Expanding the phenotype of hawkinsinuria: new insights from response to N-acetyl-L-cysteine.

Hawkinsinuria is a rare disorder of tyrosine metabolism that can manifest with metabolic acidosis and growth arrest around the time of weaning off breast milk, typically followed by spontaneous resolution of symptoms around 1 year of age. The urinary metabolites hawkinsin, quinolacetic acid, and pyroglutamic acid can aid in identifying this condition, although their relationship to the clinical manifestations is not known. Herein we describe clinical and laboratory findings in two fraternal twins with hawkinsinuria who presented with failure to thrive and metabolic acidosis. Close clinical follow-up and laboratory testing revealed previously unrecognized hypoglycemia, hypophosphatemia, combined hyperlipidemia, and anemia, along with the characteristic urinary metabolites, including massive pyroglutamic aciduria. Treatment with N-acetyl-L-cysteine (NAC) restored normal growth and normalized or improved most biochemical parameters. The dramatic response to NAC therapy supports the idea that glutathione depletion plays a key role in the pathogenesis of hawkinsinuria.

Treatment of methylmalonic acidemia by liver or combined liver-kidney transplantation.

OBJECTIVE: To assess biochemical, surgical, and long-term outcomes of liver (LT) or liver-kidney transplantation (LKT) for severe, early-onset methylmalonic acidemia/acid (MMA). STUDY DESIGN: A retrospective chart review (December 1997 to May 2012) of patients with MMA who underwent LT or LKT at Lucile Packard Children's Hospital at Stanford. RESULTS: Fourteen patients underwent LT (n = 6) or LKT (n = 8) at mean age 8.2 years (range 0.8-20.7). Eleven (79%) were diagnosed during the neonatal period, including 6 by newborn screening. All underwent deceased donor transplantation; 12 (86%) received a whole liver graft. Postoperative survival was 100%. At a mean follow-up of 3.25 ± 4.2 years, patient survival was 100%, liver allograft survival 93%, and kidney allograft survival 100%. One patient underwent liver re-transplantation because of hepatic artery thrombosis. After transplantation, there were no episodes of hyperammonemia, acidosis, or metabolic decompensation. The mean serum MMA at the time of transplantation was 1648 ± 1492 µmol/L (normal <0.3, range 99-4420). By 3 days, post-transplantation levels fell on average by 87% (mean 210 ± 154 µmol/L), and at 4 months, they were 83% below pre-transplantation levels (mean 305 ± 108 µmol/L). Developmental delay was present in 12 patients (86%) before transplantation. All patients maintained neurodevelopmental abilities or exhibited improvements in motor skills, learning abilities, and social functioning. CONCLUSIONS: LT or LKT for MMA eradicates episodes of hyperammonemia, results in excellent long-term survival, and suggests stabilization of neurocognitive development. Long-term follow-up is underway to evaluate whether patients who undergo early LT need kidney transplantation later in life.

Impact of rurality on maternal and infant health indicators and outcomes in Maine.

INTRODUCTION: Rural residents may face health challenges related to geographic barriers to care, physician shortages, poverty, lower educational attainment, and other demographic factors. In maternal and child health, these disparities may be evidenced by the health risks and behaviors of new mothers, the health of infants born to these mothers, and the care received by both mothers and infants. METHODS: To determine the impact of rurality on maternal and child health in Maine, USA, 11 years of data (2000-2010) for the state of Maine from the Pregnancy Risk Assessment Monitoring System (PRAMS) project were analyzed. PRAMS is a national public health surveillance system that uses questionnaires to survey women who had delivered live infants in the previous 2-4 months. Using a geographic information system, each questionnaire response was assigned a rurality tier (urban, suburban, large rural town, or isolated rural community) based on the rural-urban commuting area code of the town of residence of the mother. Results from the four rurality tiers were compared using the survey procedures in Statistical Analysis Software to adjust for the complex sampling strategy of the PRAMS dataset. Means (for continuous variables) and percentages (for categorical variables) were calculated for each rurality tier, along with 95% confidence intervals. Significant differences between rurality tiers were tested for using F-tests or χ2 tests. If significant differences between rurality tiers existed (p<0.05), specific tiers were judged to be different from each other if their 95% confidence intervals did not overlap. RESULTS: A total of 12 600 mothers responded to the PRAMS questionnaire during the study period. Compared to mothers from more urban areas, rural mothers were younger (10.5% of mothers from isolated rural areas were teenagers compared to 6.2% of mothers from urban areas), less well educated, less likely to be married, and more likely to live in lower income households (39.6% of isolated rural mothers had household incomes ≤US$20 000/year vs 28.8% of urban mothers). Rural mothers had higher pre-pregnancy body mass indexes (BMIs; average BMI 26.1 for isolated rural women vs 25.3 for urban women) and were more likely to smoke but less likely to drink alcohol (both before and during pregnancy). Compared to mothers from more urban areas, rural mothers were not sure they were pregnant until a later gestational age but received prenatal care just as early and were just as likely to receive prenatal care as early as they wished. There were no differences among rurality tiers in Caesarean section rates, rates of premature births (<37 weeks gestation), or rates of underweight births (<2500 g). However infants born to rural mothers were less likely to be breastfed (52.9% of isolated rural vs 60.9% of urban infants breast fed for ≥8 weeks). CONCLUSIONS: These results show that, while rural women face significant demographic and behavior challenges, their access to prenatal care, the care they receive while pregnant, and the outcomes of their pregnancies are similar to those of urban women. These results highlight areas where focused pre-pregnancy and prenatal education may improve maternal and child health in rural Maine.

Exploring the Development of Nursing Clinical Judgment Among Students Using Virtual Reality Simulation.

BACKGROUND: Virtual reality simulation (VRS) is an emerging pedagogy in nursing education. PURPOSE: The purpose of this qualitative exploratory study was 2-fold: to determine nursing students' learning experiences when engaged in VRS, and to explore learners' problem-solving/clinical reasoning approach after participation in a VRS clinical scenario. This article reports student descriptions of clinical reasoning/clinical judgment when considering their VRS experience. METHODS: Qualitative description provided a methodological orientation for the study. Widely accepted frameworks for nursing clinical judgment provided a theoretical basis. RESULTS: Focus group participant narratives reveal evidence about nursing clinical judgment when applied to established descriptions and phases. CONCLUSION: Study findings suggest that VRS experiences promote development of nursing clinical judgment among students.

Technology-Enhanced Health Promotion for College Students: A Seed Development Project.

Obesity is an issue for young adults in the U.S. This population is particularly vulnerable to weight gain as they move from adolescence to young adulthood, especially as they transition from high school to college. Adopting a health promotion approach, a university-based cluster of researchers, community advocates, and a technology partner embarked on a two-year seed development project that focused on development, implementation, and evaluation of a web-based healthy lifestyle intervention for college students. Using a mixed-method design, two convenience samples of residential university students were recruited to participate in a 4-week intervention called Eat, Move, Live, in which they interacted with a newly-created comprehensive website about management of a healthy lifestyle. Participants' post-intervention readiness for change increased by 15% (eating and life balance behaviors) to 23% (moving behaviors). Participants reported increased awareness of eating behaviors, and feelings of engagement in tracking their fruit and vegetable consumption. Findings suggest that technology may be utilized to enhance the effectiveness and efficiency of achieving students' individual goals related to healthy living. These preliminary findings have implications for increasing the development and implementation of technological approaches to health promotion for young adult students.

Triheptanoin: A Rescue Therapy for Cardiogenic Shock in Carnitine-acylcarnitine Translocase Deficiency.

Carnitine-acylcarnitine translocase (CACT) deficiency is a rare long-chain fatty acid oxidation disorder (LC-FAOD) with high mortality due to cardiomyopathy or lethal arrhythmia. Triheptanoin (UX007), an investigational drug composed of synthetic medium odd-chain triglycerides, is a novel therapy in development for LC-FAOD patients. However, cases of its safe and efficacious use to reverse severe heart failure in CACT deficiency are limited. Here, we present a detailed report of an infant with CACT deficiency admitted in metabolic crisis that progressed into severe cardiogenic shock who was successfully treated by triheptanoin. The child was managed, thereafter, on triheptanoin until her death at 3 years of age from a cardiopulmonary arrest in the setting of acute respiratory illness superimposed on chronic hypercarbic respiratory failure.

Wound wise: wounds in surgical patients who are obese.

The number of surgical patients who are obese in the United States is rising, a trend that's likely to continue. Such patients are at higher risk than nonobese patients are for surgical site infections and other complications such as dehiscence, pressure ulcers, deep tissue injury, and rhabdomyolysis. This article details the factors that can contribute to such complications, including a high number of comorbidities, and offers practical suggestions for preventing them. Nurses should understand that special equipment, precautions, and protocols may be needed at every stage of care, and that obese patients aren't anomalies but rather a part of a growing population with particular needs.

The Impact of Maternal Obesity and Excessive Gestational Weight Gain on Maternal and Infant Outcomes in Maine: Analysis of Pregnancy Risk Assessment Monitoring System Results from 2000 to 2010.

The objective of this study is to understand the relationships between prepregnancy obesity and excessive gestational weight gain (GWG) and adverse maternal and fetal outcomes. Pregnancy risk assessment monitoring system (PRAMS) data from Maine for 2000-2010 were used to determine associations between demographic, socioeconomic, and health behavioral variables and maternal and infant outcomes. Multivariate logistic regression analysis was performed on the independent variables of age, race, smoking, previous live births, marital status, education, BMI, income, rurality, alcohol use, and GWG. Dependent variables included maternal hypertension, premature birth, birth weight, infant admission to the intensive care unit (ICU), and length of hospital stay of the infant. Excessive prepregnancy BMI and excessive GWG independently predicted maternal hypertension. A high prepregnancy BMI increased the risk of the infant being born prematurely, having a longer hospital stay, and having an excessive birth weight. Excessive GWG predicted a longer infant hospital stay and excessive birth weight. A low pregnancy BMI and a lower than recommended GWG were also associated with poor outcomes: prematurity, low birth weight, and an increased risk of the infant admitted to ICU. These findings support the importance of preconception care that promotes achievement of a healthy weight to enhance optimal reproductive outcomes.

11-year trends in pregnancy-related health indicators in Maine, 2000-2010.

The objective of this study is to understand health and demographic trends among mothers and infants in Maine relative to the goals of Healthy People 2020. Pregnancy risk assessment monitoring system (PRAMS) data from Maine for 2000-2010 were used to determine yearly values of pregnancy-related variables. Means (for continuous variables) and percentages (for categorical variables) were calculated using the survey procedures in SAS. Linear trend analysis was applied with study year as the independent variable. The slope and significance of the trend were then calculated. Over the study period, new mothers in Maine became better educated but the fraction of households with incomes <$20,000/year remained stagnant. Maternal prepregnancy BMI increased. Average pregnancy weight gain decreased but the number of women whose pregnancy weight gain was within the recommended range was unchanged. The rates of smoking and alcohol consumption (before and during pregnancy) increased. The Caesarean section rate rose and the fraction of infants born premature (<37 wks gestation) or underweight (<2500 gms) remained unchanged. The fraction of infants who were breast-fed increased. These results suggest that, despite some positive trends, Maine faces significant challenges in meeting Healthy People 2020 goals.

Evaluation of pre- and postoperative physical activity participation in laparoscopic gastric banding patients.

BACKGROUND: Weight loss outcomes following laparoscopic adjustable gastric banding (LAGB) are widely variable, and physical activity (PA) participation improves these results. The purpose of this study was to retrospectively describe PA behaviors before and after LAGB and to evaluate the impact of PA on weight loss outcomes. METHODS: Participants were 172 individuals (145 females, mean age 43.3 ± 12.0 years, mean body mass index [BMI] 43.8 ± 5.1 kg/m(2)) who underwent LAGB at a university medical center. Height, weight, presence of comorbidities, and PA participation were assessed prior to and 3, 6, and 12 months after surgery. Those who reported engaging in ≥ 150 min of weekly moderate-to-vigorous PA (MVPA) were considered active. RESULTS: Less than 40 % of participants were active prior to surgery, while 31 % of those who were inactive before surgery became active at 6 months of follow-up. Unlike previous reports on gastric bypass patients, there was no statistically significant (p > 0.05) relationship between postoperative PA status and weight loss outcomes at 3, 6, or 12 months in LAGB patients. Interestingly, participants who reported ≥ 150 min of MVPA prior to surgery achieved approximately 10 % greater excess weight loss (p < 0.05) and a 2.4-kg/m(2) greater decrease in BMI (p < 0.05) at 1 year post-LAGB compared to those who were inactive preoperatively. CONCLUSIONS: In our sample, higher levels of preoperative PA participation were associated with improved weight loss outcomes following LAGB. We posit that higher preoperative volumes are indicative of habitual exercise and that those who report being active prior to surgery are likely to maintain these behaviors throughout follow-up.

Analysis of factors associated with durable remission of diabetes after Roux-en-Y gastric bypass.

BACKGROUND: Data on the durability of remission of type 2 diabetes mellitus (T2DM) after gastric bypass are limited. Our purpose was to identify the rate of long-term remission of T2DM and the factors associated with durable remission. METHODS: A total of 177 patients with T2DM who had undergone Roux-en-Y gastric bypass from 1993 to 2003 had 5-year follow-up data available. T2DM status was determined by interview and evaluation of the diabetic medications. Patients with complete remission or recurrence of T2DM were identified. RESULTS: Follow-up ranged from 5 to 16 years. Of the 177 patients, 157 (89%) had complete remission of T2DM with a decrease in their mean body mass index from baseline (50.2 +/- 8.2 kg/m(2)) to 31.3 +/- 7.2 kg/m(2) postoperatively (mean percentage of excess weight loss 70.0% +/- 18.6%). However, 20 patients (11.3%) did not have T2DM remission despite a mean percentage of excess weight loss of 58.2% +/- 12.3% (P <.0009). Of the 157 patients with initial remission of their T2DM, 68 (43%) subsequently developed T2DM recurrence. Remission of T2DM was durable in 56.9%. Durable (>5-year) resolution of T2DM was greatest in the patients who originally had either controlled their T2DM with diet (76%) or oral hypoglycemic agents (66%). The rate of T2DM remission was more likely to be durable in men (P = .00381). Weight regain was a statistically significant, but weak predictor, of T2DM recurrence. CONCLUSION: Early remission of T2DM occurred in 89% of patients after Roux-en-Y gastric bypass. T2DM recurred in 43.1%. Durable remission correlated most closely with an early disease stage at gastric bypass.

Drain amylase levels are an adjunct in detection of gastrojejunostomy leaks after Roux-en-Y gastric bypass.

BACKGROUND: Because anastomotic leaks after gastric bypass surgery can have devastating consequences for the patient, early detection is highly desirable. This and many other bariatric surgical centers have discontinued routine use of upper gastrointestinal contrast x-ray because of the lack of cost-effectiveness, discomfort to the patient, and the failure of the study to detect some leaks. We postulated that drain amylase levels from a juxta-anastomotic drain would detect the presence of salivary amylase and be a sensitive test for gastrojejunostomy leak. STUDY DESIGN: Routine measurement of amylase levels from a drain adjacent to the gastrojejunostomy was instituted in 2005. Leak was defined as anastomotic incompetence documented either by confirmatory upper gastrointestinal contrast x-rays, CT scans, or reoperation. RESULTS: On postoperative day 1, the drain amylase levels of 350 patients were tested. Seventeen patients had postoperative leaks (4.8%); 14 of the 17 had leaks at the gastrojejunal anastomosis (82%). The median peak value for patients without leak was 79.5 IU/L+/-1,436.2 SD; for patients with leak it was 6,307 IU/L+/-50,166 (p < 0.0001, Wilcoxon rank sum test). All patients but one with a leak had a drain amylase > 400 IU/L. A drain amylase value of 400 IU/L empirically defines gastrojejunostomy leaks with a sensitivity of 94.1% and a specificity of 90.0%. Negative predictive value of a drain amylase level < 400 IU/L in excluding leak was 99.6%. Positive predictive value of a drain amylase > 400 IU/L in predicting leak was 33.3%. Of the 17 leaks, 7 required reoperation at a median of 1 day (mean, 1.6+/-1.1 days). There was no perioperative mortality. CONCLUSIONS: Drain amylase levels are a simple, low-cost adjunct with high sensitivity and specificity that can help to identify patients who may have a leak after gastric bypass surgery.

Bariatric and body-contouring surgery: a continuum of care for excess and lax skin.

Obesity continues to reach epidemic proportions in the United States, with more than 60% of Americans classified as obese. Correspondingly, the number of individuals undergoing bariatric surgery has increased dramatically. There are several bariatric procedures that may be performed, with laparoscopic adjusted gastric band (LABG) the newest. Following bariatric surgery and massive weight loss, patients may be left with problematic loose, hanging skin. The loose or redundant skin may occur on the abdomen, back, upper arms, and inner and outer thighs. Body-contouring surgery may be performed to correct the residual excess tissues. Prebariatric planning for plastic surgery to correct skin defects, as well as postoperative bariatric and body-contouring care, is discussed.