Hemoglobin and Clinical Outcomes in Hemodialysis: An Analysis of US Medicare Data From 2018 to 2020.

Rationale & Objective: Anemia management in patients treated with maintenance dialysis remains a challenge. We sought to update information in this area by evaluating the association between hemoglobin and various outcome and utilization measures using data-rich Medicare sources. Study Design: Observational cohort study using data from the Consolidated Renal Operations in a Web-enabled Network and Medicare claims. Setting & Participants: We studied 371,250 prevalent patients treated with hemodialysis, covering 3,326,072 patient-months in 2019. Exposure: Monthly patient hemoglobin concentrations. Outcomes: We examined several outcomes, including mortality, all-cause hospitalization, cause-specific hospitalization, and emergency department utilization in the month following the exposure measurement. Analytical Approach: For each monthly observation period, we calculated unadjusted and adjusted (for demographics and comorbid condition) hazard ratios using Cox regression. Results: The hemoglobin concentration was <10.5 g/dL for 40% of observations. We found an inverse association between mortality and hemoglobin measured over a range from <9 g/dL (HR, 2.53; 95% CI, 2.45-2.61; P < 0.0001, reference = 10.5-11 g/dL) to 11-11.5 g/dL (HR, 0.92; 95% CI, 0.89-0.96; P < 0.0001). Mortality risk started to increase at hemoglobin levels >11.5 g/dL. All-cause hospitalization, cause-specific hospitalization (including cardiovascular, infection, and several subcategories including coronavirus disease 2019 hospitalization), and emergency department utilization were inversely associated with hemoglobin concentration, with risk reduction stabilizing at hemoglobin levels of approximately 11.5-12 g/dL and higher. Limitations: As with prior observational studies, the observed associations are not necessarily causal. Conclusions: In a large US hemodialysis population, there were better clinical outcomes at higher hemoglobin concentrations over short exposure and follow-up periods, consistent with other observational studies that generally used longer exposure and follow-up times. Mortality risk increased at hemoglobin concentrations >11.5 g/dL, consistent with findings from erythropoiesis-stimulating agent clinical trials. The apparently beneficial short-term effects associated with higher hemoglobin concentrations suggest that hemoglobin measurements capture unmeasured elements of patient risk.

Mortality Risk of Patients Treated in Dialysis Facilities with Payment Reductions under ESRD Quality Incentive Program.

BACKGROUND: The Centers for Medicare & Medicaid Services End-Stage Renal Disease Quality Incentive Program (ESRD QIP) measures quality of care delivered by dialysis facilities and imposes Medicare payment reductions for quality lapses. We assessed the association between payment reductions and patient mortality, a quality indicator not included in the ESRD QIP measure set. METHODS: Association between mortality and ESRD QIP facility payment reduction based on the year of performance was expressed as the unadjusted rate and patient case-mix-adjusted hazard ratio. We also measured association between mortality and 1-year changes in payment reductions. Retrospective patient cohorts were defined by their treating dialysis facility on the first day of each year (2010-2018). RESULTS: Facility performance resulted in payment reductions for 5%-42% of dialysis facilities over the 9 study years. Patients experienced progressively higher mortality at each payment reduction level. Across all years, unadjusted mortality was 17.3, 18.1, 18.9, 20.3, and 23.9 deaths per 100 patient-years for patients in facilities that received 0%, 0.5%, 1%, 1.5%, and 2% payment reductions, respectively. The adjusted hazard ratio showed a similar stepwise pattern by the level of payment reduction: 1.0 (reference), 1.08 (95% confidence interval [CI], 1.07 to 1.09), 1.15 (95% CI, 1.13 to 1.16), 1.19 (95% CI, 1.16 to 1.21), and 1.34 (95% CI, 1.29 to 1.39). Strength of the association increased from 2010 to 2016. Patients treated in facilities that improved over 1 year generally experienced lower mortality; patients in facilities that performed worse on ESRD QIP measures generally experienced higher mortality. CONCLUSIONS: Patient mortality was associated with ESRD QIP facility payment reductions in dose-response and temporal patterns.

Peritoneal Dialysis Patient Outcomes under the Medicare Expanded Dialysis Prospective Payment System.

BACKGROUND AND OBJECTIVES: Peritoneal dialysis (PD) use increased in the United States with the introduction of a new Medicare prospective payment system in January 2011 that likely reduced financial disincentives for facility use of this home therapy. The expansion of PD to a broader population and facilities having less PD experience may have implications for patient outcomes. We assessed the impact of PD expansion on PD discontinuation and patient mortality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A prospective cohort study was conducted of patients treated with PD at 90 days of ESKD. Patients were grouped by study start date relative to the Medicare payment reform: prereform (July 1, 2008 to December 31, 2009; n=10,585), interim (January 1, 2010 to December 31, 2010; n=7832), and reform period (January 1, 2011 to December 31, 2012; n=18,742). Patient characteristics and facility PD experience were compared at baseline (day 91 of ESKD). Patients were followed for 3 years for the major outcomes of PD discontinuation and mortality using Cox proportional hazards models. RESULTS: Patient characteristics, including age, sex, race, ethnicity, rurality, cause of ESKD, and comorbidity, were similar or showed small changes across the three study periods. There was an increasing tendency for patients on PD to be treated in facilities with less PD experience (from 34% during the prereform period being treated in facilities averaging <14 patients on PD per year to 44% in the reform period). Patients treated in facilities with less PD experience had a higher rate of PD discontinuation than patients treated in facilities with the most experience (hazard ratio [HR], 1.16; 95% confidence interval [95% CI], 1.10 to 1.23 for the first versus fifth quintile of PD experience). Nevertheless, the risk of PD discontinuation fell during the late interim period (HR, 0.88; 95% CI, 0.82 to 0.95) and most of the reform period (from HR, 0.85; 95% CI, 0.79 to 0.91 to HR, 0.94; 95% CI, 0.87 to 1.01). Mortality risk was stable across the three study periods. CONCLUSIONS: In the context of expanding PD use and declining facility PD experience, the risk of PD discontinuation fell, and there was no adverse effect on mortality. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_09_12_CJN01610219.mp3.

Risk of Cardiovascular Disease and Mortality in Young Adults With End-stage Renal Disease: An Analysis of the US Renal Data System.

Importance: Cardiovascular disease (CVD) is a leading cause of death among patients with end-stage renal disease (ESRD). Young adult (ages 22-29 years) have risks for ESRD-associated CVD that may vary from other ages. Objective: To test the hypothesis that young adult-onset ESRD is associated with higher cardiovascular (CV) hospitalizations and mortality with different characteristics than childhood-onset disease. Design, Setting, and Participants: This population-based cohort study used the US Renal Data System to categorize patients who initiated ESRD care between 2003 and 2013 by age at ESRD onset (1-11, 12-21, and 22-29 years). Cardiovascular hospitalizations were identified via International Classification of Diseases, Ninth Revision discharge codes and CV mortality from the Centers for Medicare & Medicaid ESRD Death Notification Form. Patients were censored at death from non-CVD events, loss to follow-up, recovery, or survival to December 31, 2014. Adjusted proportional hazard models (95% CI) were fit to determine risk of CV hospitalization and mortality by age group. Data analysis occurred from May 2016 and December 2017. Exposures: Onset of ESRD. Main Outcomes and Measures: Cardiovascular mortality and hospitalization. Results: A total of 33 156 patients aged 1 to 29 years were included in the study population. Young adults (aged 22-29 years) had a 1-year CV hospitalization rate of 138 (95% CI, 121-159) per 1000 patient-years. Young adults had a higher risk for CV hospitalization than children (aged 1-11 years; hazard ratio [HR], 0.41 [95% CI, 0.26-0.64]) and adolescents (aged 12-21 years; HR, 0.86 [95% CI, 0.77-0.97]). Of 4038 deaths in young adults, 1577 (39.1%) were owing to CVD. Five-year cumulative incidence of mortality in this group (7.3%) was higher than in younger patients (adolescents, 4.0%; children, 1.7%). Adjusted HRs for CV mortality were higher for young adults with all causes of ESRD than children (cystic, hereditary, and congenital conditions: HR, 0.22 [95% CI, 0.11-0.46]; P < .001; glomerulonephritis: HR, 0.21 [95% CI, 0.10-0.44]; P < .001; other conditions: HR, 0.33 [95% CI, 0.23-0.49]; P < .001). Adolescents had a lower risk for CV mortality than young adults for all causes of ESRD except glomerulonephritis (cystic, hereditary, and congenital conditions: HR, 0.45 [95% CI, 0.27-0.74]; glomerulonephritis: HR, 0.99 [95% CI, 0.76-1.11]; other: HR, 0.47 [95% CI, 0.40-0.57]). Higher risks for CV hospitalization and mortality were associated with lack of preemptive transplant compared with hemodialysis (hospital: HR, 14.24 [95% CI, 5.92-34.28]; mortality: HR, 13.64 [95% CI, 8.79-21.14]) and peritoneal dialysis [hospital: HR, 8.47 [95% CI, 3.50-20.53]; mortality: HR, 7.86 [95% CI, 4.96-12.45]). Nephrology care before ESRD was associated with lower risk for CV mortality (HR, 0.77 [95% CI, 0.70-0.85]). Conclusions and Relevance: Cardiovascular disease accounted for nearly 40% of deaths in young adults with incident ESRD in this cohort. Identified risk factors may inform development of age-appropriate ESRD strategies to improve the CV health of this population.

Explaining trends and variation in timing of dialysis initiation in the United States.

The United States Renal Data System (USRDS) registry of end-stage renal disease has often been used to study the timing of dialysis initiation, measured by estimated glomerular filtration rate (eGFR) at dialysis initiation. We conducted an observational study and examined how well variables in the USRDS database explain the trends and variation in eGFR at dialysis initiation.We identified 971,481 patients who initiated dialysis between 1995 and 2012 in the USRDS registry.The mean eGFR at dialysis initiation monotonically rose from 7.7 in 1995 to 11.1 in 2009, and then leveled off to 10.9 mL/min/1.73 m in 2012. The trend of rising, then leveling off was similar across all subgroups studied. Substantial variation in eGFR at dialysis initiation was observed, with standard deviation of 4.38 (95% CI: 2.0-18.4). A total of 11.4% of the total variation occurred across physicians and 88.6% within physicians. Adjustment for measured factors only modestly decreased the total variation. Of the total variance, 10.7% was explained by measured patient-level variables and 1.2% by measured physician and other factors, while 9.2% of physician-level variation and 78.9% of patient-level variation remained unexplained. The extent of variation explained by measured variables was similar over the entire study period.The finding that the majority of variation in eGFR at dialysis initiation is unexplained by measured variables casts doubt on how well eGFR serves as a measure for "timing" of dialysis initiation, and it indicates the need to collect more focused data to gain understanding of factors that affect timing of dialysis initiation in the US.

Dialysis dose scaled to body surface area and size-adjusted, sex-specific patient mortality.

BACKGROUND AND OBJECTIVES: When hemodialysis dose is scaled to body water (V), women typically receive a greater dose than men, but their survival is not better given a similar dose. This study sought to determine whether rescaling dose to body surface area (SA) might reveal different associations among dose, sex, and mortality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Single-pool Kt/V (spKt/V), equilibrated Kt/V, and standard Kt/V (stdKt/V) were computed using urea kinetic modeling on a prevalent cohort of 7229 patients undergoing thrice-weekly hemodialysis. Data were obtained from the Centers for Medicare & Medicaid Services 2008 ESRD Clinical Performance Measures Project. SA-normalized stdKt/V (SAN-stdKt/V) was calculated as stdKt/V × ratio of anthropometric volume to SA/17.5. Patients were grouped into sex-specific dose quintiles (reference: quintile 1 for men). Adjusted hazard ratios (HRs) for 1-year mortality were calculated using Cox regression. RESULTS: spKt/V was higher in women (1.7 ± 0.3) than in men (1.5 ± 0.2; P<0.001), but SAN-stdKt/V was lower (women: 2.3 ± 0.2; men: 2.5 ± 0.3; P<0.001). For both sexes, mortality decreased as spKt/V increased, until spKt/V was 1.6-1.7 (quintile 4 for men: HR, 0.62; quintile 3 for women: HR, 0.64); no benefit was observed with higher spKt/V. HR for mortality decreased further at higher SAN-stdKt/V in both sexes (quintile 5 for men: HR, 0.69; quintile 5 for women: HR, 0.60). CONCLUSIONS: SA-based dialysis dose results in dose-mortality relationships substantially different from those with volume-based dosing. SAN-stdKt/V analyses suggest women may be relatively underdosed when treated by V-based dosing. SAN-stdKt/V as a measure for dialysis dose may warrant further study.

Screening for diabetes in an African American community: identifying characteristics associated with abnormal blood glucose readings.

OBJECTIVE: To identify characteristics associated with abnormal blood glucose readings among African Americans and to determine the potential value of a more targeted approach to community-based screenings for type 2 diabetes. METHODS: Data were collected from 7113 participants with no previous diagnosis of diabetes at mobile screening events in Detroit, Michigan. Data collected included gender, race, age, self-reported height and weight, total diabetes risk score, blood pressure, and random capillary blood glucose. RESULTS: Nearly 9% of participants had abnormal random plasma glucose readings (RPG>or=160 mg/dL). Results indicated that higher age, elevated blood pressure, and body mass index (BMI) were significantly associated with abnormal glucose readings. CONCLUSION: These findings suggest that community-based screenings for diabetes that are targeted to adults aged more than 50 years who have high blood pressure or a BMI of at least 25 may enhance detection of abnormal glucose levels among African Americans.

Hair care practices and their association with scalp and hair disorders in African American girls.

BACKGROUND: Few studies have extensively examined the prevalence of hair care practices and their association with scalp and hair conditions in African American girls. OBJECTIVES: We sought to determine the prevalence of hair care practices and their association with traction alopecia, seborrheic dermatitis (SD), and tinea capitis (TC). METHODS: A questionnaire was administered to caregivers of African American girls aged 1 to 15 years. Multivariate analyses were performed to determine the association of hair care practices with reported disorders. RESULTS: A total of 201 surveys were completed from dermatology (n = 98) and nondermatology (n = 103) clinics. Mean patient age was 9.8 ± 4.4 years. Essentially all respondents reported use of hair oils/grease (99%). Ponytails, braids, and cornrows were worn by 81%, 67%, and 49% of girls, respectively, within the past 12 months. In all, 61% reported hair washing every 2 weeks; 80% used hot combs; and 42% used chemical relaxers. Cornrows were significantly related to traction alopecia among respondents from nondermatology clinics only: adjusted odds ratio = 5.79 (95% CI 1.35-24.8, P = .018). Hair extensions and infrequent hair oil use were significantly related to SD: adjusted odds ratio = 2.37 (95% CI 1.03-5.47, P = .04) and 3.69 (95% CI 1.07-12.7, P = .039), respectively. No significant associations were observed for TC. LIMITATIONS: Small sample size and disorders reported by caregivers were limitations. CONCLUSIONS: Certain hair care practices were strongly associated with development of traction alopecia and SD. No association was found between hair washing frequency and SD or TC, or between hair grease use and TC. These results can be used to inform practitioners, advise parents, and adapt treatment regimens to accommodate cultural preferences.

Chronic brain tissue remodeling after stroke in rat: a 1-year multiparametric magnetic resonance imaging study.

Rats subjected to 2h of transient middle cerebral artery occlusion were studied temporally over 1 year by magnetic resonance imaging (MRI) and behavioral testing. Multiparameter MRI measures of T(2), T(1), T(1) in the presence of off-resonance saturation of the bound proton signal (T(1sat)), apparent diffusion coefficient (ADC) and susceptibility-weighted imaging (SWI) were obtained at 1 day, 1, 2, 3 and 4 weeks, and 3, 6, 9 and 12 months post-ischemia. Regions of interest included: ischemic core (damaged both at 1 day and later); new lesion (normal at 1 day, but damaged later); and recovery (damaged at 1 day, but normal later) areas. Hematoxylin and eosin, Prussian blue and ED-1, a monoclonal antibody murine macrophage marker, stainings were performed for histological assessment. Core area T(2) and ADC values increased until ~6 months, and T(1) and T(1sat) until ~12 months. New lesion area MRI parameter values increased until ~6 months (T(2), T(1) and ADC), or ~1 year (T(1sat)). Lesion area was largest at 1day (mean±SD: 37.0±13.7mm(2)) and smallest at 1 year (18.1±10.5mm(2)). Recovery area was largest at 3 weeks (8.9±3.8mm(2)) and smallest at 1year (6.4±3.3mm(2)). The ipsilateral/contralateral ventricle area ratio was 0.7±0.2 at 1 day and increased significantly at 1 year (2.4±0.7). Iron-laden macrophages, histologically confirmed at 1 year, were detected in the lesion borders by SWI at 3, 6, 9 and 12 months. Our data indicate that MRI detectable changes of ischemia-damaged brain tissue continue for at least 1 year post-ischemia.

Niaspan treatment induces neuroprotection after stroke.

INTRODUCTION: Niaspan, an extended-release formulation of Niacin (vitamin B3), has been widely used to increase high density lipoprotein (HDL) cholesterol and to prevent cardiovascular diseases and stroke. In this study, we tested whether Niaspan administered acutely after stroke is neuroprotective. METHODS: Adult male rats (n=8/group) were subjected to 2h of middle cerebral artery occlusion (MCAo) and treated with or without different doses of Niaspan (20, 40 or 80 mg/kg) at 2 and 24h after MCAo. A battery of functional outcome tests was performed, and serum HDL and triglycerides were measured. Rats were sacrificed at 7 days after MCAo and lesion volumes were measured. The optimal dose of Niaspan treatment of stroke was chosen for immunostaining: deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), cleaved caspase-3, tumor necrosis factor alpha (TNF-alpha), vascular endothelial growth factor (VEGF) and phosphorylated phosphatidylinositol 3-kinase (p-PI3K). Another set of rats (n=4/group) were killed at 7 days after MCAo for Western blot assay. RESULTS: Niaspan dose-dependently reduced infarct volume and improved functional outcome after stroke. No significant difference in HDL and triglyceride levels was detected between Niaspan treatments and MCAo control groups. Niaspan treatment significantly decreased the number of TUNEL-positive cells (105+/-17) and cleaved caspase-3 expression (381+/-33) in the ischemic brain compared to MCAo control (165+/-18; 650+/-61, respectively; p

DNA hypermethylation markers of poor outcome in laryngeal cancer.

This study examined molecular (DNA hypermethylation), clinical, histopathological, demographical, smoking, and alcohol variables to assess diagnosis (early versus late stage) and prognosis (survival) outcomes in a retrospective primary laryngeal squamous cell carcinoma (LSCC) cohort. The study cohort of 79 primary LSCC was drawn from a multi-ethnic (37% African American), primary care patient population, diagnosed by surgical biopsies in the Henry Ford Health System from 1991-2004, and followed from 5-18 years (through 2009). Of the 41 variables, univariate risk factors of p<0.10 were tested in multivariate models (logistic regression {diagnosis} and Cox {survival} models {p<0.05}). Aberrant methylation of ESR1 (p=0.01), race as African American (p=0.04), and tumor necrosis (extensive) (p=0.02) were independent predictors of late stage LSCC. Independent predictors of poor survival included presence of vascular invasion (p=0.0009), late stage disease (p=0.03) and methylation of the HIC1 gene (p=0.0002). Aberrant methylation of ESR1 and HIC1 signified independent markers of poorer outcome. In this multi-ethnic, primary LSCC cohort, race remained a predictor of late stage disease supporting disparate diagnosis outcomes for African American patients with LSCC.

Exemplary data set sample size calculation for Wilcoxon-Mann-Whitney tests.

Zhao, Rahardja and Qu consider sample size calculation for Wilcoxon-Mann-Whitney (WMW) tests for data with ties, and present a straightforward formula. We observe that the 'exemplary data set' approach, usually applied in more complex situations, has a close relationship to the Zhao-Rahardja-Qu method for WMW sample size estimation and they are asymptotically equivalent. Therefore, the exemplary data set approach can be used to easily obtain estimates similar to those that the closed formula gives. We illustrate application of both methods for a WMW sample size estimation example, and also extend the simulation study presented by Zhao et al. We find that the Zhao-Rahardja-Qu formula (and by extension the exemplary data set method) can give estimates just as accurate as those obtained using either the Kolassa approach (via nQuery Advisor) or the O'Brien-Castelloe approach (via SAS 9.2 PROC POWER), for 1:1 and 1:2 allocation ratios. However, the latter two methods can be more accurate for a ratio of 1:4 or 1:19. Finally, we note the general utility of the exemplary data set approach for sample size estimation, even in other situations where closed-form sample size formulae exist.

The role of lymph node metastasis in the systemic dissemination of breast cancer.

BACKGROUND.: Lymphatic invasion is necessary for regional lymph node (RLN) metastasis in breast cancer (BC), while systemic metastasis requires blood vessel (BV) invasion. The site of BV invasion could be at the primary BC site or through lymphovascular anastomoses. The vague pathologic term "lymphovascular invasion" (LVI) encourages the belief that peri/intratumoral BV invasion may be common. We investigated the relative contribution of RLN metastasis to systemic metastasis by studying the relationship among LVI and RLN and/or systemic metastasis in a population-based cohort of breast cancer patients. METHODS.: Fisher's exact test was done to assess global associations among LVI and RLN and/or systemic metastasis in a prospective database of breast cancer patients undergoing RLN biopsy. Logistic regression was used to determine multivariable contributions of LVI to metastasis when controlling for available demographic, radiologic, and pathologic variables. RESULTS.: Of 1668 patients evaluated 25.4% were RLN positive and 10.4% had LVI. RLN metastasis was predicted by tumor size (P < .0001), HER-2/neu overexpression (P = .0022) and the interaction between LVI positive and HER-2/neu positive tumors (< .0001). Patients with LVI/HER-2-neu positive were 3 times as likely to have positive RLNs compared with patients LVI/HER-2-neu negative. Systemic metastasis was significantly (P = .0013) associated with LVI/ RLN positive, but not with LVI positive/RLN negative patients (P = .137). CONCLUSIONS.: LVI predicted RLN metastasis. LVI also significantly predicted systemic metastasis, but only when the RLN was also positive. Since RLN requires lymphatic invasion, these data support the hypothesis that primary breast cancers often invade lymphatics to gain access to the systemic circulation.

The role of lymph node metastasis in the systemic dissemination of breast cancer.

BACKGROUND: Lymphatic invasion is necessary for regional lymph node (RLN) metastasis in breast cancer (BC), while systemic metastasis requires blood vessel (BV) invasion. The site of BV invasion could be at the primary BC site or through lymphovascular anastomoses. The vague pathologic term "lymphovascular invasion" (LVI) encourages the belief that peri/intratumoral BV invasion may be common. We investigated the relative contribution of RLN metastasis to systemic metastasis by studying the relationship among LVI and RLN and/or systemic metastasis in a population-based cohort of breast cancer patients. METHODS: Fisher's exact test was done to assess global associations among LVI and RLN and/or systemic metastasis in a prospective database of breast cancer patients undergoing RLN biopsy. Logistic regression was used to determine multivariable contributions of LVI to metastasis when controlling for available demographic, radiologic, and pathologic variables. RESULTS: Of 1668 patients evaluated 25.4% were RLN positive and 10.4% had LVI. RLN metastasis was predicted by tumor size (P < .0001), HER-2/neu overexpression (P = .0022) and the interaction between LVI positive and HER-2/neu positive tumors (< .0001). Patients with LVI/HER-2-neu positive were 3 times as likely to have positive RLNs compared with patients LVI/HER-2-neu negative. Systemic metastasis was significantly (P = .0013) associated with LVI/RLN positive, but not with LVI positive/RLN negative patients (P = .137). CONCLUSIONS: LVI predicted RLN metastasis. LVI also significantly predicted systemic metastasis, but only when the RLN was also positive. Since RLN requires lymphatic invasion, these data support the hypothesis that primary breast cancers often invade lymphatics to gain access to the systemic circulation.

MRI identification of white matter reorganization enhanced by erythropoietin treatment in a rat model of focal ischemia.

BACKGROUND AND PURPOSE: The objectives of the present study were to: (1) noninvasively identify white matter reorganization and monitor its progress within 6 weeks after the onset of stroke; and (2) quantitatively investigate the effect of recombinant human erythropoietin treatment on this structural change using in vivo measurement of diffusion anisotropy. METHODS: Male Wistar rats were subjected to middle cerebral artery occlusion and treated with recombinant human erythropoietin intraperitoneally at a dose of 5000 U/kg of body weight (n=11) or the same volume of saline (n=7) daily for 7 days starting 24 hours after middle cerebral artery occlusion. MRI measurements of T2- and diffusion-weighted images and cerebral blood flow were performed and neurological severity score was assessed at 1 day and weekly for 6 weeks after middle cerebral artery occlusion. Luxol fast blue and Bielschowsky staining were used to demonstrate myelin and axons, respectively. RESULTS: White matter reorganization occurred along the ischemic lesion boundary after stroke. The region of white matter reorganization seen on the tissue slice coincided with the elevated area on the fractional anisotropy map, which can be accurately identified. The increase in elevated fractional anisotropy pixels corresponded with progress of white matter reorganization and was associated with improvement of neurological function. Treatment with recombinant human erythropoietin after stroke significantly enhanced white matter reorganization, restored local cerebral blood flow, and expedited functional recovery. CONCLUSIONS: White matter reorganization can be detected by fractional anisotropy. Elevated fractional anisotropy pixels may be a good MRI index to stage white matter remodeling and predict functional outcome.

Treatment of vitamin D depletion after Roux-en-Y gastric bypass: a randomized prospective clinical trial.

BACKGROUND: A high prevalence (60%) of vitamin D (VitD) depletion, defined as a serum 25-hydroxyvitamin D level of < or =20 ng/mL, is present in preoperative morbidly obese patients. Despite daily supplementation with 800 IU VitD and 1500 mg calcium after Roux-en-Y gastric bypass (RYGB), VitD depletion persists in almost one half (44%) of patients. However, the optimal management of VitD depletion after RYGB and the potential benefits of such treatment are currently unknown. METHODS: A total of 60 VitD-depleted morbidly obese women were randomly assigned to receive 50,000 IU of VitD weekly after RYGB (group 1; n = 30) or no additional VitD after RYGB (group 2; n = 30). All patients received a daily supplement of 800 IU VitD and 1500 mg calcium. The serum calcium, parathyroid hormone, 25-hydroxyvitamin D, bone-specific alkaline phosphatase, urinary N-telopeptide, and bone mineral density were measured preoperatively and 1 year after RYGB. Questionnaires were used to assess other potential sources of VitD, including sunlight exposure and ingestion of VitD-containing foods/liquids. RESULTS: At 1 year after RYGB, VitD depletion and mean 25-hydroxyvitamin D level had improved significantly in group 1 (14% and 37.8 ng/mL, respectively) compared with the values in group 2 (85% and 15.2 ng/mL, respectively; P <.001 for both). A significant 33% retardation in hip bone mineral density decline (P = .043) and a significantly greater resolution of hypertension was seen in group 1 (75% versus 32%; P = .029). No significant adverse effects were encountered from pharmacologic VitD therapy. CONCLUSION: The results of our study have shown that 50,000 IU of VitD weekly after RYGB safely corrects VitD depletion in most women, attenuates cortical bone loss, and improves resolution of hypertension.