Direct-acting antiviral agents (DAAs) for hepatitis C treatment tend to fare better in individuals who are also likely to respond well to interferon-alpha (IFN), a surprising correlation given that DAAs target specific viral proteins whereas IFN triggers a generic antiviral immune response. Here, we posit a causal relationship between IFN-responsiveness and DAA treatment outcome. IFN-responsiveness restricts viral replication, which would prevent the growth of viral variants resistant to DAAs and improve treatment outcome. To test this hypothesis, we developed a multiscale mathematical model integrating IFN-responsiveness at the cellular level, viral kinetics and evolution leading to drug resistance at the individual level, and treatment outcome at the population level. Model predictions quantitatively captured data from over 50 clinical trials demonstrating poorer response to DAAs in previous non-responders to IFN than treatment-naïve individuals, presenting strong evidence supporting the hypothesis. Model predictions additionally described several unexplained clinical observations, viz., the percentages of infected individuals who 1) spontaneously clear HCV, 2) get chronically infected but respond to IFN-based therapy, and 3) fail IFN-based therapy but respond to DAA-based therapy, resulting in a comprehensive understanding of HCV infection and treatment. An implication of the causal relationship is that failure of DAA-based treatments may be averted by adding IFN, a strategy of potential use in settings with limited access to DAAs. A second, wider implication is that individuals with greater IFN-responsiveness would require shorter DAA-based treatment durations, presenting a basis and a promising population for response-guided therapy.
Variations in the arterial pattern of the upper limb are very common as observed in many cadaveric and angiographic studies. Knowledge of variations in the origin and course of the radial artery is important because they are used for many diagnostic procedures as well as vascular and reconstructive surgeries like coronary angiography, percutaneous coronary intervention and coronary artery bypass surgery. During routine dissection in our institute, we observed a case of high origin of the radial artery in a 33 year old male cadaver. It was found to be unilateral; on left side, radial artery was taking origin from 3 rd part of the axillary artery at the lower border of pectoralis minor before the origin of subscapular artery and anterior circumflex humeral artery. It had a superficial course in the arm crossing the median nerve from medial to lateral side. The further course of this superficial radial artery in the forearm was normal and it terminated by forming a deep Palmar arch in hand. These variations may be of great clinical implications for vascular and plastic surgeons and radiologists. Superficial course of radial artery makes it vulnerable to accidental injuries and elevates the risk of bleeding.
Background: Remdesivir (RDV) in coronavirus disease 2019 (COVID-19) has been found to be beneficial in patients with severe disease; however, its role in mild-moderate disease and its optimal timing need to be identified. Objective: To assess the course of illness and final outcome in patients who received RDV at various stages of illness, and compare it to the non-RDV group. Methods: This is a retrospective data analysis of 1262 COVID-19 patients hospitalized from May5, 2020 to August 31, 2020. The primary outcomes were progression to mechanical ventilation (MV) or death. Kaplan Meier survival analysis and log rank test were used for evaluating primary outcomes. Results: 398 patients comprised the RDV group and 260 patients comprised the non-RDV group. 2/3rd of patients were above 50 years of age in both the groups and 3/4th patients were male. Mortality rate was 5.8% in RDV group (10.4% in non-RDV group). Mortality rate was 3.6%, 4% and 16.7% when RDV was started within 5 days, 5 to 10 days and after 10 days of symptom onset respectively. Fewer patients in RDV group progressed to MV (4.0% v/s 8.2%). Earlier discharge occurred in RDV group. Use of supplemental oxygen was observed in 44.7% patients in RDV group (54.2% in non-RDV group). No significant adverse events were observed with RDV. Survival analysis showed that probability of event (death) was significant for patients with hypertension (HT) and/or diabetes mellitus (DM) in RDV group. Conclusion: Early initiation of RDV is associated with shorter hospital stay, lower mortality as well as reduced need for supplemental oxygen and mechanical ventilation.
Background: Pancreatitis has been recognized since antiquity. Acute pancreatitis is an acute inflammatory process of the pancreas with variable involvement of other tissues or remote organ systems, presenting with variable clinical and systemic manifestations, presenting with mild self-limiting disease to severe life-threatening multi-organ failure.Methods: This was a prospective study of 60 patients, who were admitted with the diagnosis of acute pancreatitis (AP) during the period from December 2017 to June 2019. The data was collected from the all the patients who met the inclusion criteria, and recorded in the proforma prepared for the study.Results: Out of 60 patients 86.7% were male and 13.3% were female. The highest incidence was noted in 40-51 years age group (35%). Alcohol was the most common cause (75% patients). Abdominal pain was the most common mode of presentation (100%), and epigastric tenderness was the most common sign (100%). More than 3-fold elevation of serum amylase and lipase was seen in 26.7% and 33.3% of patients respectively. USG and CT scan was diagnostic only in 58.5% and 76.7% of patients respectively. All patients were managed conservatively. There was no mortality.Conclusions: In AP patients one should not only rely on enzyme level elevations for diagnosing AP. Patients with only a small increase in amylase and/or lipase levels or even with normal levels may also have or develop acute pancreatitis. High degree of suspicion is required; USG, CT scan and enzyme levels study are complimentary to the clinical suspicion.
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