In vitro blood cell responsiveness to IFN-α predicts clinical response independently of IL28B in hepatitis C virus genotype 1 infected patients.

BACKGROUND: Treatment with interferon-alpha (IFN-α) and ribavirin successfully clears hepatitis C virus (HCV) infection in 50% of patients infected with genotype 1. Addition of NS3-4A protease inhibitors (PIs) increases response rates but results in additional side effects and significant economic costs. Here, we hypothesised that in vitro responsiveness of peripheral blood mononuclear cells (PBMCs) to IFN-α stimulation would identify patients who achieved sustained virological response (SVR) on dual therapy alone and thus not require addition of PIs. METHODS: PBMCs were isolated from HCV infected patients (n = 42), infected with either HCV genotype 1 or genotype 3, before commencing therapy and stimulated in vitro with IFN-α. Expression of the IFN stimulated genes (ISGs) PKR, OAS and MxA was measured and correlated with subsequent treatment response and IL28B genotype. RESULTS: Genotype 1 infected patients who achieved SVR had significantly higher pre-treatment expression of PKR (p = 0.0148), OAS (p = 0.0019) and MxA (p = 0.0019) in IFN-α stimulated PBMCs, compared to genotype 1 infected patients who did not achieve SVR or patients infected with genotype 3, whose in vitro ISG expression did not correlate with clinical responsiveness. IL28B genotype (rs12979860) did not correlate with endogenous or IFN-α stimulated ISG responsiveness. CONCLUSIONS: In vitro responsiveness of PBMCs to IFN-α from genotype 1 infected patients predicts clinical responsiveness to dual therapy, independently of IL28B genotype. These results indicate that this sub-group of HCV infected patients could be identified pre-treatment and successfully treated without PIs, thus reducing adverse side effects and emergence of PI resistant virus while making significant economic savings.

Forecast and evaluation of asymptomatic COVID-19 patients spreading in China.

In this paper, we propose a new SAIR model to depict the transmission dynamics of a novel coronavirus in China. We focus on the ability of asymptomatic COVID-19 patients to transmit and the potential impact of population movements on renewed outbreak transmission. Qualitative analysis of the model shows that when the basic productive number R 0 > 1 , the system will stabilize towards a unique endemic equilibrium and pass through a transcritical bifurcation around its disease-free equilibrium. Furthermore, by constructing an appropriate Lyapunov function, we prove that the disease-free equilibrium and endemic equilibrium are globally asymptotically stable under appropriate parameter conditions. Finally, some important results have been verified by numerical simulations.

Hepatic iron overload following liver transplantation of a C282y homozygous allograft: a case report and literature review.

Hereditary haemochromatosis is a common genetic disease associated with progressive iron overload and parenchymal organ damage including liver, pancreas and heart. We report a case of inadvertent transplantation of a liver from a haemochromatosis donor to a 56-year-old Asian female. Progressive iron overload occurred over a 2 year follow up as assessed by liver biopsy and iron studies in the absence of a secondary cause of iron overload, supporting a primary role of liver rather than small intestine in the regulation of iron homeostasis in hereditary haemochromatosis.

Improved outcome in early induction deaths in patients with acute promyelocytic leukemia after therapeutic and supportive interventions: a follow up study of seven-years' experience at a tertiary care center.

INTRODUCTION AND OBJECTIVES: Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia with characteristic morphology and clinical features. Early mortality rate of 30% has been reported in developed countries despite prompt initiation of treatment. We have previously reported an early induction mortality of approximately 62% in our cohort. Based on this mortality rate, we made changes in our treatment protocol. The objective of this follow-up study was to report the early induction mortality and overall survival of patients with APL after incorporating changes in chemotherapy and supportive care regimen. SUBJECTS AND METHODS: This was a prospective descriptive study conducted at Aga Khan University Karachi, Pakistan from October 2012 till October 2019. Data of patients included clinical features, morphological findings, cytogenetic and PCR studies, cytotoxic protocols, overall outcome and causes of early induction mortality. The changes in treatment protocol included prophylactic infusion of fresh frozen plasma, dexamethasone therapy and other changes in supportive care regimen. Results were recorded as frequencies and percentages. Statistical Package for the Social Sciences version 19.0 (SPSS Inc., Chicago, IL, USA) was used to analyze patient's data. Survival curves were calculated using the Kaplan-Meier method. RESULTS: During the study period, total of 447 patients presented with acute myeloid leukemia at our institution out of which 40 patients were diagnosed with acute promyelocytic leukemia (9%). Out of these 40 patients 24 were males and 16 were females. The median age was 37 years. Twenty-five patients were in low risk group whereas 15 were high-risk. Differentiation syndrome was seen in 14 patients. As a part of induction chemotherapy, 13 patients received only ATRA because they were not eligible for chemotherapy and 17 patients received a combination of ATRA and anthracycline. Among the remaining patients, four received ATRA, arsenic and anthracycline while two received ATRA and arsenic only. Four patients did not receive any treatment because of rapid deterioration of clinical condition and death. The overall survival was 65% and early induction mortality was 30%. CONCLUSION: The early induction mortality decreased to 30% from 62% in this study and the overall survival was 65%. With the introduction of prophylactic infusion of fresh frozen plasma, dexamethasone and appropriate supportive treatment during the induction chemotherapy, we were able to improve the induction mortality and overall survival of patients.

Pulse oximetry during gastrointestinal endoscopic procedures.

OBJECTIVE: To determine the changes in oxygen saturation, blood pressure and pulse rate during various endoscopic procedures and to find out the risk factors for these changes. DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of Gastroenterology, Shaikh Zayed Postgraduate Medical Institute, Lahore, Pakistan from June 2001 to December 2001 were included in the study. PATIENTS AND METHODS: Oxygen saturation, blood pressure and pulse were monitored during various endoscopic procedures using pulse oximeter. These changes were recorded from the start until 5 minutes after the procedure. The important variables which were evaluated in relation to these changes included age, gender, history of smoking, associated chronic obstructive airway disease (COAD), coronary artery disease (CAD), duration of procedure, elective versus emergency and diagnostic versus therapeutic procedures. RESULTS: Base line mean oxygen saturation was 98.1+/-0.98 %. The saturation decreased to 93.5+/-4.8 % (p=0.002) during the procedures and returned to base line after the procedures. Mild to moderate hypoxia was found in 59 (20.2%) patients. Severe hypoxia was found in 32 (11.5%) patients. Of these 21(65.6%) patients were having history of COAD. No patient developed serious complications. The changes in blood pressure and pulse were not significant. The variables which reached statistical significance for desaturation were age>50 years, history of smoking, emergency procedures, therapeutic procedures and associated COAD. Diabetes mellitus (DM) and hypertension (HTN) alone, CAD and duration of procedures did not affect oxygen saturation. CONCLUSION: Mild to moderate hypoxia is common during endoscopic procedures and of no serious consequence. Severe hypoxia is less common and is associated with underlying risk factors. Continuous monitoring is required in patients with age>50 years, history of smoking, emergency procedures, therapeutic procedures and history of COAD. Routine monitoring with pulse oximetry may not be required in patients with no risk factors.

Paroxysmal Nocturnal Haemoglobinuria Type III Presenting as Portal and Mesenteric Vein Thrombosis in a Young Girl.

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired, life-threatening haematological disorder. It is characterised by complement induced haemolytic anaemia, thrombosis and impaired bone marrow function. Thrombosis most commonly occurs in the hepatic, portal, superior mesenteric and cerebral veins. A22-year female, previously diagnosed with severe aplastic anaemia treated with anti-lymphocyte globulin (ALG) and cyclosporine, had become transfusion independent for more than 10 years. She presented with abdominal pain and vomiting, initially diagnosed with portal and superior mesenteric vein thrombosis. Immunophenotyping by flow cytometry revealed a diagnosis of paroxysmal nocturnal haemoglobinuria type III. She was treated with vitmamin K anatagonist and platelet transfusion.