Citations

Abstract Background: Palliative care guidelines recommend plain radiographs to assess constipation based on the presumption that visible fecal shadowing represents stool retention. Despite this, using plain radiographs in this way is not well validated. Objectives: This work's main aim was to compare clinicians' reports of fecal loading on radiographs. This study also compares clinicians' assessments with radio-opaque marker transit studies and patients' self-reported constipation symptoms. Methods: This study was conducted in a sample of 30 constipated palliative care patients taking laxatives who had all undergone colon transit studies and contemporaneous assessment of constipation symptoms with the Patient Assessment of Constipation Symptom (PAC-SYM) questionnaire. Four separate clinicians independently reported their opinions of fecal loading using a previously developed fecal loading scale. Participant details were summarized and pair-wise inter-rater agreement among all four raters were examined using the Bland-Altman approach. For the comparisons of the clinician-assigned fecal loading score between the radiographic assessment of the normal and slow colon transit time, the nonparametric approach of Mann-Whitney U tests were applied. Spearman's correlation analyses were employed to investigate the association between the clinician-assigned fecal loading score and the patient self-reported PAC-SYM score. Results: The results of this study are very similar to other studies conducted in functional constipation, highlighting systematic disagreement between observers. Further poor correlations were noted between fecal loading scores and colon transit times and with patient self-reported symptoms. Conclusion: These results, when considered with other work in chronic constipation, question the ongoing use of radiographs in the diagnosis of constipation.

Non‐invasive tests to identify age and early disease‐associated pathology within the kidney are needed. Specific populations of urinary extracellular vesicles (EVs) could potentially be used for such a diagnostic test. Random urine samples were obtained from age‐ and sex‐stratified living kidney donors before kidney donation. A biopsy of the donor kidney was obtained at the time of transplantation to identify nephron hypertrophy (larger glomerular volume, cortex per glomerulus and mean profile tubular area) and nephrosclerosis (% fibrosis, % glomerulosclerosis and arteriosclerosis). Renal parenchymal‐derived EVs in cell‐free urine were quantified by digital flow cytometry. The relationship between these EV populations and structural pathology on the kidney biopsy was assessed. Clinical characteristics of the kidney donors (n=138, age range: 20–70 years, 50% women) were within the normative range. Overall, urine from women contained more EVs than that from men. The number of exosomes, juxtaglomerular cells and podocyte marker–positive EVs decreased (p<0.05) with increasing age. There were fewer total EVs as well as EVs positive for mesangial cell, parietal cell, descending limb of Henle's loop (simple squamous epithelium), collecting tubule‐intercalated cell and monocyte chemoattractant protein‐1 markers (p<0.05) in persons with nephron hypertrophy. The number of EVs positive for intercellular adhesion molecule‐1, juxtaglomerular cell, podocyte, parietal cell, proximal tubular epithelial cell, distal tubular epithelial cell and collecting duct cells were fewer (p<0.05) in persons with nephrosclerosis. EVs carrying markers of cells from the renal pelvis epithelium did not associate with any indices of nephron hypertrophy or nephrosclerosis. Therefore, specific populations of EVs derived from cells of the glomerulus and nephron associate with underlying kidney structural changes. Further validation of these findings in other cohorts is needed to determine their clinical utility.

Gastric polyps are found in 1% to 4% of patients undergoing gastroscopy. The vast majority are sporadic, but some gastric polyps indicate an underlying syndrome. Gastric polyps can manifest in each of the gastrointestinal polyposis syndromes, including the recently described gastric adenocarcinoma and proximal polyposis of the stomach syndrome. In addition, gastric polyps occur in Lynch syndrome and in a few rare conditions that are not primarily gastrointestinal. While some of these syndromes are clearly associated with an increased risk of gastric cancer, others are not. Interestingly, even in disorders with a well-established risk of gastric cancer, the neoplastic potential and the precursor status of these gastric polyps are not always clear. Although rare, recognition of syndromic gastric polyps is important for individual patient management. These conditions also serve as important models to study gastric homeostasis and gastric tumorigenesis.

AbstractPrescription narcotic use among living kidney donors is not well described. Using a unique database that integrates national registry identifiers for living kidney donors (1987–2007) in the United States with billing claims from a private health insurer (2000–2007), we identified pharmacy fills for prescription narcotic medications in periods 1–4 and >4 yr post‐donation and estimated relative likelihoods of post‐donation narcotic use by Cox regression. We also compared narcotic fill rates and medication possession ratios (MPRs, defined as (days of medication supplied)/(days observed)), between donors and age‐ and sex‐matched non‐donors. Overall, rates of narcotic medication fills were 32.3 and 32.4 per 100 person‐years in periods 1–4 and >4 yr post‐donation. After age and race adjustment, women were approximately twice as likely as men to fill a narcotic prescription in years 1–4 (adjusted hazard ratio, aHR, 2.28; 95% confidence interval, CI, 1.86–2.79) and >4 yr (aHR 1.70; 95% CI 1.50–1.93). MPRs in donors were low (<2.5% days exposed), and lower than among age‐ and sex‐matched non‐donors. Prescription narcotic medication use is more common among women than men in the intermediate term after live kidney donation. Overall, total narcotic exposure is low, and lower than among non‐donors from the general population.

Abstract Summary: Structural variations (SVs) are large genomic rearrangements that vary significantly in size, making them challenging to detect with the relatively short reads from next-generation sequencing (NGS). Different SV detection methods have been developed; however, each is limited to specific kinds of SVs with varying accuracy and resolution. Previous works have attempted to combine different methods, but they still suffer from poor accuracy particularly for insertions. We propose MetaSV, an integrated SV caller which leverages multiple orthogonal SV signals for high accuracy and resolution. MetaSV proceeds by merging SVs from multiple tools for all types of SVs. It also analyzes soft-clipped reads from alignment to detect insertions accurately since existing tools underestimate insertion SVs. Local assembly in combination with dynamic programming is used to improve breakpoint resolution. Paired-end and coverage information is used to predict SV genotypes. Using simulation and experimental data, we demonstrate the effectiveness of MetaSV across various SV types and sizes. Availability and implementation: Code in Python is at http://bioinform.github.io/metasv/. Contact: rd@bina.com Supplementary information: Supplementary data are available at Bioinformatics online.