Bilateral renal haematuria and obstructive renal failure from acquired haemophilia A: a medical cause for a surgical problem.

A 55-year-old male presented to our emergency department with haematuria and abdominal pain. Investigations including a computed tomography (CT) scan revealed an intraluminal filling defect within the left collecting system, consistent in appearance with blood clot. With an initial working diagnosis of upper tract urothelial cell carcinoma, he was discharged with plans for an urgent cystoscopy and ureteroscopy. He subsequently represented with ongoing frank haematuria, anasarca, dropping haemoglobin and new right collecting system blood clot. Subsequent investigations showed that the patient had acquired haemophilia A resulting in the episodes of haematuria, highlighted after an elevated activated partial thromboplastic time prompted a thrombophilia screen. The patient was subsequently treated with factor eight inhibitor bypass activity, corticosteroids and cyclophosphamide.

Spot urinary 5-hydroxyindoleacetic acid is not an ideal diagnostic test for acute appendicitis.

BACKGROUND AND PURPOSE OF THE STUDY: There is growing evidence to suggest the use of urinary 5-hydroxyindoleacetic acid (5-HIAA) test to help with the diagnosis of appendicitis. The aim of our study was to establish whether urinary 5-HIAA could be used as an effective diagnostic test for acute appendicitis. DESIGN AND METHODS: A prospective double-blinded study was carried out from December 2014 to October 2015. Patients admitted to the emergency surgical ward of a teaching hospital with suspected appendicitis were included in the study. The diagnostic accuracy of the test was measured by receiver operating characteristic curve. RESULTS: Ninety-seven patients were divided into 2 groups: acute appendicitis (n=38) and other diagnosis (n=59). The median value of urinary 5-HIAA was 24.19µmol/L (range, 5.39-138.27) for acute appendicitis vs 18.87µmol/L (range, 2.27-120.59) for other diagnosis group (P=.038). The sensitivity and specificity of urinary 5-HIAA at a cutoff value of 19µmol/L were 71% and 50%, respectively. Receiver operating characteristic analysis showed that the area under curve was 0.64 (confidence interval [CI], 0.513-0.737) for urinary 5-HIAA, which was lower than white blood cell count (0.69; CI, 0.574-0.797), neutrophil count (0.68; CI, 0.565-0.792), and C-reactive protein (0.76; CI, 0.657-0.857). There was no significant difference in the median values of 5-HIAA between different grades of severity of appendicitis (P=.704). CONCLUSION: Urinary 5-HIAA is not an ideal test for the diagnosis of acute appendicitis.

Advancing Urinary Protein Biomarker Discovery by Data-Independent Acquisition on a Quadrupole-Orbitrap Mass Spectrometer.

The promises of data-independent acquisition (DIA) strategies are a comprehensive and reproducible digital qualitative and quantitative record of the proteins present in a sample. We developed a fast and robust DIA method for comprehensive mapping of the urinary proteome that enables large scale urine proteomics studies. Compared to a data-dependent acquisition (DDA) experiments, our DIA assay doubled the number of identified peptides and proteins per sample at half the coefficients of variation observed for DDA data (DIA = ∼8%; DDA = ∼16%). We also tested different spectral libraries and their effects on overall protein and peptide identifications and their reproducibilities, which provided clear evidence that sample type-specific spectral libraries are preferred for reliable data analysis. To show applicability for biomarker discovery experiments, we analyzed a sample set of 87 urine samples from children seen in the emergency department with abdominal pain. The whole set was analyzed with high proteome coverage (∼1300 proteins/sample) in less than 4 days. The data set revealed excellent biomarker candidates for ovarian cyst and urinary tract infection. The improved throughput and quantitative performance of our optimized DIA workflow allow for the efficient simultaneous discovery and verification of biomarker candidates without the requirement for an early bias toward selected proteins.

Electronic alerts for triage protocol compliance among emergency department triage nurses: a randomized controlled trial.

BACKGROUND: Alerts embedded in electronic health records (EHRs) are designed to improve processes at the point of care. OBJECTIVE: The aim of this study was to determine if an EHR alert-at emergency department (ED) triage-increases the ED triage nurse's utilization of triage protocols. METHODS: ED triage nurses were randomized to receive either a passive EHR alert or no intervention for patients with the following complaints: minor trauma with extremity injuries or female patients with abdominal pain. The EHR alert notified the nurse that the patient was eligible for diagnostic testing: radiographs for patients with injured extremities or urinalysis for female patients with abdominal pain. RESULTS: Twenty-eight nurses triaged 20,410 patients in the 6 months before the intervention and 19,157 in the 6 months after the intervention. Before the intervention, the urinalysis protocol was implemented in 101/624 (16.2%) patients triaged by the intervention group and 116/711 (16.3%) triaged by the control group. After the intervention, the urinalysis protocol was implemented in 146/530 (27.6%) patients triaged by the intervention group and 174/679 (25.6%) triaged by the control group. Before the intervention, the radiograph protocol was implemented in 58/774 (7.5%) patients triaged by the intervention group and 45/684 (6.6%) triaged by the control group. After the intervention, the radiograph protocol was implemented in 78/614 (12.7%) patients triaged by the intervention group and 79/609 (13.0%) triaged by the control group. CONCLUSION: The use of a passive EHR alert to promote ED triage protocols showed little benefit. Before the widespread implementation of EHR alerts for patient care, rigorous studies are required to determine the best alert methods and the impacts of such interventions.

Does melatonin homeostasis play a role in continuous epigastric pain syndrome?

Two clinical forms of functional dyspepsia (FD) are listed in the Rome III criteria: postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS), differing in the recurrence of ailments depending on the diet. Continuous EPS (CEPS) is observed in some EPS patients, also at night, but its cause is still unknown. We showed previously that melatonin (MEL) homeostasis may be associated with FD. In the present work we evaluated selected components of melatonin homeostasis in patients with CEPS. The study included 30 patients with CEPS, 21 women and nine men, aged 21-49 years and 30 control subjects (EPS excluded); organic and mental diseases, as well as Helicobacter pylori infection, were excluded in both groups. The average severity of abdominal pain in the last three months was estimated in a 10-point scale (Visual Analog Scale). The levels of mRNA expression of arylalkylamine-N-acetyltransferase (AANAT) and hydroxyindole-O-methyltransferase (HIOMT), the main components of MEL homeostasis, were determined in gastric mucosa with real time PCR. The fasting serum level of MEL (at 09:00 a.m.) and circadian urine excretion of 6-sulfatoxymelatonin (6-HMS) were determined with ELISA. AANAT expression in antral mucosa of control subjects was 1.76 ± 0.41, in the gastric body 1.35 ± 0.38, and in the dyspeptic group 1.42 ± 0.38 (p < 0.05) and 0.92 ± 0.55 (p < 0.05), respectively. HIOMT expression in the control was 2.05 ± 0.70 in the antrum and 1.57 ± 0.69 in the body and in the CEPS group, it was: 1.51 ± 0.57 (p < 0.05) and 0.74 ± 0.31 (p < 0.001), respectively. MEL concentration (pg/mL) was 9.41 ± 3.09 in the control group and 5.62 ± 1.34 (p < 0.01) in the CEPS group. Urinary 6-HMS excretion (µg/24 h) was 11.40 ± 4.46 in the controls and 7.68 ± 2.88 (p < 0.05) in the CEPS. Moreover, a negative correlation was found between the tested parameters and severity of epigastric pain. These results indicate that patients with CEPS may display low level of AANAT and HIOMT expression in gastric mucosa, resulting in decreased MEL synthesis.

Anti-nociceptive activity and toxicity evaluation of Cu(II)-fenoprofenate complexes in mice.

The proposed curative properties of copper(II)-non-steroidal anti-inflammatory drugs (NSAIDs) have led to the development of numerous copper(II)-NSAID complexes with enhanced anti-inflammatory activity. In this work, the antinociceptive and toxic effects of two new coordination complexes: Cu2(fen)4(caf)2 [fen: fenoprofenate anion; caf: caffeine] and Cu2(fen)4(dmf)2 [dmf: N-N'-dimethylformamide] were evaluated in mice. The antinociceptive effect was evaluated with two models: acetic acid-induced writhing response and formalin test. For the sub-acute exposure, the complexes were added to the diet at different doses for 28days. Behavioral and functional nervous system parameters in a functional observational battery were assessed. Also, hematological, biochemical and histopathological studies were performed. Cu2(fen)4(caf)2 and Cu2(fen)4(dmf)2 significantly decreased the acetic acid-induced writhing response and the licking time on the late phase in the formalin test with respect to the control and fenoprofen salt groups. The sub-acute exposure to Cu2(fen)4(caf)2 complex increased the motor activity, the number of rearings and the arousal with respect to the control and fenoprofen salt groups. These impaired parameters in mice exposed to Cu2(fen)4(caf)2 can be attributable to the presence of caffeine as stimulating agent. On the other hand, all exposed groups decreased the urine pools in the functional observational battery and increased the plasmatic urea. These effects could be due to the decrease in the glomerular filtration caused by NSAIDs. In conclusion, both complexes Cu2(fen)4(dmf)2 and Cu2(fen)4(caf)2 were more potent antinociceptive agents than fenoprofen salt. Sub-acute exposure to different doses of these complexes did not produce significant changes in the parameters that evaluate toxicity.

Heterotopic pancreas of the gallbladder associated with chronic cholecystitis and high levels of amylasuria.

CONTEXT: Heterotopic pancreas of the gallbladder is an extremely rare entity, especially when pancreatic tissue appears histologically with an exclusively exocrine structure. CASE REPORT: We report the case of a 35-year-old man who presented with symptoms of acalculous gallbladder disease with high levels of amylasuria. Immunohistochemical analysis of the surgical specimen of the cholecystectomy revealed pancreatic tissue at the gallbladder wall. CONCLUSIONS: Heterotopic pancreatic tissue is a rare pathological finding in the gallbladder. It requires consideration and sensitization in the differential diagnosis of acalculous gallbladder disease, which can explain hyperamylasuria in cases of unknown origin.

Navigating recurrent abdominal pain through clinical clues, red flags, and initial testing.

Recurrent abdominal pain is a common chronic complaint that presents to your office. The constant challenge is one of detecting those with organic disease from the majority who have a functional pain disorder including functional dyspepsia, irritable bowel syndrome, functional abdominal pain, and abdominal migraine. Beginning with a detailed history and physical exam, you can: 1) apply the symptom-based Rome III criteria to positively identify a functional disorder, and 2) filter these findings through the diagnostic clues and red flags that point toward specific organic disease and/or further testing. Once a functional diagnosis has been made or an organic disease is suspected, you can initiate a self-limited empiric therapeutic trial. With this diagnostic approach, you should feel confident navigating through the initial evaluation, management, and consultation referral for a child or adolescent with recurrent abdominal pain.

A liquid chromatography/mass spectrometry method for the evaluation of intestinal permeability.

OBJECTIVES: Lactulose to mannitol ratio (L/M) in urine is used as a non invasive assay to measure intestinal permeability. We describe here a rapid, specific and sensitive LC-MS/MS method for the measurement of these compounds in urine of children affected by abdominal recurrent pain (ARP). DESIGN AND METHODS: The study has been performed on 50 children from the Pediatric Unit. The chromatographic separation was accomplished by using an NH(2)-column, the detection with a Q-Trap 2000 system. RESULTS: Multiple calibration curve exhibited consistent linearity and reproducibility. Linear responses were observed in the concentration range 0-400 microg/mL for both mannitol and lactulose. Limits of detection were 12.5 mg/L for lactulose and 1.25 mg/L for mannitol with a signal-to-noise ratio of 10. CONCLUSIONS: The comparison of L/M values of healthy children with those found in children affected by idiopathic ARP demonstrates that in the latter subjects an alteration of intestinal permeability occurs. The method can represent a useful tool to monitor the intestinal functionality in children with ARP conditions and help for an accurate patient discrimination for diet restrictions.

Urine leukotriene B4 in familial Mediterranean fever and other forms of right lower abdominal pain.

BACKGROUND: Acute right lower abdominal pain may present a diagnostic dilemma. Leukotrienes have been found to be elevated in familial Mediterranean fever (FMF), a disease manifesting with recurrent episodes of "acute abdomen." OBJECTIVES: To determine whether urine leukotriene B4 (LTB4) may differentiate between an FMF attack and some other forms of acute right lower abdominal pain. METHODS: The LTB4 level was determined, using a commercial enzyme-linked immunosorbent assay (ELISA), in urine samples obtained from 36 patients with acute (< 24 hours) right lower abdominal pain presenting to the emergency department, and from 18 healthy volunteers. RESULTS: Compared with the healthy control subjects, LTB4 was significantly higher in those who had FMF (12 patients, p < 0.03). In other forms of acute right lower abdominal pain, including appendicitis (eight patients), urologic disorders (eight patients), and nonspecific abdominal pain (eight patients), intermediate levels of LTB4 were observed, not significantly different from those of either FMF patients or healthy control subjects. CONCLUSIONS: In the samples tested, urine LTB4 levels were not instrumental in differentiating FMF from other acute right lower abdominal pain.

Rapid urinary trypsinogen-2 test strip in the diagnosis of acute pancreatitis.

OBJECTIVES: Early diagnosis of acute pancreatitis remains a challenge. A rapid dipstick screening test for acute pancreatitis has been developed. This prospective study was designed to evaluate the diagnostic value and time course of the rapid urinary trypsinogen-2 test strip in acute pancreatitis, with comparisons with serum amylase and serum lipase. METHODS: A total of 165 patients with acute abdominal pain (67 with acute pancreatitis and 98 with other acute abdominal diseases) attending our emergency unit were included. All patients were tested with the urinary trypsinogen-2 test strip, and serum amylase and serum lipase concentrations were determined simultaneously. To measure the time course of the urinary trypsinogen-2 test, 32 patients with acute pancreatitis were tested with a urinary trypsinogen-2 test strip on days 1, 2, 3, and 4 after admission. RESULTS: Using a cutoff level of 50 microg/L for urinary trypsinogen-2, the sensitivity, specificity, and accuracy of the urinary trypsinogen-2 test strip for recognition of acute pancreatitis were 89.6%, 85.7%, and 87.3%, respectively. The diagnostic accuracy rates of serum amylase and serum lipase were 88.5% and 93.3%, using cutoff values of 3 times the upper normal limits for serum amylase and serum lipase, respectively. All but one of the 17 patients with severe acute pancreatitis was detected by the test strip (sensitivity, 94.1%). The time-course study of the urinary trypsinogen-2 test strip revealed that the sensitivity on days 1, 2, 3, and 4 was 90.6%, 81.2%, 59.4%, and 50%, respectively. There was no significant difference in the sensitivity between urinary trypsinogen-2 and serum lipase; however, the sensitivity values of serum lipase were significantly higher than those of serum amylase from days 1 to 4. CONCLUSION: The rapid urinary trypsinogen-2 test is a reliable and simple method for the early diagnosis of acute pancreatitis. A positive test identifies patients in need of further diagnostic measures. The urinary trypsinogen-2 test can be performed in health care units where laboratory testing facilities are not immediately available.

A comparative study of the activation peptide of carboxypeptidase B and trypsinogen as early predictors of the severity of acute pancreatitis.

BACKGROUND: Serum and urine concentrations of the activation peptide of carboxypeptidase B (CAPAP) and urinary trypsinogen activation peptide (TAP) as prognostic markers in acute pancreatitis were compared. METHOD: Fifty-two patients with acute pancreatitis hospitalized within 24 hours after symptom onset were prospectively studied. Blood and urine samples were obtained during the first 3 days of the hospital stay. RESULTS: Pancreatitis was severe in 17 patients and mild in 35 (Atlanta criteria). Median serum CAPAP levels on days 1 and 2 and of urine CAPAP and TAP on days 1, 2, and 3 were significantly higher in severe pancreatitis than in mild disease. On the first day of admission, TAP was the most accurate predictor of severity (sensitivity, 92.3%; specificity, 80%; positive and negative predictive values, 63.2% and 96.6%, respectively), with a 4.61 positive likelihood ratio for a cutoff value of 18.10 nmol/L, whereas within 24 hours after symptom onset, urinary CAPAP was superior (sensitivity, 88.9%; specificity, 81.3%; positive and negative predictive values 72.7% and 92.9%, respectively), with a 4.72 positive likelihood ratio for a cutoff value of 15.45 nmol/L. CONCLUSION: Serum and urine CAPAP levels and urinary TAP are accurate in the early assessment of severity in acute pancreatitis. Urine CAPAP levels was the most accurate marker 24 hours after onset of symptoms.

"Abdominal crunch"-induced rhabdomyolysis presenting as right upper quadrant pain.

A young, active duty sailor presented with right upper quadrant abdominal pain. History, physical, and laboratory findings initially suggested cholecystitis or related disease. Further evaluation found myoglobinuria and a recently increased exercise program, leading to the diagnosis of exercise-induced right upper abdominal wall rhabdomyolysis. Although not a common cause of abdominal pain, this diagnosis should be considered in the patient with abdominal pain and a recently increased exercise program, particularly exercises of the abdominal wall such as "abdominal crunches."

Evaluation of a new urinary amylase test strip in the diagnosis of acute pancreatitis.

We have developed a novel rapid test strip for detecting pancreatic amylase in urine and prospectively evaluated its accuracy in screening for acute pancreatitis (AP). The test strip is based on the immunochromatography principle and uses two monoclonal antibodies specific for pancreatic amylase. Urine samples were collected from 500 consecutive patients with acute abdominal disease (52 with AP) and prospectively tested with the strip. The accuracy of the test strip was compared with that of two quantitative urine amylase determinations and a urinary dipstick test for amylase (Rapignost). Sensitivity of the test was 69% and specificity was 97% in differentiating patients with AP from those with acute abdominal extrapancreatic disease at admission. The negative predictive value was 0.986. The test showed moderate agreement both with an assay measuring total amylase activity and with another measuring pancreatic amylase immunoreactivity. At similar high specificity (97%), quantitative determination of total amylase activity (cut-off 3960 U/L) and pancreatic amylase (cut-off 2180 micrograms/L) showed lower sensitivity (54% and 41%) than the test strip (69%). The test is specific and rapid to perform, and it rules out AP with high probability. It could therefore be useful in an emergency setting without laboratory facilities in the differential diagnosis of acute abdominal pain.