Weight loss in achalasia is determined by its phenotype.

Patients with achalasia present with dysphagia, regurgitation, and varying degrees of weight loss. However, despite it being a disorder of the lower esophageal sphincter with functional obstruction in all patients, it is unclear why certain patients lose significantly more weight compared to others. The aims of this study are to assess demographic, clinical, and manometric characteristics of a large cohort of patients with achalasia to determine potential correlates of weight loss in this population. Patients with diagnosis of achalasia referred to our center between 2009 and 2016 were evaluated. Demographic and physiologic tests between those with and without weight loss were compared. The cohort of patients with initial self-reported weight loss were studied to determine change in weight after intervention (pneumatic dilation or myotomy). The Kruskal-Wallis test was used for comparison of continuous variables between groups and Pearson's χ2 test was used for comparison of categorical variables between groups. 138 patients with achalasia were evaluated. 35 patients were excluded due to lack of manometric data and 3 from lack of documented weight resulting in the study population of 100 patients with achalasia [51% male, median age: 56 years]. Weight loss was reported in 51/100 (51%) patients. BMI was lower in patients who reported weight loss (25 vs. 31, P < 0.001) with a median weight loss of 28 lbs (14-40 lbs). There were no significant differences in age at diagnosis, gender, or symptom presentation (dysphagia, regurgitation, or chest pain) between the groups. However, more patients with type II achalasia (63%) reported weight loss as compared to other sub-types (P = 0.013). 73% of type III achalasia denied having weight loss. Patients who denied weight loss had symptoms for longer duration (24 vs. 12 months, P < 0.001) and had lower mean residual LES pressure (20 vs. 30 mmHg, P = 0.006). Postintervention 42% of patients reported no weight regain despite appropriate therapy for achalasia with median follow-up of 22 months (range: 6-90 months). Type II achalasia patients are most likely and type III achalasia are least likely to have weight loss compared to type I achalasia. Given that no other demographic/physiologic parameters predicted weight loss, the role of underlying inflammatory cascade in achalasia phenotypes deserves special attention.

Randomized controlled trial comparing esophageal dilation to no dilation among adults with esophageal eosinophilia and dysphagia.

The role of esophageal dilation in patients with esophageal eosinophilia with dysphagia remains unknown. The practice of dilation is currently based on center preferences and expert opinion. The aim of this study is to determine if, and to what extent, dysphagia improves in response to initial esophageal dilation followed by standard medical therapies. We conducted a randomized, blinded, controlled trial evaluating adult patients with dysphagia and newly diagnosed esophageal eosinophilia from 2008 to 2013. Patients were randomized to dilation or no dilation at time of endoscopy and blinded to dilation status. Endoscopic features were graded as major and minor. Subsequent to randomization and endoscopy, all patients received fluticasone and dexlansoprazole for 2 months. The primary study outcome was reduction in overall dysphagia score, assessed at 30 and 60 days post-intervention. Patients with severe strictures (less than 7-mm esophageal diameter) were excluded from the study. Thirty-one patients were randomized and completed the protocol: 17 randomized to dilation and 14 to no dilation. Both groups were similar with regard to gender, age, eosinophil density, endoscopic score, and baseline dysphagia score. The population exhibited moderate to severe dysphagia and moderate esophageal stricturing at baseline. Overall, there was a significant (P < 0.001) but similar reduction in mean dysphagia score at 30 and 60 days post-randomization compared with baseline in both groups. No significant difference in dysphagia scores between treatment groups after 30 (P = 0.93) or 60 (P = 0.21) days post-intervention was observed. Esophageal dilation did not result in additional improvement in dysphagia score compared with treatment with proton pump inhibitor and fluticasone alone. In patients with symptomatic esophageal eosinophilia without severe stricture, dilation does not appear to be a necessary initial treatment strategy.

Symptom association probability does not reliably distinguish functional heartburn from reflux hypersensitivity.

BACKGROUND: Symptom association probability (SAP) is thought to distinguish reflux hypersensitivity from functional disorders. A diagnosis of hypersensitive oesophagus (SAP-positive) indicates that gastro-oesophageal reflux disease (GERD) is the cause of continued symptoms. AIM: To conduct an analysis of pH and symptom criteria that lead to a diagnosis of SAP-positivity METHODS: We calculated SAP for 205 patients with GERD symptoms refractory to proton pump inhibitor (PPI) therapy who underwent endoscopy with wireless pH monitoring from 2007 to 2014. Patients were divided into three groups: pH-negative with no oesophagitis (n = 45), pH-positive with no oesophagitis (n = 130), and patients with oesophagitis (n = 30). We constructed a 2 × 2 table of symptom and reflux event association and quantified the number of 2-minute intervals for each of the 2 × 2 variables that distinguished SAP-positive from SAP-negative. In a separate cohort of 58 patients who had undergone anti-reflux surgery, we evaluated the effects of pre-surgery SAP. RESULTS: The difference in symptom association parameters that led to a diagnosis of an SAP-positive was small (2.98% in oesophagitis-positive; 1.56% in oesophagitis-negative/pH-positive; 0.48% in oesophagitis-negative/pH-negative). In the pH-negative/oesophagitis-negative group, a difference of 0.48% led to a diagnosis of hypersensitivity. There was significant variability in SAP values between day 1 and day 2 of pH testing in all groups, with the greatest in the oesophagitis-positive group, despite objective evidence for reflux (27% in oesophagitis-positive, 19% pH-positive/oesophagitis-negative, and 7% in pH-negative/oesophagitis-negative). Pre-surgery SAP was not associated with response to anti-reflux surgery. CONCLUSION: In PPI-refractory GERD, SAP cannot accurately distinguish reflux hypersensitivity from functional oesophageal symptoms.

Oral colostrum priming shortens hospitalization without changing the immunomicrobial milieu.

OBJECTIVE: Oral colostrum priming (OCP) after birth in preterm infants is associated with improved weight gain and modification of the oral immunomicrobial environment. We hypothesized that OCP would modify salivary immune peptides and the oral microbiota in preterm infants. STUDY DESIGN: We conducted a prospective, randomized clinical trial to determine the effects of OCP on salivary immune peptide representation in preterm infants (<32 weeks completed gestation at birth). Saliva samples were collected before and after OCP. Salivary immune peptide representation was determined via mass spectroscopy. Oral microbiota representation was determined via sequencing of the 16S rRNA gene. RESULTS: Neonates who received OCP (n=48) had a 16-day reduction in the median length of hospitalization as compared with infants who did not receive OCP (n=51). No differences in salivary immune peptide sequence representation before OCP between groups were found. Longitudinal changes in peptides were detected (lysozyme C, immunoglobulin A, lactoferrin) but were limited to a single peptide difference (α-defensin 1) between primed and unprimed infants after OCP. We found no difference in microbial diversity between treatment groups at any time point, but diversity decreased significantly over time in both groups. OCP treatment marginally modified oral taxa with a decline in abundance of Streptococci in the OCP group at 30 days of life. CONCLUSIONS: OCP had neither an effect on the salivary peptides we examined nor on overall oral bacterial diversity and composition. Infants who received OCP had a reduced length of hospitalization and warrants further investigation.

Dietary carbohydrate intake, insulin resistance and gastro-oesophageal reflux disease: a pilot study in European- and African-American obese women.

BACKGROUND: Although obesity rates are higher in African-American than European-American women, gastro-oesophageal reflux disease (GERD) and its comorbidities are more prevalent in European-American women. A common denominator for increased adiposity, and consequent insulin resistance, is excess dietary macronutrient intake - which may promote greater prevalence and severity of GERD in women. AIM: To investigate whether GERD is more robustly associated with dietary carbohydrate intake, particularly dietary simple carbohydrate intake, and insulin resistance in European-American women. METHODS: About 144 obese women were assessed at baseline and 16 weeks after consuming a high-fat/low-carbohydrate diet. GERD diagnosis and medication usage was confirmed in medical records with symptoms and medications assessed weekly. RESULTS: About 33.3% (N = 33) of European-American and 20.0% (N = 9) of African-American women had GERD at baseline. Total carbohydrate (r = 0.34, P < 0.001), sugars (r = 0.30, P = 0.005), glycaemic load (r = 0.34, P = 0.001) and HOMAIR (r = 0.30, P = 0.004) were associated with GERD, but only in European-American women. In response to high-fat/low-carbohydrate diet, reduced intake of sugars was associated with reduced insulin resistance. By the end of diet week 10, all GERD symptoms and medication usage had resolved in all women. CONCLUSIONS: GERD symptoms and medication usage was more prevalent in European-American women, for whom the relationships between dietary carbohydrate intake, insulin resistance and GERD were most significant. Nevertheless, high-fat/low-carbohydrate diet benefited all women with regard to reducing GERD symptoms and frequency of medication use.

Increasing F2-isoprostanes in the first month after birth predicts poor respiratory and neurodevelopmental outcomes in very preterm infants.

OBJECTIVE: This study examined the association between increased early oxidative stress, measured by F2-isoprostanes (IsoPs), and respiratory morbidity at term equivalent age and neurological impairment at 12 months of corrected age (CA). STUDY DESIGN: Plasma samples were collected from 136 premature infants on days 14 and 28 after birth. All participants were infants born at ⩽28 weeks of gestational age enrolled into the Prematurity and Respiratory Outcomes Program (PROP) study. Respiratory morbidity was determined at 40 weeks of postmenstrual age (PMA) by the Respiratory Severity Index (RSI), a composite measure of oxygen and pressure support. Neurodevelopmental assessment was performed using the Developmental Assessment of Young Children (DAYC) at 12 months of CA. Multivariable logistic regression models estimated associations between IsoP change, RSI and DAYC scores. Mediation analysis was performed to determine the relationship between IsoPs and later outcomes. RESULTS: Developmental data were available for 121 patients (90% of enrolled) at 12 months. For each 50-unit increase in IsoPs, regression modeling predicted decreases in cognitive, communication and motor scores of -1.9, -1.2 and -2.4 points, respectively (P<0.001). IsoP increase was also associated with increased RSI at 40 weeks of PMA (odds ratio=1.23; P=0.01). RSI mediated 25% of the IsoP effect on DAYC motor scores (P=0.02) and had no significant impact on cognitive or communication scores. CONCLUSIONS: In the first month after birth, increases in plasma IsoPs identify preterm infants at risk for respiratory morbidity at term equivalent age and worse developmental outcomes at 12 months of CA. Poor neurodevelopment is largely independent of respiratory morbidity.

Volume guarantee pressure support ventilation in extremely preterm infants and neurodevelopmental outcome at 18 months.

OBJECTIVE: Compared with pressure-controlled ventilation (PCV), volume-targeted ventilation is associated with decreased neonatal complications, including the combined outcome of death or bronchopulmonary dysplasia. However, little is known about its effect on neurodevelopmental outcome. We evaluated the hypothesis that as compared with PCV, volume-targeted ventilation reduces the risk of the combined outcome of neurodevelopmental impairment or death in very low birth weight infants. STUDY DESIGN: We studied a cohort of extremely preterm infants managed with either volume guarantee pressure support ventilation (VGPSV; n=135) or PCV (n=135). Infants were evaluated at 18 months adjusted age with a standardized neurological examination and the Bayley Scales of Infant and Toddler Development-third edition. Logistic regression models were used to evaluate the association of ventilation mode and neurodevelopmental outcome. RESULT: Rates of pulmonary interstitial emphysema (odds ratio 0.6; 95% confidence limits: 0.4, 0.8), hypotension (odds ratio: 0.7; 95% confidence limits: 0.5, 0.9) and mortality (odds ratio 0.45; 95% confidence limits: 0.22, 0.9) were lower among infants treated with VGPSV. The infants in the VGPSV group had a significantly shorter duration on mechanical ventilation compared with infants in the PCV group (log-rank test P<0.01). Seventy percent (155/221) of survivors were evaluated at 18 months adjusted age. A trend towards benefit for the combined outcome of death or neurodevelopmental impairment was seen in the VGPSV group but did not reach statistical significance (odds ratio: 0.59; 95% confidence limits: 0.32, 1.08). CONCLUSION: VGPSV was associated with a decreased risk of short-term complications but not long-term developmental impairment in this modest-sized cohort.

Asymmetric septal hypertrophy in patients on long-term hemodialysis.

Echocardiographic studies were performed in 23 hypertensive patients who were receiving therapy with long-term hemodialysis. Five patients (22 percent) had normal thickness of the left ventricular wall. Eleven (48 percent) had symmetric left ventricular hypertrophy, and seven (30 percent) showed asymmetric septal hypertrophy, with a ratio of septal to posterior wall thickness of 1.3 or greater. The latter group differed from patients with hypertrophic cardiomyopathy in that patients on long-term hemodialysis had a dilated left ventricular dimension, a relatively normal diastolic slope of the mitral valve, absence of systolic motion of the mitral valve, and a septal to posterior wall ratio of less than 1.5. A high incidence of asymmetric septal hypertrophy in this and other studies indicates that this condition is not specific for hypertrophic cardiomyopathy. We suggest that in addition to asymmetric septal hypertrophy, the diagnosis of hypertrophic cardiomyopathy should be made in the light of the clinical picture, as well as other echocardiographic features.

Electrically enhanced extraction of penicillin G into dichloromethane.

The application of electrically enhanced liquid-liquid extraction techniques to the recovery and purification of penicillin G from aqueous solutions and from untreated mycelial culture broth is described. Experiments at laboratory scale have shown that extraction rates into dichloromethane at pH 4.0 may be increased by factors of up to five-fold by electrostatically spraying penicillin G solutions into a continuum of solvent held in electrical tension. The experimental studies revealed that in small spray column contactors, electrostatic spray conditions, once initiated at nozzle voltages in excess of 10 kV, could be sustained at nozzle voltages as little as 4 kV. The results demonstrate the potential of this technique as an alternative to mechanically augmented liquid-liquid contact for the intensification of whole broth extraction processes.

Adverse neurodevelopmental outcomes after exposure to phenobarbital and levetiracetam for the treatment of neonatal seizures.

OBJECTIVE: Compare neurodevelopment after levetiracetam (LEV) and phenobarbital (PB) for neonatal seizures. STUDY DESIGN: Retrospective study of infants who received antiepileptic drugs (AEDs) for neonatal seizures. Effect of cumulative exposure to LEV and PB on outcomes of death, cerebral palsy (CP) and Bayley Scales of Infant Development (BSID) scores were evaluated at 24 months corrected age. Analyses were adjusted for number of electrographic seizures and gestational age. RESULT: In 280 infants with comparable seizure etiology and cranial imaging results, increased exposure to PB was associated with worse BSID cognitive and motor scores (8.1- and 9-point decrease per 100 mg kg(-1); P=0.01). The effect was less with LEV (2.2- and 2.6-point decrease per 300 mg kg(-1) LEV (P=0.01)). CP probability increased by 2.3-fold per 100 mg kg(-1) PB and was not associated with increasing LEV. CONCLUSION: Increased exposure to PB is associated with worse neurodevelopmental outcomes than LEV. Prospective studies of outcomes of neonatal exposure to AEDs are essential.

An oropharyngeal pH monitoring device to evaluate patients with chronic laryngitis.

BACKGROUND: Diagnostics for gastro-esophageal reflux disease (GERD) are suboptimal because of limited sensitivity. We performed in vitro and in vivo studies to systematically assess the performance characteristics of an oropharyngeal pH probe. METHODS: In vitro studies compared the oropharyngeal probe with a standard pH catheter in liquid and aerosolized solutions, pH 1-7. The accuracy of measurements, deviation from target pH, and time to equilibrium pH were determined. Simultaneous distal esophageal pH measurements were obtained in 11 patients with GERD. Oropharyngeal and distal esophageal reflux parameters were measured for controls (n = 20), patients with GERD (n = 17), and patients with chronic laryngitis (n = 10). KEY RESULTS: In the liquid phase, at pH 4-5, the oropharyngeal probe had less deviation from the target value than the standard catheter; deviation in the vapor phase was similar (0.4 pH units). Median (interquartile) time to reach equilibrium pH was significantly (P < 0.001) faster with the oropharyngeal than the standard probe. In comparing simultaneous distal esophageal pH characteristics, 96% of recordings with the new and standard probes were in agreement to within ± 1.0 pH unit; 71% of recordings were in agreement within ± 0.5 pH units. Patients with chronic laryngitis had significantly higher levels of oropharyngeal acid exposure at pH <4, <5, and <6, in the upright position than patients with GERD or controls (P < .001). CONCLUSIONS & INFERENCES: Oropharyngeal pH monitoring appears to be more sensitive than traditional pH monitoring in evaluation of patients with extraesophageal reflux. It is a promising tool in evaluation of this difficult group of patients.

Correlation of abdominal rSO2 with superior mesenteric artery velocities in preterm infants.

OBJECTIVE: Near-infrared spectroscopy (NIRS) is used to monitor brain and kidney perfusion in at-risk premature and term neonates. Although NIRS holds potential for bedside monitoring of intestinal perfusion, there is insufficient evidence showing correlation with mesenteric blood flow. To determine if an association exists between abdominal regional oxygen saturation (A-rSO2) and mesenteric blood flow, we compared changes in A-rSO2 to changes in blood flow velocity in the superior mesenteric artery (SMA) before and after feedings in very-low birthweight infants. STUDY DESIGN: A-rSO2 was continuously monitored midline below the umbilicus for 3 days in 18 stable 25 to 31 week bolus-fed infants (median BW 1203 g, median age 5 days). We compared change in SMA velocity from immediately before to 10 min and 60 to 120 min after feeding with change in A-rSO2 over the same time. Spearman's rank correlation was used to ascertain if a significant association existed. RESULT: Change in A-rSO2 was significantly associated with change in systolic, diastolic, and mean SMA velocity from fasting to 60 to 120 min after feeding (P=0.016, 0.021, 0.010) and from 10 min after a feed to 60 to 120 min after feeding (P=0.009, 0.035, 0.032). CONCLUSION: In very preterm infants, A-rSO2 reflects blood flow in the SMA and can provide non-invasive continuous monitoring of intestinal perfusion. Further studies are indicated to determine the sensitivity of NIRS to detect early intestinal pathology in this population.

Necrotizing enterocolitis in infants with periventricular hemorrhagic infarction: associations and outcomes.

BACKGROUND: Necrotizing enterocolitis (NEC) and periventricular hemorrhagic infarction (PVHI) are complications of prematurity associated with poor neurodevelopmental outcomes. OBJECTIVES: We characterized temporal and causal associations between NEC and type of PVHI as well as associations with outcomes. METHODS: This was a multicenter retrospective study of infants with birth weight <1,500 g and diagnosis of PVHI by a pediatric radiologist at 3 neonatal intensive care units in North Carolina, USA, between January 1998 and December 2004. NEC was confirmed using radiological and surgical pathology findings. Infants were assessed by 3 years using the Bayley Scales of Infant Development, second edition. RESULTS: 35 of 112 (31%) of study patients developed NEC. NEC was diagnosed subsequent to PVHI by a median of 16.6 days (95% CI [9.5, 24.9], p < 0.0001). Indomethacin use and the presence of bilateral PVHI were associated with an increased risk of subsequent NEC (OR 2.8, 95% CI [1.1, 7.2] and OR 2.4, 95% CI [1.1, 5.7], respectively). Having bilateral versus unilateral PVHI was associated with a 2.34-fold increased risk of death (95% CI [1.27, 4.33], p = 0.007). NEC was not associated with worse motor outcomes in this population. Overall, the probability of a mental development index >70 was greatest for infants with unilateral PVHI versus bilateral PVHI, although the presence of NEC was associated with worse cognitive outcomes in both groups. CONCLUSIONS: Premature infants with PVHI often subsequently develop NEC, especially if they have bilateral PVHI and are exposed to indomethacin. While NEC results in worse neurodevelopmental outcomes, PVHI severity appears more important to the outcome of these infants.

A silver-alginate-coated dressing to reduce peripherally inserted central catheter (PICC) infections in NICU patients: a pilot randomized controlled trial.

OBJECTIVE: Our aim was to evaluate the safety of a silver-alginate-containing dressing to reduce peripherally inserted central catheter (PICC) infections in neonatal intensive care unit (NICU) patients. STUDY DESIGN: Patients were randomized 3:1 to receive a patch containing silver, alginate and maltodextrin or standard of care. Patches were placed under the regular transparent retention dressing at the PICC exit site at insertion and were replaced with every dressing change at least every 2 weeks until PICC discontinuation. All study infants were monitored for adverse skin reactions. RESULT: A total of 100 infants were followed up for 1922 person-days, including 75 subjects with 89 PICCs who received the patch. The median birth weight (1330 g) and median gestational age (30 weeks) was lower in the patch group when compared with the controls (P=0.001 and 0.005, respectively). Study patients received the patch with their PICC at a median age of 5 days; the patch stayed in place for a median of 13 days. We noted no adverse skin reactions and found no evidence that the patch alters the microbiology of PICC-associated infections. CONCLUSION: This pilot trial suggests that silver-alginate-coated dressings are skin safe and their inclusion in future trials aimed at reduction of PICC-associated bloodstream infections in the NICU should be considered.

Dilated intercellular space in chronic laryngitis and gastro-oesophageal reflux disease: at baseline and post-lansoprazole therapy.

BACKGROUND: Dilation of intercellular spaces is reported to be an early morphological marker in gastro-oesophageal reflux. It remains unknown if this marker is useful in diagnosing reflux-related chronic laryngitis. AIM: To determine histopathology and electron microscopic changes in oesophageal and laryngeal epithelium in chronic laryngitis. METHODS: In this prospective blinded study, we enrolled 53 participants: 15 controls, 20 patients with GERD and 18 patients with chronic laryngitis. The latter two groups were subsequently treated with lansoprazole 30 mg bid for 12-weeks. Baseline and postacid suppressive therapy biopsies were obtained from distal oesophagus and laryngeal postcricoid areas. Biopsy specimens were evaluated for histopathology and dilated intercellular space changes. RESULTS: There was no significant increase in oesophageal or laryngeal epithelium intercellular spaces among GERD or laryngitis patients compared with controls at baseline or postacid suppressive therapy. Only patients with GERD had significantly (P = 0.03) higher proportion of moderate-to-severe oesophageal spongiosis and basal cell hyperplasia, which normalized postacid suppressive therapy. CONCLUSIONS: There was no increase in the width of intercellular spaces in the oesophagus or larynx in GERD or chronic laryngitis at baseline or postacid suppressive therapy. Our findings question the uniform presence of dilated intercellular space in patients with GERD.

Inhibition of 3-phosphoglycerate dehydrogenase from Pisum sativum by purine nucleotides.

The inhibition of 3-phosphoglycerate dehydrogenase from etiolated pea epicotyls by purine nucleoside di- and tri-phosphates is linear, competitive with regard to NADH, and the nucleotides are mutually exclusive in their binding. Free ATP and ADP are more effective inhibitors than are the respective magnesium complexes.

The isolation and characterization of 3-phosphoglycerate dehydrogenase from peas.

1. 3-Phosphoglycerate dehydrogenase was purified 400-fold from crude extracts of etiolated pea epicotyls. 2. Michaelis constants were determined for all four substrates. 3. Loss of sensitivity to inhibition by l-serine occurs on purification. 4. The purified enzyme is inhibited by thiol-group reagents and, with N-ethyl-maleimide, protection is afforded by 3-phosphoglycerate though not by NAD(+).