Orthognathic surgery in Melnick-Needles syndrome: a review of the literature and report of two siblings.

Melnick-Needles syndrome (MNS) is a rare congenital X-linked dominant skeletal dysplasia, characterized by exophthalmos, a prominent forehead, and mandibular hypoplasia and retrognathism. Dental features may include anodontia, hypodontia, or oligodontia. Increased collagen content, unpredictable collagen synthesis, and abnormal bony architecture have raised concerns regarding bone splitting intraoperatively and bone healing postoperatively. This report describes the cases of two sisters with MNS, who successfully underwent orthognathic surgery consisting of bilateral mandibular ramus osteotomies combined with advancement genioplasty and iliac crest bone grafting, to correct the classical MNS facial deformity of mandibular retrognathia.

Long-term follow-up of the incidence of Helicobacter pylori.

OBJECTIVES: Helicobacter pylori causes peptic ulcer disease and gastric cancer. Understanding the incidence of H. pylori could help guide research on potential infection prevention strategies. Previous studies indicate infection occurs in young children, but the risk of infection in older children and adolescents is unclear. Our hypothesis was that H. pylori infection is rare in adolescence or adulthood. Our aim was to determine the incidence of H. pylori over a prolonged follow-up in a cohort of 626 noninfected individuals. METHODS: Participants, including index children, mothers, fathers and siblings, from a previous study (1997-2002) were traced, and 883 of 946 participated in this extended follow-up. We used the 13C urea breath test (13C-UBT) to determine the incidence of H. pylori among 626 family members not infected in 2002, including 75 younger siblings who were not born or too young for testing in 2002. RESULTS: Eight (3.8%) of 210 index participants (mean ± standard deviation age 17.92 ± 0.77 years) became infected during 11.07 ± 0.56 years of follow-up (incidence, 3.42 per 1000 person-years; 95% confidence interval (CI), 1.48-6.74). Only one (0.6%) of 165 older siblings became infected (incidence, 0.57 per 1000 person-years; 95% CI, 0.007-3.16) and one of 176 parents became infected (incidence, 0.63 per 1000 person-years; 95% CI, 0.01-3.5). Of 75 younger siblings (age 10.9 ± 2.85 years) who were too young for testing or not yet born in 2002, nine (12%) became infected (incidence, 11.32 per 1000 person-years; 95% CI, 5.27-21.49). The highest incidence of H. pylori infection was in those born after 2005. CONCLUSIONS: The incidence of H. pylori was extremely low in older children and adults in developed countries. Spontaneous clearance of infection was uncommon in our study population.

Association between metformin prescription and growth rates of abdominal aortic aneurysms.

BACKGROUND: It has been suggested that diabetes medications, such as metformin, may have effects that inhibit abdominal aortic aneurysm (AAA) growth. The aim of this study was to examine the association of diabetes treatments with AAA growth in three patient cohorts. METHODS: AAA growth was studied using ultrasound surveillance in cohort 1, repeated CT in cohort 2 and more detailed repeat CT in cohort 3. Growth was estimated by the mean annual increase in maximum AAA diameter. RESULTS: A total of 1697 patients with an AAA were studied, of whom 118, 39 and 16 patients were prescribed metformin for the treatment of diabetes in cohorts 1, 2 and 3 respectively. Prescription of metformin was associated with a reduced likelihood of median or greater AAA growth in all three cohorts (cohort 1: adjusted odds ratio (OR) 0·59, 95 per cent c.i. 0·39 to 0·87, P = 0·008; cohort 2: adjusted OR 0·38, 0·18 to 0·80, P = 0·011; cohort 3: adjusted OR 0·13, 0·03 to 0·61, P = 0·010). No other diabetes treatment was significantly associated with AAA growth in any cohort. CONCLUSION: These findings suggest a potential role for metformin in limiting AAA growth.

A rising incidence and poorer male outcomes characterise early onset paediatric inflammatory bowel disease.

BACKGROUND: The incidence of paediatric inflammatory bowel disease diagnosed before age 10 years is reportedly increasing, but national data are limited. AIM: To characterise the epidemiology, phenotype and clinical outcomes of children diagnosed with inflammatory bowel disease before age 10 years, and compare with data from children diagnosed aged 10-16 years. METHODS: A review of all Irish cases of early onset inflammatory bowel disease (diagnosis <10 years, EO-IBD) presenting between January 2000 and December 2014 was undertaken and compared to a cohort of later onset paediatric inflammatory bowel disease patients (diagnosis between 10 and 16 years, LO-IBD). Diagnostic investigations, phenotype, treatments, and long-term clinical and surgical outcomes were analysed. RESULTS: One hundred and ninety children (99 male) with EO-IBD were identified; 92 (48%) CD, 77 (41%) UC and 21 (11%) IBDU. The incidence of EO-IBD increased by 0.6 per 100 000 per year (0.8-3.2 per 100 000 per year), with a significant increase in UC by 0.06 per 100 000 per year (P=.02). Males with CD had more upper GI disease (L4a; 48% vs 21%; P=.007), more extensive disease distribution (L3±L4; 31% vs 11%; P=.05) and more severe disease activity at presentation (52% vs 31%; P=.05) than females. Fewer patients with early onset than later onset Crohn's disease had ileocolonic disease (L3; 10% vs 20%; P<.001). More relapses were observed in the first year post-diagnosis in early onset than later onset IBD (1.02 vs 0.5 mean relapses; P<.001). CONCLUSIONS: EO-IBD is increasing in incidence. Males have more extensive and severe disease phenotypes, and younger patients have higher relapse rates than older children. Further research to explain these findings is warranted.

Operative Factors Associated with the Development of New Brain Lesions During Awake Carotid Endarterectomy.

OBJECTIVES: The aim was to analyse a prospective, consecutive series of awake carotid endarterectomy (CEA) patients undergoing, when possible, pre- and postoperative diffusion-weighted magnetic resonance imaging brain scans (DWI). METHODS: All CEA patients from June 23, 2006, to January 13, 2012, were prospectively entered in the study. CEA was performed under regional cervical block. Only patients demonstrating shunt dependence were shunted. Before August 7, 2008, all longitudinal endarterectomy had been performed with a vein patch. From that date all CEA were eversions without a patch, except shunted patients who were vein patched. DWI was performed 2 days before and 5 days after (3 Tesla). Scans were reported by MRI-trained radiologists. Logistic regression analysis (LRA) identified predictive variables for MRI changes using backward stepwise elimination of variables with p > .05. RESULTS: There was a total of 295 consecutive CEA. There were no deaths but four clinical strokes (1.4 %); 89 excluded from DWI leaving 206; of these 27 (13%) developed new DWI lesions including four of 57 (7%) in the asymptomatic group and 23 of 149 (15%) symptomatic patients. Nineteen of the 206 (9.2%) were shunted. LRA showed that shunt dependence was highly associated with new DWI lesions: odds ratio (OR) 6.43; 95% confidence interval (CI) 2.3-17.9; p < .001. Both the vein patched, non-shunted group (OR .25; CI 0.09-0.72; p = .010) and the eversion (all non-shunted and all non-patched) group (OR 0.05; CI 0.01-0.22; p < .001) were associated with a low risk of new lesions, with the eversion group a lower risk than the patched group. CONCLUSIONS: One in every eight CEA patients developed new DWI lesions (rate doubled in symptomatic patients). Shunt dependence in conscious CEA patients is highly associated with the development of new DWI lesions compared with non-shunted patients. For non-shunted patients the new lesion risk is low, and in those patients the risk in the eversion group is lower than in the patched group.

Investigation of outcomes following recombinant activated FVII use for refractory bleeding during abdominal aortic aneurysm repair.

OBJECTIVE: To evaluate the outcomes following recombinant activated factor VII (rFVIIa) use during abdominal aortic aneurysms (AAA) repair. DESIGN: AAA patients were selected from the Australian and New Zealand Haemostasis Registry (ANZHR) who received off-licence rFVIIa to control critical bleeding. METHODS: Patient characteristics and outcomes were compared between responders (bleeding stopped/attenuated) and non-responders (bleeding continued) to rFVIIa, stratified by aneurysm status (ruptured (r-AAA) vs. non-ruptured (nr-AAA)). Patients were also scored using POSSUM (Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity) and Hardman Index mortality predictive models. RESULTS: In total, 77 AAA patients were included in the analysis. Approximately 73% (n = 56) of them had ruptured aneurysms and about 50% (n = 35/70 with known data) responded positively to rFVIIa. Eleven incidents of thromboembolic adverse events were reported in 9 patients (6 r-AAA and 3 nr-AAA). Responders in both ruptured and non-ruptured groups had significantly lower 28-day mortality than non-responders (r-AAA: 40% (10/25) vs. 92% (24/26); P < 0.001; nr-AAA: 30% (3/10) vs. 67% (6/9); P < 0.01). Mortality predictive models did not show any difference between overall observed and expected mortality in ANZHR patients. CONCLUSION: Patients who responded to rFVIIa had a lower mortality than those who did not respond to the treatment.

Cyclical vomiting syndrome in children: a prospective study.

BACKGROUND: Cyclical vomiting syndrome (CVS) is a disorder that affects all ages and is characterized by episodes of severe nausea and vomiting with symptom-free intervals between episodes. The incidence in children is 3.15/100 000 children per year. Our objective was to evaluate the natural history of CVS and examine factors that predict symptom resolution. METHODS: Thirty newly diagnosed children (mean 9.15 years, SD 3.31 range 3.5-15.7) were enrolled. All children had a follow-up interview at 3 months, 27/30 at 6 months, and 22/30 at 9 months. KEY RESULTS: Following diagnosis of CVS, only 5/22(22.7%) children had no further episodes of vomiting at 9 months, whereas 17/22 (77.3%) continued to vomit. In the year prior to diagnosis, 15/30 (50%) children were admitted to hospital. Of the 22 children with follow-up for 9 months, only one child required hospital admission. Children who continued to vomit had higher internalizing scores on CBCL compared with those who stopped vomiting (P = NS). The Pediatric Quality-of-Life Score suggested those who continued to vomit had a poorer quality of life at diagnosis compared with those who stopped vomiting (P < 0.05). CONCLUSIONS & INFERENCES: Making a positive diagnosis of CVS and providing families with information is very important in the management of CVS. Although 75% of children reported regular episodes of vomiting 9 months after diagnosis, there was a significant reduction in the frequency and severity of symptoms in addition to a marked reduction in the use of medical services.

Rapid rise in incidence of Irish paediatric inflammatory bowel disease.

AIMS: To describe the change in incidence of paediatric inflammatory bowel disease (IBD) observed at the National Centre for Paediatric Gastroenterology, Hepatology and Nutrition, and to determine whether the presenting disease phenotype and disease outcomes have changed during the past decade. METHODS: The annual incidence of IBD in Irish children aged <16 years was calculated for the years 2000-2010. Two subsets of patients, group A (diagnosed between 1 January 2000 and 31 December 2001), and group B (diagnosed between 1 January and 31 December 2008) were phenotyped according to the Paris Classification. Phenotype at diagnosis and 2-year follow-up were then compared. RESULTS: 406 new cases of IBD were identified. The incidence was 2.5/100 000/year in 2001, 7.3 in 2008 and 5.6 in 2010, representing a significant increase in the number of new cases of Crohn's disease (CD) and ulcerative colitis (UC). There were 238 cases of CD; 129 of UC; and 39 of IBD unclassified. Comparing groups A and B, no differences were found in disease location at diagnosis or, for CD, in its behaviour. CONCLUSIONS: There has been a substantial and sustained increase in the incidence of childhood UC and CD in Ireland over a relatively short period of time. However, disease phenotype at diagnosis has not changed. At 2 years follow-up, CD appears to progress less frequently than in some neighbouring countries. These variations remain unexplained. Prospective longitudinal studies will help to elucidate further the epidemiology of childhood IBD.

The effects of anti-TNF-α treatment with adalimumab on growth in children with Crohn's disease (CD).

INTRODUCTION: Adalimumab is used to treat children with Crohn's disease (CD), but the effects of adalimumab on growth in CD have not been studied. AIM: To study growth and disease activity over 12 months (6 months prior to (T-6), baseline (T0) and for 6 months following (T+6) adalimumab). SUBJECTS AND METHODS: Growth and treatment details of 36 children (M: 22) who started adalimumab at a median (10th, 90th) age of 14.7 years (11.3, 16.8) were reviewed. RESULTS: Of 36 cases, 28 (78%) went into remission. Overall 42% of children showed catch up growth, which was more likely in: (i) those who achieved remission (median change in height SDS (ΔHtSDS) increased from -0.2 (-0.9, 1.0) at T0 to 0.2 (-0.6, 1.6) at T+6, (p=0.007)), (ii) in those who were on immunosuppression ΔHtSDS increased from -0.2 (-0.9, 1.0) at T0 to 0.1 (-0.8, 1.3) at T+6, (p=0.03) and (iii) in those whose indication for using adalimumab therapy was an allergic reaction to infliximab, median ΔHtSDS increased significantly from -0.3 (-0.9, 1.0) at T0 to 0.3 (-0.5, 1.6) at T+6, (p=0.02). Median ΔHtSDS also increased from -0.4 (-0.8, 0.7) at T0 to 0.0 (-0.6, 1.6) at T+6, (p=0.04) in 15 children who were on prednisolone therapy when starting adalimumab. CONCLUSION: Clinical response to adalimumab therapy is associated with an improvement in linear growth in a proportion of children with CD. Improved growth is more likely in patients entering remission and on immunosuppression but is not solely due to a steroid sparing effect.

Disease outcome for children who present with oral manifestations of Crohn's disease.

AIM: To describe the outcome for children with oral Crohn's disease (OCD) at diagnosis, and to determine if there was a difference in the Paediatric Crohn's Disease Activity Index (PCDAI) scores between those with and those without oral lesions at follow-up. METHODS: Thirty-one patients with OCD who had enrolled in two previous studies were invited to participate. Clinical and laboratory data were collected to calculate the PCDAI. Details of the management of Crohn's disease were also recorded. RESULTS: Twenty-four of 31 patients participated (77%), of whom 17 were boys (M:F = 2.4:1). Mean age at follow-up was 15.7 years (SD 1.98, range 11.9-19.7 years). Mean duration of follow-up was 55 months (SD 22, range 20-97 months). Oral manifestations were present at follow-up in 7 (29%) of 24 patients. There were no differences between patients with and without OCD at follow-up with regard to medical treatments received or intestinal disease location. There was no difference in median PCDAI scores between those who had and those who had not oral lesions at follow-up. CONCLUSIONS: OCD resolved in the majority of children treated for intestinal Crohn's disease. The occurrence of mouth lesions during follow-up of children who had oral manifestations at initial diagnosis was not a marker for Crohn's disease activity elsewhere in the intestinal tract.

A British Society of Paediatric Gastroenterology, Hepatology and Nutrition survey of the effectiveness and safety of adalimumab in children with inflammatory bowel disease.

BACKGROUND: Adalimumab is efficacious therapy for adults with Crohn's disease (CD). AIM: To summarise the United Kingdom and Republic of Ireland paediatric adalimumab experience. METHODS: British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) members with Inflammatory Bowel Disease (IBD) patients <18 years old commencing adalimumab with at least 4 weeks follow-up. Patient demographics and details of treatment were then collected. Response and remission was assessed using the Paediatric Crohn's Disease Activity Index (PCDAI)/Physicians Global Assessment (PGA). RESULTS: Seventy-two patients [70 CD, 1 ulcerative colitis (UC), 1 IBD unclassified (IBDU)] from 19 paediatric-centres received adalimumab at a median age of 14.8 (IQR 3.1, range 6.1-17.8) years; 66/70 CD (94%) had previously received infliximab. A dose of 80 mg then 40 mg was used for induction in 41(59%) and 40 mg fortnightly for maintenance in 61 (90%). Remission rates were 24%, 58% and 41% at 1, 6 and 12 months, respectively. Overall 43 (61%) went into remission at some point, with 24 (35%) requiring escalation of therapy. Remission rates were higher in those on concomitant immunosuppression cf. those not on immunosuppression [34/46 (74%) vs. 9/24 (37%), respectively, (χ(2) 8.8, P=0.003)]. There were 15 adverse events (21%) including four (6%) serious adverse events with two sepsis related deaths in patients who were also on immunosuppression and home parenteral nutrition (3% mortality rate). CONCLUSIONS: Adalimumab is useful in treatment of refractory paediatric patients with a remission rate of 61%. This treatment benefit should be balanced against side effects, including in this study a 3% mortality rate.

Campylobacter jejuni cocultured with epithelial cells reduces surface capsular polysaccharide expression.

The host cell environment can alter bacterial pathogenicity. We employed a combination of cellular and molecular techniques to study the expression of Campylobacter jejuni polysaccharides cocultured with HCT-8 epithelial cells. After two passages, the amount of membrane-bound high-molecular-weight polysaccharide was considerably reduced. Microarray profiling confirmed significant downregulation of capsular polysaccharide (CPS) locus genes. Experiments using conditioned media showed that sugar depletion occurred only when the bacterial and epithelial cells were cocultured. CPS depletion occurred when C. jejuni organisms were exposed to conditioned media from a different C. jejuni strain but not when exposed to conditioned media from other bacterial species. Proteinase K or heat treatment of conditioned media under coculture conditions abrogated the effect on the sugars, as did formaldehyde fixation and cycloheximide treatment of host cells or chloramphenicol treatment of the bacteria. However, sugar depletion was not affected in flagellar export (fliQ) and quorum-sensing (luxS) gene mutants. Passaged C. jejuni showed reduced invasiveness and increased serum sensitivity in vitro. C. jejuni alters its surface polysaccharides when cocultured with epithelial cells, suggesting the existence of a cross talk mechanism that modulates CPS expression during infection.

Septic arthritis: clinical audits would help optimise the management.

We audited management of septic arthritis (SA) in our institution comparing them with the British Society for Rheumatology (BSR) guidelines and also ascertained awareness regarding these guidelines among trainee doctors. All adult patients who were admitted to our institution between January 2005 and December 2006 with symptoms and signs of SA and had positive synovial fluid culture were included, and a structured proforma was used to extract the relevant information from the case notes and laboratory tests. Management of 21 patients with SA was audited. In several areas (such as appropriate samples for cultures prior to initiation of antibiotics and use of inflammatory markers in monitoring the response to treatment), management of both native and prosthetic joint SA fell short of compliance with the BSR guidelines. A total of 58% trainee doctors surveyed were unaware of these guidelines. Our audit identified deficiencies in standards of care of SA. Lack of awareness regarding these guidelines contributes to the suboptimal care of patients with SA. Wider dissemination of the BSR guidelines with similar audits being a starting point would help in optimising the management of SA.

Outcome for children with cyclical vomiting syndrome.

OBJECTIVE: Cyclical vomiting syndrome (CVS) is a disorder that carries a significant burden of disease for children and their families. The aim of this study was to examine the outcome of a group of children diagnosed with CVS from 1993 to 2003. METHODS: Children diagnosed with CVS over a 10-year period were identified and a review of the clinical records was carried out to define demographic features and the spectrum of disease at presentation. The patient's parent was contacted to establish the child's current well-being. Ethical approval for the study was obtained. RESULTS: Fifty one children were diagnosed with CVS and 41 agreed to participate in follow-up. Mean age was 5.8 (SD 3.3) years at onset of CVS, 8.2 (SD 3.5) years at diagnosis, and 12.8 (SD 4.8) years at follow-up. Vomiting had resolved at the time of follow-up in 25/41 (61%) children. Sixteen of 41 (39%) children reported resolution of symptoms either immediately or within weeks of diagnosis. However, a large number of children from the group whose vomiting resolved and the group that were still vomiting continued to have somatic symptoms, with 42% of children suffering regular headaches and 37% having abdominal pain. 32 (78%) parents felt that the provision of a positive diagnosis and information made a significant impact on the severity of vomiting. CONCLUSIONS: While 60% of children with CVS have resolution of symptoms, a significant proportion of both those in whom symptoms have resolved and those in whom vomiting persists continue to suffer from other somatic symptoms.

The significance of cutaneous spider naevi in children.

BACKGROUND: Cutaneous spider naevi are commonly considered to be a clinical sign of chronic liver disease. Little is known about their occurrence in children. AIM: To evaluate the occurrence of spider naevi in children with and without liver disease. METHODS: The presence of spider naevi was investigated in 460 children, 34 of whom had chronic liver disease. RESULTS: Of children without liver involvement, 38% had at least one spider naevus. The prevalence of spider naevi increased with age. Of control patients aged 5 to 15 years, 2.5% had more than five spiders present. Although eight of 10 children with cirrhosis had at least one spider naevus, only four of 34 children with chronic liver disease had five or more spiders present. Most spiders were on the hands and very few were >5 mm in size. CONCLUSIONS: Children with liver disease rarely have large numbers of spider naevi. Although the finding of five or more spider naevi is more common in liver disease, many normal children also have one or more of these lesions.

Focally enhanced gastritis in children with Crohn's disease and ulcerative colitis.

OBJECTIVES: Focally enhanced gastritis (FEG) has been suggested as a specific diagnostic marker for patients with Crohn's disease. However, the utility of FEG for distinguishing Crohn's disease from ulcerative colitis is uncertain in adults, and the occurrence of this lesion in children has not been defined. The aim of this study was to evaluate the occurrence of FEG and other gastric histological abnormalities in children with inflammatory bowel disease (IBD) and to examine the utility of FEG in discriminating between ulcerative colitis and Crohn's disease. METHODS: This is a retrospective, case-controlled study of upper GI histopathological findings in children with IBD. Gastric histopathology was defined and graded according to the Updated Sydney System. RESULTS: FEG was present in 28 of 43 (65.1%) children with Crohn's disease and five of 24 (20.8%) children with ulcerative colitis, compared to three of 132 (2.3%) children without IBD or one of 39 (2.6%) children with Helicobacter pylori infection. There were no differences between those with and without FEG with regard to upper GI symptoms or previous anti-inflammatory drug ingestion (5-aminosalicylic acid compounds or steroids). All patients with H. pylori infection had chronic antral gastritis, but only one child with H. pylori had FEG. In addition, mild to moderate chronic gastritis was present in 15 of 43 (34.9%) children with Crohn's disease and in 12 of 24 (50%) patients with ulcerative colitis. CONCLUSIONS: The presence of FEG suggests underlying IBD. Although FEG is particularly common in children with Crohn's disease, it does not reliably differentiate between Crohn's disease and ulcerative colitis.

The importance of a dedicated patch test clinic.

BACKGROUND: A specialist patch test clinic was set up in April 1997 at the Department of Dermatology, South Infirmary-Victoria Hospital, Cork, Ireland. The number of batteries available was expanded from six to 21 and the routine testing of patients to their own products was introduced, as was prick testing for latex hypersensitivity. OBJECTIVES: To assess the impact of introducing this clinic on the detection of allergic contact dermatitis. METHODS: Patch test results for the first full year of operation of the clinic (1998) were compared with those in the year prior to setting it up (1996). RESULTS: Although the number of patients tested rose after the introduction of the new clinic, the difference was not significant as the number of new dermatology general referrals had also risen. Thirty-one of the 91 patients tested in 1996 had positive patch tests compared with 84 of 158 tested in 1998 (P = 0.0036). Eighteen allergens were detected in 1996 and 53 in 1998. Two patients were positive to their own products in 1996, compared with 12 in 1998 (P = 0.04). The commercial batteries were negative in four of these cases. Three cases of latex hypersensitivity were detected in 1998. CONCLUSIONS: The introduction of a specialist patch test clinic resulted in an increase in detected cases of allergic contact dermatitis. The larger range of batteries available and the more widespread testing of patients' own products were the principal factors involved.