Adolescent gallstones-need for early intervention in symptomatic idiopathic gallstones.

BACKGROUND AND AIM: Currently, there is a paucity of the literature describing the natural history of cholelithiasis (CL) and choledocholithiasis (CDL) in adolescent children. This study aims to analyse the changing demographics of paediatric and adolescent gallstones. METHODOLOGY: Retrospective review of all children (Age 0-18 years) presenting with symptomatic gallstones over the last 15 years (2002-2017) at a single tertiary institution. Demographics, diagnostic and therapeutic information were collected, with a 5-year median follow-up. Statistics were accomplished by Chi-squared analysis of trend and Student t test. RESULTS AND DISCUSSIONS: 188 children were seen with symptomatic CL. In the 0-11-year-old group, there were 13 females and 16 males (0.8: female to male ratio). There were 130 females and 29 males in the 12-18-year-old group (4.5:1 female to male ratio). The mean weight at presentation was 81.78 kg and the median age was 16 years. Idiopathic gallstones were found in 131 patients (82%). 137 required cholecystectomy (86%) and ERCP was required in 32 patients (20%). 48 adolescents (30.2%) with gallstones had an associated CDL, compared to six children (20%). All of the adolescent patients with CDL had idiopathic gallstones. Gallstone pancreatitis was noted in eighteen adolescents (11%) and one child (3%). We analysed the ideal time to operate on adolescent patients with symptomatic gallstones using the relationship between the length of delay from initial diagnosis to definitive management of CDL and incidence of complications. The analysis demonstrated that for every 10 days treatment was delayed, the risk of subsequent presentations with a symptomatic episode was increased by 5% (p = 0.0004). CONCLUSION: The current trend of gallstones in adolescent children seems to be a disease primarily of adolescent girls. Symptomatic idiopathic gallstones in adolescents are associated with high rates of common bile duct obstruction and pancreatitis and consequently warrant an early cholecystectomy for all adolescents. LEVEL OF EVIDENCE: Level IV Treatment Study.

Variants in ACTG2 underlie a substantial number of Australasian patients with primary chronic intestinal pseudo-obstruction.

BACKGROUND: Primary chronic intestinal pseudo-obstruction (CIPO) is a rare, potentially life-threatening disorder characterized by severely impaired gastrointestinal motility. The objective of this study was to examine the contribution of ACTG2, LMOD1, MYH11, and MYLK mutations in an Australasian cohort of patients with a diagnosis of primary CIPO associated with visceral myopathy. METHODS: Pediatric and adult patients with primary CIPO and suspected visceral myopathy were recruited from across Australia and New Zealand. Sanger sequencing of the genes encoding enteric gamma-actin (ACTG2) and smooth muscle leiomodin (LMOD1) was performed on DNA from patients, and their relatives, where available. MYH11 and MYLK were screened by next-generation sequencing. KEY RESULTS: We identified heterozygous missense variants in ACTG2 in 7 of 17 families (~41%) diagnosed with CIPO and its associated conditions. We also identified a previously unpublished missense mutation (c.443C>T, p.Arg148Leu) in one family. One case presented with megacystis-microcolon-intestinal hypoperistalsis syndrome in utero with subsequent termination of pregnancy at 28 weeks' gestation. All of the substitutions identified occurred at arginine residues. No likely pathogenic variants in LMOD1, MYH11, or MYLK were identified within our cohort. CONCLUSIONS AND INFERENCES: ACTG2 mutations represent a significant underlying cause of primary CIPO with visceral myopathy and associated phenotypes in Australasian patients. Thus, ACTG2 sequencing should be considered in cases presenting with hypoperistalsis phenotypes with suspected visceral myopathy. It is likely that variants in other genes encoding enteric smooth muscle contractile proteins will contribute further to the genetic heterogeneity of hypoperistalsis phenotypes.

Functional dyspepsia is associated with duodenal eosinophilia in an Australian paediatric cohort.

BACKGROUND: The pathophysiology of functional dyspepsia (FD) remains unknown. Duodenal eosinophil infiltration has been reported. AIM: To assess the association between dyspeptic symptoms and duodenal eosinophilia in children undergoing upper gastrointestinal endoscopy. METHODS: In this retrospective cohort study, children with normal upper endoscopy and routine histology at a single tertiary paediatric centre between 2010 and 2014 were included. FD was defined as epigastric pain or discomfort >2 months without response to acid suppression. Controls presented with nonerosive reflux disease, dysphagia or rumination syndrome. Intramucosal eosinophil counts were compared between the groups using uni- and multivariate regression analyses. RESULTS: Thirty-six cases and 36 nonmatched controls were identified. Atopic history (39% vs. 25%) and psychological comorbidity (53% vs. 39%; both P = 0.2) were frequent in cases and controls. Self-reported nausea (64% vs. 17%; P < 0.0001), lethargy (19% vs. 0%; P = 0.005) and family functional gastrointestinal disorder(FGID) (28% vs. 3%; P = 0.003) were more common in cases than controls. Duodenal eosinophil counts [median (IQR): 151 (118-207) vs. 76 (60-106) per mm2 ; P < 0.001] were significantly higher in cases than controls with >112 eosinophils per mm2 predictive for FD (OR: 33.6, 95% CI: 7.1-159.0; P < 0.001). Duodenal eosinophilia was associated with weight loss (OR: 7.1, 95% CI: 1.1-45.5; P = 0.04). CONCLUSIONS: Functional dyspepsia in children is strongly associated with duodenal eosinophilia, in the absence of endoscopic or routine histological findings. Frequent atopic and psychological comorbidity illustrate likely multifactorial mechanisms.

Paradoxical embolism causing stroke and migraine.

This case report describes a lady who underwent investigations as a part of a clinical study. A 32-year-old woman with a history of episodes of severe migraine with aura, deep vein thrombosis and recurrent epistaxis, presented with two episodes of stroke with no particular cause evident on routine investigations. A contrast echocardiogram demonstrated a patent foramen ovale (PFO). She was found to be positive for the Factor V Leiden mutation. The PFO was closed percutaneously. However, a substantial right to left shunt of 14% persisted. Pulmonary angiography revealed multiple arterio-venous malformations (AVMs) and she was diagnosed with hereditary hemorrhagic telangiectasia. The AVMs were embolized and she has had no further cerebral events. Interestingly, her episodes of 'migraine' have also improved dramatically following the closure of the PFO and the embolization of the AVMs. This case demonstrates the complex relationship between right to left shunts, cryptogenic stroke and migraine.

Clopidogrel reduces migraine with aura after transcatheter closure of persistent foramen ovale and atrial septal defects.

OBJECTIVE: To report the clinical events leading to alteration of an anticoagulation regimen for patients undergoing transcatheter closure of an atrial shunt and how this affected migraine symptoms after the closure procedure. METHOD: Audit of a change of anticoagulant regimen. RESULTS: In the first few weeks after a closure procedure migraine frequency and severity increased despite treatment with aspirin for six months in 71 patients. Severe attacks of migraine with aura, including status migrainosus, in the first few weeks after transcatheter closure were terminated by addition of clopidogrel to aspirin treatment. Therefore, the anticoagulant regimen was changed with addition of clopidogrel for the first month after the closure procedure (90 procedures in 89 patients). Fewer patients had migraine with aura in the first month after transcatheter closure when taking the combination of clopidogrel and aspirin compared with aspirin alone (11 of 90 (12.2%) v 30 of 71 (42.3%), p < 0.001). Episodes of migraine with aura were more severe and more frequent in patients taking aspirin alone. CONCLUSION: The combination of clopidogrel for four weeks and aspirin for six months is superior to aspirin alone for six months for preventing migraine with aura after transcatheter closure of an atrial shunt. This beneficial effect of a powerful inhibitor of platelet aggregation suggests that platelets may have a role in pathogenesis of migraine. This may be because of an effect on serotonin stores. Whether clopidogrel has a role in treatment of migraine in other clinical situations requires investigation.

Supermarket baker's asthma: how accurate is routine health surveillance?

BACKGROUND: Regular health surveillance is commonly recommended for workers exposed to occupational antigens but little is known about how effective it is in identifying cases. AIMS: To report one large company's surveillance and compare its findings with those of a standard cross-sectional survey in the same workforce. METHODS: A supermarket company with 324 in-store bakeries producing bread from raw ingredients conducted a three-stage health surveillance programme in around 3000 bakery employees. The first stage involved the administration of a simple respiratory questionnaire. If chest symptoms were present a second questionnaire focusing on their work relationship was administered. If positive a blood sample was requested for the measurement of specific IgE to flour and fungal alpha-amylase. The results were compared to an independent cross-sectional survey of employees in 20 of the company's stores. RESULTS: Two hundred and ninety nine (92%) of the company's bakeries took part in surveillance. The overall employee response for the first stage was 77%; a quarter of those with respiratory symptoms reported that they were work related. Seventy four (61%) of those with work related chest symptoms had a measurement of specific IgE to either flour or fungal alpha-amylase, of whom 30 (41%) had a positive result. Surveillance estimated that 1% of bakery employees (1% bakers, 2% managers, 0.6% confectioners) had work related symptoms with specific IgE. This compared with 4% (7.5% bakers, 3.3% managers, 0% confectioners) in the cross-sectional survey (n = 166, 93% response). CONCLUSION: Comparison with a standard cross-sectional survey suggests that routine surveillance can underestimate the workplace burden of disease. The reasons may include technical or resource issues and uncertainties over confidentiality or the perceived consequences of participation. More research needs to be done looking into the design and efficacy of surveillance in occupational asthma.

The association between narcolepsy and REM behavior disorder (RBD).

BACKGROUND AND PURPOSE: Rapid eye movement (REM) sleep Behavior Disorder (RBD) is a movement disorder associated with loss of REM-related muscle atonia and is characterized by complex, vigorous and frequently violent dream-enacting behavior during REM sleep. RBD is usually idiopathic or secondary to neurological problems such as Parkinson's disease. This study looked at the association of RBD with another sleep disorder, narcolepsy. PATIENTS AND METHODS: Seventy-eight questionnaires were sent to known narcoleptics chosen at random from those with contact details available at the center. The questionnaire addressed current narcolepsy symptoms, medication use and symptoms of RBD. Positive questionnaire results were followed up with a telephone interview. Limited polysomnography (PSG) data was also analyzed. RESULTS: Fifty-five patients responded (response rate 71%). Of these, 20 (36%) had symptoms suggestive of RBD. The typical RBD patient is an older male (mean age of onset 60.9 years, 87% male); however, in this study, females were as likely to have RBD as males, and the mean age was 41 years. Sixty-eight percent of patients who regularly experienced cataplexy and the associated symptoms of narcolepsy (sleep paralysis, hypnogogic hallucinations and automatic behavior) had RBD, compared to 14% of those who never or rarely experienced these symptoms. CONCLUSION: This study implies a stronger relationship between these disorders than a previously published figure of 7-12% This is clinically significant as RBD is a potentially distressing but readily treatable disorder. It follows that narcoleptics, especially those with cataplexy and other associated symptoms, should be questioned about symptoms of RBD and treated accordingly. Similarly, anyone presenting with RBD should be assessed for symptoms of narcolepsy, particularly if female or of a younger age group than would otherwise be expected.

Inheritance of persistent foramen ovale and atrial septal defects and the relation to familial migraine with aura.

OBJECTIVE: To determine whether smaller atrial shunts (large persistent foramen ovale (PFO) and small atrial septal defect (ASD)) are inherited and whether this has a role in the inheritance of migraine with aura. METHODS: Contrast echocardiography was used to detect atrial shunts in 71 relatives of 20 probands with a significantly sized atrial shunt (large PFO or ASD). Four families with three generations, 14 families with two generations, and two sibships were studied. The contrast echocardiograms were performed blind to history of migraine. A consultant neurologist, who was blinded to cardiac findings, categorised migraine symptoms in subjects. RESULTS: The occurrence of atrial shunts was consistent with autosomal dominant inheritance. Usually shunts were large PFOs, but in some cases they were ASDs. There was also evidence that inheritance of more complex congenital heart disease may be related to the inheritance of PFOs. When the proband had migraine with aura and an atrial shunt, 15 of the 21(71.4%) first degree relatives with a significant right to left shunt also had migraine with aura compared with three of 14 (21.4%) without a significant shunt (p < 0.02). CONCLUSIONS: There is dominant inheritance of atrial shunts. This is linked to inheritance of migraine with aura in some families.

Psychiatric illness and mortality after hip fracture.

People with dementia or delirium have increased mortality in the 6 months after hip fracture, but depression might take longer to have an effect. We assessed the psychiatric status of 731 participants with hip fracture and analysed the effect of psychiatric illness on mortality during the next 2 years. We found that dementia, delirium, and depression all increased the risk of mortality (p<0.0001, p<0.0001, and p=0.0359, respectively), and that mortality differed significantly between hospitals (p=0.0003). We suggest that psychiatric interventions should be asssessed in hip-fracture patients with adequate follow up of outcome measures.

Relationship between migraine and cardiac and pulmonary right-to-left shunts.

A relationship between migraine with aura and the presence of right-to-left shunts has been reported in two studies. Right-to-left shunts are also associated with some forms of decompression illness. While conducting research in divers with decompression illness, it was our impression that divers with a large shunt often had a history of migraine with aura in everyday life and after dives. Therefore we routinely asked all divers about migraine symptoms. The medical records of the last 200 individuals referred for investigation of decompression illness were reviewed to determine the association between right-to-left shunts and migraine aura after diving, and migraine in daily life unconnected with diving. Migraine with aura in daily life unconnected with diving occurred significantly more frequently in individuals who had a large shunt which was present at rest (38 of 80; 47.5%) compared with those who had a shunt which was smaller or only seen after a Valsalva manoeuvre (four of 40; 10%) or those with no shunt (11 of 80; 13.8%) (P<0.001). Hemiplegic migraine occurred in 10 divers, each of whom had a shunt that was present at rest; in eight of these cases the shunt was large. The prevalence of migraine without aura was similar in all groups. Post-dive migraine aura was significantly more frequent in individuals who had a large shunt present at rest (21 of 80; 26.3%) compared with those who had a shunt that was smaller or only seen after a Valsalva manoeuvre (five of 40; 12.5%) or no shunt (one of 80; 1.3%) (P<0.001). Thus individuals with a large right-to-left shunt have an increased prevalence of migraine with aura in daily life unconnected with diving, and they also have an increased incidence of migraine aura after dives, but only when the dives liberate venous bubbles. These data suggest the possibility that, in some individuals, right-to-left shunts have a role in the aetiology of migraine with aura. The observations suggest that paradoxical gas embolism may precipitate migraine with aura.

Effect on migraine of closure of cardiac right-to-left shunts to prevent recurrence of decompression illness or stroke or for haemodynamic reasons.

BACKGROUND: A relation between migraine with aura and cardiac right-to-left shunts has been reported. Right-to-left shunts are also associated with stroke and certain forms of decompression illness. We investigated the effect of closure of right-to-left shunts on migraine symptoms. METHODS: A consultant neurologist, who was unaware of information about residual shunt, undertook a structured interview with individuals who had had transcatheter closure of an atrial septal defect or patent foramen ovale to assess how the procedure affected migraine symptoms. FINDINGS: 37 of 40 consecutive patients who had had a closure procedure (to permit resumption of diving after decompression illness in 29, after stroke when paradoxical thromboembolism was suspected in four, or to close a large atrial septal defect in four) could be contacted. 21 (57%) had a history of migraine before the procedure (with aura in 16, without aura in five). 11 individuals had fortification spectra in the period immediately after closure. During long-term follow-up, no migraine symptoms were reported by seven individuals who had previously had migraine with aura and three who had previously had migraine without aura. Eight others who had had migraine with aura before closure reported improvement in frequency and severity of migraines. Three (one migraine with aura, two migraine without aura) reported no alteration in migraine episodes. INTERPRETATION: These observations suggest a causal association between right-to-left shunts and migraine with aura. There may be a subgroup of patients who have severe migraine associated with a large right-to-left shunt in whom closure of the atrial defect may improve or abolish migraine.

A controlled study of vigabatrin and visual abnormalities.

AIMS: To assess the visual function in epileptic patients who have received vigabatrin; to compare this with the visual function in similar epileptic patients who have never received vigabatrin; to investigate whether the severity of visual field defect (VFD) is related to the dose of vigabatrin; to consider other factors that may correlate with the severity of VFD. METHODS: 21 consecutive patients who had taken vigabatrin at some time in their lives were enrolled from the epilepsy clinic of the Royal Shrewsbury Hospital and were compared with a group of 11 otherwise similar patients with epilepsy who had never received vigabatrin. One patient taking vigabatrin was excluded from the study because her visual field results were unreliable because of multi-infarct dementia. 15 patients were taking vigabatrin at the time of the study (VC), the other five had taken vigabatrin some time in the past (VP). Each patient underwent static perimetry using either the two point or the three point full field 120 screening program on the Humphrey visual field analyser, followed by an ophthalmic examination to rule out ocular causes for VFDs. The visual fields from each patient were then analysed using a method devised to convert the VFD into percentage defect in both eyes. In patients with known cerebral pathology that may affect the visual pathway, only the unaffected homonymous hemifield was used. RESULTS: Nine of 20 (45%) patients in the vigabatrin group (VC and VP) complained of blurring of vision compared with two of 11 (18%) controls. Four patients (20%) in the vigabatrin group described flickering lights compared with one control (9%). None had a posterior vitreous detachment. Three of 30 (7.5%) eyes in the VC group had distant visual acuity of 6/12 or worse compared with three of 22 (9%) controls and five of 30 (16.7%) had near visual acuity worse than N6 compared with one of 22 (4.5%) in the control group. A mean of 1.73 Ishihara plates were misread in VC patients compared with 0.2 in the VP group and 0.18 in the controls. 11 of 15 (73.3%) patients in the VC group had greater than 10% VFDs as opposed to one of 11 (9.1%) controls (chi(2) test, p=0. 002). In 12 of 15 (80%) VC patients the percentage VFD was greater in the nasal hemifields than the temporal hemifields compared with six of 11 (54.5%) controls. Significant correlation was found between the severity of VFD and the total dose of vigabatrin ingested for the 20 patients exposed to vigabatrin (VC and VP: Spearman correlation coefficient=0.525; p=0.002), for the 15 patients taking vigabatrin at the time of examination (VC: Spearman correlation coefficient=0.568; p=0.002). CONCLUSION: This pilot study suggested that epileptic patients taking vigabatrin are at much higher risk of developing VFDs compared with epileptic patients on other antiepileptic drugs. The total ingested dose of vigabatrin correlated significantly with the severity of VFDs especially in those patients who had not stopped taking vigabatrin. In our group we found that those who had taken a total dose of 1500 g or more of vigabatrin were at risk of developing significant visual field defects.

Plasmin-alpha2-antiplasmin complex in patients with atrial fibrillation. Stroke Prevention in Atrial Fibrillation Investigators.

Plasmin-alpha2-antiplasmin complex (PAP) is an index of recent fibrinolytic activity. We examined PAP levels in patients with atrial fibrillation (AF) to determine whether these levels are correlated with clinical characteristics associated with stroke risk. We obtained blood for measurement of PAP in a non-random sample of 586 patients with AF on entering the Stroke Prevention in Atrial Fibrillation III Study. PAP levels were measured with an ELISA assay. PAP values were transformed with a natural logarithm (PAPln) prior to all analyses. Older age, female gender, recent congestive heart failure, decreasing fractional shortening, recent onset of AF, and coronary artery disease were each univariately associated with higher levels of PAP (all p<0.05, two-sample t-test, simple linear regression). Older age, recent congestive heart failure, decreasing fractional shortening, and recent onset of AF were independently associated with higher PAP levels by multivariate analysis (linear regression). Among patients receiving warfarin, PAP levels were not correlated with INR levels (linear regression, p=0.60). Patients classified as high-risk for thromboembolism by our risk stratification criteria (systolic blood pressure > 160 mm Hg, prior thromboembolism, recent congestive heart failure, poor left ventricular function, and women over age 75) had higher PAP levels than low-risk patients (antilog mean PAPln 5.6 vs 4.9. p<0.001, two-sample t-test). PAP levels in patients with AF are associated with clinical characteristics predictive of thromboembolism. Elevated PAP levels are particularly associated with poor left ventricular function and are not affected by anticoagulation. PAP levels may be a marker of stroke risk in patients with AF.