Use of a New Standardized Unfractionated Heparin Protocol for Left-Sided Ablation Procedures Improves Time in the Therapeutic ACT Range.

OBJECTIVES: This study evaluated whether a novel standardized heparin dosing protocol used during atrial fibrillation catheter ablation resulted in a higher percentage of therapeutic activated clotting time (ACT) values compared to historic nonstandardized procedures. DESIGN: A retrospective cohort study SETTING: This study was conducted at Ochsner Medical Center, the largest tertiary-care teaching hospital in New Orleans, LA PARTICIPANTS: Patients undergoing catheter-based atrial fibrillation ablation INTERVENTIONS: The authors implemented a standardized heparin protocol, and enrolled 202 patients between November 2020 and March 2021. The historic controls consisted of 173 patients who underwent atrial fibrillation ablation between April 2020 and September 2020. Heparin administration in the control group was based on physician preference and was nonstandardized. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the percentage of intraprocedural ACTs in therapeutic range (≥300 to <450 s). Secondary endpoints included first measured ACT at ≥300 s and percent of measured ACTs in the supratherapeutic range (>450 s). Comparisons were performed using chi-squared tests or Fisher exact tests. Patients in the intervention group had a higher mean percentage of ACTs in the therapeutic range compared to the control group (84.9% vs. 75.8%, p<0.001). More patients in the intervention group reached therapeutic ACT on the first measurement compared to the control group (70.3% vs. 31.2%, p<0.001). CONCLUSION: During catheter-based cardiac ablation procedures, a novel standardized unfractionated heparin dosing protocol resulted in a higher percentage of ACTs in the target range, and a higher proportion of initial ACTs in the therapeutic range compared with baseline nonstandardized heparin dosing.

Eculizumab in paediatric atypical haemolytic uraemic syndrome: Lessons learned from a single-centre experience in the United Arab Emirates.

AIM: Atypical haemolytic uraemic syndrome (aHUS) is a debilitating condition that can cause significant morbidity and mortality in children if not adequately and promptly treated. This report shares real-world data on the use of eculizumab in children with aHUS. METHODS: We report our experience with the use of eculizumab in 14 children with aHUS. RESULTS: The median age at aHUS diagnosis was 12 months (range: 2-108 months), with six (42.9%) patients presenting in infancy and six (42.9%) being males. Eculizumab therapy was associated with haematological and thrombotic microangiopathy responses in 14 (100%) and 13 (92.9%) patients after a median of 9 days (range: 7-12 days) and 9.5 days (range: 7-14 days), respectively. None of the six patients who were previously treated with plasma therapy required any further infusions. Of the six patients who previously required dialysis, only one patient continued to do so and eventually received a renal transplant. The median time to ≥25% decrease in serum creatinine level in the remaining patients was 16 days (range: 14-21 days), and estimated glomerular filtration rate increased from a median of 17-101 mL/min/1.73 m2 . The safety profile was similar to that reported in the literature, and 10 patients continue to receive therapy, with 3 being on the drug for 4 or more years. CONCLUSION: Our study adds to the growing body of evidence highlighting the efficacy and safety of eculizumab for the management of children with aHUS.

Clinical phenotype and outcome of hepatitis E virus-associated neuralgic amyotrophy.

OBJECTIVE: To determine the clinical phenotype and outcome in hepatitis E virus-associated neuralgic amyotrophy (HEV-NA). METHODS: Cases of NA were identified in 11 centers from 7 European countries, with retrospective analysis of demographics, clinical/laboratory findings, and treatment and outcome. Cases of HEV-NA were compared with NA cases without evidence of HEV infection. RESULTS: Fifty-seven cases of HEV-NA and 61 NA cases without HEV were studied. Fifty-six of 57 HEV-NA cases were anti-HEV IgM positive; 53/57 were IgG positive. In 38 cases, HEV RNA was recovered from the serum and in 1 from the CSF (all genotype 3). Fifty-one of 57 HEV-NA cases were anicteric; median alanine aminotransferase 259 IU/L (range 12-2,961 IU/L); in 6 cases, liver function tests were normal. HEV-NA cases were more likely to have bilateral involvement (80.0% vs 8.6%, p < 0.001), damage outside the brachial plexus (58.5% vs 10.5%, p < 0.01), including phrenic nerve and lumbosacral plexus injury (25.0% vs 3.5%, p = 0.01, and 26.4% vs 7.0%, p = 0.001), reduced reflexes (p = 0.03), sensory symptoms (p = 0.04) with more extensive damage to the brachial plexus. There was no difference in outcome between the 2 groups at 12 months. CONCLUSIONS: Patients with HEV-NA are usually anicteric and have a distinct clinical phenotype, with predominately bilateral asymmetrical involvement of, and more extensive damage to, the brachial plexus. Involvement outside the brachial plexus is more common in HEV-NA. The relationship between HEV and NA is likely to be causal, but is easily overlooked. Patients presenting with NA should be tested for HEV, irrespective of liver function test results. Prospective treatment/outcome studies of HEV-NA are warranted.

The role of EUS and EUS-guided FNA in the management of subepithelial lesions of the esophagus: A large, single-center experience.

BACKGROUND: Referral for endosonographic evaluation of subepithelial lesions seen in the gastrointestinal (GI) tract is fairly common. Although rarely studied separately in details, esophageal lesions have some unique differences from other GI sites and might deserve some special considerations regarding follow-up and management. MATERIALS AND METHODS: All cases referred for endoscopic ultrasound (EUS) evaluation of subepithelial esophageal lesions at Bezmialem University Hospital, a tertiary center in Istanbul, Turkey were retrospectively reviewed. Data were collected for patient and lesion characteristics as well as for pathology results and follow-up if available. Lesions were subcategorized according to their size, location, and final diagnosis. RESULTS: A total of 164 EUS examinations were identified. In 22.5% of cases, the lesion could not be identified by EUS. Of the remaining cases, 57.6% had a lesion larger than 1 cm in size. Extramural compression was the diagnosis in 12% and leiomyoma in around 60%. Thirteen patients had follow-up examinations with only two showing an increase in size after 12 months. Sixty-five EUS-guided fine needle aspirations (EUS-guided FNAs) were performed, with around 50% having nondiagnostic samples and 94% of the remaining samples confirming the presumptive diagnosis. CONCLUSIONS: The majority of subepithelial lesions in the esophagus are benign with extremely low malignancy potential. EUS examinations performed for lesions smaller than 2 cm as well as FNAs taken from lesions smaller than 3 cm might have minimal impact on their ultimate management and outcome. More than one FNA pass should be attempted in order to improve the yield.

A Novel Round Insulated Tip Papillotome as an Alternative to the Classic Needle-Knife for Precut Sphincterotomy in Endoscopic Retrograde Cholangiopancreatography.

Objective. The purpose of this study was to investigate the efficacy and safety of a new round insulated tip papillotome (r-ITP) as compared to that of the classic needle-knife sphincterotome (NKS) in difficult-to-cannulate endoscopic retrograde cholangiopancreatography (ERCP) patients. Materials and Methods. Patients with no exclusion criteria and an intact papilla referred for ERCP were invited to participate in the study. "Difficult-to-cannulate" patients, defined as failure to achieve deep biliary cannulation within five minutes from the first touch of papilla, with no more than ten attempts permitted, were randomly assigned for precut sphincterotomy using either the classic NKS or r-ITP. Results. Seventy and 69 patients were randomly assigned to the NKS and r-ITP groups, respectively. The groups were comparable regarding age, sex, indications, and associated conditions. There was no statistically significant difference in terms of successful cannulation or post-ERCP complications between the two groups. Only five patients (3.6%) developed mild to moderate post-ERCP pancreatitis and two had mild bleeding. No perforations or deaths were encountered. Conclusions. Although the round insulated tip papillotome was not shown to be superior to the classic NKS concerning efficacy and safety when used by an experienced endoscopist, it remains a simple, safe, and efficacious alternative.

Role of vitamins in gastrointestinal diseases.

A tremendous amount of data from research was published over the past decades concerning the roles of different vitamins in various gastrointestinal diseases. For instance, most vitamins showed an inverse relationship with the risk of colorectal carcinoma as well as other malignancies like gastric and esophageal cancer in observational trials, however interventional trials failed to prove a clear beneficial preventive role. On the other hand, more solid evidence was obtained from high quality studies for a role of certain vitamins in specific entities. Examples for this include the therapeutic role of vitamin E in patients with non-alcoholic steatohepatitis, the additive role of vitamins B12 and D to the standard therapy of chronic hepatitis C virus, the role of vitamin C in reducing the risk of gallstones, the positive outcome with vitamin B12 in patients with aphthous stomatitis, and the beneficial effect of vitamin D and B1 in patients with inflammatory bowel disease. Other potential uses are yet to be elaborated, like those on celiac disease, pancreatic cancer, pancreatitis, cholestasis and other potential fields. Data from several ongoing interventional trials are expected to add to the current knowledge over the coming few years. Given that vitamin supplementation is psychologically accepted by patients as a natural compound with relative safety and low cost, their use should be encouraged in the fields where positive data are available.

Prevalence of Barrett's esophagus in Lebanon.

BACKGROUND/AIMS: To determine the prevalence of Barrett's Esophagus (BE) in a tertiary care center in Lebanon and to compare IT with regional and global data. MATERIALS AND METHODS: All esophagogastroduodenoscopies (EGDs) performed between January 2003 and October 2013 at the American University of Beirut Medical Center (AUBMC) were reviewed, and cases of endoscopically suspected esophageal metaplasia (ESEM) were identified. Definite BE was considered only if histologically proven intestinal metaplasia was present. RESULTS: Totally, 16,787 patients underwent EGD; 219 patients (1.3%) were labeled as having ESEM. Only 41 patients had biopsyproven BE (18.7% of ESEM and 0.24% of total patients). The mean age of the patients with BE was 58.1 years [Standard deviation (SD) =13.7] and 78% were men. Of the 41 patients, 14 (34.1%) had long-segment BE (LSBE) (>3 cm) while 27 had short segment Barrett's Esophagus (SSBE) (≤3 cm). Hiatal hernia was identified in 54% of the patients, more commonly in those with LSBE. Only four patients had low-grade dysplasia, and none had high-grade dysplasia. CONCLUSION: The prevalence of BE in Lebanon is much lower than that in Western countries. The reasons for this East-West divide are unknown and require further investigation.

Effect of pantoprazole and Helicobacter pylori therapy on uninvestigated dyspeptic patients.

BACKGROUND/AIMS: This study aimed to test the efficacy of empirical proton pump inhibitor use and Helicobacter pylori therapy for uninvestigated dyspepsia in a population with a high prevalence of H. pylori. MATERIAL AND METHODS: The study had a two-stage design. In the first stage, the efficacy of 4-week pantoprazole treatment was compared with placebo in patients with uninvestigated dyspepsia. In the second stage, the efficacies of 2-week treatment with pantoprazole in H. pylori-negative patients and H. pylori eradication therapy (pantoprazole + amoxicillin + clarithromycin) in H. pylori-positive patients were compared. The primary endpoint was sufficient overall symptom relief (Global Overall Symptom score ≤2; no or minimal symptoms) at the end of treatment. RESULTS: In the first stage, sufficient overall symptom relief was achieved by 25.2% of patients in the pantoprazole group and 15.5% of patients in the placebo group, a difference that was not statistically significant (p=0.06). In the second stage, the rate of sufficient overall symptom relief was higher in the H. pylori therapy group than in the pantoprazole group (37.1% vs. 23.4%; p=0.02). After untreated follow-up, sufficient overall symptom relief remained significantly higher in the H. pylori therapy group than in the pantoprazole group (39.7% vs. 18%; p<0.001). Almost all patients receiving pantoprazole experienced symptom relapse after treatment. CONCLUSIONS: This study validated the use of a test-and-treat strategy against H. pylori in uninvestigated dyspepsia, which may be an advisable treatment approach for uninvestigated dyspeptic patients in countries with a high prevalence of H. pylori.

Split-dose menthol-enhanced PEG vs PEG-ascorbic acid for colonoscopy preparation.

AIM: To compare the efficacy and palatability of 4 L polyethylene glycol electrolyte (PEG) plus sugar-free menthol candy (PEG + M) vs reduced-volume 2 L ascorbic acid-supplemented PEG (AscPEG). METHODS: In a randomized controlled trial setting, ambulatory patients scheduled for elective colonoscopy were prospectively enrolled. Patients were randomized to receive either PEG + M or AscPEG, both split-dosed with minimal dietary restriction. Palatability was assessed on a linear scale of 1 to 5 (1 = disgusting; 5 = tasty). Quality of preparation was scored by assignment-blinded endoscopists using the modified Aronchick and Ottawa scales. The main outcomes were the palatability and efficacy of the preparation. Secondary outcomes included patient willingness to retake the same preparation again in the future and completion of the prescribed preparation. RESULTS: Overall, 200 patients were enrolled (100 patients per arm). PEG + M was more palatable than AscPEG (76% vs 62%, P = 0.03). Completing the preparation was not different between study groups (91% PEG + M vs 86% AscPEG, P = 0.38) but more patients were willing to retake PEG + M (54% vs 40% respectively, P = 0.047). There was no significant difference between PEG + M vs AscPEG in adequate cleansing on both the modified Aronchick (82% vs 77%, P = 0.31) and the Ottawa scale (85% vs 74%, P = 0.054). However, PEG + M was superior in the left colon on the Ottawa subsegmental score (score 0-2: 94% for PEG + M vs 81% for AscPEG, P = 0.005) and received significantly more excellent ratings than AscPEG on the modified Aronchick scale (61% vs 43%, P = 0.009). Both preparations performed less well in afternoon vs morning examinations (inadequate: 29% vs 15.2%, P = 0.02). CONCLUSION: 4 L PEG plus menthol has better palatability and acceptability than 2 L ascorbic acid- PEG and is associated with a higher rate of excellent preparations; Clinicaltrial.gov identifier: NCT01788709.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC): report of three cases with a novel mutation in CLDN19 gene.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive disorder that is caused by mutation in the genes coding for tight junction proteins Claudin-16 and Claudin-19. Affected individuals usually develop nephrocalcinosis and progressive renal failure; some of them may have ophthalmologic involvement as well. Phenotypic description of three affected individuals from the same Middle Eastern kindred (two sisters and their cousin) is presented. This includes both clinical and laboratory findings upon initial presentation and subsequent follow-up. Molecular analysis of the CLDN19 gene was performed on the three cases and one set of parents. A novel homozygous missense mutation in CLDN19 (c.241C>T, p.Arg81Cys) was detected in all three affected children. The parents were heterozygous. Clinical and laboratory data in the three children with renal and ocular manifestations of FHHNC are described. Genetic analysis revealed a novel mutation in the CLDN19 gene. FHHNC is a rare cause of nephrocalcinosis, and we believe that it should be considered in the presence of nephrocalcinosis with hypercalcuria and hypermagnesuria.

Diagnosis of hydatid cyto-biliary disease by intraductal ultrasound (with video).

Hydatid disease is one of the relatively common infections in the Middle Eastern countries. It is seen in areas where dogs are used to raise livestock. In humans, the majority of Echinococcus cysts tends to develop in the liver (70%) and is asymptomatic. The two most common complications of hydatid cysts are abscess formation and rupture. Furthermore, in 5-25% of patients, rupture occurs into the biliary tract and patients may present with cholangitis, jaundice, abscess, or bilio-cutaneous fistula after surgery. Intraductal ultrasound (IDUS) is reportedly superior to conventional endoscopic ultrasound for the depiction of bile duct obstruction owing to its additional capability of providing higher resolution images due to the use of higher frequency transducers. Unfortunately IDUS is rarely used, possibly due to the limited availability of appropriate IDUS equipment, cost of the procedure and interventional endoscopists trained in its interpretation. IDUS with wire-guided, thin-caliber, high-frequency probes is a promising imaging modality, yet no previous reports discuss its usefulness in hydatid disease investigation. We hereby present the first report of biliary hydatid disease being diagnosed by IDUS.

Acquired glomerular lesions in patients with Down syndrome.

The long-term survival of persons with Down syndrome has dramatically increased over the past 50 years. There are no studies addressing the spectrum of glomerular lesions in these patients. We reviewed the clinical-pathologic characteristics of 17 patients with Down syndrome who underwent renal biopsy. The cohort consisted of 12 whites and 5 African Americans with mean age of 29 years (range, 6-45 years). History of hypothyroidism was present in 8 patients. Renal presentations included renal insufficiency (15 patients, mean serum creatinine 3.4 mg/dL), proteinuria (all patients, including 3 with nephrotic syndrome, mean 24-hour urine protein 4.2 g), and hematuria (14 patients, including 4 with gross hematuria). The glomerular diseases found on biopsy were IgA nephropathy (n = 5 patients), focal segmental glomerulosclerosis (n = 4), membranoproliferative glomerulonephritis (n = 2), acute postinfectious glomerulonephritis (n = 2), pauci-immune crescentic glomerulonephritis (n = 2), membranous glomerulonephritis (n = 1), and lupus nephritis (n = 1). Follow-up (mean, 47 months; range, 2-141 months) was available on 16 patients (94%). Two patients (1 with membranous glomerulonephritis and 1 with acute postinfectious glomerulonephritis) had complete remission; 8 patients (4 with IgA nephropathy, 2 with focal segmental glomerulosclerosis, 1 with lupus nephritis, and 1 with acute postinfectious glomerulonephritis) had chronic kidney disease; and 6 patients (2 with pauci-immune crescentic glomerulonephritis, 2 with membranoproliferative glomerulonephritis, 1 with IgA nephropathy, and 1 with focal segmental glomerulosclerosis) progressed to end-stage renal disease, 4 of whom died. In summary, a wide spectrum of glomerular diseases can be seen in patients with Down syndrome, with IgA nephropathy and focal segmental glomerulosclerosis being the most common. Renal biopsy is necessary to determine the type of glomerular lesion and appropriate treatment.

Epilepsy, ataxia, sensorineural deafness, tubulopathy, and KCNJ10 mutations.

BACKGROUND: Five children from two consanguineous families presented with epilepsy beginning in infancy and severe ataxia, moderate sensorineural deafness, and a renal salt-losing tubulopathy with normotensive hypokalemic metabolic alkalosis. We investigated the genetic basis of this autosomal recessive disease, which we call the EAST syndrome (the presence of epilepsy, ataxia, sensorineural deafness, and tubulopathy). METHODS: Whole-genome linkage analysis was performed in the four affected children in one of the families. Newly identified mutations in a potassium-channel gene were evaluated with the use of a heterologous expression system. Protein expression and function were further investigated in genetically modified mice. RESULTS: Linkage analysis identified a single significant locus on chromosome 1q23.2 with a lod score of 4.98. This region contained the KCNJ10 gene, which encodes a potassium channel expressed in the brain, inner ear, and kidney. Sequencing of this candidate gene revealed homozygous missense mutations in affected persons in both families. These mutations, when expressed heterologously in xenopus oocytes, caused significant and specific decreases in potassium currents. Mice with Kcnj10 deletions became dehydrated, with definitive evidence of renal salt wasting. CONCLUSIONS: Mutations in KCNJ10 cause a specific disorder, consisting of epilepsy, ataxia, sensorineural deafness, and tubulopathy. Our findings indicate that KCNJ10 plays a major role in renal salt handling and, hence, possibly also in blood-pressure maintenance and its regulation.

Recovery of tacrolimus-associated brachial neuritis after conversion to everolimus in a pediatric renal transplant recipient--case report and review of the literature.

TAC has been shown to be a potent immunosuppressive agent for solid organ transplantation in pediatrics. Neurotoxicity is a potentially serious toxic effect. It is characterized by encephalopathy, headaches, seizures, or neurological deficits. Here, we describe an eight-and-a-half-yr-old male renal transplant recipient with right BN. MRI demonstrated hyperintense T2 signals in the cervical cord and right brachial plexus roots indicative of both myelitis and right brachial plexitis. Symptoms persisted for three months despite TAC dose reduction, administration of IVIG and four doses of methylprednisolone pulse therapy. Improvement and eventually full recovery only occurred after TAC was completely discontinued and successfully replaced by everolimus.