The Phenotypic Spectrum of New-onset IBD in Canadian Children of South Asian Ethnicity: A Prospective Multi-Centre Comparative Study.

BACKGROUND: Canadian-born children of South Asian [SA] ethnicity develop inflammatory bowel disease [IBD] at similar rates to those among Caucasian children. We evaluated the variation in phenotypic spectrum of IBD in SA and Caucasian children in a national paediatric inception cohort of new-onset IBD. METHODS: Patients aged <17 years, enrolled in a Canadian nationwide inception cohort study, were included. Baseline demographic and IBD phenotypic features were compared between SA and Caucasian children. Longitudinal outcomes through 18 months of follow-up were compared matched by propensity scores. RESULTS: Of 1156 children enrolled over 2014 to 2019, 623 were Caucasian [98% and 88% parents Canadian born] and 114 SA [79% Canadian born, 87% parents SA born]. Fewer SAs have a first-degree relative with IBD, 6% vs 19% in Caucasians, p = 0.002. SAs present at a younger age, median age 11.4 years (interquartile range [IQR] 9.2-14.3) vs 13 years [IQR 10.9-15 years], p = 0.03 and more commonly with a UC/IBD-U [ulcerative colitis/IBD-unclassified] subtype [ratio of UC/IBD-U to CD 1.2:1 vs 1:1.8 for Caucasians, p <0.001]. Additionally, a greater proportion of SA CD patients present with colonic-only disease [colonic-only CD/UC/IBD-U in SAs 67% vs 57% for Caucasians, p = 0.001], and among those with CD, colonic CD in SAs 31% vs 23% in Caucasians, p = 0.20]. Perianal fistulising disease was also numerically more common in SAs (14 [27%] vs 64 [18%], p = 0.06]. Adjusting for differences in phenotypic presentation, anti-tumour necrosis factor [TNF] exposure, and time to initiation was similar, and two-thirds of children, whether anti-TNF exposed or naïve, were in corticosteroid-free clinical remission at 18 months irrespective of ethnicity. CONCLUSIONS: The phenotypic spectrum of new-onset IBD in SA children differs from that of Caucasian children, but treatment and clinical course are similar within phenotypic subgroups.

Phenotypic Variation in Paediatric Inflammatory Bowel Disease by Age: A Multicentre Prospective Inception Cohort Study of the Canadian Children IBD Network.

BACKGROUND AND AIMS: Incidence of paediatric inflammatory bowel disease [IBD] in Canada is among the highest worldwide, and age of onset may be decreasing. In a multicentre nationwide inception cohort study, we examined variation in phenotype of IBD throughout the paediatric age spectrum. METHODS: Children aged ≥2 years [y] and <17y [A1 age at diagnosis], with new onset IBD, were systematically evaluated at sites of the Canadian Children IBD Network. Prospectively recorded phenotypic data were compared between age groups. RESULTS: Among 1092 children (70% Caucasian; 64% Crohn's disease [CD], 36% ulcerative colitis/inflammatory bowel disease unclassified [UC/IBD-U]; median age 13 y, interquartile range [IQR] 11-15 y), 210 [19%] were diagnosed before the age of age 10 y [Paris A1a] and 43 [4%] before age 6 y (very-early-onset [VEO-IBD]). CD was less common in younger children [42%, 56%, 66%, respectively, of VEO-IBD, A1a; A1b]. Colon-only IBD [UC/IBDU or CD-colon] was present in 81% of VEO-IBD and 65% of A1a; ileal disease increased progressively, reaching plateau at age 10 y. CD location was ileocolonic [L3] in 53% overall. Ileitis [L1] increased with age [6% of VEO-IBD; 13% of A1a; 21% of A1b], as did stricturing/penetrating CD [4% of A1a; 11% of A1b]. At all ages UC was extensive [E3/E4] in >85%, and disease activity moderate to severe according to Physician's Global Assessment [PGA] and weighted Paediatric Crohn's Disease Activity Index/Paediatric Ulcerative Colitis Activity Index [wPCDAI/PUCAI] in >70%. Heights were modestly reduced in CD [mean height z score -0.30 ± 1.23], but normal in UC/IBD-U. CONCLUSIONS: Paris classification of age at diagnosis is supported by age-related increases in ileal disease until age 10 years. Other phenotypic features, including severity, are similar across all ages. Linear growth is less impaired in CD than in historical cohorts, reflecting earlier diagnosis.

Treatment outcomes for eosinophilic esophagitis in children with esophageal atresia.

Eosinophilic esophagitis (EoE) has been reported to be more prevalent in patients with esophageal atresia/tracheoesophageal fistula (EA-TEF). To date, there is limited data on the management of EoE in this group of patients. The aim of this study is to evaluate the treatment outcomes of EoE in children with EA-TEF. A retrospective chart review was performed on all EA-TEF children who were diagnosed with and treated for EoE between January 2000 and September 2013 at the Sydney Children's Hospital. Data collected included details of the patient's treatment, post-treatment endoscopy, symptoms and nutrition. Twenty patients were included in the study. Median age at diagnosis was 26 months (8-103 months), and median time from diagnosis to last follow-up was 23 months (2-132 months). Patients were treated with budesonide slurry, swallowed fluticasone, elimination diet alone or in combination. All patients were on proton pump inhibitors at time of diagnosis of EoE which was continued. Six out of seven patients who had furrowing/exudate in endoscopy at diagnosis had complete resolution at a median follow-up period of 26 months (P = 0.031). Median peak intraepithelial eosinophil count reduced significantly from 30/high-powered field (HPF) (19-80/HPF) to 8/HPF (0-85/HPF) (median time for improvement = 24 months) (P = 0.015). There was a significant reduction in symptoms of dysphagia and reflux post-treatment (P < 0.001). Prevalence of strictures significantly decreased (P = 0.016), as did need for dilatations (P = 0.004). In four out of six patients with gastrostomies at baseline, the feeding improved on treatment of EoE and the gastrostomy could be closed. There was also a nonsignificant trend towards improvement in weight and height 'z scores' of the patients. Treatment of EoE in children with EA-TEF was found to significantly reduce intraepithelial eosinophil count, symptoms, strictures and need for dilatations.

Eosinophilic esophagitis in children with esophageal atresia.

Eosinophilic esophagitis (EoE) has only rarely been reported in esophageal atresia (EA) patients. A retrospective case analysis of all EA patients born at our center between January 1999 and April 2012 was performed. A total of 113 of patients were identified; 10 patients were excluded as a result of inadequate data. Eighteen patients (17%) were diagnosed with EoE. The average number of eosinophilis was 30/high-power field (HPF) (19/HPF-80/HPF). The median age for diagnosis of EoE was 1 year and 6 months (8 months-8 years and 7 months). Children with EoE had a significantly greater incidence of reflux symptoms, dysphagia, tracheomalacia, and 'hypoxic spells' (P < 0.05). EoE patients also underwent significantly more surgery including fundoplication and aortopexy when compared with those without EoE (P < 0.0001). Although the incidence of gastrostomy was greater in the EoE group (33% vs. 13%), this was not statistically significant. Half of the EoE patients had a coexisting atopic condition at time of diagnosis. The commonest condition was asthma 7/18 (38%) followed by specific food allergy 6/18 (33%). EoE was treated in 11 patients with either swallowed fluticasone or budesonide slurry. All improved clinically. Histologically, five had complete resolution and six had partial improvement. Six children with EoE were treated with acid suppression alone. All improved clinically, and 5/6 had subsequent histological resolution. One child who received acid suppression and an exclusion diet also improved. Seven patients (38%) had an esophageal stricture at time of EoE diagnosis. Five were dilated at time of the initial endoscopy, prior to the diagnosis of EoE being available. Two patients had resolution of their strictures on medical treatment of their EoE alone and did not require further dilatation. EoE was seen in 17% of children with EA in this study. EoE should be considered in EA patients with persistent symptoms on standard reflux treatment, increasing dysphagia, and recurrent strictures.

Failures of the Dual Articular knee prosthesis due to fracture of the polyethylene post.

The Dual Articular (DA) total knee replacement was designed for revision and complex primary knee arthroplasty. A number of these knees failed due to fracture of the polyethylene post. We aimed to identify the proportion of DA prostheses that failed in this manner in our hospital. The hospital database was interrogated to identify all patients undergoing revision total knee replacement under the care of one surgeon from 1995 to 2007. Case notes were then reviewed to collect information about the history surrounding the knee surgery, and determine the patient's weight at the time of surgery. Telephone follow-up was carried out to obtain complete contemporary data. Forty-eight prostheses were implanted into 39 patients (21 male, 18 female). Thirty-two of the prostheses were DA and of these, 7 underwent arthroscopy or arthrotomy to reveal a fracture of the polyethylene post (22%). T-tests showed no statistical difference in age (p=0.73) or weight (p=0.79) between the group of DA patients with fractured posts and those without. Six of the 7 fractures were in male patients (Chi-squared; p=0.01). Patients complained of pain, clicking and instability at a mean of 7 years post-surgery. Sixteen DA2000 prostheses were implanted, but none of these had failed due to a fractured polyethylene post. A high proportion of DA prostheses failed due to post fracture. We recommend that patients with DA prostheses be kept under review to detect failures early. Pain, clicking and instability should be investigated with arthroscopy and the tibial insert exchanged as appropriate.

Hospital morbidity due to post-operative infections in obstetrics & gynecology.

OBJECTIVE: To study the incidence and risk factors for postoperative infection following cesarean sections and major gynecological surgery. METHODS: Postoperative infection was documented in the specified registers in all patients following cesarean sections and major gynecological surgery from January 1997 to December 1998. This study was a part of the prospective analysis of hospital-based morbidity and mortality in the Department of Obstetrics and Gynecology. RESULTS: There were a total of 89 cases of postoperative infections amongst 4,032 patients undergoing major operations giving an overall infection rate of 2.2%. The morbidity due to infections was 3.3% in cesarean sections and 0.9% in major gynecological surgery. Abdominal hysterectomies had a higher infection rate than vaginal surgery. The most common causative organisms isolated were Enterococcus, Staphylococcus and Klebsiella species. CONCLUSION: It was found that vaginal flora was a significant source of contamination during surgery, which could be minimised by local sterilisation methods. The high infective morbidity in abdominal hysterectomies needs further analysis of the risk factors. Infection surveillance with a regular review of antibiotic protocols is recommended.

Perinatal mortality in Bahrain.

A review of 583 perinatal deaths at the Ministry of Health hospitals in Bahrain, during the years 1985-1987 revealed a perinatal mortality rate of 19.6 per 1,000 total births. Lethal congenital malformations accounted for 145 (24.9%) deaths. Of the 438 normally formed infants there were 42.2% antepartum, 115 (26.3%) intrapartum and 138 (31.5%) early neonatal deaths; in 82.7% of cases the death was considered to be unavoidable. The population of Bahrain for 1986 according to the Central Statistics Organization (1) was 435,065, the majority of which was served by the Ministry of Health Maternity Service with approximately 10,000 deliveries per annum. The Ministry of Health provides maternity services through one main maternity hospital and 2 peripheral hospitals with consultant obstetric care. In addition to these, there are 3 maternity units run by midwives. High risk cases are usually delivered in the main hospital as there is a neonatal intensive care unit attached to it. The latter also acts as a referral centre for all sick babies in Bahrain. An analysis of the causes of perinatal deaths is an effective way of assessing the efficiency of maternity services. The objective of this study was to identify and improve the various factors influencing perinatal mortality in Bahrain.

PIP: In Bahrain, the Ministry of Health (MOH) medical facilities, which included 1 main maternity hospital, 2 peripheral hospitals, and 3 maternity units under the direction of midwives, reported 29,644 births during January 1985-December 1987. 355 of these were stillbirth and 228 infants died within the 1st week which made up a perinatal mortality rate of 19.6/1000 births. The leading causes of perinatal deaths included, in descending order, low birth weight, mainly due to prematurity (29.3%); congenital malformations (24.9%); mechanical problems, especially cord complications (12%), antepartum hemorrhage, most caused by abruptio placentae (9.1%), and preeclampsia (9.1%). Of the 438 normally formed infants that died, 185 (42.2%) of these were antepartum, 115 (26.3%) intrapartum, and 138 (31.5%) postpartum. 45 (10%) of the normally formed infants that died weighed above the 10th percentile for their gestational age and there were no maternal complications. The researchers classified 101 of all the infant deaths (17.3%) as avoidable perinatal deaths--70% due to poor patient compliance, 28% due to medical mismanagement, and 2% due to a combination of these factors. The MOH must emphasize health education and regular prenatal visits for pregnant mothers. Health practitioners need to reevaluate present prenatal and intrapartum clinical methods and to routinely screen for diabetes and other possible high risk factors.

Maternal mortality in Bahrain with special reference to sickle cell disease.

The maternal mortality in Bahrain during the 10-year period, 1977-1986, was 33.9 per 100,000 livebirths; the second 5-year period showed a significant reduction (26.9) compared to the first 5-year period (42.3). Haemorrhage, pulmonary embolism, hypertensive diseases of pregnancy and infection were the main causes of maternal mortality. Sickle cell disease was found to be an underlying cause in about one third of the maternal deaths. Avoidable factors were present in 38% of the cases, the majority being due to the failure of the patients to seek medical care or follow medical advice. Health education, premarital counselling and family planning were identified as significant factors in reducing the maternal mortality rate.

PIP: There were 37 maternal deaths among the 109,221 livebirths registered during the period 1977-86 in Bahrain, Arabian Gulf. The maternal mortality rate was 33.9/100,000 for the 10-year study period; however, disaggregation reveals a decline in this rate from 42.3/100,000 in 1977-81 to 26.9/100,000 in 1982-86. This decline presumably reflects streamlining of the Ministry of Health's maternity services, including a central maternity hospital with all modern facilities that serves as a referral center for all of Bahrain, 2 peripheral hospitals with provision for blood transfusion and surgical deliveries, and 3 maternity units managed by fully qualified midwives. About 80% of deliveries are covered by these maternity services; only 2.5% of deliveries occur in the home. Despite this highly developed maternity care system, 18 of the maternal deaths were due to direct obstetric cause: hemorrhage, 7; pre-eclampsia and eclampsia, 5; abortion septicemia, 2; bowel perforation during cesarean section, 1; thromboembolism, 2; and amniotic fluid embolism, 1. The causes of the 19 indirect maternal deaths were: pulmonary embolism, 5; infection, 7; cardiac failure, 2; cerebrovascular accident, 2; pulmonary hypertension, 1; and uncertain, 2. Of interest is the finding that sickle cell disease was the underlying cause of maternal death in 12 of the 37 deaths in this series. Sickle cell disease was implicated in 3 of the deaths from hemorrhage, all 5 deaths from pulmonary embolism, 2 deaths from septicemia, and the 2 cases of cardiac failure. In this series, 50% of the patients with sickle cell disease had thromboembolic crises following treatment of anemia with packed cell transfusion. Blood transfusion, especially of packed cells, should be given with caution to these patients since it may precipitate vaso-occlusive crisis by increasing blood viscosity. Since sickle cell disease represents a high risk during pregnancy in this Arab population, such patients should have frequent prenatal check-ups and deliver in a well-equipped hospital.

Distinctive cellular immunity in genetically susceptible BALB/c mice recovered from Leishmania major infection or after subcutaneous immunization with killed parasites.

Genetically susceptible BALB/c mice are refractory to further infection after recovery from Leishmania major infection after a sublethal dose of gamma-irradiation. In contrast, mice immunized with killed promastigotes s.c. develop exacerbated lesions after infection. Both groups of mice produce only a low level of specific antibody and no detectable cytotoxic T cells, but do have a strong antigen-specific DTH, which is adoptively transferable with Lyt-1+2-, L3T4+ T cells. Kinetic and histological studies revealed that mice immunized s.c. developed Jones-Mote hypersensitivity, peaking at 15 hr. with little mononuclear cell infiltration at the site of antigen administration; whereas mice that had recovered from infection developed tuberculin-type of reactivity, peaking at 24 to 48 hr, with intense mononuclear cell infiltration. Splenic T cells from recovered mice, when injected into the footpads of normal recipients together with live promastigotes, were able to retard lesion development; whereas T cells from s.c. immunized mice, when similarly transferred, accelerated disease progression. Antigen-specific culture supernatant of spleen cells from recovered mice also activated normal resident peritoneal macrophages to kill intracellular L. major amastigotes and tumor cells. Culture supernatants of spleen cells from s.c. immunized or normal mice were devoid of such activities. Part of the macrophage-activating potential can be inhibited by antibody specific for IFN-gamma. These results therefore demonstrate that whereas the Jones-Mote reaction is correlated with disease exacerbation, the tuberculin-type of DTH may be protective. Furthermore, in vivo immunity is directly related to the capacity of T cells to produce macrophage-activating factor.