An integrated platform for small-animal hyperthermia investigations under ultra-high-field MRI guidance

Purpose: Integrating small-animal experimental hyperthermia instrumentation with magnetic resonance imaging (MRI) affords real-time monitoring of spatial temperature profiles. This study reports on the development and preliminary in vivo characterisation of a 2.45?GHz microwave hyperthermia system for pre-clinical small animal investigations, integrated within a 14 T ultra-high-field MRI scanner.

Materials and methods: The presented system incorporates a 3.5?mm (OD) directional microwave hyperthermia antenna, positioned adjacent to the small-animal target, radiating microwave energy for localised heating of subcutaneous tumours. The applicator is integrated within the 30?mm bore of the MRI system. 3D electromagnetic and biothermal simulations were implemented to characterise hyperthermia profiles from the directional microwave antenna. Experiments in tissue mimicking phantoms were performed to assess hyperthermia profiles and validate MR thermometry against fibre-optic temperature measurements. The feasibility of delivering in vivo hyperthermia exposures to subcutaneous 4T1 tumours in experimental mice under simultaneous MR thermometry guidance was assessed.

Results: Simulations and experiments in tissue mimicking phantoms demonstrated the feasibility of heating 21–982?mm³ targets with 8–12 W input power. Minimal susceptibility and electrical artefacts introduced by the hyperthermia applicator were observed on MR imaging. MR thermometry was in excellent agreement with fibre-optic temperatures measurements (max. discrepancy ≤0.6?°C). Heating experiments with the reported system demonstrated the feasibility of heating subcutaneous tumours in vivo with simultaneous MR thermometry.

Conclusions: A platform for small-animal hyperthermia investigations under ultra-high-field MR thermometry was developed and applied to heating subcutaneous tumours in vivo.     

Causes of death in patients with Non-alcoholic Fatty Liver Disease (NAFLD), alcoholic liver disease and chronic viral Hepatitis B and C

Introduction and objectivesCause of mortality in patients with chronic liver diseases (CLDs) may differ based on underlying etiology of liver disease. Our aim was to assess different causes of death in patients with the most common types of CLD using a national database from the United States.Materials and methodsDeath data from 2008 and 2018 from the National Vital Statistics System (NVSS) by the National Center for Health Statistics (NCHS) were used. The rank of cause-of-death for each etiology of CLDs was assessed. Causes of death were classified by the ICD-10 codes. Liver-related deaths included liver cancer, cirrhosis and CLDs.ResultsAmong a total of 2,826,531 deaths in 2018, there were 85,807 (3.04%) with underlying CLD (mean age at death 63.0 years, 63.8% male, 70.8% white). Liver-related mortality was the leading cause of death for all types of CLD [45.8% in non-alcoholic fatty liver disease (NAFLD), 53.0% in chronic hepatitis C (CHC), 57.8% in chronic hepatitis B (CHB), 81.8% in alcoholic liver disease (ALD)]. This was followed by death from cardiac causes (NAFLD 10.3%, CHC 9.1%, CHB 4.6%, ALD 4.2%) and extrahepatic cancer (NAFLD 7.0%, CHC 11.9%, CHB 14.9%, ALD 2.1%). Although liver cancer was the leading cause of cancer death, lung, colorectal and pancreatic cancer were also common causes of cancer death.ConclusionsAmong deceased patients with CLD, underlying liver disease was the leading cause of death. Among solid cancers, liver cancer was the leading cause of cancer-related mortality.     

Cloning,expression, and functional characterization of the von Willebrand factor-cleaving protease (ADAMTS13)

Deficient von Willebrand factor (VWF) degradation has been associated with thrombotic thrombocytopenic purpura (TTP). In hereditary TTP, the specific VWF-cleaving protease (VWF-cp) is absent or functionally defective, whereas in the nonfamilial, acquired form of TTP, an autoantibody inhibiting VWF-cp activity is found transiently in most patients. The gene encoding for VWF-cp has recently been identified as a member of the metalloprotease family and designated ADAMTS13, but the functional activity of the ADAMTS13 gene product has not been verified. To establish the functional activity of recombinant VWF-cp, we cloned the complete cDNA sequence in a eukaryotic expression vector and transiently expressed the encoded recombinant ADAMTS13 in HEK 293 cells. The expressed protein degraded VWF multimers and proteolytically cleaved VWF to the same fragments as those generated by plasma VWF-cp. Furthermore, recombinant ADAMTS13-mediated degradation of VWF multimers was entirely inhibited in the presence of plasma from a patient with acquired TTP. These data show that ADAMTS13 is responsible for the physiologic proteolytic degradation of VWF multimers.     

Efficacy of Prolonged Treatment With Pegylated Interferon (Peg-IFN) and Ribavirin in Thalassemic Patients With Hepatitis C Who Relapsed After Previous Peg-IFN-Based Therapy

Background:

Most thalassemic patients with chronic hepatitis C virus (HCV) infection do not respond to therapy with pegylated interferon (Peg-IFN) plus ribavirin (RBV) due to hepatic siderosis and RBV dose reduction caused by RBV-induced anemia.

Objectives:

In the present study, we recruited HCV genotype 1-infected thalassemic patients who had relapsed after a 48-week treatment with Peg-IFN plus RBV in order to evaluate the efficacy of a 72-week regimen of Peg-IFN plus RBV.

Patients and Methods:

In this retrospective study, 23 thalassemic patients with HCV genotype 1 infection who had prior relapse after treatment with Peg-IFN and RBV for 48 weeks were consecutively enrolled in this study for evaluation of the efficacy of a 72-week treatment regimen.

Results:

For the 21 included cases, mean age was 29.7 years; 81% were men and 28.6% had cirrhosis. At the end of the treatment, nine (42.9%) patients had an undetectable level of HCV RNA in their sera. However, six months after treatment completion four of these patients relapsed and a sustained virological response (SVR) was found in five (23.8%) patients. Undetectable HCV RNA level at week 4 (P = 0.03) and undetectable HCV RNA level at week 12 (P < 0.01) were found to be predictors of SVR. There was an average 47.9% increase in blood transfusion during therapy and treatment was discontinued for 12 (57.1%) patients prematurely.

Conclusions:

The present study suggests that thalassemic patients with chronic hepatitis C genotype 1 infection who did not achieve SVR after a course of therapy with Peg-IFN and RBV may benefit from being retreated with a 72-week regimen.     

Percutaneous Left Atrial Appendage Closure: Review of Anatomy,Imaging, and Outcomes

Current Treatment Options in Cardiovascular Medicine - Percutaneous left atrial appendage closure (LAAC) with WATCHMAN (Boston Scientific Inc.) has emerged as a viable non-pharmacological...     

Shoulder pain prevalence and risk factors in middle-aged women: A cross-sectional study

PurposeThe aim of the current study was to investigate the prevalence of shoulder pain and to explore the possible associated risk factors in middle-aged women.MethodsA total of 500 middle-aged women, aged 45–65 years, participated in this cross-sectional study. The point and lifetime prevalence of shoulder pain were calculated. Linear and logistic regressions were used to determine the possible associations between the risk factors and present shoulder pain.ResultsThe point and lifetime prevalence of shoulder pain were 18.6% and 27.6%, respectively. The logistic regression analysis demonstrated a significant association between present shoulder pain and history of shoulder pain and trauma, osteoporosis, trapezius muscle pain, and cervical radiculopathy (p < 0.05). However, there was no significant association between present shoulder pain and diabetes mellitus or postural deviation (p > 0.05).ConclusionThe results indicated that shoulder pain has considerable prevalence in middle-aged women. In addition, a history of shoulder pain and trauma, osteoporosis, trapezius muscle pain, and cervical radiculopathy were found to be associated with present shoulder pain. Future research should concentrate on longitudinal designs that explore preventive strategies and risk factors for shoulder pain.     

PTPN22 R620W functional variant in type 1 diabetes and autoimmunity related traits

The PTPN22 gene, encoding the lymphoid-specific protein tyrosine phosphatase, a negative regulator in the T-cell activation and development, has been associated with the susceptibility to several autoimmune diseases, including type 1 diabetes. Based on combined case-control and family-based association studies, we replicated the finding of an association of the PTPN22 C1858T (R620W) functional variant with type 1 diabetes, which was independent from the susceptibility status at the insulin gene and at HLA-DR (DR3/4 compared with others). The risk contributed by the 1858T allele was increased in patients with a family history of other autoimmune diseases, further supporting a general role for this variant on autoimmunity. In addition, we found evidence for an association of 1858T allele with the presence of GAD autoantibodies (GADA), which was restricted to patients with long disease duration (>10 years, P < 0.001). This may help define a subgroup of patients with long-term persistence of GADA. The risk conferred by 1858T allele on GAD positivity was additive, and our meta-analysis also supported an additive rather than dominant effect of this variant on type 1 diabetes, similar to previous reports on rheumatoid arthritis and systemic lupus erythematosus.