Differential diagnosis of diarrhoea in patients with neuroendocrine tumours:A systematic review

BACKGROUND Approximately 20% of patients with neuroendocrine tumours(NETs) develop carcinoid syndrome(CS),characterised by flushing and diarrhoea.Somatostatin analogues or telotristat can be used to control symptoms of CS through inhibition of serotonin secretion.Although CS is often the cause of diarrhoea among patients with gastroenteropancreatic NETs(GEP-NETs),other causes to consider include pancreatic enzyme insufficiency(PEI),bile acid malabsorption and small intestinal bacterial overgrowth.If other causes of diarrhoea unrelated to serotonin secretion are mistaken for CS diarrhoea,these treatments may be ineffective against the diarrhoea,risking detrimental effects to patient quality of life.AIM To identify and synthesise qualitative and quantitative evidence relating to the differential diagnosis of diarrhoea in patients with GEP-NETs.METHODS Electronic databases(MEDLINE,Embase and the Cochrane Library) were searched from inception to September 12,2018 using terms for NETs and diarrhoea.Congresses,systematic literature review bibliographies and included articles were also hand-searched.Any study designs and publication types were eligible for inclusion if relevant data on a cause(s) of diarrhoea in patients with GEP-NETs were reported.Studies were screened by two independent reviewers at abstract and full-text stages.Framework synthesis was adapted to synthesise quantitative and qualitative data.The definition of qualitative data was expanded to include all textual data in any section of relevant publications.RESULTS Forty-seven publications(44 studies) were included,comprising a variety of publication types,including observational studies,reviews,guidelines,case reports,interventional studies,and opinion pieces.Most reported on PEI on/after treatment with somatostatin analogs;9.5%-84% of patients with GEP-NETs had experienced steatorrhoea or confirmed PEI.Where reported,14.3%–50.7% of patients received pancreatic enzyme replacement therapy.Other causes of diarrhoea reported in patients with GEP-NETs included bile acid malabsorption(80%),small intestinal bacterial overgrowth(23.6%-62%),colitis(20%) and infection(7.1%).Diagnostic approaches included faecal elastase,breath tests,tauroselcholic(selenium-75) acid(Se HCAT) scan and stool culture,although evidence on the effectiveness or diagnostic accuracy of these approaches was limited.Assessment of patient history or diarrhoea characteristics was also reported as initial approaches for investigation.From the identified evidence,if diarrhoea is assumed to be CS diarrhoea,consequences include uncontrolled diarrhoea,malnutrition,and perceived ineffectiveness of CS treatment.Approaches for facilitating differential diagnosis of diarrhoea include improving patient and clinician awareness of non-CS causes and involvement of a multidisciplinary clinical team,including gastroenterologists.CONCLUSION Diarrhoea in GEP-NETs can be multifactorial with misdiagnosis leading to delayed patient recovery and inefficient resource use.This systematic literature review highlights gaps for further research on prevalence of non-CS diarrhoea and suitability of diagnostic approaches,to determine an effective algorithm for differential diagnosis of GEP-NET diarrhoea.     

The development and validation of the Score for the Prediction of Postoperative Respiratory Complications (SPORC-2) to predict the requirement for early postoperative tracheal re-intubation: a hospital registry study

Postoperative pulmonary complications are associated with an increase in mortality, morbidity and healthcare utilisation. The Agency for Healthcare Research and Quality recommends risk assessment for postoperative respiratory complications in patients undergoing surgery. In this hospital registry study of adult patients undergoing non-cardiac surgery between 2005 and 2017 at two independent healthcare networks, a prediction instrument for early postoperative tracheal re-intubation was developed and externally validated. This was based on the development of the Score for Prediction Of Postoperative Respiratory Complications. For predictor selection, stepwise backward logistic regression and bootstrap resampling were applied. Development and validation cohorts were represented by 90,893 patients at Partners Healthcare and 67,046 patients at Beth Israel Deaconess Medical Center, of whom 699 (0.8%) and 587 (0.9%) patients, respectively, had their tracheas re-intubated. In addition to five pre-operative predictors identified in the Score for Prediction Of Postoperative Respiratory Complications, the final model included seven additional intra-operative predictors: early post-tracheal intubation desaturation; prolonged duration of surgery; high fraction of inspired oxygen; high vasopressor dose; blood transfusion; the absence of volatile anaesthetic use; and the absence of lung-protective ventilation. The area under the receiver operating characteristic curve for the new score was significantly greater than that of the original Score for Prediction Of Postoperative Respiratory Complications (0.84 [95%CI 0.82–0.85] vs. 0.76 [95%CI 0.75–0.78], respectively; p < 0.001). This may allow clinicians to develop and implement strategies to decrease the risk of early postoperative tracheal re-intubation.     

Brain serotonin transporter binding in non-depressed patients with Parkinson's disease

Early post-mortem data suggest that damage to brain serotonin neurones might play a role in some features (e.g., depression) of Parkinson's disease (PD). However, it is not known whether such damage is a typical characteristic of living patients with PD or whether the changes are regionally widespread. To address this question we measured, by positron emission tomography imaging, levels of the brain serotonin transporter (SERT), a marker for serotonin neurones, as inferred from binding of [¹¹C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB), a second generation SERT radioligand, in subcortical and cerebral cortical brain areas of clinically advanced non-depressed (confirmed by structured psychiatric interview) patients with PD. SERT binding levels in PD were lower than those in controls in all examined brain areas, with the changes statistically significant in orbitofrontal cortex (−22%), caudate (−30%), putamen (−26%), and midbrain (−29%). However, only a slight non-significant reduction (−7%) was observed in dorsolateral pre-frontal cortex, an area implicated in major depression. Our imaging data suggests that a modest, regionally widespread loss of brain serotonergic innervation might be a common feature of advanced PD. Further investigation will be required to establish whether SERT binding is more or less decreased in those patients with PD who also have major depressive disorder.     

Guidelines for Trials of Behavioral Treatments for Recurrent Headache, First Edition: American Headache Society Behavioral Clinical Trials Workgroup

Guidelines for design of clinical trials evaluating behavioral headache treatments were developed to facilitate production of quality research evaluating behavioral therapies for management of primary headache disorders. These guidelines were produced by a Workgroup of headache researchers under auspices of the American Headache Society. The guidelines are complementary to and modeled after guidelines for pharmacological trials published by the International Headache Society, but they address methodologic considerations unique to behavioral and other nonpharmacological treatments. Explicit guidelines for evaluating behavioral headache therapies are needed as the optimal methodology for behavioral (and other nonpharmacologic) trials necessarily differs from the preferred methodology for drug trials. In addition, trials comparing and integrating drug and behavioral therapies present methodological challenges not addressed by guidelines for pharmacologic research. These guidelines address patient selection, trial design for behavioral treatments and for comparisons across multiple treatment modalities (eg, behavioral vs pharmacologic), evaluation of results, and research ethics. Although developed specifically for behavioral therapies, the guidelines may apply to the design of clinical trials evaluating many forms of nonpharmacologic therapies for headache.     

Effect of silymarin and its polyphenolic fraction on cholesterol absorption in rats.

This study evaluated the influence of silymarin (SM) and polyphenolic fraction (PF) of silymarin on cholesterol absorption in rats fed on high cholesterol diet (HCD). HCD induced a remarkable increase in hepatic, plasma, VLDL and LDL cholesterol, a decrease in HDL cholesterol and an elevation in triacylglycerol (TAG) levels in plasma, VLDL and in the liver. SM and PF were administered as dietary supplements (1.0%) in HCD for 18 days. Intestinal cholesterol absorption was measured by dual-isotope plasma ratio method, which calculates percent of cholesterol absorption from the ratio of two labelled cholesterol doses, one given intragastrically (14C) and one intravenously (3H). Silymarin and PF significantly reduced cholesterol absorption in rats fed on HCD and caused significant decreases in plasma and VLDL cholesterol and content of cholesterol and TAG in the liver. The level of HDL cholesterol was significantly increased after silymarin, but not after administration of PF. The levels of TAG in plasma and VLDL were not affected by either silymarin or PF. These results suggest that the inhibition of cholesterol absorption caused by silymarin and its polyphenolic fraction could be a mechanism contributing to the positive changes in plasma cholesterol lipoprotein profile and in lipid content in liver.     

A Brief Mental Health Outcomes Measure: Translation and Validation of the Czech Version of the Schwartz Outcomes Scale-10

The Schwartz Outcomes Scale-10 (SOS-10) is a 10-item scale developed to measure the effectiveness of psychiatric treatments. Using standard methodology, we translated the scale into Czech and examined the psychometric properties of the Czech version. 207 in-patients admitted to Prague Psychiatric Center were included in the study. All patients completed the SOS at admission and discharge. The SOS-10 scale was also administered to 170 persons from the general population. Reliability, validity and sensitivity to treatment change of the Czech SOS-10 were analyzed. The Cronbach’s α coefficient was 0.92. The item-total correlation coefficients varied from 0.56 to 0.82. The SOS-10 correlated well with condition-specific measures including depression (BDI) and anxiety (BAI) and a global self-rated symptom severity scale (CGI). The SOS-10 also had significant correlations with the Health, Basic needs, Relationship, and Leisure time domains of the Czech version of the Subjective Quality of Life Analysis (SQUALA-CZ). The scale discriminated well between patients and controls, with patients scoring significantly lower on all SOS items. The patient sample’s admission and discharge scores were significantly different, indicating that the scale is sensitive to treatment changes. We concluded that the Czech SOS-10 is valid with reliability and factor structure similar to the American language version.     

Evaluation of the polymorphisms associated with tandem repeats for Pseudomonas aeruginosa strain typing

We report on the development of a scheme for the typing of Pseudomonas aeruginosa, multiple-locus variable number of tandem repeat (VNTR) analysis (MLVA). We first evaluated the polymorphisms of 201 tandem repeat loci selected from more than 3,000 such sequences present in strain PAO1 with a test collection of 12 genotypically distinct clinical strains. Seven VNTR loci which can be easily scored with the technology used here were identified and used to genotype a collection of 89 clinical isolates that had previously been classified into 46 ribotypes, including 2 widespread ribotypes. Seventy-one different MLVA genotypes could be distinguished. With only two exceptions, strains with identical ribotypes were grouped together upon cluster analysis of the MLVA data. The 27 isolates with the most frequent ribotype were divided into 14 MLVA types, and the 18 isolates with the second most frequent ribotype were divided into 15 MLVA types. Analysis of a subset of 17 strains belonging to the major ribotype by pulsed-field gel electrophoresis with the enzyme SpeI distinguished seven types, identical to the number of MLVA types in this subset. Our data show that MLVA typing of P. aeruginosa based on the first set of loci has a high discriminatory power. Because MLVA is highly reproducible and easily portable among laboratories, it represents a very promising tool for the molecular surveillance of P. aeruginosa. A free, online strain identification service based on the genotyping data produced herein has been developed.