Reducing Social Disparity in Liver Transplantation Utilization through Governmental Financial Support

Background

A high proportion of patients suffering from end stage liver disease are from low socioeconomic classes , which limits their access to liver transplantation as the most effctive treatment of this condition because of cost barrier.

Objectives

one of the most challenging aspects of liver transplantation is its affordability and utilization by those who need it the most.

Patients and Methods

Since November 2005, Iran Ministry of Health had covered 100% of the costs of in-patient liver transplantation care. To determine the effects of this policy, patterns of utilization of liver transplantation were compared before and after implementation of the policy. Group one included 112 and group two included 120 individuals who received transplantation before (from early January 2003 to November 2005) and after (from November 2005 to the end of December 2007) the legislation entered into the effect, respectively. Socioeconomic characteristics of these patients were evaluated by data collected about house and car ownership, education level, employment status, and place of residence.

Results

Coverage of the costs allowed more illiterate and semiliterate people (P = 0.032) as well as more unemployed or unskilled workers to receive transplantation (P = 0.021). The number of transplantations also increased in children and geriatric age group. This legislation also led to greater countrywide regional coverage of indigent patients.

Conclusions

This survey provides evidence that coverage of the costs by Ministry of Health was effective in reducing social discrimination in utilization of liver transplantation, and narrowed the gap between low and high socioeconomic classes in Iranian society.     

Low Weight and Overweightness in Older Adults: Risk and Clinical Management

The prevalence of individuals who are overweight or obese is growing exponentially in the United States and worldwide. This growth is concerning, as both overweightness and obesity lead to impaired physical function, decreased quality of life, and increased risk of chronic diseases. Additionally, overweightness and obesity are related to increased mortality among young and middle-aged adults. This weight-related risk of mortality is more ambiguous among older adults. In fact, obesity may be protective in this population, a relationship described as the “obesity paradox”. In this review we discuss the effects of overweightness and obesity among the elderly on cardiovascular disease and all-cause mortality, along with the risks of low weight. We conclude by discussing the goal of weight management among older adults, focusing particularly on benefits of preserving lean body mass and muscular strength while stabilizing body fat. Ideally, overweight or mildly obese elderly individuals should devise a plan with their physicians to maintain their weight, while increasing lean body mass through a plan of healthy diet, behavioral therapy, and physical activity.     

Clinical resistance associated with a novel MAP2K1 mutation in a patient with Langerhans cell histiocytosis

Patients with Langerhans cell histiocytosis (LCH) harbor BRAF V600E and activating mutations of MAP2K1/MEK1 in 50% and 25% of cases, respectively. We evaluated a patient with treatment‐refractory LCH for mutations in the RAS‐RAF‐MEK‐ERK pathway and identified a novel mutation in the MAP2K1 gene resulting in a p.L98_K104 > Q deletion and predicted to be auto‐activating. During treatment with the MEK inhibitor trametinib, the patient's disease showed significant progression. In vitro characterization of the MAP2K1 p.L98_K104 > Q deletion confirmed its effect on cellular activation of the ERK pathway and drug resistance.     

Dependence of cisplatin-induced cell death in vitro and in vivo on cyclin-dependent kinase 2

Cisplatin is one of the most effective chemotherapeutics, but its usefulness is limited by its toxicity to normal tissues, including cells of the kidney proximal tubule. The purpose of these studies was to determine the mechanism of cisplatin cytotoxicity. It was shown in vivo that cisplatin administration induces upregulation of the gene for the p21 cyclin-dependent kinase (cdk) inhibitor in kidney cells. This protein is a positive effector on the fate of cisplatin-exposed renal tubule cells in vivo and in vitro; adenoviral transduction of p21 completely protected proximal tubule cells from cisplatin toxicity. Herein is reported that cdk2 inhibitory drugs protect kidney cells in vivo and in vitro, that transduction of kidney cells in vitro with dominant-negative cdk2 also protected, and that cdk2 knockout cells were resistant to cisplatin. The cdk2 knockout cells regained cisplatin sensitivity after transduction with wild-type cdk2. It is concluded that cisplatin cytotoxicity depends on cdk2 activation and that the mechanism of p21 protection is by direct inhibition of cdk2. This demonstrated the involvement of a protein that previously was associated with cell-cycle progression with pathways of apoptosis. It also was demonstrated that this pathway of cisplatin-induced cell death can be interceded in vivo to prevent nephrotoxicity.     

Inhibin-B levels in healthy young adult men and prepubertal boys: is obesity the cause for the contemporary decline in sperm count because of fewer Sertoli cells?

Inhibin-B is a heterodimeric glycoprotein produced by Sertoli cells. Although inhibin-B levels are low when seminiferous tubules are damaged, studies in normal monkeys reveal that inhibin-B levels also correlate positively with Sertoli cell number. In this study, we measured inhibin-B levels in healthy young adult men aged 18-24 years and in prepubertal boys aged 5-9 years in relation to body mass index (BMI). Inhibin-B levels declined with increasing obesity in young adult men; values were 26% lower in men who were obese compared to normal-weight men. Sex hormone-binding globulin and total testosterone, but not free testosterone, were also lower with increasing BMI; serum follicle-stimulating hormone and luteinizing hormone levels were unaffected by obesity. In prepubertal boys, by contrast, inhibin-B was unaffected by obesity. We propose that reduced levels of inhibin-B indicate that obese men have fewer Sertoli cells than men of normal weight. Moreover, normal values in obese prepubertal boys suggest that the effect of obesity on inhibin-B is established during puberty. Finally, because each Sertoli cell is thought to support a finite number of germ cells, fewer Sertoli cells in obesity may predispose to a lower sperm count in adulthood. We speculate that the escalating prevalence of obesity and insulin resistance among adolescents might negatively influence male reproductive function for the next generation.