Hepatocellular carcinoma in a non‐cirrhotic liver with a tumor thrombus

Young adults with HCC tend to have a poor prognosis because of advanced disease despite preserved liver function. Screening and early diagnosis for HCC are needed for young adults to demonstrate an improved prognosis, especially in HBsAg positive patients.     

Mortality and morbidity patterns in under-five children with severe acute malnutrition (SAM) in Zambia: a five-year retrospective review of hospital-based records (2009–2013)

Background

Severe acute malnutrition has continued to be growing problem in Sub Saharan Africa. We investigated the factors associated with morbidity and mortality of under-five children admitted and managed in hospital for severe acute malnutrition.

Methods

It was a retrospective quantitative review of hospital based records using patient files, ward death and discharge registers. It was conducted focussing on demographic, clinical and mortality data which was extracted on all children aged 0–60 months admitted to the University Teaching Hospital in Zambia from 2009 to 2013. Cox proportional Hazards regression was used to identify predictors of mortality and Kaplan Meier curves where used to predict the length of stay on the ward.

Results

Overall (n = 9540) under-five children with severe acute malnutrition were admitted during the period under review, comprising 5148 (54%) males and 4386 (46%) females. Kwashiorkor was the most common type of severe acute malnutrition (62%) while diarrhoea and pneumonia were the most common co-morbidities. Overall mortality was at 46% with children with marasmus having the lowest survival rates on Kaplan Meier graphs. HIV infected children were 80% more likely to die compared to HIV uninfected children (HR = 1.8; 95%CI: 1.6-1.2). However, over time (2009–2013), admissions and mortality rates declined significantly (mortality 51% vs. 35%, P < 0.0001).

Conclusions

We find evidence of declining mortality among the core morbid nutritional conditions, namely kwashiorkor, marasmus and marasmic-kwashiorkor among under-five children admitted at this hospital. The reasons for this are unclear or could be beyond the scope of this study. This decline in numbers could be either be associated with declining admissions or due to the interventions that have been implemented at community level to combat malnutrition such as provision of “Ready to Use therapeutic food” and prevention of mother to child transmission of HIV at health centre level. Strategies that enhance and expand growth monitoring interventions at community level to detect malnutrition early to reduce incidence of severe cases and mortality need to be strengthened.     

Development of an immunofluorescence assay using recombinant proteins expressed in insect cells to screen and confirm presence of human herpesvirus 8-specific antibodies

Human herpesvirus 8 (HHV-8), or Kaposi's sarcoma (KS)-associated herpesvirus, has been linked to all forms of KS. The results of most current serological assays for the detection of HHV-8-specific antibodies have low levels of concordance among themselves. To establish a sensitive and specific testing strategy that can be used to screen for HHV-8-specific antibodies, three HHV-8 proteins, ORF65, ORF73, and K8.1A, were expressed by using baculoviral vectors in insect cells and incorporated into a monoclonal antibody-enhanced immunofluorescence assay (mIFA) termed the Sf9 three-antigen mIFA. The results obtained by this mIFA were compared to those obtained by a standard mIFA with an HHV-8-infected B-cell line (BC3 mIFA). Test sera were obtained from patients diagnosed with KS, human immunodeficiency virus type 1-infected patients at high risk for HHV-8 infection, and healthy controls from a local blood bank. The combined use of both assays had a sensitivity of 94% and a specificity of 96%. The performance of these two assays when they were used together indicates that they may be useful for the reliable detection of HHV-8-specific immunoglobulin G antibodies in a population.     

A homozygous <Emphasis Type="Italic">PIGN</Emphasis> missense mutation in Soft-Coated Wheaten Terriers with a canine paroxysmal dyskinesia

Hereditary paroxysmal dyskinesias (PxD) are a heterogeneous group of movement disorders classified by frequency, duration, and triggers of the episodes. A young-adult onset canine PxD has segregated as an autosomal recessive trait in Soft-Coated Wheaten Terriers. The medical records and videos of episodes from 25 affected dogs were reviewed. The episodes of hyperkinesia and dystonia lasted from several minutes to several hours and could occur as often as >10/day. They were not associated with strenuous exercise or fasting but were sometimes triggered by excitement. The canine PxD phenotype most closely resembled paroxysmal non-kinesigenic dyskinesia (PNKD) of humans. Whole genome sequences were generated with DNA from 2 affected dogs and analyzed in comparison to 100 control canid whole genome sequences. The two whole genome sequences from dogs with PxD had a rare homozygous PIGN:c.398C > T transition, which predicted the substitution of an isoleucine for a highly conserved threonine in the encoded enzyme. All 25 PxD-affected dogs were PIGN:c.398T allele homozygotes, whereas there were no c.398T homozygotes among 1185 genotyped dogs without known histories of PxD. PIGN encodes an enzyme involved in the biosynthesis of glycosylphosphatidylinositol (GPI), which anchors a variety of proteins including CD59 to the cell surface. Flow cytometry of PIGN-knockout HEK239 cells expressing recombinant human PIGN with the c.398T variant showed reduced CD59 expression. Mutations in human PIGN have been associated with multiple congenital anomalies-hypotonia-seizures syndrome-1 (MCAHS1). Movement disorders can be a part of MCAHS1, but this is the first PxD associated with altered GPI anchor function.     

A systematic review of the effects of platelet rich plasma on outcomes for patients with knee osteoarthritis and following total knee arthroplasty

Introduction

Platelet rich plasma (PRP) has been suggested to be effective in the management of knee osteoarthritis. Review of current literature reveals conflicting evidence regarding the benefits of PRP in treating knee OA. Preclinical evidence supports the use of PRP injections to promote a favorable environment for joint tissue healing, targeting not only cartilage but also synovial and meniscal tissues which has a positive effect on delaying the progression of OA. Growth factors found in platelet granules are postulated to influence outcomes in knee OA and after total knee arthroplasty (TKA).

Maintenance of peripheral naive T cells is sustained by thymus output in mice but not humans

Parallels between T cell kinetics in mice and men have fueled the idea that a young mouse is a good model system for a young human, and an old mouse, for an elderly human. By combining in vivo kinetic labeling using deuterated water, thymectomy experiments, analysis of T cell receptor excision circles and CD31 expression, and mathematical modeling, we have quantified the contribution of thymus output and peripheral naive T cell division to the maintenance of T cells in mice and men. Aging affected naive T cell maintenance fundamentally differently in mice and men. Whereas the naive T cell pool in mice was almost exclusively sustained by thymus output throughout their lifetime, the maintenance of the adult human naive T cell pool occurred almost exclusively through peripheral T cell division. These findings put constraints on the extrapolation of insights into T cell dynamics from mouse to man and vice versa.     

Characterization of genetic and phenotypic diversity of invasive nontypeable Haemophilus influenzae

The ability of unencapsulated (nontypeable) Haemophilus influenzae (NTHi) to cause systemic disease in healthy children has been recognized only in the past decade. To determine the extent of similarity among invasive nontypeable isolates, we compared strain R2866 with 16 additional NTHi isolates from blood and spinal fluid, 17 nasopharyngeal or throat isolates from healthy children, and 19 isolates from middle ear aspirates. The strains were evaluated for the presence of several genetic loci that affect bacterial surface structures and for biochemical reactions that are known to differ among H. influenzae strains. Eight strains, including four blood isolates, shared several properties with R2866: they were biotype V (indole and ornithine decarboxylase positive, urease negative), contained sequence from the adhesin gene hia, and lacked a genetic island flanked by the infA and ksgA genes. Multilocus sequence typing showed that most biotype V isolates belonged to the same phylogenetic cluster as strain R2866. When present, the infA-ksgA island contains lipopolysaccharide biosynthetic genes, either lic2B and lic2C or homologs of the losA and losB genes described for Haemophilus ducreyi. The island was found in most nasopharyngeal and otitis isolates but was absent from 40% of invasive isolates. Overall, the 33 hmw-negative isolates were much more likely than hmw-containing isolates to have tryptophanase, ornithine decarboxylase, or lysine decarboxylase activity or to contain the hif genes. We conclude (i) that invasive isolates are genetically and phenotypically diverse and (ii) that certain genetic loci of NTHi are frequently found in association among NTHi strains.