Long-term outcome of pneumatic dilation in the treatment of achalasia

OBJECTIVE: Achalasia is a well-defined esophageal motor disorder for which pneumatic dilation is an established therapeutic method. Even though it has been used for several years, there are limited data on the long-term outcomes of patients treated with this procedure. Hence, we aimed to evaluate the long-term efficacy of pneumatic dilation to control the symptoms of achalasia. METHODS: The medical records of all patients treated in our unit for achalasia with pneumatic dilation were reviewed. We identified the long-term result of the initial procedure, the date of the first dilation, and the time interval between dilation and retreatment. RESULTS: Of 260 patients who were treated with pneumatic dilation, 153 (67 men, 86 women) were followed up for more than 5 yr. The mean follow-up period was 11.09 +/- 3.91 yr, and the success rate of the dilation was 75.8%. Among these patients, 35 (19 men, 16 women) had follow-up periods of more than 15 yr. The mean follow-up time of those patients was 16.56 +/- 1.09 yr, and the success rate was 51.4%. Kaplan-Meier survival analysis showed that, overall, 50% of patients develop recurring symptoms after 10.92 yr. CONCLUSIONS: Although 51.4% of patients continued to be in clinical remission more than 15 yr after the initial pneumatic dilation, the long-term success rate of pneumatic dilation seems to drop progressively with time.     

Resampling to Address the Winner's Curse in Genetic Association Analysis of Time to Event

The “winner's curse” is a subtle and difficult problem in interpretation of genetic association, in which association estimates from large‐scale gene detection studies are larger in magnitude than those from subsequent replication studies. This is practically important because use of a biased estimate from the original study will yield an underestimate of sample size requirements for replication, leaving the investigators with an underpowered study. Motivated by investigation of the genetics of type 1 diabetes complications in a longitudinal cohort of participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Genetics Study, we apply a bootstrap resampling method in analysis of time to nephropathy under a Cox proportional hazards model, examining 1,213 single‐nucleotide polymorphisms (SNPs) in 201 candidate genes custom genotyped in 1,361 white probands. Among 15 top‐ranked SNPs, bias reduction in log hazard ratio estimates ranges from 43.1% to 80.5%. In simulation studies based on the observed DCCT/EDIC genotype data, genome‐wide bootstrap estimates for false‐positive SNPs and for true‐positive SNPs with low‐to‐moderate power are closer to the true values than uncorrected naïve estimates, but tend to overcorrect SNPs with high power. This bias‐reduction technique is generally applicable for complex trait studies including quantitative, binary, and time‐to‐event traits.     

Postbiopsy intramural hematoma of the duodenum in an adult with Noonan's syndrome

Intramural duodenal hematoma is a rare complication of endoscopic biopsy. It is usually seen in children with growth failure and in patients with bleeding disorders or who are anticoagulated. It is frequently associated with acute pancreatitis. We present a case of an adult patient with Noonan's syndrome who developed postbiopsy intraduodenal hematoma. Abdominal ultrasound and computed tomography scan established the diagnosis. Conservative treatment was successful. According to a brief review of the literature, patients with Noonan's syndrome may develop hematoma after sampling of the duodenum because they present all the main predisposing factors. Additionally, pulmonic valve stenosis may be another predisposing factor, but this may warrant further investigation.     

Peridevice Leak Following Amplatzer Left Atrial Appendage Occlusion: Cardiac Computed Tomography Classification and Clinical Outcomes

ObjectivesThis study aimed to investigate cardiac computed tomography (CT) and transesophageal echocardiography (TEE) peridevice leak (PDL) assessments, and the clinical relevance of PDL.BackgroundPDL assessment is integral during follow-up after left atrial appendage (LAA) occlusion. Comparative studies of TEE and cardiac CT are sparse, and the clinical relevance of PDL is uncertain.MethodsThis was a single-center observational study of consecutive patients undergoing LAA occlusion with Amplatzer devices (Amplatzer Cardiac Plug/Amulet) between 2010 and 2018 (N = 415). Patients with both 8-week CT and TEE were included for analysis (n = 346). Images were analyzed by blinded investigators (K.K. and A.S.). PDL on cardiac CT was classified from grade 1 to 3, based on PDL at the device disc, device lobe, and LAA contrast patency. Primary clinical outcome was a composite of ischemic stroke, transient ischemic attack, systemic embolism, or all-cause death.ResultsPDL was present in 110 patients (32%) by TEE, with 29 (8%) >3 mm. By cardiac CT, 210 patients (61%) had PDL at the disc, with contrast patency in 204 patients (59%). A grade 3 PDL (gap at disc, lobe, and LAA contrast patency) was present in 63 patients (18%). Bland-Altman analysis showed poor agreement between CT and TEE for leak sizing. CT and TEE detected PDL was not significantly associated with worse outcome, hazard ratio: 1.82 (95 % confidence interval: 0.95 to 3.50); p = 0.07 and hazard ratio: 1.43 (95% confidence interval: 0.74 to 2.76); p = 0.28, respectively.ConclusionsPDL occurrence is substantially higher with CT compared with TEE, with a large discrepancy between modalities in leak quantification. A novel CT-based classification is proposed, yet PDL was not associated with worse clinical outcome.     

Effects of atorvastatin on red-blood cell Na(+)/Li(+) countertransport in hyperlipidemic patients with and without hypertension

BACKGROUND: To explore the effect of short-term cholesterol-lowering treatment with atorvastatin on erythrocyte sodium-lithium countertransport (Na(+)/Li(+) CT) activity. METHODS: Group A consisted of 30 patients (14 men) with mild essential hypertension (systolic blood pressure (SBP), 140-159 mm Hg and/or diastolic BP, 90-99 mm Hg) and primary hypercholesterolemia low-density lipoprotein (LDL) cholesterol >4.1 mmol/l and triglycerides (TG) <2.8 mmol/l), group B of 30 normotensive patients (16 men) with primary hypercholesterolemia, while 37 (18 men) healthy volunteers comprised the control group. After a 6-week dietary lead-in, all eligible patients were prescribed 20 mg/day of atorvastatin. Anthropometric data, blood-pressure (BP) measurements and determinations of lipid, non-lipid metabolic parameters (including homeostasis model assessment index, (HOMA-IR)) and erythrocyte Na(+)/Li(+) CT activity were collected at baseline and after 12 weeks of treatment. RESULTS: At baseline Na(+)/Li(+) CT activity was significantly higher in group A and B compared with the control group and correlated directly with obesity indices, systolic and diastolic BP, total cholesterol, LDL-cholesterol, TG, apolipoprotein B (apoB), HOMA-IR, uric acid and inversely with high-density lipoprotein (HDL)-cholesterol and apoA1. Systolic and diastolic BP levels, HOMA-IR and Na(+)/Li(+) CT activity were significantly decreased after atorvastatin treatment in both patient groups. The reduction in Na(+)/Li(+) CT activity correlated with baseline Na(+)/Li(+) CT activity and the changes in HOMA-IR values. CONCLUSIONS: Short-term treatment with atorvastatin for patients with hypercholesterolemia, and with or without essential hypertension, is associated with a significant reduction in the erythrocyte Na(+)/Li(+) CT activity, BP levels and insulin resistance independent of concomitant changes in lipid parameters.     

The number of cysteine residues per mole in apolipoprotein E affects systematically synchronous neural interactions in women’s healthy brains

Apolipoprotein E (apoE) is involved in lipid metabolism in the brain, but its effects on brain function are not understood. Three apoE isoforms (E4, E3, and E2) are the result of cysteine–arginine interchanges at two sites: there are zero interchanges in E4, one interchange in E3, and two interchanges in E2. The resulting six apoE genotypes (E4/4, E4/3, E4/2, E3/3, E3/2, E2/2) yield five groups with respect to the number of cysteine residues per mole (CysR/mole), as follows. ApoE4/4 has zero cysteine residues per mole (0-CysR/mole), E4/3 has one (1-CysR/mole), E4/2 and E3/3 each has two (2-CysR/mole), E3/2 has three (3-CysR/mole), and E2/2 has four (4-CysR/mole). The use of the number of CysR/mole to characterize the apoE molecule converts the categorical apoE genotype scale, consisting of 6 distinct genotypes above, to a 5-point continuous scale (0–4 CysR/mole). This allows the use of statistical analyses suitable for continuous variables (e.g. regression) to quantify the relations between various variables and apoE. Using such analyses, here, we show for the first time that apoE affects in a graded and orderly manner neural communication, as assessed by analyzing the relation between the number of CysR/mole and synchronous neural interactions (SNI) measured by magnetoencephalography (MEG) in 130 cognitively healthy women. At the one end of the CysR/mole range, the 4-CysR/mole (E2/2) SNI distribution had the highest mean, lowest variance, lowest range, and lowest coefficient of variation, whereas at the other end, 0-CysR/mole (E4/4) SNI distribution had the lowest mean, highest variance, highest range, and highest coefficient of variation. The special status of the 4-CysR/mole distribution was reinforced by the results of a hierarchical tree analysis where the 4-CysR/mole (E2/2) SNI distribution occupied a separate branch by itself and the remaining CysR/mole SNI distributions were placed at increasing distances from the 4-CysR/mole distribution, according to their number of CysR/mole, with the 0-CysR/mole (E4/4) being farthest away. These findings suggest that the 4-CysR/mole (E2/2) SNI distribution could serve as a reference distribution. When the SNI distributions of individual women were expressed as distances from this reference distribution, there was a substantial overlap among women of various CysR/mole. This refocuses the placement of individual brains along a continuous distance from the 4-CysR/mole SNI distribution, in contrast to the common categorical assignment to a specific apoE genotype. Finally, the orderly variation of SNI with the number of CysR/mole found here is in keeping with recent advances and ideas regarding the molecular mechanisms underlying the differential effects of apoE in the brain which emphasize the healthier stability conferred on the apoE molecule by the increasing number of cysteine–arginine interchanges, with 4-CysR/mole (E2/2) being the best case, as opposed to the instability and increased chance of toxic fragmentation of the apoE molecule with lower number of CysR/mole, with 0-CysR/mole (E4/4) as the worst case (Mahley and Huang in Neuron 76:871–885, 2012a). However, our results also document the appreciable variation of SNI properties within the various CysR/mole groups and individuals which points to the existence and important role of other factors involved in shaping brain function at the network level.     

A comparative study of postendoscopic sphincterotomy complications with various types of electrosurgical current in patients with choledocholithiasis

BACKGROUND: Whether the type of electrosurgical current used for endoscopic sphincterotomy influences the frequency of postsphincterotomy complications is unknown. METHODS: One hundred eighty-six patients with choledocholithiasis were prospectively randomized to undergo endoscopic sphincterotomy with pure cutting current (n = 62, Group A), blended current (n = 62, Group B), or pure cutting initially followed by blended current (n = 62, Group C). Serum concentrations of amylase and lipase were evaluated in all patients 12 and 24 hours after sphincterotomy. Clinical pancreatitis was classified as mild, moderate, or severe. Postsphincterotomy bleeding was defined as a decrease in hematocrit of greater than 5%. RESULTS: Serum concentrations of amylase and lipase were greater in Groups B and C at 12 and 24 hours after the procedure, as compared with Group A. Clinical mild pancreatitis occurred in 2 patients in Group A (3.2%), 8 in Group B (12.9%), and in 8 in Group C (12.9%). The differences were statistically significant for Group A compared with either Group B or Group C (p = 0.048). Postsphincterotomy bleeding occurred in 3 patients (1.6%), one in each group. CONCLUSION: The use of pure cutting electrosurgical current during endoscopic sphincterotomy in patients with choledocholithiasis is associated with a lesser degree of pancreatic enzyme elevation and lower frequency of pancreatitis, whereas bleeding is not increased compared with blended current. Changing from pure cutting to blended current after the first 3 to 5 mm of the incision is associated with an increased rate of complications compared to the use of pure cutting current for the entire sphincterotomy.     

The role of disease management programs in the health behavior of chronically ill patients

Objective

Investigate the effects of disease management program (DMP) implementation on physical activity, smoking, and physical quality of life among chronically ill patients.

Methods

This study used a mixed-methods approach involving qualitative (35 interviews with project managers) and quantitative (survey of patients from 18 DMPs) data collection. Questionnaire response rates were 51% (2010; 2619/5108) at T0 and 47% (2011; 2191/4693) at T1.

Results

Physical activity and the percentage of smokers improved significantly over time, whereas physical quality of life declined. After adjusting for patients’ physical quality of life at T0, age, educational level, marital status, and gender, physical activity at T0 (p < 0.01), changes in physical activity (p < 0.001), and percentage of smokers at T0 (p < 0.05) predicted physical quality of life at T1. Project managers reported that DMPs improved patient–professional interaction. The ability to set more concrete targets improved patients’ health behaviors.

Conclusions

DMPs appear to improve physical activity among chronically ill patients over time. Furthermore, (changes in) health behavior are important for the physical quality of life of chronically ill patients.

Practice implications

Redesigning care systems and implementing DMPs based on the chronic care model may improve health behavior among chronically ill patients.