Jonathan Yabes

Revised Atlanta and Determinant-Based Classification: Application in a Prospective Cohort of Acute Pancreatitis Patients

OBJECTIVES:Atlanta classification (Atlanta 1992) of acute pancreatitis (AP) has several limitations. Two new classification systems were recently proposed: the Atlanta reclassification (Atlanta 2012) and the determinant-based classification (DBC). The aim of our study was to: (i) determine the association between different severity categories and clinical outcomes and (ii) perform a head-to-head comparison between Atlanta 1992, Atlanta 2012, and DBC in predicting these clinical outcomes.METHODS:A total of 256 prospectively enrolled patients were assigned a severity category for all three classifications. Five clinical outcomes were evaluated: mortality, intensive care unit (ICU) admission and length of stay (LOS), need for interventions, and hospital LOS. Pairwise testing between severity grades within a classification system was performed using Fishers exact and Kruskal–Wallis tests. Predictive accuracies were evaluated using area under the ROC curve (AUC) and Somers D co-efficient.RESULTS:Overall, higher grades of severity were associated with worse clinical outcomes for all three classification systems. Atlanta 2012 and DBC performed better than Atlanta 1992 and were comparable in predicting mortality (AUC 0.89 for both vs. 0.76, P<0.001), ICU admission (AUC 0.91 for both vs. 0.80, P<0.001), and ICU LOS (Somers D 0.21 and 0.28 vs. 0.07, P<0.05). DBC performed better in predicting need for interventions (AUC 0.93 vs. 0.85, P<0.001), whereas Atlanta 2012 performed better in predicting hospital LOS (Somers D 0.43 vs. 0.37, P=0.04).CONCLUSIONS:Atlanta 2012 and DBC severity categories accurately reflected clinical outcomes in our cohort and were superior to Atlanta 1992. These novel classification systems can guide the selection of homogeneous patient populations for clinical research and provide an accurate spectrum of disease severity categories in the clinical setting.

Diagnostic Value of Somatosensory Evoked Potential Changes During Carotid Endarterectomy: A Systematic Review and Meta-analysis

IMPORTANCE Perioperative stroke is a persistent complication of carotid endarterectomy (CEA) for patients with symptomatic carotid stenosis (CS). OBJECTIVE To evaluate whether changes in somatosensory evoked potential (SSEP) during CEA are diagnostic of perioperative stroke in patients with symptomatic CS. DESIGN, SETTING, AND PARTICIPANTS We searched PubMed and the World Science Database for reference lists of retrieved studies and/or experiments on SSEP use in postoperative outcomes following CEA in patients with symptomatic CS from January 1, 1950, through January 1, 2013. We independently screened all titles and abstracts to identify studies that met the inclusion criteria and extracted relevant articles in a uniform manner. Inclusion criteria included randomized clinical trials, prospective studies, or retrospective cohort reviews; population of symptomatic CS; use of intraoperative SSEP monitoring during CEA; immediate postoperative assessment and/or as long as a 3-month follow-up; a total sample size of 50 or more patients; studies with adult humans 18 years or older; and studies published in English. MAIN OUTCOME AND MEASURE Whether intraoperative SSEP changes were diagnostic of perioperative stroke indicated by postoperative neurological examination. RESULTS Four-hundred sixty-four articles were retrieved, and 15 prospective and retrospective cohort studies were included in the data analysis. A 4557-patient cohort composed the total sample population for all the studies, 3899 of whom had symptomatic CS. A change in SSEP exhibited a strong pooled mean specificity of 91% (95% CI, 86-94) but a weaker pooled mean sensitivity of 58% (95% CI, 49-68). A pooled diagnostic odds ratio for individual studies of patients with neurological deficit with changes in SSEPs was 14.39 (95% CI, 8.34-24.82), indicating that the odds of observing an SSEP change among those with neurologic deficits were 14 times higher than in individuals without neurologic deficit. CONCLUSIONS AND RELEVANCE Intraoperative SSEP is a highly specific test in predicting neurological outcome following CEA. Patients with perioperative neurological deficits are 14 times more likely to have had changes in SSEPs during the procedure. The use of SSEPs to design prevention strategies is valuable in reducing perioperative cerebral infarctions during CEA.

Prevalence and correlates of fatigue in chronic kidney disease and end-stage renal disease: are sleep disorders a key to understanding fatigue?

Background: Fatigue is an important symptom to patients with advanced chronic kidney disease (CKD). The aim of this study is to examine the prevalence and severity of fatigue among non-dialysis-dependent CKD and end-stage renal disease (ESRD) patients, to examine the association of fatigue with subjective and objective sleep quality, and to identify other modifiable factors associated with fatigue. Methods: A cross-sectional survey of 87 non-dialysis-dependent CKD (eGFR ≤45 ml/min/1.73 m2) and 86 ESRD patients was done using the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) and 36-Item Short-Form (SF-36) vitality scale. Higher FACIT-F score denoted less fatigue. Objective sleep was assessed using in-home polysomnography. Predictors of fatigue were determined using a linear regression model. Results: The mean FACIT-F score among all participants was 34.5 ± 11.0. Mean scores were similar among CKD and ESRD groups (34.25 ± 11.28 vs. 34.73 ± 10.86; p = 0.73). On univariate analyses, patients with higher levels of fatigue were more likely to have cardiovascular disease, benzodiazepine use, depressive symptoms, and slightly lower hemoglobin and serum albumin levels. There was no significant association between severity of sleep apnea and level of fatigue (Apnea Hypopnea Index 20.1 ± 27.6 vs. 20.3 ± 22.0; p = 0.69). Presence of cardiovascular disease, low serum albumin, depressive symptoms, poor subjective sleep quality, excessive daytime sleepiness and restless legs syndrome were independently associated with greater fatigue in multivariable regression models. The FACIT-F score correlated closely with the SF-36 vitality score (r = 0.81, p < 0.0001). Conclusions: Patients with advanced CKD and ESRD experience profound fatigue. Depressive symptoms, restless legs syndrome, excessive daytime sleepiness, and low albumin levels may provide targets for interventions to improve fatigue in patients with advanced CKD.

Effect of Vitamin D3 Supplementation in Black and in White Children: A Randomized, Placebo-Controlled Trial

CONTEXT Dosages of vitamin D necessary to prevent or treat vitamin D deficiency in children remain to be clarified. OBJECTIVE To determine the effects of vitamin D3 1000 IU/d on serum 25-hydroxyvitamin D [25(OH)D], PTH, and markers of bone turnover (osteocalcin and collagen type 1 cross-linked C-telopeptide) in black children and white children, and to explore whether there is a threshold level of 25(OH)D associated with maximal suppression of serum PTH concentration. DESIGN Healthy 8- to 14-year-old Pittsburgh-area black (n = 84) and white (n = 73) children not receiving vitamin supplements, enrolled from October through March from 2008 through 2011, were randomized to vitamin D3 1000 IU or placebo daily for 6 months. RESULTS The mean baseline concentration of 25(OH)D was <20 ng/mL in both the vitamin D-supplemented group and the placebo group (19.8 ± 7.6 and 18.8 ± 6.9 ng/mL, respectively). The mean concentration was higher in the supplemented group than in the placebo group at 2 months (26.4 ± 8.1 vs 18.9 ± 8.1 ng/mL; P < .0001) and also at 6 months (26.7 ± 7.6 vs 22.4 ± 7.3; P = .003), after adjusting for baseline 25(OH)D, race, gender, pubertal status, dietary vitamin D intake, body mass index, and sunlight exposure. Increases were only significant in black children, when examined by race. The association between 25(OH)D and PTH concentrations was inverse and linear, without evidence of a plateau. Overall, vitamin D supplementation had no effect on PTH and bone turnover. CONCLUSIONS Vitamin D3 supplementation with 1000 IU/d in children with mean baseline 25(OH)D concentration <20 ng/mL effectively raised their mean 25(OH)D concentration to ≥20 ng/mL but failed to reach 30 ng/mL. Vitamin D supplementation had no effect on PTH concentrations.

Changes in Anthropometry and Mortality in Maintenance Hemodialysis Patients in the HEMO Study

BACKGROUND Poor nutritional status has been associated with worse patient survival in maintenance hemodialysis patients. Anthropometric values are important nutritional measures, incorporating muscle and fat mass. However, the association of changes in anthropometry, including midarm circumference (MAC) and skinfold measurements, with mortality in hemodialysis patients remains unknown. Accordingly, we explored this association in the Hemodialysis (HEMO) Study. STUDY DESIGN Post hoc analysis of cohort data from a clinical trial. SETTING & PARTICIPANTS 1,846 hemodialysis patients enrolled in the HEMO Study. PREDICTORS MAC and skinfold measurements. OUTCOMES Longitudinal changes in MAC and skinfolds were jointly modeled using repeated measures and survival modeling. Time-to-event outcomes were all-cause mortality, cardiac death and hospitalization, and infection-related death. RESULTS Mean MAC was 30.1 cm, and mean baseline sum of subscapular, biceps, and triceps skinfolds was 42.4 mm. During a median follow-up of 2.5 years, there were 845 deaths. During follow-up, MAC and the skinfold measurement declined 0.26 cm and 1.1 mm per year, respectively. Declines in MAC (per cm) and skinfold (per mm) measurements were associated with higher all-cause mortality (HRs of 1.58 [95% CI, 1.29-1.94; P < 0.001] and 1.06 [95% CI, 0.99-1.13; P = 0.09], respectively), poorer cardiac outcomes (HRs of 1.49 [95% CI, 1.23-1.81; P < 0.001] and 1.05 [95% CI, 0.99-1.10; P = 0.09], respectively), and higher infection-related hospitalization (HRs of 2.45 [95% CI, 1.55-3.88; P < 0.001] and 1.16 [95% CI, 0.98-1.37; P = 0.08], respectively). The association between declining MAC and skinfold with patient survival was most notable for those with body mass index (BMI) ≤25 kg/m2 (HRs of 2.41 [95% CI, 1.81-3.19; P < 0.001] and 1.22 [95% CI, 1.10-1.35; P < 0.001], respectively). LIMITATIONS Prevalent dialysis patients only, excluding individuals weighing >85 kg. CONCLUSIONS Declines in skinfold thickness were not associated significantly with outcomes except for participants with BMI ≤25 kg/m2. Declines in MAC are associated significantly with all-cause mortality and cardiac outcomes in hemodialysis patients, most notably in those with BMI ≤25 kg/m2.

Association of Sleep Disordered Breathing With Cognitive Dysfunction in CKD Stages 4–5

BACKGROUND Sleep-disordered breathing and cognitive impairment are common in patients with chronic kidney disease (CKD). Sleep-disordered breathing is known to be a risk factor for cognitive dysfunction in the general population, but this association has not been studied in patients with CKD. STUDY DESIGN Cross-sectional study. SETTINGS & PARTICIPANTS A cohort of 169 patients with CKD stages 4-5. PREDICTORS Sleep-disordered breathing; covariates included demographics, diabetes, cardiovascular disease, depression, and dialysis modality. OUTCOMES Cognitive impairment, generally defined as a score 1.5 standard deviations or more from the age- and education level-adjusted normative cognitive test score. MEASUREMENTS Standardized health interview, neurocognitive assessment, sleep-related questionnaires, and polysomnography. RESULTS Sleep-disordered breathing (apnea-hypopnea index >15) was diagnosed in 83 (49.1%) individuals. This group had a significantly higher prevalence of nocturnal hypoxemia (65.8% vs 26.8%; P < 0.001) and excessive daytime sleepiness (38.6% vs 20.7%; P = 0.01). In addition, this group had significantly lower scores in tests measuring verbal memory, working memory, attention, and psychomotor speed. Sleep-disordered breathing was associated with higher risk of immediate verbal memory impairment after adjustment for known confounders (adjusted OR, 2.67; 95% CI, 1.17-6.08). However, in a subgroup analysis of older adults (aged >60 years), there were no significant differences in cognitive testing between the groups with and without sleep-disordered breathing. LIMITATIONS Cross-sectional design, limited sample size. CONCLUSIONS Sleep-disordered breathing is associated with cognitive impairments, especially impaired verbal memory, in patients with advanced CKD. However, the impact appeared limited in older adults. Early evaluation and management of sleep-disordered breathing in patients with CKD may provide an opportunity to improve cognitive function.

Does Deficiency of von Willebrand Factor Protect Against Cardiovascular Disease? Analysis of a National Discharge Register

von Willebrand factor (VWF) plays a critical role in platelet adhesion and aggregation after vascular injury and at sites of high shear rate. Elevated VWF levels are associated with an increased risk of ischemic cardiovascular events; however, it is unclear whether VWF deficiency is protective against atherosclerosis. We aimed to compare the prevalence of cardiovascular disease (CVD) among patients with and without von Willebrand disease (VWD).

Peripheral blood cytokine and chemokine profiles in juvenile localized scleroderma: T-helper cell-associated cytokine profiles ☆, ☆☆, ★

OBJECTIVE To evaluate peripheral blood T-helper (TH) cell-associated cytokine and chemokine profiles in localized scleroderma (LS), and correlate them with clinical disease features, including disease activity parameters. METHODS A 29-plex Luminex platform was used to analyze the humoral profile of plasma samples from 69 pediatric LS patients and 71 healthy pediatric controls. Cytokine/chemokine levels were compared between these two groups and within LS patients, focusing on validated clinical outcome measures of disease activity and damage in LS. RESULTS Plasma levels of IP-10, MCP-1, IL-17a, IL-12p70, GM-CSF, PDGF-bb, IFN-α2, and IFN-γ were significantly higher in LS subjects compared to healthy controls. Analysis within the LS group demonstrated IP-10, TNF-α, and GM-CSF correlated with clinical measures of disease activity. Several cytokines/chemokines correlated with anti-histone antibody, while only a few correlated with positive ANA and single-stranded DNA antibody. CONCLUSION This is the first time that multiple cytokines and chemokines have been examined simultaneously in LS. In general, a TH1 (IFN-γ) and TH17 (IL-17a) predominance was demonstrated in LS compared to healthy controls. There is also an IFN-γ signature with elevated IP-10, MCP-1, and IFN-γ, which has been previously demonstrated in systemic sclerosis, suggesting a shared pathophysiology. Within the LS patients, those with active disease demonstrated IP-10, TNF-α, and GM-CSF, which may potentially serve as biomarkers of disease activity in the clinical setting.

Venous thromboembolism in pregnant women with sickle cell disease: A retrospective database analysis☆

INTRODUCTION The risk of venous thromboembolism (VTE) is higher during pregnancy, with an incidence between 0.05 and 0.2%, and among persons with sickle cell disease (SCD), yet the rates and risk factors, such as pneumonia, vasooclusive crisis (VOC), and acute chest syndrome (ACS), associated with pregnancy-related VTE are not firmly established in SCD. METHODS Inpatient hospital discharge data from 2007-2011 were obtained from the Pennsylvania Health Care Cost Containment Council to estimate the rate of VTE among African American delivery hospitalizations with SCD and to compare pregnancy complications and medical comorbidities among pregnant women with SCD. RESULTS Among 212 hospitalized deliveries in African-American women with SCD, 6 (2.8%, 95% CI 1.0%-5.9%) had VTE compared to 0.05 to 2.0% in the general population. Risk factors for VTE included pneumonia and diabetes mellitus. Overall, the prevalence of VTE, among hospitalized deliveries in SCD women with pneumonia, VOC, and/or ACS, 6.6%, was significantly greater than among those without these conditions, 2.2%, p<0.001. CONCLUSION Pregnancy-related VTE in women with SCD appears to be 1.5 to 5 times greater than pregnancy-related VTE in the general population. The higher prevalence of VTE among pregnant women with pneumonia, VOC, and/or ACS, and their potential clinical overlap, suggests that VTE may be missed in such women. We conclude that VTE in pregnant women with SCD may be more common than previously reported, and such women might be candidates for thromboprophylaxis.

Estimations of dietary vitamin D requirements in black and white children

Background:The Institute of Medicine (IOM) dietary guidelines for vitamin D are based on limited pediatric data. Our objective was to estimate the dietary vitamin D requirements for maintaining serum 25-hydroxyvitamin D [25(OH)D] concentrations at the various IOM-considered thresholds of vitamin D status (12, 16, and 20 ng/ml) during fall and winter in children.Methods:Ninety-six healthy 8- to 14-y-old Pittsburgh-area black and white children enrolled in a randomized, placebo-controlled trial of vitamin D3 1,000 IU daily for 6 mo with baseline and 2-mo follow-up assessments completed during October through April were studied. Vitamin D intake from diet and study supplement adjusted for adherence and serum 25(OH)D were measured.Results:The vitamin D intakes needed to maintain serum 25(OH)D concentrations at 12, 16, and 20 ng/ml in 90% of the children were 581, 1,062, and 1543 IU/day, respectively. The estimated vitamin D intakes needed to maintain serum 25(OH)D concentrations at 20 ng/ml in 97.5% of the children was 2,098 IU/day.Conclusion:Our data suggest that the current vitamin D recommended dietary allowance (RDA) (600 IU/day) is insufficient to cover the skeletal health needs of at least 50% of black and white children.