Citations

AbstractBackground/purposeRefractory rejections still occur in the liver transplantation (LT) field. The aim of this study was to investigate significant factors for the introduction of therapy with muromonab‐CD3 (MCD3) after LT.MethodsA total of 1415 LT patients were retrospectively evaluated, and 11 of the recipients received MCD3 therapy because of steroid‐resistant rejections. The clinical factors before LT and before MCD3 therapy were investigated.ResultsThe recipients were retrospectively divided into two groups based on responses to MCD3 therapy, including their clinical courses after MCD3 therapy and their outcomes. The MCD3 therapy had positive effects in LT recipients with the following four factors: low score of model for end‐stage liver disease or pediatric end‐stage liver disease; earlier time point of the first incidence of rejection; more frequent steroid pulse therapy (SPT) within 2 weeks after LT; and the expression of CD3 in the peripheral blood before MCD3 introduction.ConclusionOptimal induction of MCD3 triggered recovery from refractory rejections, especially in LT recipients in a stable condition, but not in those in a critical or compromised condition.

A recently identified variant within the fat mass and obesity-associated ( FTO ) gene is carried by 46% of Western Europeans and is associated with an ~1.2 kg higher weight, on average, in adults and an ~1 cm greater waist circumference. With >1 billion overweight and 300 million obese persons worldwide, it is crucial to understand the implications of carrying this very common allele for the health of our aging population. FTO is highly expressed in the brain and elevated body mass index (BMI) is associated with brain atrophy, but it is unknown how the obesity-associated risk allele affects human brain structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scanned with MRI and genotyped as part of the Alzheimer's Disease Neuroimaging Initiative. We found a pattern of systematic brain volume deficits in carriers of the obesity-associated risk allele versus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain volume difference of ~8% in the frontal lobes and 12% in the occipital lobes—these regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain maps reveal that a commonly carried susceptibility allele for obesity is associated with structural brain atrophy, with implications for the health of the elderly.

The high prevalence of no-shows in residents’ primary care clinic acts as a barrier to continuity of care, results in loss of outpatient learning opportunities, and may result in more emergency department (ED) visits. The authors seek to identify if high rates of no-shows correlate with more ED visits. In a selected primary care internal medicine (PCIM) continuity clinic, 650 patients were randomly selected, with 325 patients each from the faculty and resident practices. The number of ED visits between January 1, 2006, and December 30, 2008, was recorded. Demographic characteristics of the population were obtained, and comparisons between the faculty and resident groups were performed using Student t test. Linear multiple regression analysis was performed to compare frequency of ED visits between the faculty and the resident groups, controlling for age, interpreter requirement, number of ED visits, proportion of no-shows, and insurance type. A P value <.05 was considered statistically significant. During 2006-2008, the average number of ED visits per patient in the faculty’s practice was 2.1 compared with 4.1 in the resident’s practice ( P < .001). A multiple linear regression model showed that patients who had more ED visits were likely to be younger ( P = .004), had shorter duration of care in the PCIM clinic ( P < .001), and had a higher proportion of no-shows to the PCIM clinic ( P < .001). There was no statistical difference between faculty and resident practice after adjusting for the above-mentioned variables. Shorter duration in the PCIM clinic and higher proportion of missed appointments were associated with more ED visits, but the use of interpreters and Medicaid insurance did not result in more ED visits. Future interventions are necessary to reduce the no-show rate in the clinic as this may result in a reduction of ED visits.

Abstract Bone mass and its mineral content are under genetic control. The vitamin D receptor (VDR) gene has been shown to be a major locus for genetic effects on bone mineral density (BMD), and polymorphisms in this gene accounted for a large proportion of genetic variance in BMD in an Australian population. In this study, we investigated whether similar associations are present in a North American population. We studied 139 normal healthy women (age 53.2 ± 14.5, mean ± SD) and 43 severely osteoporotic postmenopausal women (age 65.8 ± 5.9). In the 127 of them with complete genetic studies, the distribution of genotypes, determined by polymerase chain reaction on leukocyte DNA samples, agreed closely with that in the Australian population. BMD was strongly related to age and weight, and, thus was adjusted for these parameters prior to genetic analysis. We found that age modulated the effect of VDR genotypes on femoral neck BMD (FN-BMD) (TaqI, p = 0.036;BsmI, p = 0.118; ApaI, p = 0.041) such that the effect of genotype was greatest among younger (premenopausal) women and declined with age so that there was no discernible difference by age 70. Among the younger women, a high FN-BMD was associated with the TT (or aa or bb) genotype while low FN-BMD was associated with the tt (or AA or BB) genotype. In osteoporotic women, although the difference in FN-BMD between alternate TaqI homozygotes (TT vs. tt) was 0.13 g/cm2 (or about 18%), the overall difference among the genotype groups was not significant (TaqI, p = 0.13; BsmI, p = 0.21; ApaI, p = 0.09), possibly due to the small sample of osteoporotic women. There was no relationship of VDR genotype to lumbar spine BMD. We conclude that the VDR gene modulates differences in BMD in premenopausal women. Subsequent interaction of the gene and environmental factors and the role of VDR genotypes in predisposing to osteoporosis needs further study.

Ubiquitin (Ub) sorting receptors facilitate the targeting of ubiquitinated membrane proteins into multivesicular bodies (MVBs). Ub-binding domains (UBDs) have been described in several endosomal sorting complexes required for transport (ESCRT). Using available structural information, we have investigated the role of the multiple UBDs within ESCRTs during MVB cargo selection. We found a novel UBD within ESCRT-I and show that it contributes to MVB sorting in concert with the known UBDs within the ESCRT complexes. These experiments reveal an unexpected level of coordination among the ESCRT UBDs, suggesting that they collectively recognize a diverse set of cargo rather than act sequentially at discrete steps.

Abstract Background Portal vein–superior mesenteric vein resection is frequently required after surgical resection of tumours of the pancreas head. The ideal graft for portal vein reconstruction (PVR) remains undefined. Methods Between May 2000 and July 2007, 28 patients had portal vein–superior mesenteric vein resection and PVR during pancreaticoduodenectomy. Their clinical reports were reviewed retrospectively with specific attention to the methods of PVR and outcomes. Results Ten patients had PVR with primary anastomosis, seven had PVR with autologous vein, one had a polytetrafluoroethylene (PTFE) patch, one did not have PVR and nine had PVR with a PTFE interposition graft. There was no infection after PTFE grafting. Six patients had PVR thrombosis after surgery: four after primary anastomosis, one after interposition PTFE and one after vein repair. Conclusion PTFE appeared to be an effective and safe option as an interposition graft for portomesenteric venous reconstruction after pancreaticoduodenectomy.

Abstract Rash from epidermal growth factor receptor inhibitors is common and negatively impacts the quality of life of cancer patients. Published guidelines recommend holding cancer therapy if the rash is severe. Does this recommendation hinge solely on improving patients' quality of life, or does it also hinge on the prevention of a potentially fatal, cutaneous adverse event? In other words, do patients die from rashes from epidermal growth factor receptor inhibitors? To our knowledge, the latter question has never before been asked and answered in an evidence-based fashion. Therefore, we conducted a systematic review of the published, prospectively conducted clinical trial literature on epidermal growth factor receptor inhibitors. The primary aim was to determine whether rash-related death has ever been reported in such trials. Among 117 such trials, which included 8,998 cancer patients, the rate of rash development was &gt;50%, as expected. However, there were no reported deaths from a rash. Although we cannot conclude that a rash-related death from this class of agents can never occur, this systematic review provides evidence-based guidance on how best to counsel cancer patients who develop a rash from an epidermal growth factor receptor inhibitor. It suggests that quality of life issues should remain at the forefront as cancer patients and health care providers make decisions about holding cancer therapy.