Effect of Loop Diuretics on the Fractional Excretion of Urea in Decompensated Heart Failure.

BACKGROUND: Fractional excretion of urea (FEUrea) is often used to understand the etiology of acute kidney injury (AKI) in patients receiving diuretics. Although FEUrea demonstrates diagnostic superiority over fractional excretion of sodium (FENa), clinicians often assume FEUrea is not affected by diuretics. OBJECTIVE: To assess the intravenous loop diuretic effect on FEUrea. METHODS: We analyzed a prospective cohort (n=297) hospitalized with hypervolemic heart failure at Yale New Haven Hospital System. FENa and FEUrea were calculated at baseline and serially after diuretics. The change in FEUrea at peak diuresis was compared with the pre-diuretic baseline. RESULTS: Mean baseline FEUrea was 35.2% ± 10.5% and increased by a mean 5.6% ± 10.5% following 80 mg (40-160 mg) of furosemide equivalents (P < .001). The magnitude of change in FEUrea was clinically important as the distribution of change in FEUrea was similar to the overall distribution of baseline FEUrea. Change in FEUrea was related to the diuretic response (r = 0.61, P < .001), with a larger FEUrea increase in diuretic responders (8.8%, interquartile range [IQR]: 1.8-16.9) than non-responders (1.2%, IQR: -3.2 to 5.5; P < .001). Diuretic administration reclassified 27% of patients between low and high FEUrea groups across a 35% threshold. Neither change in FEUrea nor percentage reclassified out of a low FEUrea category differed between patients with and without AKI (P > .63 for both). CONCLUSIONS: FEUrea is meaningfully affected by loop diuretics. The degree of change in FEUrea is highly variable between patients and commonly of a magnitude that could reclassify across categories of FEUrea.

Late gastrointestinal effects of pelvic radiation: a nurse-led service.

There are currently at least 2 million people in the UK living with and following a cancer diagnosis. Typically four out of every ten people with cancer will receive radiotherapy, but a large proportion of people who have pelvic radiotherapy may go on to develop gastrointestinal (GI) symptoms. This includes rectal bleeding and faecal incontinence, which can have a huge impact on quality of life. These problems often go under-reported by patients and are also under-recognised or under-treated by health professionals. Cancer survivorship is a growing topic that is likely to have a major impact on the NHS, with increasing numbers of patients presenting. A late GI effects of pelvic radiotherapy clinic was set up to address these growing needs of patients with GI symptoms following radiotherapy. This article also shares insights from a doctoral study that is underway looking at people's experiences of living with symptoms following their treatment, in order to improve awareness of the major impact that this can have.

Interobserver agreement in the reporting of colorectal polyp pathology among bowel cancer screening pathologists in Wales.

AIMS: To assess the interobserver agreement in the reporting of colorectal polyps among histopathologists participating in the Welsh Bowel Cancer Screening (BCS) programme. METHODS AND RESULTS: Twelve benign polyps representative of BCS cases were identified from pathology files and reported by 28 BCS histopathologists using proforma sheets. The level of agreement between the participants and a gold standard was determined using kappa (κ) statistics. A moderate level of agreement was achieved in the reporting of polyp type [κ = 0.45; 95% confidence interval (CI) 0.34-0.59] and adenomatous lesions were distinguished from non-adenomatous lesions in 96% of cases. Substantial agreement was obtained in distinguishing low- and high-grade dysplasias (κ = 0.67; 95% CI 0.50-0.86), but there was only fair agreement in reporting excision margin status (κ = 0.24; 95% CI 0.07-0.43) with frequent use of the 'uncertain' category. Significant issues included categorizing serrated lesions, recognizing focal high-grade dysplasia and epithelial misplacement, and apparent overdiagnosis of villous change in adenomas. CONCLUSIONS: Interobserver variability in some aspects of reporting colorectal polyps by BCS pathologists is suboptimal, with a potential impact upon patient management and the efficient running of the screening service. Approaches to addressing this are discussed.

Clinical characteristics of hepatitis E in a "Non-Endemic" population.

Hepatitis E virus (HEV) is a ribonucleic acid (RNA) virus with predominant fecal oral spread. Traditionally in Western Europe it is associated with travel to endemic countries, but an increasing number of locally acquired cases have been reported throughout England. Patients presenting with acute non-travel associated HEV infection in south Wales over a 25-month period were monitored, in an attempt to understand the clinical picture and epidemiology in our patient population. Twenty-four patients were identified with non-travel associated HEV infection and studied prospectively. Patient demographics, symptoms, and serial laboratory results were recorded. There was a male/female ratio of 3:1, with a median patient age of 65.5 years old. Patients developed a significant icteric hepatitis (median peak bilirubin: 139 µmol/L, median peak AST: 1,973 IU/L and ALT: 2,021 IU/L), with liver function remaining abnormal for ∼7 weeks. All patients in whom HEV RNA was isolated were infected with genotype 3. Forty-six percent of patients presented during winter months. The data show a group mortality rate of 4.2%, similar to that reported in endemic countries. HEV results in a severe and occasionally fatal hepatitis. Testing for hepatitis E is now recommended in any patient presenting with acute hepatitis of unknown etiology.

Impact of a simulation-based induction programme in gastroscopy on trainee outcomes and learning curves.

BACKGROUND: Pre-clinical simulation-based training (SBT) in endoscopy has been shown to augment trainee performance in the short-term, but longer-term data are lacking. AIM: To assess the impact of a two-day gastroscopy induction course combining theory and SBT (Structured PRogramme of INduction and Training - SPRINT) on trainee outcomes over a 16-mo period. METHODS: This prospective case-control study compared outcomes between novice SPRINT attendees and controls matched from a United Kingdom training database. Study outcomes comprised: (1) Unassisted D2 intubation rates; (2) Procedural discomfort scores; (3) Sedation practice; (4) Time to 200 procedures; and (5) Time to certification. RESULTS: Total 15 cases and 24 controls were included, with mean procedure counts of 10 and 3 (P = 0.739) pre-SPRINT. Post-SPRINT, no significant differences between the groups were detected in long-term D2 intubation rates (P = 0.332) or discomfort scores (P = 0.090). However, the cases had a significantly higher rate of unsedated procedures than controls post-SPRINT (58% vs 44%, P = 0.018), which was maintained over the subsequent 200 procedures. Cases tended to perform procedures at a greater frequency than controls in the post-SPRINT period (median: 16.2 vs 13.8 per mo, P = 0.051), resulting in a significantly greater proportion of cases achieving gastroscopy certification by the end of follow up (75% vs 36%, P = 0.017). CONCLUSION: In this pilot study, attendees of the SPRINT cohort tended to perform more procedures and achieved gastroscopy certification earlier than controls. These data support the role for wider evaluation of pre-clinical induction involving SBT.

Exchange versus simple transfusion for acute chest syndrome in sickle cell anemia adults.

BACKGROUND: There are scant data regarding the relative efficacy of exchange transfusion (XC) versus simple transfusion (ST) for treatment of sickle cell anemia acute chest syndrome (ACS). STUDY DESIGN AND METHODS: Twenty patients who received XC for ACS were compared with 20 ST patients. Hemoglobin (Hb) levels, platelet and white blood cell counts, lactate dehydrogenase (LDH), indirect bilirubin, and temperature were used to assess disease severity. Primary outcome was postprocedure length of hospital stay; secondary outcome was total length of stay. RESULTS: Cohorts were similar with regard to age; sex; prior ACS episodes; echocardiogram results; and antibiotic, bronchodilator, and hydroxyurea use. Maximum temperature recorded was higher in the XC group (39.1 degrees C vs. 38.4 degrees C, p = 0.02), but LDH, WBCs, and indirect bilirubin were comparable. Admission Hb levels were higher for XC (XC 8.6 g/dL vs. ST 7.4 g/dL, p = 0.02) and XC had higher peak Hb levels during hospitalization (10.4 +/- 1.4 g/dL vs. 9.3 +/- 1.0 g/dL, p < or = 0.01). No differences were demonstrable in postprocedure length of stay (XC 5.6 days vs. ST 5.9 days, p = 0.82) or total length of stay (XC 8.4 days vs. ST 8.0 days, p = 0.76). A total of 10.3 +/- 3.0 units were transfused for XC compared to 2.4 +/- 1.2 units for ST (p < 0.001). CONCLUSIONS: Based on postprocedure length of stay or total length of stay, we could not detect a difference in the efficacy of XC compared to ST in populations despite red blood cell product usage fourfold higher in the XC group. We suggest that it is time for an adequately powered, randomized trial to examine the true risk:benefit ratio of XC in ACS.

A prospective study of the accuracy and concordance between in-situ and postfixation measurements of colorectal polyp size and their potential impact upon surveillance.

OBJECTIVES: To determine the differences between in-situ, prefixation and postfixation colorectal polyp measurements, their clinical impact upon determining adenoma surveillance intervals, and to compare postfixation measurements using three different devices. PATIENTS AND METHODS: A prospective study of 107 colorectal polyps resected from 65 consecutive patients (45 men, 20 women) undergoing colonoscopy as part of the Bowel Cancer Screening Programme was undertaken. The polyps were measured in situ, prefixation (study gold standard) and using three measurement devices (ruler, callipers and magnifying lens) postfixation in formalin. RESULTS: Prefixation ruler measurements were significantly higher than in-situ (P=0.02) and postfixation ruler measurements (P=0.04). No significant difference was observed between in-situ and postfixation ruler measurements (P=0.36), although in-situ measurements were more variable. In-situ measurements also generated more variation in surveillance intervals than postfixation measurements (9.3 vs. 5.6%). No significant difference was seen between measurements obtained by the three different devices postfixation (P=0.89). CONCLUSION: This study provides evidence supporting the use of postfixation polyp size measurements as advised by recent European pathology colorectal cancer screening recommendations. In the absence of a clinically significant difference between measurement devices, we advise the ruler to be used as a standard for postfixation measurements because of its widespread availability.

Upper gastrointestinal cancer in its early stages is predominantly asymptomatic.

BACKGROUND: Current guidelines for urgent endoscopic investigation of dyspepsia are based on alarm features and age criteria. However, there is concern that this type of guideline may delay the diagnosis of upper gastrointestinal (GI) cancer. OBJECTIVE: To evaluate the timescale of symptoms in upper GI cancer, determining whether patients experience dyspepsia before developing alarm features, and hence whether the current guidelines may delay diagnosis. METHOD: A prospective study of patients diagnosed with upper GI cancer between May 2004 and January 2007. A structured interview was performed directly after endoscopic diagnosis regarding the nature and duration of symptoms. RESULTS: Alarm features were present in 56 of the 60 patients interviewed. Only eight patients reported dyspepsia before developing their alarm feature; three of these had complained of dyspepsia for >10 years, one reported dyspepsia preceding the alarm feature by 18 months and in four patients dyspepsia preceded the alarm feature by ≤8 weeks. Preceding dyspepsia did not cause significant delay in referral for endoscopy (p=0.670), or affect tumour stage at diagnosis (p=0.436) or length of survival (p=0.325). CONCLUSION: It is rare for patients with upper GI cancer to experience significant dyspepsia before the onset of their alarm symptoms, therefore limiting the prospect of an earlier diagnosis. Early upper GI cancer is largely asymptomatic, and guidelines should limit the availability of open-access gastroscopy in simple dyspepsia. Increased awareness of the need to urgently investigate patients with concurrent anaemia or weight loss is required.

Two for the price of one: a dual treatment benefit of long-acting octreotide in occult bleeding and diuretic intractable ascites.

Transfusion-dependent anaemia and portal hypertension are recognised complications of hereditary haemorrhagic telangiectasia (HHT). The anaemia is a result of chronic bleeding from gastrointestinal telangiectasias, which are usually multiple and located throughout the gastrointestinal tract. As a result, treatment with argon plasma coagulation via gastroscopy and or colonoscopy is often insufficient to prevent ongoing blood loss. Portal hypertension in HHT occurs as a result of blood shunting between the hepatic artery and the portal vein within the liver. The somatostatin analogue octreotide has been used as a treatment for bleeding angiodysplasia; however, its possible role as a treatment for diuretic intractable ascites secondary to portal hypertension has not been previously established. The authors report a case that apparently illustrates a dual benefit of long-acting octreotide in the management of both occult bleeding and refractory ascites in a patient with HHT.

Stents and stentability: treatment for malignant bowel obstruction.

Colonic stents offer a palliative treatment for patients with malignant bowel obstruction otherwise requiring surgery and possible stoma, or as a bridge to surgery for potentially curative malignant disease. This article reviews the indications, risks and benefits of stent insertion.

Noncontact temperature measurement in microliter-sized volumes using fluorescent-labeled DNA oligomers.

A new method of noncontact temperature measurement in microliter-sized volumes is demonstrated, based on the temperature sensitivity of the fluorescence lifetime of rhodamine-G when it is attached to a DNA oligomer. As temperature changes, the spacing between the fluorescent dye and a designed sequence of DNA bases is modulated by conformation changes of the DNA chain, and as a result the ability of dye molecules to fluoresce is also modulated according to differential quenching by bases on the DNA. In the system that we studied, the temperature sensitivity of the fluorescence lifetime was 36-42 ps/ degrees C depending on specific solution conditions. Although this strategy of temperature measurement is demonstrated using a specific sequence of DNA, it can also be generalized to a dye attached to any other intrinsic quencher of fluorescence whose conformation changes with temperature.