The levels of inflammatory biomarkers in hemodialysis and peritoneal dialysis patients.

OBJECTIVE: In this study, we aimed to determine fibroblast growth factor 23, soluble alpha klotho, osteocalcin, indoxyl sulphate, sclerostin, Procollagen 1 N Terminal Propeptide, and beta-CrossLaps levels in hemodialysis and peritoneal dialysis patients, and to compare the levels of these markers among hemodialysis and peritoneal dialysis patients, as well as healthy individuals. METHODS: The study included 30 hemodialysis and 23 peritoneal dialysis patients who were followed-up for at least six months at the Sakarya University Hospital, besides 30 healthy volunteers. RESULTS: The participants were divided into three groups with similar characteristics in terms of age, gender and body mass index. Fibroblast growth factor 23, soluble alpha klotho, indoxyl sulphate, beta-CrossLaps, and Procollagen 1 N Terminal Propeptide levels were significantly higher in patients of both the hemodialysis and peritoneal dialysis groups than in the healthy volunteers' group. There was no difference in levels of these molecules between hemodialysis and peritoneal dialysis groups. CONCLUSIONS: Fibroblast growth factor 23, sclerostin, indoxyl sulphate, beta-CrossLaps, and Paclitaxel-induced neuropathic pain levels were higher in patients of both groups as inflammatory markers. In our study, we found higher soluble alpha klotho levels in patients of both groups than in the healthy volunteers' group, suggesting that blood soluble alpha klotho levels may not correlate with renal klotho levels.

Immune checkpoint inhibitor associated vitiligo and its impact on survival in patients with metastatic melanoma: an Italian Melanoma Intergroup study.

BACKGROUND: Checkpoint inhibitors in melanoma can lead to self-immune side-effects such as vitiligo-like depigmentation (VLD). Beyond the reported association with favorable prognosis, there are limited data regarding VLD patient features and their echo on the therapeutic outcomes. METHODS: To assess the association between VLD and a series of clinical and biological features as well as therapeutic outcomes, we built an observational cohort study by recruiting patients who developed VLD during checkpoint inhibitors. RESULTS: A total of 148 patients from 15 centers (101 men, median age 66 years, BRAF mutated 23%, M1c 42%, Eastern Cooperative Oncology Group (ECOG) status 0/1 99%, normal lactate dehydrogenase 74%) were enrolled. VLD was induced by ipilimumab, programmed cell death-1 (PD-1) inhibitors, and their combination in 32%, 56%, and 12%, respectively. The median onset was 26 weeks and it was associated with other skin and nonskin toxicities in 27% and 28%, respectively. After 3 years of VLD onset, 52% (95% confidence interval 39% to 63%) were progression free and 82% (95% confidence interval 70% to 89%) were still alive. The overall response rate was 73% with 26% complete response. Univariable analysis indicated that BRAF V600 mutation was associated with a better overall survival (P = 0.028), while in multivariable analysis a longer progression-free survival was associated with BRAF V600 (P = 0.093), female sex (P = 0.008), and M stage other than 1a (P = 0.024). When VLD occurred, there was a significant decrease of white blood cell (WBC) count (P = 0.05) and derived WBC-to-lymphocytes ratio (dWLR; P = 0.003). A lower monocyte count (P = 0.02) and dWLR (P = 0.01) were also reported in responder patients. CONCLUSIONS: Among VLD population, some features might help to identify patients with an effective response to immunotherapy, allowing clinicians to make more appropriate choices in terms of therapeutic options and duration.

Cortical thinness and volume differences associated with marijuana abuse in emerging adults.

BACKGROUND: The prevalence of marijuana (MJ) use among youth and its legalization for medical or recreational use has intensified public health endeavors of understanding MJ effects on brain structure and function. Studies indicate that MJ use is related to impaired cognitive performance, and altered functional brain activation and chemistry in adolescents and adults, but MJ effects on brain morphology in emerging adults are less understood. METHODS: Fifteen MJ users (age 21.8±3.6, 2 females) and 15 non-user (NU) participants (age 22.3±3.5, 2 females) were included, demographically matched on age, education and alcohol use. High-resolution structural MR images were acquired at 3Tesla. Cortical thickness (CT) and volumetric analyses were performed using Freesurfer. A priori regions of interest (ROI) included orbitofrontal and cingulate cortices, amygdala, hippocampus and thalamus. RESULTS: Whole brain CT analysis did not result in significant group differences in a priori ROIs but revealed MJ users had significantly less CT (i.e., thinness) in right fusiform gyrus (rFG) compared to NU (p<0.05). Thalamic volume was significantly smaller in MJ users compared to NU (right, p=0.05; left, p=0.01) and associated with greater non-planning (p<0.01) and overall impulsivity (p=0.04). There were no other group differences. CONCLUSIONS: RFG cortical thinness and smaller thalamic volume in emerging adults is associated with MJ abuse. Furthermore, smaller thalamic volume associated with greater impulsivity contributes to growing evidence that the thalamus is neurobiologically perturbed by MJ use. Collectively, altered thalamic and rFG structural integrity may interfere with their known roles in regulating visuoperceptual and object information processing.

The responsive amygdala: treatment-induced alterations in functional connectivity in pediatric complex regional pain syndrome.

The amygdala is a key brain region with efferent and afferent neural connections that involve complex behaviors such as pain, reward, fear, and anxiety. This study evaluated resting state functional connectivity of the amygdala with cortical and subcortical regions in a group of chronic pain patients (pediatric complex regional pain syndrome) with age-sex matched control subjects before and after intensive physical-biobehavioral pain treatment. Our main findings include (1) enhanced functional connectivity from the amygdala to multiple cortical, subcortical, and cerebellar regions in patients compared with control subjects, with differences predominantly in the left amygdala in the pretreated condition (disease state); (2) dampened hyperconnectivity from the left amygdala to the motor cortex, parietal lobe, and cingulate cortex after intensive pain rehabilitation treatment within patients with nominal differences observed among healthy control subjects from time 1 to time 2 (treatment effects); (3) functional connectivity to several regions key to fear circuitry (prefrontal cortex, bilateral middle temporal lobe, bilateral cingulate, hippocampus) correlated with higher pain-related fear scores; and (4) decreases in pain-related fear associated with decreased connectivity between the amygdala and the motor and somatosensory cortex, cingulate, and frontal areas. Our data suggest that there are rapid changes in amygdala connectivity after an aggressive treatment program in children with chronic pain and intrinsic amygdala functional connectivity activity serving as a potential indicator of treatment response.

Managed care for uninsured patients at an academic health center: a case study.

In 1997, the University of New Mexico Health Sciences Center ("the Center") created a managed care plan ("the Plan") for its uninsured patients who were county residents. The Plan's features include pooling the resources of existing county safety-net providers, enrolling patients with primary care providers at easily accessible neighborhood-based clinics, and investing in social support services, case management, and 24-hour telephone triage. After two years of the Plan's operation, the utilization of ambulatory care services by Plan enrollees, the number of discharges per 1,000 enrollees from the Center-affiliated University Hospital, and the number of hospital days per 1,000 enrollees had all dropped significantly (p < .001 for all). For the 13,114 enrollees in the Plan, University Hospital saved an estimated $1,904,872 per year in costs. The replacement of unpaid hospital days with paying patients is estimated to have yielded over $695,000 in additional revenues per year. The authors conclude that managing the care of uninsured patients in an academic health center can reduce ambulatory care and inpatient utilization and reduce the cost of care. To achieve these favorable outcomes requires the organization of services to meet the unique needs of the uninsured and underserved population.

Academic models for practice relief, recruitment, and retention at the University of New Mexico Medical Center and East Carolina University School of Medicine.

Locum tenens programs were independently developed by the University of New Mexico Health Sciences Center and East Carolina University School of Medicine to address health care needs within their states. The programs represent distinct models to provide locum tenens services for practices in rural and medically underserved regions through collaboration with stage government representatives and agencies. Differences between programs include years of operation, days of coverage provided, types of learners and providers involved, sources of funding, costs of the programs, and extent of institutional support. Common beneficial outcomes of the programs include coverage for struggling practices, training in rural medicine for locum tenens providers, recruitment of physicians to rural practice sites, and improved relationships with program partners. Adequate funding and institutional support are essential for success of locum tenens programs.

Toxic megacolon secondary to acute ischemic colitis.

A 72-year-old woman without significant medical history was admitted with abdominal pain, high fever, leukocytosis, bloody diarrhea and marked dilation of the transverse, descending and sigmoid colon. Toxic megacolon was diagnosed and responded well to medical treatment. Seven weeks after her admission, however, the patient developed a stenotic lesion in the sigmoid colon. The lesion was managed surgically. Histological examination of the resected colon revealed resolving ischemic colitis affecting only part of the thickness of the intestinal wall. The patient has been healthy since the surgery, i.e., for two years.

Tribal differences in diabetes: prevalence among American Indians in New Mexico.

The prevalence of diagnosed diabetes among American Indians in New Mexico with varied genetic and cultural backgrounds is reported. Utilizing community-based registries, the prevalence in persons ages 35 years and older ranged from 9.8 percent among Jicarilla Apache Indians to 28.2 percent among Zuni Indians. All rates were significantly higher than the U.S. rate of 5.3 percent for the same age group. In addition, in three of the five tribal groups examined, the rates of diagnosed diabetes in Indians less than 35 years of age (range from 0.5 percent to 1.3 percent) were significantly higher than the U.S. rate of 0.4 percent for the same age group. The prevalence rates of diagnosed diabetes found in this study of American Indians in New Mexico were intermediate between those for the United States as a whole and the Pima Indians of southern Arizona. Reasons for the variations and the relative contribution of obesity, fitness, or genetic risk in the development of diabetes need further study.