An unusual case of pancreatic fistula.

We report an unusual case of a pancreatic fistula communicating with an appendicectomy wound. This occurred following an episode of acute haemorrhagic pancreatitis. The patient was initially admitted with signs and symptoms indicating appendicitis and went to theatre for an open appendicectomy. However, this did not resolve his symptoms and a laparotomy was performed the next day revealing haemorrhagic pancreatitis. He endured a stormy post-operative course, the cause of which was found to be an external pancreatic fistula with discharge of amylase-rich fluid from the Lanz incision. A trial of conservative management failed despite multiple percutaneous drainage procedures and treatment with broad-spectrum antibiotics. After a second opinion was sought, it was decided to fit a roux loop anastomosis between the head of the pancreas and the duodenum to divert the fistulous fluid. This procedure was a success and the patient remains well 2 years later

Diagnostic work-up of patients presenting in primary care with lower abdominal symptoms:which faecal test and triage strategy should be used?

Bowel endoscopy referrals from primary care have increased steadily over recent years. However, most patients do not have significant colorectal disease (SCD). Therefore, strategies to select those who would benefit most from endoscopy are of current interest. A recent study developed a multivariable diagnostic model for SCD with routine clinical information, extended with quantitative faecal calprotectin (f-C) point-of-care (POC) testing and/or qualitative POC faecal immunochemical test (FIT) for haemoglobin (f-Hb) results. This study used POC tests for both f-C and f-Hb; however, POC tests have many disadvantages and there are several reasons why quantitative measurements of f-Hb are advantageous. Quantitative faecal immunochemical tests have been used very successfully in triage of patients presenting in primary care as a rule-out test. Studies have compared f-C and f-Hb in this clinical context and consider that f-C is not required in diagnosis. A single quantitative f-Hb result, without any clinical information, could be sufficient to decide whom to refer for endoscopy and, because of the significant overlap of symptoms in those with and without SCD, could be the primary investigation performed. Please see related article: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0684-5

Cortical oscillatory dysrhythmias in visual snow syndrome: a magnetoencephalography study

Visual Snow refers to the persistent visual experience of static in the whole visual field of both eyes. It is often reported by patients with migraine and co-occurs with conditions like tinnitus and tremor. The underlying pathophysiology of the condition is poorly understood. Previously we hypothesised, that visual snow syndrome may be characterised by disruptions to rhythmical activity within the visual system. To test this, data from 18 patients diagnosed with visual snow syndrome, and 16 matched controls, were acquired using magnetoencephalography. Participants were presented with visual grating stimuli, known to elicit decreases in alpha-band (8-13Hz) power and increases in gamma-band power (40-70Hz). Data were mapped to source-space using a beamformer. Across both groups, decreased alpha power and increased gamma power localised to early visual cortex. Data from the primary visual cortex were compared between groups. No differences were found in either alpha or gamma peak frequency or the magnitude of alpha power, p>0.05. However, compared with controls, our visual snow syndrome cohort displayed significantly increased primary visual cortex gamma power, p=0.035. This new electromagnetic finding concurs with previous functional MRI and PET findings suggesting that in visual snow syndrome, the visual cortex is hyper-excitable. The coupling of alpha-phase to gamma amplitude within the primary visual cortex was also quantified. Compared with controls, the visual snow syndrome group had significantly reduced alpha-gamma phase-amplitude coupling, p<0.05, indicating a potential excitation-inhibition imbalance in visual snow syndrome, as well as a potential disruption to top-down “noise-cancellation” mechanisms. Overall, these results suggest that rhythmical brain activity in primary visual cortex is both hyperexcitable and disorganised in visual snow syndrome, consistent with this being a condition of thalamocortical dysrhythmia

Flecainide exerts paradoxical effects on sodium currents and atrial arrhythmia in murine RyR2-P2328S hearts.

AIMS: Cardiac ryanodine receptor mutations are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT), and some, including RyR2-P2328S, also predispose to atrial fibrillation. Recent work associates reduced atrial Nav 1.5 currents in homozygous RyR2-P2328S (RyR2(S/S) ) mice with slowed conduction and increased arrhythmogenicity. Yet clinically, and in murine models, the Nav 1.5 blocker flecainide reduces ventricular arrhythmogenicity in CPVT. We aimed to determine whether, and how, flecainide influences atrial arrhythmogenicity in RyR2(S/S) mice and their wild-type (WT) littermates. METHODS: We explored effects of 1 μm flecainide on WT and RyR2(S/S) atria. Arrhythmic incidence, action potential (AP) conduction velocity (CV), atrial effective refractory period (AERP) and AP wavelength (λ = CV × AERP) were measured using multi-electrode array recordings in Langendorff-perfused hearts; Na(+) currents (INa ) were recorded using loose patch clamping of superfused atria. RESULTS: RyR2(S/S) showed more frequent atrial arrhythmias, slower CV, reduced INa and unchanged AERP compared to WT. Flecainide was anti-arrhythmic in RyR2(S/S) but pro-arrhythmic in WT. It increased INa in RyR2(S/S) atria, whereas it reduced INa as expected in WT. It increased AERP while sparing CV in RyR2(S/S) , but reduced CV while sparing AERP in WT. Thus, RyR2(S/S) hearts have low λ relative to WT; flecainide then increases λ in RyR2(S/S) but decreases λ in WT. CONCLUSIONS: Flecainide (1 μm) rescues the RyR2-P2328S atrial arrhythmogenic phenotype by restoring compromised INa and λ, changes recently attributed to increased sarcoplasmic reticular Ca(2+) release. This contrasts with the increased arrhythmic incidence and reduced INa and λ with flecainide in WT.This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC, UK) under a David Phillips Fellowship held by JAF (BB/FO23863/1) and by the Isaac Newton Trust/Wellcome Trust ISSF/University of Cambridge Joint Research Grants Scheme.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/apha.1250

Arrhythmic substrate, slowed propagation and increased dispersion in conduction direction in the right ventricular outflow tract of murine Scn5a+/- hearts.

AIM: To test a hypothesis attributing arrhythmia in Brugada Syndrome to right ventricular (RV) outflow tract (RVOT) conduction abnormalities arising from Nav 1.5 insufficiency and fibrotic change. METHODS: Arrhythmic properties of Langendorff-perfused Scn5a+/- and wild-type mouse hearts were correlated with ventricular effective refractory periods (VERPs), multi-electrode array (MEA) measurements of action potential (AP) conduction velocities and dispersions in conduction direction (CD), Nav 1.5 expression levels, and fibrotic change, as measured at the RVOT and RV. Two-way anova was used to test for both independent and interacting effects of anatomical region and genotype on these parameters. RESULTS: Scn5a+/- hearts showed greater arrhythmic frequencies during programmed electrical stimulation at the RVOT but not the RV. The Scn5a+/- genotype caused an independent increase of VERP regardless of whether the recording site was the RVOT or RV. Effective AP conduction velocities (CV†s), derived from fitting regression planes to arrays of observed local activation times were reduced in Scn5a+/- hearts and at the RVOT independently. AP conduction velocity magnitudes derived by averaging MEA results from local vector analyses, CV*, were reduced by the Scn5a+/- genotype alone. In contrast, dispersions in conduction direction, were greater in the RVOT than the RV, when the atrioventricular node was used as the pacing site. The observed reductions in Nav 1.5 expression were attributable to Scn5a+/-, whereas increased levels of fibrosis were associated with the RVOT. CONCLUSIONS: The Scn5a+/- RVOT recapitulates clinical findings of increased arrhythmogenicity through reduced CV† reflecting reduced CV* attributable to reduced Nav 1.5 expression and increased CD attributable to fibrosis

Field-study science classrooms as positive and enjoyable learning environments

We investigated differences between field-study classrooms and traditional science classrooms in terms of the learning environment and students’ attitudes to science, as well as the differential effectiveness of field-study classrooms for students differing in sex and English proficiency. A modified version of selected scales from the What Is Happening In this Class? questionnaire was used to assess the learning environment, whereas students’ attitudes were assessed with a shortened version of a scale from the Test of Science Related Attitudes. A sample of 765 grade 5 students from 17 schools responded to the learning environment and attitude scales in terms of both their traditional science classrooms and classrooms at a field-study centre in Florida. Large effect sizes supported the effectiveness of the field-studies classroom in terms of both the learning environment and student attitudes. Relative to the home school science class, the field-study class was considerably more effective for students with limited English proficiency than for native English speakers

Changes in ponderal index and body mass index across childhood and their associations with fat mass and cardiovascular risk factors at age 15

Background: Little is known about whether associations between childhood adiposity and later adverse cardiovascular health outcomes are driven by tracking of overweight from childhood to adulthood and/or by vascular and metabolic changes from childhood overweight that persist into adulthood. Our objective is to characterise associations between trajectories of adiposity across childhood and a wide range of cardiovascular risk factors measured in adolescence, and explore the extent to which these are mediated by fat mass at age 15. Methods and Findings: Using data from the Avon Longitudinal Study of Parents and Children, we estimated individual trajectories of ponderal index (PI) from 0-2 years and BMI from 2-10 years using random-effects linear spline models (N = 4601). We explored associations between PI/BMI trajectories and DXA-determined total-body fat-mass and cardiovascular risk factors at 15 years (systolic and diastolic blood pressure, fasting LDL-and HDL-cholesterol, triglycerides, C-reactive protein, glucose, insulin) with and without adjustment for confounders. Changes in PI/BMI during all periods of infancy and childhood were associated with greater DXA-determined fat-mass at age 15. BMI changes in childhood, but not PI changes from 0-2 years, were associated with most cardiovascular risk factors in adolescence; associations tended to be strongest for BMI changes in later childhood (ages 8.5-10), and were largely mediated by fat mass at age 15. Conclusion: Changes in PI/BMI from 0-10 years were associated with greater fat-mass at age 15. Greater increases in BMI from age 8.5-10 years are most strongly associated with cardiovascular risk factors at age 15, with much of these associations mediated by fat-mass at this age. We found little evidence supporting previous reports that rapid PI changes in infancy are associated with future cardiovascular risk. This study suggests that associations between early overweight and subsequent adverse cardiovascular health are largely due to overweight children tending to remain overweight

The investigation of acute optic neuritis: a review and proposed protocol

Optic neuritis is an inflammatory optic neuropathy that affects many patients with multiple sclerosis (MS) at some point during their disease course. Differentiation of acute episodes of MS-associated optic neuritis from other autoimmune and inflammatory optic neuropathies is vital for treatment choice and further patient management, but is not always straightforward. Over the past decade, a number of new imaging, laboratory and electrophysiological techniques have entered the clinical arena. To date, however, no consensus guidelines have been devised to specify how and when these techniques can be most rationally applied for the diagnostic work-up of patients with acute optic neuritis. In this article, we review the literature and attempt to formulate a consensus for the investigation of patients with acute optic neuritis, both in standard care and in research with relevance to clinical treatment trials

Young Adults With Anterior Ischemic Optic Neuropathy: A Multicenter Optic Disc Drusen Study.

PURPOSE: Optic disc drusen (ODD), present in 2% of the general population, have occasionally been reported in patients with nonarteritic anterior ischemic optic neuropathy (NA-AION). The purpose of this study was to examine the prevalence of ODD in young patients with NA-AION. DESIGN: Retrospective, cross-sectional multicenter study. METHODS: All patients with NA-AION 50 years old or younger, seen in neuro-ophthalmology clinics of the international ODDS (Optic Disc Drusen Studies) Consortium between April 1, 2017, and March 31, 2019, were identified. Patients were included if ODD were diagnosed by any method, or if ODD were excluded by enhanced-depth imaging optical coherence tomography (EDI-OCT) using ODDS Consortium guidelines. NA-AION eyes with ODD were termed "ODD-AION"; those without were termed "NODD-AION". RESULTS: A total of 65 patients (127 eyes) with NA-AION were included (mean 41 years old). Of the 74 eyes with NA-AION, 51% had ODD-AION, whereas 43% of fellow eyes without NA-AION had ODD (P = .36). No significant differences were found between ODD-AION and NODD-AION eyes in terms of Snellen best-corrected VA or perimetric mean deviation. According to EDI-OCT results, 28% of eyes with NODD-AION had peripapillary hyperreflective ovoid mass-like structures (PHOMS); 7% had hyperreflective lines, whereas 54% with ODD-AION had PHOMS; and 66% had hyperreflective lines (P = .006 and P < .001, respectively). CONCLUSIONS: Most of these young NA-AION patients had ODD. This indicates that ODD may be an independent risk factor for the development of NA-AION, at least in younger patients. This study suggests ODD-AION be recognized as a novel diagnosis