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Background and Objectives: YLB113 is being developed as a biosimilar of the antitumor necrosis factor-alpha antagonist etanercept, which is approved for the treatment of moderate-to-severe rheumatoid arthritis (RA) and other chronic immune-mediated inflammatory diseases. An open-label, crossover, pharmacokinetic study was conducted to compare the relative bioavailability and safety of YLB113 and the etanercept reference product (RP) Enbrel ® ., Methods: Healthy male subjects aged 18-50 years were randomized to receive a single subcutaneous dose of YLB113 in one period and the etanercept RP in another period. A washout period of 28 days separated the two treatment periods. Blood samples were collected for pharmacokinetic analysis predose and until 480 h postdose during both periods., Results: Overall, 52 subjects were enrolled, including 51 subjects who completed the first period and 43 subjects who completed the second period. The 90% confidence intervals for the least squares means derived from an analysis of the log-transformed pharmacokinetic parameters maximum serum concentration (C max ), area under the serum concentration-time curve (AUC) from 0 to the last measurable concentration (AUC (0-t) ) and AUC from 0 to infinity (AUC (0-∞) ) for etanercept were between the limits of 80 and 125%. Thus, YLB113 met the bioequivalence criterion. YLB113 and the etanercept RP were well tolerated, with 24 subjects reporting 53 adverse events, including 42 mild and 11 moderate events. Treatment-emergent adverse events were reported by 14 and 16 subjects following the administration of YLB113 and the etanercept RP, respectively., Conclusions: A single dose of YLB113 exhibited pharmacokinetic and safety profiles comparable with those of the etanercept RP in healthy adult male subjects. Therefore, YLB113 and the etanercept RP can be considered bioequivalent. These findings support the continued development of YLB113 for use in patients with RA., Jordan Food & Drug Administration Unique Trial Number: 31/Clinical/2018.

Importance: Current treatments for long-term prophylaxis in hereditary angioedema have limitations., Objective: To assess the efficacy of lanadelumab, a fully human monoclonal antibody that selectively inhibits active plasma kallikrein, in preventing hereditary angioedema attacks., Design, Setting, and Participants: Phase 3, randomized, double-blind, parallel-group, placebo-controlled trial conducted at 41 sites in Canada, Europe, Jordan, and the United States. Patients were randomized between March 3, 2016, and September 9, 2016; last day of follow-up was April 13, 2017. Randomization was 2:1 lanadelumab to placebo; patients assigned to lanadelumab were further randomized 1:1:1 to 1 of the 3 dose regimens. Patients 12 years or older with hereditary angioedema type I or II underwent a 4-week run-in period and those with 1 or more hereditary angioedema attacks during run-in were randomized., Interventions: Twenty-six-week treatment with subcutaneous lanadelumab 150 mg every 4 weeks (n = 28), 300 mg every 4 weeks (n = 29), 300 mg every 2 weeks (n = 27), or placebo (n = 41). All patients received injections every 2 weeks, with those in the every-4-week group receiving placebo in between active treatments., Main Outcome and Measures: Primary efficacy end point was the number of investigator-confirmed attacks of hereditary angioedema over the treatment period., Results: Among 125 patients randomized (mean age, 40.7 years [SD, 14.7 years]; 88 females [70.4%]; 113 white [90.4%]), 113 (90.4%) completed the study. During the run-in period, the mean number of hereditary angioedema attacks per month in the placebo group was 4.0; for the lanadelumab groups, 3.2 for the every-4-week 150-mg group; 3.7 for the every-4-week 300-mg group; and 3.5 for the every-2-week 300-mg group. During the treatment period, the mean number of attacks per month for the placebo group was 1.97; for the lanadelumab groups, 0.48 for the every-4-week 150-mg group; 0.53 for the every-4-week 300-mg group; and 0.26 for the every-2-week 300-mg group. Compared with placebo, the mean differences in the attack rate per month were -1.49 (95% CI, -1.90 to -1.08; P < .001); -1.44 (95% CI, -1.84 to -1.04; P < .001); and -1.71 (95% CI, -2.09 to -1.33; P < .001). The most commonly occurring adverse events with greater frequency in the lanadelumab treatment groups were injection site reactions (34.1% placebo, 52.4% lanadelumab) and dizziness (0% placebo, 6.0% lanadelumab)., Conclusions and Relevance: Among patients with hereditary angioedema type I or II, treatment with subcutaneous lanadelumab for 26 weeks significantly reduced the attack rate compared with placebo. These findings support the use of lanadelumab as a prophylactic therapy for hereditary angioedema. Further research is needed to determine long-term safety and efficacy., Trial Registration: EudraCT Identifier: 2015-003943-20; ClinicalTrials.gov Identifier: NCT02586805.

Background: Hereditary angioedema with C1 inhibitor deficiency is characterized by recurrent, unpredictable swelling episodes caused by uncontrolled plasma kallikrein generation and excessive bradykinin release resulting from cleavage of high-molecular-weight kininogen. Lanadelumab (DX-2930) is a new kallikrein inhibitor with the potential for prophylactic treatment of hereditary angioedema with C1 inhibitor deficiency., Methods: We conducted a phase 1b, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial. Patients with hereditary angioedema with C1 inhibitor deficiency were randomly assigned in a 2:1 ratio to receive either lanadelumab (24 patients) or placebo (13 patients), in two administrations 14 days apart. Patients assigned to lanadelumab were enrolled in sequential dose groups: total dose of 30 mg (4 patients), 100 mg (4 patients), 300 mg (5 patients), or 400 mg (11 patients). The pharmacodynamic profile of lanadelumab was assessed by measurement of plasma levels of cleaved high-molecular-weight kininogen, and efficacy was assessed by the rate of attacks of angioedema during a prespecified period (day 8 to day 50) in the 300-mg and 400-mg groups as compared with the placebo group., Results: No discontinuations occurred because of adverse events, serious adverse events, or deaths in patients who received lanadelumab. The most common adverse events that emerged during treatment were attacks of angioedema, injection-site pain, and headache. Dose-proportional increases in serum concentrations of lanadelumab were observed; the mean elimination half-life was approximately 2 weeks. Lanadelumab at a dose of 300 mg or 400 mg reduced cleavage of high-molecular-weight kininogen in plasma from patients with hereditary angioedema with C1 inhibitor deficiency to levels approaching that from patients without the disorder. From day 8 to day 50, the 300-mg and 400-mg groups had 100% and 88% fewer attacks, respectively, than the placebo group. All patients in the 300-mg group and 82% (9 of 11) in the 400-mg group were attack-free, as compared with 27% (3 of 11) in the placebo group., Conclusions: In this small trial, administration of lanadelumab to patients with hereditary angioedema with C1 inhibitor deficiency reduced cleavage of high-molecular-weight kininogen and attacks of angioedema. (Funded by Dyax; ClinicalTrials.gov number, NCT02093923 .).

The prevalence of coeliac disease among patients with autoimmune hypothyroidism has not been studied before in Jordan and other Arab countries. A cross-sectional record-based review was made of all adult autoimmune hypothyroidism patients who attended a referral centre in Jordan, during an 8-month period. Coeliac disease in these patients was diagnosed by the attending physician based on positive serological tests for anti-endomysial antibodies IgA and IgG followed by duodenal biopsy to confirm the diagnosis of coeliac disease. Of 914 patients recruited, 117 (12.8%) were seropositive for coeliac disease. Of 87 seropositive patients who underwent duodenal biopsy, 39 had positive histological findings of coeliac disease (44.8%). Extrapolating from these findings the overall rate of coeliac disease among autoimmune hypothyroidism patients was estimated to be 5.7%. In multivariate logistic regression coeliac disease was significantly associated with older age (> 40 years), presence of other autoimmune diseases, vitamin B12 deficiency and anaemia.

Background/aims: To determine the value of serum bilirubin levels in selecting patients for MRCP., Methodology: The medical records of 142 patients who underwent MRCP between January 2002 and December 2004 were retrospectively reviewed. Clinical features, serum bilirubin levels, and MRCP results were recorded. The patients were categorized into 4 groups, according to serum bilirubin levels and MRCP findings. Bilirubin levels were considered elevated above 23.9 micromol/L for total bilirubin and above 6.8 micromol/L for direct bilirubin. Sensitivity, specificity, accuracy, and predictive values of serum bilirubin levels in identifying pancreatobiliary duct diseases were assessed., Results: Complete medical records were found for 135 patients. Abnormal MRCP results were found in 75 patients (56%). Choledocholithiasis and both malignant and benign bile duct strictures represented 40%, 28%, and 23% of abnormal MRCP findings, respectively, with mean values of total and direct serum bilirubin levels of 77.9 +/- 51.6 microM and 34.7 +/- 30.3 microM (for choledocholithiasis), 170 +/- 115 microM and 56 +/- 40 microM (for malignant bile duct stricture), and 44 +/- 32 microM and 20 +/- 16 microM (for benign bile duct stricture), respectively. Sensitivity, specificity, and accuracy of serum bilirubin level tests, for the diagnoses of pancreatobiliary duct diseases, were 77%, 80%, and 79%, respectively; the positive and negative predictive values were 83% and 74%, respectively, and the corresponding likelihood ratios were 3.8 and 0.3., Conclusions: Serum bilirubin level tests alone are not sufficiently accurate for the diagnoses of pancreatobiliary duct diseases, and hence, such tests are of low importance in selecting patients for MRCP.

Background/aims: To determine the role of magnetic resonance cholangiopancreatogram with conventional abdominal magnetic resonance examination in patients presenting clinically with upper abdominal pain and abnormal liver function tests and to compare the findings with endoscopic retrograde cholangiopancreatogram results., Methodology: Magnetic resonance cholangiopancreatogram and endoscopic retrograde cholangiopancreatogram were done in 77 patients. Conventional magnetic resonance examination of the liver and upper abdomen was done first followed by magnetic resonance cholangiopancreatogram using a half fourrier single shot turbo spin echo sequence. Conventional endoscopic retrograde cholangiopancreatogram was done by direct intraductal injection of radiographic contrast material through a duodenoscope under fluoroscopy control., Results: Endoscopic retrograde cholangiopancreatogram failed in 7 patients (9%) and Magnetic resonance cholangiopancreatogram images were inadequate in 3 patients (4%). The findings of adequate magnetic resonance exams in 74 patients were: choledocholithiasis in 24 patients (32%), bile duct stricture in 19 patients (26%), normal biliary ducts in 29 patients (39%) and dilated biliary ducts with no definite cause in 2 patients (3%). The findings of successful endoscopic retrograde cholangiopancreatograms in 67 patients after exclusion of inadequate magnetic resonance cholangiopancreatograms were: choledocholithiasis in 25 patients (37%), bile duct stricture in 18 patients (27%), normal biliary ducts in 21 patients (31%) and dilated biliary ducts with no evident cause in 2 patients (3%) and hemobilia in 1 patient (2%)., Conclusions: Magnetic resonance cholangiopancreatogram is a non-invasive technique, its accuracy is increased if it is combined with conventional abdominal magnetic resonance exam and it can replace the endoscopic retrograde cholangiopancreatogram.

Wolfram syndrome (WS) is a recessively inherited disorder associated with recognised clinical features. Bleeding tendency was noticed in some of our patients, although this has not been reported before. We therefore studied this problem in all our WS patients and tried to postulate a possible pathogenesis. At the same time, a genetic linkage study provided evidence of locus heterogeneity of this syndrome and showed that the majority of our patients belong to the second WS locus identified in that study. Our study group consisted of 13 WS patients, belonging to WSF2 locus (group I). Controls consisted of 4 healthy siblings of WS patients (group II) and 7 diabetics who do not have WS (group III). Relevant clinical data were obtained, and a coagulation screen was carried out for all groups. All individuals in the three study groups have normal platelet count, thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (aPTT), clot retraction, Factor VIII activity (FVIIIc) and von Willebrand factor antigen (vWAg). Eleven of the WS patients have prolonged template bleeding time (BT) compared with both control groups. Patients with WS have a longer BT (mean 9.6 min, 95% CL 8.61-10.53 min) than the siblings group (mean 6.75 min, 95% CL 5.52-7.98 min) and the diabetic group (mean 5.49 min, 95% CL 4.56-6.42 min). The differences between the study group and controls are statistically significant, p = 0.02 and 0.0002, respectively. In the three groups, platelet aggregation studies were normal using adenosine diphosphate (ADP), ristocetin and epinephrine. Aggregation with collagen was either absent or impaired, with failure of secondary wave being noticed in 11 of the WS patients (85%) and normal in the control groups. The pathogenesis of this problem is not known, but could be due to an inhibitory effect of vWAgII, deficiency of thrombospondin or a defect in the platelet membrane GPIa/IIa. Bleeding diathesis is a new additional feature to the clinical spectrum of WS, which is probably a feature of the disorder WFS2 and not WFS1, as bleeding has never been reported in the latter. This provides further evidence for the phenotypic and genotypic heterogeneity of this complex disorder and may provide clues to the search for the second gene responsible for this phenotype.

Background/aims: Management of common bile duct stones in the era of laparoscopic surgery is still controversial. The purpose of this study is to investigate the safety, feasibility, success rate and short-term results of the selective use of endoscopic retrograde cholangiopancreatography in patients undergoing laparoscopic cholecystectomy., Methodology: A prospective study comprising 300 consecutive patients with either symptomatic or complicated gallbladder stones was performed between January 1994 and November 1996. Depending on clinical, laboratory and ultrasonographic criteria, 73 patients (24.3%) underwent endoscopic retrograde cholangiopancreatography with or without endoscopic sphincterotomy. The procedure was successful in 71 patients (97%) either preoperatively in 62 patients (21%) or postoperatively in 9 patients (3%)., Results: Endoscopic retrograde cholangiopancreatography was positive in 37 cases (52%), endoscopic sphincterotomy and stone extraction was performed in 35 cases and endoscopic sphincterotomy alone was performed in 2 cases for benign papillary stenosis. The overall predictive value for the presence of common bile duct stone was 52%, the predictive value for patients with jaundice, dilated common bile duct together with elevated liver enzymes was 73.3%. Complications of perioperative endoscopic retrograde cholangiopancreatography were encountered in 4 patients (5.5%) with no mortality., Conclusions: We conclude that the combination of perioperative endoscopic retrograde cholangiopancreatography and laparoscopic cholecystectomy is a useful approach for the management of choledochocholelithiasis.

Objective: As a measure of the quality of care provided to patients in the intensive care unit, comparison of nosocomial infection rates with those of the National Nosocomial Infection surveillance was completed during a 3-year observation period., Design: The study design was a prospective study during 3 years between 1993 and 1995. During that period, patients at the medical/surgical and neurosurgical intensive care units and the high-risk nursery were surveyed for nosocomial infections. Device use, bloodstream infection, urinary tract infection, and ventilator-associated pneumonia nosocomial infection rates were calculated and compared with the National Nosocomial Infection Surveillance published rates for the same period., Setting: The study setting was the medical/surgical intensive care unit, the neurosurgical intensive care unit, and the high-risk nursery at the Jordan University Hospital., Results: Overall infection rates were 17.2 per 100 patients in the medical/surgical intensive care unit, 14.2 to 18.5 per 100 patients in the neurosurgical intensive care unit, and 13.4 to 73.5 per 100 patients in the high-risk nursery. When compared with the weight of the infants, these rates were 61.9 to 94 per 100 in infants weighing <1500 g, 26 to 30.8 per 100 patients in infants weighing >1500 g to 2500 g, and 11.7 to 14.4 per 100 in infants weighing >2500 g. Whereas device use was moderate, bloodstream infection and ventilator-associated pneumonia rates were >90th percentile for National Nosocomial Infection Surveillance in the high-risk nursery, and urinary tract infection was >90th percentile in the medical/surgical and neurosurgical intensive care units. Nosocomial infections at the intensive care units in developing countries need further investigation and control.

Unlabelled: To study the prevalence of Helicobacter pylori infection in dyspeptic Jordanian patients., Patients and Methods: Two hundred and twenty seven consecutive dyspeptic Jordanian patients were studied with endoscopy, endoscopic biopsies, culture, and CLO urease testing for the detection of H. pylori., Results: Helicobacter pylori positivity in both culture and CLO urease testing was 86%, being 78% in culture and 80% in CLO test separately. The majority of our patients were in the age range 21-60 years and H. pylori positivity was more than 90% in them., Conclusion: Helicobacter pylori is a common infection in dyspeptic Jordanian patients regardless of the underlying cause. Males were affected more than females.

Purpose: This study was developed to document causes of rectal bleeding of Jordanian patients and compare them with results from several parts of the world., Methods: Diagnostic and therapeutic colonoscopy was used as a first-line investigation on 701 consecutive Jordanian patients presenting with rectal bleeding. When indicated, technetium 99m-labeled red blood counts or selective angiography were used also., Results: Most common causes according to frequency were hemorrhoids, polyps, ulcerative colitis, amebic colitis, neoplasm, diverticulosis, anal fissure, Crohn's disease, and arteriovenous malformations., Conclusions: This is the first study addressing this problem from this part of the world. Findings were different from many other results published in western and eastern studies in certain disease entities.

Endoscopy within 24 hours from the onset of upper gastrointestinal (UGI) bleeding was carried out on 853 Jordanian patients. Lesions as a bleeding source were identified in 799 (93.7%) patients. Radioactively tagged red blood cell (RBC) scan, angiography and upper gastrointestinal follow-through radiography were complementary studies in endoscopy negative patients. Etiology remained unidentified in 16 patients. The six most common causes of UGI bleeding in this study were duodenal ulcer, gastric erosions, duodenal erosions, esophagitis, gastric ulcer and esophageal varices. Nonsteroidal anti-inflammatory drugs (NSAIDs) were a significant predisposing factor for UGI bleeding (28.6%). Mortality at the first admission was 3.4% and increased during 12 month follow-up to 6.9%. To our knowledge, this is the first study from Jordan concerning the causes of upper GI bleeding of all clinical types.

Endoscopic retrograde cholangiopancreatography (ERCP) is the method of choice in establishing the nature and the site of common bile and pancreatic duct disease and related complications. It was used in 668 Jordanian patients who presented with biliary or pancreatic disease and unexplained upper abdominal pain. Common bile duct (CBD) stones, postsurgical traumatic CBD strictures, papillary stenosis and malignant strictures were the most common findings in this study. The incidence of malignant strictures was less and the postsurgical CBD injuries, mainly CBD complete ligation, were more than what was reported by others. This procedure was also valuable in the investigation of unexplained upper abdominal pain and pancreatic disease.

A 50 year old man presented with progressive unilateral cranial nerve palsies (Garcin's syndrome) for one year. Skull radiography and computed tomography (CT) showed intracranial extension of a soft tissue tumour from the right base of the skull. Necropsy revealed a papillary cell carcinoma of the right kidney and metastases in the base of the skull.

Eight hundred Jordanians with liver enlargement were studied: 369 (46%) were males and 431 (54%) females. Ages ranged between 13 and 85 years, with a mean of 47.4%: 766 cases demonstrated a single pathological process while 34 cases showed two or more processes. The most significant findings were: congestion secondary to cardiac failure in 323 cases (38.5%); inflammatory and parasitic processes in 192 cases (22.9%), including acute hepatitis (81 cases), hydatid cyst (63 cases), chronic hepatitis (27 cases), liver abscess (19 cases), brucellosis (one case) and malaria (one case); malignancy in 164 cases (19.6%); liver cirrhosis in 80 cases (9.5%); fatty metamorphosis in 47 cases (5.6%); metabolic and genetic disease in 11 cases (1.3%); miscellaneous conditions in nine cases (1.1%); and 15 apparently normal individuals (1.8%). Cardiac failure was the most frequent cause of hepatomegaly in this sample of Jordanians. Inflammatory processes were the second major cause, followed by malignancy and cirrhosis of the liver.