunological risk kidney transplant recipients. However, the role of IL2-RA in the setting of tacrolimus-based immunosuppression has not been fully investigated. Aims To compare different induction therapeutic strategies with 2 doses of basiliximab vs. no induction in low immunologic risk kidney transplant recipients as per KFSHRC protocol. Methods Prospective, randomized, double blind, non-inferiority, controlled clinical trial Expected outcomes 1. Primary outcomes: Biopsy-proven acute rejection within first year following transplant 2. Secondary outcomes: a. Patient and graft survival at 1 year b. eGFR at 6 months and at 12 months c. Emergence of de novo donor-specific antibodies (DSAs) Trial registration The study has been prospectively registered at clinicaltrials.gov (NTC: 04404127). Registered on 27 May 2020.

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