Indications and methodology for video-electroencephalographic studies in the epilepsy monitoring unit

Summary

Although the epilepsy and neurology communities have position papers on a number of topics pertaining to epilepsy diagnosis and management, no current paper exists for the rationale and appropriate indications for epilepsy monitoring unit (EMU) evaluation. General neurologists, hospital administrators, and insurers also have yet to fully understand the role this type of testing has in the diagnosis and management of individuals with paroxysmal neurologic symptoms. This review outlines the indications for long-term video-electroencephalography (VEEG) for typical elective admissions to a specialized inpatient setting. The common techniques used in EMUs to obtain diagnostic information are reviewed. The added benefit of safety measures and clinical testing above that available for routine or long-term ambulatory electroencephalography is also discussed. The indications for admission to the EMU include differential diagnosis of paroxysmal spells, characterization of seizure types, presurgical epilepsy evaluations, seizure quantification, monitoring medication adjustment in a safe setting, and differentiation between seizures and side effects. We conclude that the appropriate use of this specialized testing can lead to an early and correct diagnosis in a variety of clinical circumstances. The EMU evaluation is considered the gold standard test for the definitive diagnosis of epilepsy and seizure-like spells.

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The relation between cortisol and functional connectivity in people with and without stress-sensitive epilepsy

Summary

Objective

The most common reported seizure-precipitant is stress. We recently showed a biologic basis for stress sensitivity of seizures: cortisol levels in people with stress-sensitive epilepsy correlated with focal interictal epileptiform discharges (IEDs) on electroencephalography (EEG). Here we aimed to determine whether the effect of cortisol on the epileptic brain is global or focal, and whether cortisol affects all brains or just those of stress-sensitive people. Because epilepsy is associated with changes in functional brain connectivity, we studied the relationship between cortisol and changes in global and focal (node-centered) functional connectivity measures for individuals with stress-sensitive and non–stress-sensitive epilepsy.

Methods

Seventeen people with epilepsy underwent long-term (>24 h) EEG recording. During the first 5 h after waking, saliva was collected every 15 min for cortisol measurements. Theta-band functional connectivity was assessed for every 15 min of the recording. We calculated the average phase-lag index (PLI) between all channels as a measure of global functional connectivity. We used network Strength, the averaged PLI per channel, as focal functional connectivity measure. We correlated cortisol, global, and focal functional connectivity (Strength) with IED frequency using linear mixed models. Analyses were split for people with and without stress-sensitivity of seizures.

Results

Cortisol was negatively correlated with global functional connectivity in people with stress-sensitive seizures (estimate −0.0020; P < .01), whereas not in those without stress-sensitivity (estimate −0.0003; P = .46). This relationship occurred irrespective of the presence of IEDs on a channel (channels without IEDs and stress-sensitivity: estimate −0.0019; P < .01, non–stress-sensitive −0.0003; P = .41). Global and focal functional connectivity were negatively correlated with IED frequency, irrespective of stress sensitivity of seizures or channel type.

Significance

People with stress-sensitive epilepsy have a whole-brain neuronal response to cortisol that is different from that of people with non–stress-sensitive epilepsy. This offers a basis for understanding seizure genesis in stress-sensitive epilepsy, which might require a different treatment approach.

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Nephrotic syndrome and acute kidney injury induced by malathion toxicity

We treated a case of acute kidney injury and nephrotic syndrome after malathion inhalation. A 69-year-old Japanese man presented with oedema 15 days after inhalation of malathion, a widely used pesticide. Serum albumin was 2.4 g/dL, urinary protein 8.6 g/gCr and serum creatinine 2.5 mg/dL. Kidney biopsy revealed tubular cell damage, epithelial cell damage in glomeruli and diffuse foot process effacement in electron microscopy. Acute kidney injury progressed to treatment with dialysis. Renal function recovered after corticosteroid administration from the 43rd day after admission. Malathion inhalation should be ruled out as a differential diagnosis in individuals who develop acute kidney injury and nephrotic syndrome, especially in rural-dwelling patients.

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Radiation retinopathy treated successfully with aflibercept

Aflibercept (aflibercept) is a novel anti-vascular endothelial growth factor drug indicated for wet age-related macular degeneration and macular oedema secondary to retinal vein occlusion and diabetic macular oedema. While only newly introduced on the market, it is growing in popularity and over 5.5 million doses have been prescribed worldwide. Due to its versatile mechanism, it is indicated for numerous eye pathologies, and in particular, has been adapted to treat various types of retinopathy. To our knowledge, this is the first case report of solely using aflibercept to treat cystoid macular oedema in radiation retinopathy.

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Eosinophilic oesophagitis and coeliac disease: is there an association?

A 25-year-old man was seen in outpatient clinic for progressive solid food dysphagia. He was already medicated with a proton pump inhibitor with no improvement. His blood tests showed a slight microcytic anaemia and peripheral eosinophilia. The oesophago-gastro-duodenoscopy showed longitudinal furrows in the distal two-thirds of the oesophagus and a concentric distal stenosis. The biopsies taken showed eosinophilic infiltrates consistent with eosinophilic oesophagitis. There was no improvement with topical fluticasone, so the patient was started on a systemic corticosteroid with resolution of dysphagia and of the oesophageal stenosis. He was kept on topical steroids for symptomatic control. On repeat endoscopy, the duodenal mucosa showed multiple papules that were biopsied. Histology showed features consistent with coeliacdisease. The patient was asymptomatic but there was evidence of iron deficiency anaemia, and so a gluten-free diet was started. Despite only a partial adherence to the diet, the iron deficiency anaemia resolved.

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Traditional Chinese medicine-facilitated treatments may relieve anxiety symptoms during drug switching from methadone to buprenorphine/naloxone for treating opioid dependence

This study investigated a 51-year-old married man with a history of heroin dependence who underwent methadone maintenance treatment for 7 years. He received traditional Chinese medicine (TCM)-facilitated treatments and switched from methadone to buprenorphine/naloxone. Strong anxiety symptoms were observed during the initial stage; therefore, we prescribed a combination of Chaihu-Shugan-San, Zhi Bai Di Huang and Chin-Gin-Kuan-Ming decoction as the major herbal synergic regimen to relieve the symptoms of opioid withdrawal, anxiety and insomnia. During the treatment course, no precipitating withdrawal syndromes were noted, and the subject was gradually relieved of his anxiety symptoms through continual TCM treatments. In conclusion, TCM is effective in facilitating the switch from methadone to buprenorphine/naloxone and relieving anxiety symptoms. Therefore, focus on TCM-facilitated treatments for heroin dependence should be increased.

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All sorts of tests, only one question: an unexpected cause of hypertension

A 48-year-old woman presented to the Accident and Emergency department with a 4 month history of headaches, nausea and dizziness. She was found to have severe hypertension and hypokalaemia. Extensive investigations did not find any secondary cause for hypertension. The patient was discharged with oral doxazosin therapy which controlled the blood pressure. Before the follow-up appointment at the hypertension clinic, the patient and her husband identified that her headaches coincided with liquorice tea consumption of up to three cups per day. This information was not obtained in the clinical assessment. The patient is now headache and medication free after cessation of liquorice tea. Liquorice ingestion is often a forgotten reversible cause of hypertension. A good history is key to this diagnosis.

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Tuberculosis epididymitis complicated by a cutaneous fistula

A 63-year-old man developed scrotal swelling that became bilateral over 2 months. His symptoms persisted after treatment for epididymitis, and he developed a scrotal fistula with drainage. Mycobacterium tuberculosis grew from the urine and fistula. His symptoms resolved and fistula closed with medical therapy. His case highlights the importance of early recognition, diagnosis and treatment of this form of extrapulmonary tuberculosis.

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Pleomorphic sarcoma of the breast

Description

This is an 81-year-old man with a history of small bowel carcinoid. He was undergoing routine surveillance (every 6 months) CT chest, abdomen and pelvis with contrast, which showed an incidental left breast mass in the lower inner quadrant, 12x9 mm concerning for breast neoplasm, there was left axillary lymphadenopathy (LAD) as well (figure 1). Correlation with clinical examination, mammography and ultrasound were recommended. A left breast ultrasound noted a hypoechoic irregular mass with indistinct margins, 7 mm in size at the 10 o'clock position on the left breast, 3 cm from the nipple (figure 2). Breast imaging-reporting and data system (BI-RADS) category 4. Bilateral mammogram demonstrated a 1.3 cm irregular shaped mass at the 10 o'clock position of the left breast. No lymphadenopathy (LAD) was noted on the mammogram or ultrasound. It was categorised as BI-RADS 5 on the mammogram. Bilateral axillary ultrasonography was obtained to evaluate for...

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Dermoscopy of pseudoxanthoma elasticum

Description

A 22-year-old woman presented with complaints of gradually progressive yellowish asymptomatic papules coalescing to form plaques over the lateral aspects of the neck since last 3 years. There were no associated systemic complaints. No similar complaints were noted in any of the family members. Systemic examination was normal while mucocutaneous examination revealed the presence of symmetrically distributed yellowish monomorphic papules arranged in a linear and reticulate manner on both sides of the neck, axillae and periumbilical area (figure 1). These plaques were confluent at most of the places, occasionally studded with telangiectasias and had a pebble-like feel on palpation with poor elastic recoil. Polarised light dermoscopy at x10 magnification of these plaques showed multiple irregular yellowish areas alternating with multiple linear vessels. These yellowish plaques coalesced to form parallel strands (figure 2A). The fundus examination was within normal limits except diffuse pigmentary degeneration (figure...

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Abrikossoffs tumour on the upper limb: a rare presentation

Abrikossoff's tumour or granular cell tumour is a rare entity. Most common locations are the head and neck, with only a few cases reported on the upper limbs. A 55-year-old man with a nodular lesion on the left arm resorted to surgery consultation. Nodule was firm, mobile, painless and non-ulcerated. Total excision using a Limberg flap procedure was performed. Following 3 months of follow-up, the patient is fine. Abrikossoff's tumour is frequently presented in the second to sixth decade of life as an ulcerated nodule with progressive growth. Malignant form is rare, with metastases occurring in up to 3% of patients. Excision must be accomplished with free margins. Recurrence is rare. Abrikossoff's tumour on the upper limbs is rare. Although benignity is the rule, doctors must be aware of the possibility of harbouring a cancer. Surgery is the treatment of choice.

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Selective aplasia of global fibres of all extraocular muscles in congenital fibrosis of extraocular muscles (CFEOM): a rare presentation

Description

A 15-year-old boy presented in our strabismus clinic with complaints of bilateral ptosis and limitation of ocular movements since birth. He had a positive family history of consanguinity and similar ocular movement abnormalities in his three siblings. There was no history of systemic illness. Physical examination showed normal growth parameters without craniofacial dysmorphism except blepharoptosis and lagophthalmos in both eyes, more marked in the right eye. Right eye best-corrected visual acuity (BCVA) was 6/12 and left eye BCVA was 6/9. Slit-lamp biomicroscopy of right eye showed exposure keratopathy, rest was unremarkable. Fundus examination was within normal limits, with no pigmentary retinopathy or optic atrophy changes. There was almost total external ophthalmoplegia, with normal reacting pupils to both direct and consensual light reflex in each eye. The patient preferred fixation with the left eye as his right eye had severe ptosis covering the pupillary area. The patient had chin up and 15° right...

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Heart failure in dilated cardiomyopathy mimicking asthma triggered by pneumonia

Heart failure is a rare cause of wheezing and may develop into a critical condition in children. Few cases report patients with heart failure, secondary to dilated cardiomyopathy, with high fever. A 23-month-old girl visited the emergency department with high fever, cough, first wheezing episode, chest retraction and tachycardia. The chest X-ray revealed consolidation on the left lower lung field; the cardiothoracic ratio was 60%. She was diagnosed with bronchial asthma triggered by pneumonia, which remained unchanged during four visits. Subsequently, she was diagnosed with heart failure in idiopathic dilated cardiomyopathy and discharged without sequelae. During the first wheezing episode in children with abnormal vital signs, heart failure should be considered in the differential diagnosis, and a chest X-ray should be performed. Additionally, when the cardiothoracic ratio is greater than 50%, 12-lead ECG and echocardiography should be performed. Moreover, cognitive bias should be considered in all emergency care unit situations.

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Vancomycin-resistant Enterococcus faecium bacteraemia as a complication of Kayexalate (sodium polystyrene sulfonate, SPS) in sorbitol-induced ischaemic colitis

We present the case report of an 80-year-old woman with chronic kidney disease stage G5 admitted to the hospital with fluid overload and hyperkalaemia. Sodium polystyrene sulfonate (SPS, Kayexalate) in sorbitol suspension was given orally to treat her hyperkalaemia, which precipitated an episode of SPS in sorbitol-induced ischaemic colitis with the subsequent complication of vancomycin-resistant Enterococcus (VRE) bacteraemia. SPS (Kayexalate) in sorbitol suspension has been implicated in the development of intestinal necrosis. Sorbitol, which is added as a cathartic agent to decrease the chance of faecal impaction, may be primarily responsible through several proposed mechanisms. The gold standard of diagnosis is the presence of SPS crystals in the colon biopsy. On a MEDLINE search, no previous reports of a VRE bacteraemia as a complication of biopsy-confirmed SPS in sorbitol ischaemic colitis were found. To the best of our knowledge, ours would be the first such case ever reported.

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Giant atrium, giant clot: need for anticoagulation

Description

We present a patient with medical history of atrial fibrillation, rheumatic mitral valve stenosis and ulcerative colitis who came to the emergency room with onset of bilateral lower extremity pain 2 hours prior to presentation. On examination, feet were pale, cold and pulses were absent. Patient used to be on warfarin for atrial fibrillation which was discontinued 1 month ago by his primary care physician due to recurrent bleeding. Atrial fibrillation with controlled ventricular response was seen on ECG. Emergent arterial Doppler revealed occlusion of the bilateral calf arteries at the level of the tibioperoneal trunk. Patient underwent emergent bilateral right and left groin exploration with bilateral embolectomy and thromboembolectomy. Restoration of flow with no haemodynamically significant atheromatous changes was confirmed by repeat Doppler. Echocardiography revealed severely dilated left atrium measuring 10 cm x 7 cm with large left atrial thrombi (figure 1, online) and severe mitral valve stenosis (mean gradient...

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Atraumatic bilateral humeral head fracture secondary to single seizure

Description

Case 1: A 51-year-old man presented with a single unprovoked generalised tonic clonic seizure (GTCSz), lasting for 4 min, he developed postseizure bilateral shoulder pain and was unable to move his arms as they were painful; there was a history of seizure 7 years ago, he was not on any antiepileptic drugs (AEDs). His sX-ray shoulder showed bilateral comminuted humeral head fracture, which was confirmed by CT of shoulders, see figure 1.He was started on AEDs from a seizure perspective. His neuroimaging, which included an MRI brain (epilepsy protocol) and electroencephalogram (EEG), were normal, see figure 1. From a shoulder management perspective, he was transferred to an orthopaedic surgeon which resulted in corrective surgery.

Figure 1

X-ray and CT of shoulders showing bilateral comminuted humeral head fracture and fracture fragment displacement.

Case 2: A 65-year-old man presented with first seizure of his lifetime, GTCSz, lasting for 3 min, developed...

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Evaluation of psychometric properties of the German Hospital Survey on Patient Safety Culture and its potential for cross-cultural comparisons: a cross-sectional study

Objective

To study the psychometric characteristics of German version of the Hospital Survey on Patient Safety Culture and to compare its dimensionality to other language versions in order to understand the instrument's potential for cross-national studies.

Design

Cross-sectional multicentre study to establish psychometric properties of German version of the survey instrument.

Setting

73 units from 37 departments of two German university hospitals.

Participants

Clinical personnel (n=995 responses, response rate 39.6%).

Primary and secondary outcome measures

Psychometric properties (eg, model fit, internal consistency, construct validity) of the instrument and comparison of dimensionality across different language translations.

Results

The instrument demonstrated acceptable to good internal consistency (Cronbach's alpha 0.64–0.88). Confirmatory factor analysis of the original 12-factor model resulted in marginally satisfactory model fit (root mean square error of approximation (RMSEA)=0.05; standardised root mean residual (SRMR)=0.05; comparative fit index (CFI)=0.90; goodness of fit index (GFI)=0.88; Tucker-Lewis Index (TLI)=0.88). Exploratory factor analysis resulted in an alternative eight-factor model with good model fit (RMSEA=0.05; SRMR=0.05; CFI=0.95; GFI=0.91; TLI=0.94) and good internal consistency (Cronbach's alpha 0.73–0.87) and construct validity. Analysis of the dimensionality compared with models from 10 other language versions revealed eight dimensions with relatively stable composition and appearance across different versions and four dimensions requiring further improvement.

Conclusions

The German version of Hospital Survey on Patient Safety Culture demonstrated satisfactory psychometric properties for use in German hospitals. However, our comparison of instrument dimensionality across different language versions indicates limitations concerning cross-national studies. Results of this study can be considered in interpreting findings across national contexts, in further refinement of the instrument for cross-national studies and in better understanding the various facets and dimensions of patient safety culture.

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Relationship between hormone replacement therapy and spinal osteoarthritis: a nationwide health survey analysis of the elderly Korean population

Objectives

To identify the effects of hormone replacement therapy (HRT) on spinal osteoarthritis (OA).

Methods and design

A cross-sectional study of a nationwide survey was performed.

Setting

This study collected data from the fifth Korean National Health and Nutrition Examination Survey (2010–2012).

Participants

After excluding ineligible respondents, the total number of participants in this study was 4265 females. Participants were asked to report symptoms and disabilities related to spinal OA. In addition, plain radiographs of the spine were taken of all patients.

Primary and secondary outcome measures

Demographic and lifestyle variables were compared between the HRT and non-HRT groups. In addition, radiographic examination and symptom assessment were performed to determine the existence of spinal OA.

Results

Marital status, education, income and HRT were correlated with spinal OA. A risk analysis of related factors showed that HRT and age had effects on spinal OA (ORs 0.717 and 1.257). Nevertheless, in the HRT group, smokers had a increased risk of spinal OA. In addition, the HRT group demonstrated a lower prevalence of spinal OA. The calculated risk for compromised morbidity with HRT compared with the prevalence of spinal OA was 0.717 (OR). The duration of HRT was also related to the risk for spinal OA. The group that had been taking HRT for more than 1 year showed decreased risk (OR 0.686) compared with patients with <1 year of HRT (OR 0.744; P<0.05).

Conclusion

Women receiving HRT showed a lower prevalence of spinal OA. HRT also correlated with a decrease in spinal OA morbidity.

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Exploring the characteristics of the high-cost population from the family perspective: a cross-sectional study in Jiangsu Province, China

Background

Across a range of healthcare settings, 5% of the population accounts for half of healthcare spending: these patients are identified as a 'high-cost population'. Characterising high-cost users is essential for predicting potential high-cost patients and the development of appropriate interventions to improve the management and financing of these patients.

Objective

This cross-sectional study aimed to explore the characteristics of this high-cost population from a family perspective in China and provide suggestions for social health insurance policy development.

Methods

This study used data from the Fifth Health Service Investigation of Jiangsu Province (2013), and 12 600 families were enrolled for analysis. Households whose medical expenditures were among the top 5% were identified to be high-cost families. A t-test, a X² test, and a binary logistic regression were used.

Results

High-cost families (n=631, 5%) accounted for 44.9% of the total medical expenditure of sampled families. High-cost families had 3.2 members and 1.2 chronic disease patients per household, which is significantly more than the 2.9 members and 0.7 people in the remaining families, respectively (p<0.05). Bi-weekly emergency department visits and annual hospitalisations preceding the household investigation of high-cost families were 1.19 and 0.98 per household, which is significantly more than the 0.68 and 0.17 of the remaining families, respectively (p<0.05). A binary logistic regression indicated that the number of family members (OR 1.152), the number of chronic disease patients (OR 1.508), bi-weekly emergency department visits (OR 1.218), and annual hospitalisations (OR 4.577) were associated with high costs.

Conclusion

The 5% high-cost families in Jiangsu Province accounted for approximately half of medical expenditures. The effectiveness of Chinese Social Health Insurance in lowering high-cost families' risk of catastrophic health expenditure was modest. Policymakers need to ascertain the priority of lowering the burden of high-cost families' out-of-pocket expenses through improving the reimbursement proportion and reducing avoidable medical services.

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Clinical prediction rule for neurological sequelae due to acute encephalopathy: a medical community-based validation study in Harima, Japan

Objectives

This study aimed to verify the screening performance of our clinical prediction rule for neurological sequelae due to acute encephalopathy (NSAE-CPR), which previously identified the following three variables as predictive of poor outcomes: (1) refractory status epilepticus; (2) consciousness disturbance and/or hemiplegia at 6 hours from onset and (3) aspartate aminotransferase >90 IU/L within 6 hours of onset.

Design

Medical community-based multicentre retrospective cohort study.

Setting

Six regional hospitals in Harima and one tertiary centre in Kobe, Japan, from 2008 to 2012.

Participants

We enrolled a total of 1612 patients aged <16 years who met the diagnostic criteria for an initial diagnosis of complex febrile seizure. Patients with a history of neurological disease and those included in the derivation cohort were excluded.

Primary outcome measures

Univariate and multivariate analyses were performed to determine the association between each of the three predictor variables and poor AE outcome (Pediatric Cerebral Performance Category score ≥2). Receiver operating characteristic curve (ROC) analysis was also performed to assess the screening performance of the NSAE-CPR.

Results

The ROC analysis identified at least one of the three predictive variables as an optimal cut-off point, with an area under the curve of 0.915 (95% CI 0.825 to 1.000). The sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios and Matthews correlation coefficient were 0.867, 0.954, 0.149, 0.999, 18.704, 0.140 and 0.349, respectively.

Conclusions

Our findings indicate that the NSAE-CPR can be used for the screening and identification of patients with poor outcomes due to acute encephalopathy within 6 hours of onset.

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Protocol for hospital based-surveillance of cerebral palsy (CP) in Hanoi using the Paediatric Active Enhanced Disease Surveillance mechanism (PAEDS-Vietnam): a study towards developing hospital-based disease surveillance in Vietnam

Introduction

The epidemiology, pathogenesis, management and outcomes of cerebral palsy (CP) in low-income and middle-income countries including Vietnam are unknown because of the lack of mechanisms for standardised collection of data. In this paper, we outline the protocol for developing a hospital-based surveillance system modelled on the Paediatric Active Enhanced Disease Surveillance (PAEDS) system in Australia. Using PAEDS-Vietnam we will define the aetiology, motor function and its severity, associated impairments, and nutritional and rehabilitation status of children with CP in Hanoi, Vietnam. These essential baseline data will inform future health service planning, health professional education and training, and family support.

Methods and analysis

This is a hospital-based prospective surveillance of children with CP presenting to the rehabilitation, neurology and general paediatric services at the National Children's Hospital and St Paul Hospital in Hanoi. We will use active, prospective daily case-finding for all children with CP aged <18 years who are hospitalised or present to outpatient departments. Following parental consent, data will be collected using a modified version of the Australian Cerebral Palsy Register questionnaire. The data collection form has been developed in consultation with local and international experts and translated into Vietnamese. Information collected will include demographics, maternal health and birth history, type and severity of CP, known risk factors for CP, and nutrition, immunisation, education and rehabilitation status.

Ethics and dissemination

This study was approved by the Hanoi Medical University Institutional Review Board (decision no 1722) and The University of Sydney Human Research Ethics Committee (approval no 2016/456). Establishment of PAEDS-Vietnam will enable hospital-based surveillance of CP for the first time in Vietnam. It will identify preventable causes of CP, patient needs and service gaps, and facilitate early diagnosis and intervention. Study findings will be disseminated through local and international conferences and peer-reviewed publications.

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Primary care management of headaches and how direct-access MRI fits: a qualitative study of UK general practitioners views

Objectives

To develop a better understanding of general practitioners' (GPs) views and experiences of the management of patients with headaches and use of direct-access MRI scans, and observe outcomes of an educational session offered by a GP with a special interest (GPwSI) to GPs.

Design

A qualitative study using semistructured interviews, analysed using thematic analysis. A GPwSI in headaches visited practices delivering a talk on headache medication, diagnosis and management.

Setting

Sixteen (16) primary care family practices in South London, UK.

Participants

Twenty (20) GPs.

Results

Not all GPs were aware of the availability of direct-access MRI, but all acknowledged having used referral or direct scans to manage patients' concern about their headaches. A normal scan result helped resolve uncertainty for patient and GP and helped management towards discussion of preventative treatment. However, patients with psychological and/or severe headache symptoms could not necessarily be reassured. GPs reported difficulty interpreting radiology reports, particularly incidental abnormalities. Those who received the educational talk gained knowledge in diagnosis and medication, improving their confidence in management.

Conclusions

Increased access to imaging, training in headache management, addressing physical and psychological symptoms and standardised reporting of scans may improve GPs' use of direct-access MRI in the future.

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Eosinophilic esophagitis and proton pump inhibitors: is there a new link?

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HISTOLOGICAL FEATURES OF EOSINOPHILIC ESOPHAGITIS IN CHILDREN AND ADOLESCENTS

ABSTRACT BACKGROUND: Eosinophilic esophagitis is an emerging disease featured by eosinophilic esophageal infiltrate not responsive to proton pump inhibitors. OBJECTIVE: To characterize histological features of children and adolescents with eosinophilic esophagitis. METHODS: Cross-sectional study in a tertiary hospital. Biopsies from each esophageal third from 14 patients (median age 7 years) with eosinophilic esophagitis were evaluated. Histological features evaluated included morphometry of esophageal epithelium, esophageal density (per high power field), extracellular eosinophilic granules, eosinophilic microabscesses, surface disposition of eosinophils, epithelial desquamation, peripapillary eosinophilia, basal layer hyperplasia and papillary elongation. RESULTS: Several patients presented a normal esophageal macroscopy in the upper digestive endoscopy (6, 42.8%), and the most common abnormality were vertical lines (7, 50%) and whitish spots over esophageal mucosa (7, 50%). Basal layer hyperplasia was observed in 88.8%, 100% e 80% of biopsies from proximal, middle and lower esophagus, respectively (P=0.22). Esophageal density ranges from 0 to more than 50 per hpf. Extracellular eosinophilic granules (70%-100%), surface disposition of eosinophils (60%-93%), epithelial desquamation (60%-100%), peripapillary eosinophilia (70%-80%) were common, but evenly distributed among each esophageal third. Just one patient did not present eosinophils in the lower third, four in the middle third and four in the upper esophageal third. CONCLUSION: In the absence of hypereosinophilia, other histological features are present in eosinophilic esophagitis and may contribute to diagnosis. Eosinophilic infiltrate is focal, therefore multiple biopsies are needed for diagnosis.

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RESUMO CONTEXTO: Esofagite eosinofílica é uma doença emergente caracterizada por infiltrado eosinofílico esofágico não responsivo a inibidores de bomba de prótons. OBJETIVO: Caracterizar os achados histopatológicos de uma coorte de crianças e adolescentes com diagnóstico de esofagite eosinofílica. MÉTODOS: Estudo transversal conduzido em hospital terciário. Biópsias de terços proximal, médio e distal de 14 pacientes (idade mediana 7 anos) com diagnóstico de esofagite eosinofílica. Estudo morfométrico e variáveis histológicas analisadas em fragmentos de biópsias nos terços esofágicos: contagem de eosinófilos/CGA, grânulos eosinofílicos extracelulares, microabscessos eosinofílicos, disposição superficial de eosinófilos, descamação epitelial, eosinofilia peripapilar, hiperplasia da camada basal e alongamento de papilas. RESULTADOS: Vários pacientes apresentaram aspecto macroscópico normal da mucosa esofágica à endoscopia (6, 42.8%), e a anormalidade mais comumente observada foi linhas verticais (7, 50%) e exsudato branco (7, 50%). Hiperplasia da camada basal foi observada em 88,8%, 100% e 80% das biópsias do terço proximal, médio e distal respectivamente (P=0,22); contagem de eosinófilos nos terços variou de 0 a ≥50/CGA, grânulos eosinofílicos extracelulares (70%-100%), disposição superficial de eosinófilos (60%-93%), descamação epitelial (60%-100%), eosinofilia peripapilar (70%-80%), sem diferença estatística entre os terços esofágicos. Ausência de eosinofilia ocorreu raramente em terço distal (uma do distal, quatro do proximal, quatro do médio). CONCLUSÃO: Na ausência de hipereosinofilia, outros achados histopatológicos de inflamação eosinofílica estão presentes. A infiltração eosinofílica apresentou caráter focal, sugerindo-se a realização de múltiplas biópsias de diversos segmentos.

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PRIMARY SCLEROSING CHOLANGITIS IN CHILDREN AND ADOLESCENTS

ABSTRACT BACKGROUND: Primary sclerosing cholangitis is a rare disease, but its prevalence has been underestimated in children and adolescents due to broad variation in clinical presentation as well as diagnostic challenges in this life period. OBJECTIVE: To evaluate children and adolescents with primary sclerosing cholangitis and to describe their clinical, laboratorial, histopathological, and cholangiography conditions. METHODS: This is an observational descriptive research that took place from 2005 to 2016 and included all the patients seen in the Outpatient Unit for Pediatric Hepatology of Hospital das Clinicas of UFMG who had been diagnosed with primary sclerosing cholangitis before the age of 18. Diagnosis was established through clinical, laboratory, radiographic and/or histopathologic criteria. Other chronic liver diseases were excluded, as well as secondary causes of cholangitis. Data analysis used statistic resources in SPSS software. Variables were expressed as averages, standard deviation, absolute frequency, and percentage. RESULTS: Twenty-one patients fulfilled criteria to be included in the research sample. Male patients predominated (3.2:1) and average age at diagnosis was 6.7±3.9 years. Five (23.8%) patients had associated inflammatory bowel disease, four had ulcerative colitis and one indeterminate colitis. Signs and symptoms vary and are usually discrete at presentation. The most frequent symptom was abdominal pain (47.6%) followed less frequently by jaundice (28.6%) and itching (14.3%). The reason for medical investigation was asymptomatic or oligosymptomatic enzyme alterations in 33.3% of patients. All patients presented increased hepatic enzymes: aminotransferases, gamma glutamyl transferase, and alkaline phosphatase. Twenty patients had alterations compatible to primary sclerosing cholangitis in their cholangiography exam; one patient had no alterations at magnetic resonance cholangiography, but presented histopathologic alterations that were compatible to small duct cholangitis. Hepatic fibrosis was present in 60% of 15 patients who were biopsied upon admission; cirrhosis being present in four (26.7%) patients. A total of 28.5% of patients had unfavorable outcomes, including two (9.5%) deaths and four (19%) transplants. CONCLUSION: Primary sclerosing cholangitis is a rare disease in childhood and adolescence and its initial diagnosis may be delayed or overlooked due to asymptomatic or unspecific clinical manifestations. The association with inflammatory bowel disease is common. Prognosis may be unfavorable as the disease progresses and hepatic transplant is the definitive treatment.

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RESUMO CONTEXTO: A colangite esclerosante primária é uma doença rara, mas sua prevalência tem sido subestimada em crianças e adolescentes, tanto pela variedade de apresentação clínica quanto pela dificuldade diagnóstica neste período. OBJETIVO: Avaliar crianças e adolescentes com colangite esclerosante primária descrevendo seu quadro clínico, laboratorial, histopatológico e colangiográfico. MÉTODOS: Trata-se de um estudo descritivo observacional, de 2005 a 2016, de todos os pacientes atendidos no Ambulatório de Hepatologia Pediátrica do Hospital das Clínicas da UFMG, com o diagnóstico de colangite esclerosante primária até a idade de 18 anos. O diagnóstico foi estabelecido segundo os critérios clínicos, laboratoriais, radiológicos e/ou histopatológicos. Foi realizada investigação para exclusão de outras doenças hepáticas crônicas e causas secundárias de colangite. A análise dos dados foi efetuada com os recursos estatísticos do software SPSS. As variáveis foram expressas por meio de médias, desvio-padrão, frequência absoluta e porcentagem. RESULTADOS: Vinte e um pacientes preencheram os critérios de inclusão. Houve predomínio no sexo masculino (3,2:1). A média de idade ao diagnóstico foi 6,7±3,9 anos. Cinco (23,8%) pacientes apresentavam doença inflamatória intestinal associada, sendo quatro casos de colite ulcerativa e um de colite indeterminada. Na apresentação, os sinais e sintomas são variados, em geral discretos. O sintoma mais frequente foi dor abdominal (47,6%), seguido menos frequentemente por icterícia (28,6%) e prurido (14,3%). Em 33,3% dos pacientes, o motivo de início da investigação foi alteração de enzimas em pacientes assintomáticos ou oligossintomáticos. Todos os pacientes exibiam aumento das enzimas hepáticas: aminotransferases, gama glutamiltransferase e fosfatase alcalina. Vinte pacientes apresentavam alterações em exame colangiográfico, compatíveis com colangite esclerosante primária; um paciente não apresentava alterações na colangiorressonância, mas apresentava alterações histopatológicas compatíveis com colangite de pequenos ductos. Fibrose hepática já estava presente em 60% dos 15 pacientes com biópsia à admissão; com cirrose estabelecida em quatro pacientes. 28,5% dos pacientes tiveram evolução desfavorável, com dois (9,5%) óbitos e quatro (19%) pacientes transplantados. CONCLUSÃO: Colangite esclerosante primária é uma doença rara na criança e no adolescente, cujo diagnóstico inicial pode ser atrasado ou passar despercebido, principalmente por apresentar manifestações clínicas inespecíficas ou cursar de forma assintomática. É frequente a associação com doença inflamatória intestinal. O prognóstico pode ser reservado com o avançar da doença, sendo o transplante hepático o tratamento definitivo.

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Comparative study on gastrostomy and orally nutrition of children and adolescents with tetraparesis cerebral palsy

ABSTRACT BACKGROUND: Gastrostomy tube feeding (GTF) is indicated for children with feeding difficulties due to tetraspastic cerebral palsy, although there are no definitive conclusions about the benefits of GTF. OBJECTIVE: To compare nutritional status and diet of pediatric patients with tetraparesis cerebral palsy who are fed by GTF with those fed orally (PO). METHODS: A transversal and descriptive study on 54 patients with spastic tetraparesis was held. The referred parameters were: weight, knee height and estimated height, cutaneous folds and circumferences. The Frisancho reference was used to compare the skin folds and body circumferences. The Brooks et al. curve was adopted as a reference for weight, height, and BMI. Food inquiry was performed using the Habitual Dietary Recall method. The total energetic value (TEV) of macronutrients and fibers was performed by Avanutri® version 4.0, a nutrition software program. The differences of nutritional parameters between the GTF and the PO groups were calculated by chi-squared and Fisher's exact tests, and the comparison between the groups for variable numbers was performed using the Mann-Whitney test. The significance level adopted was 5%. RESULTS: The PO group presented more individuals in the malnourished range (24.14%) and high levels of adipose and thin mass depletion. The ingestion of lipids was larger in the GTF group, even though the proteins and fibers were higher in the PO group. The comparison between the diets in the GTF group indicated that the mixed diet (industrialized and artisanal) supplied a greater contribution of proteins and fibers. CONCLUSION: Comparing the groups, the tetraparesis cerebral palsy patients fed orally have a greater impairment of their nutritional status, even though they have higher intakes of protein and fiber than those patients fed by gastrostomy, demonstrating a consistent argument for the use of gastrostomy.

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RESUMO CONTEXTO: A alimentação por gastrostomia é indicada para crianças com dificuldades de alimentação devido à paralisia cerebral tetraespástica, embora não haja conclusões definitivas sobre a colocação da alimentação por gastrostomia. OBJETIVO: Comparar o estado nutricional e dieta de crianças e adolescentes com paralisia cerebral tetraespástica alimentados via oral (VO) e via gastrostomia. MÉTODOS: Estudo transversal e descritivo de 54 pacientes com paralisia cerebral tetraespástica. Os parâmetros aferidos foram: peso, altura do joelho e estatura estimada, dobras cutâneas e circunferências. Curvas de Brooks et al. foram adotadas como referência. O inquérito alimentar foi realizado pelo método Recordatório Alimentar Habitual. As diferenças dos parâmetros nutricionais entre os grupos Gastrostomia e VO foram calculadas por testes qui-quadrado e Exato de Fisher e a comparação entre os grupos para as variáveis numéricas foi realizada pelo teste de Mann-Whitney. O nível de significância adotado foi de 5%. RESULTADOS: O grupo alimentado via oral apresentou mais indivíduos na faixa da desnutrição (24,14%) e maior depleção de massa magra e adiposa. A ingestão de lipídeos foi maior no grupo Gastrostomia, enquanto que de proteínas e de fibras foi superior no grupo VO. A comparação entre as dietas no grupo Gastrostomia indicou que a dieta mista (industrializada + artesanal) fornece maior aporte de proteínas e fibras. CONCLUSÃO: Os pacientes com paralisia cerebral tetraespástica alimentados por via oral têm um maior comprometimento do estado nutricional, mesmo que eles tenham um maior consumo de proteínas e fibras que os pacientes alimentados por gastrostomia, demonstrando um argumento consistente para o uso de gastrostomia.

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FLOW MEDIATED DILATION AND CAROTID INTIMA MEDIA THICKNESS IN PATIENTS WITH CHRONIC GASTRITIS ASSOCIATED WITH HELICOBACTER PYLORI INFECTION

ABSTRACT BACKGROUND: Endothelial dysfunction is one of the early stages of vascular diseases. OBJECTIVE: The aim of this study was to investigate the endothelial dysfunction markers in patients with chronic gastritis associated with Helicobacter pylori (H. pylori) infection. METHODS: By a cross sectional study, basic and clinical information of 120 participants (40 patients with positive H. pylori infection, 40 patients with negative H. pylori infection and 40 healthy people) were analyzed. Carotid intima media thickness and flow-mediated dilation levels were measured in all patients and controls. Soluble vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were measured with Elisa for all subjects. IgG level was assessed in chronic gastritis patients. RESULTS: The flow-mediated dilation level in patients with positive H. pylori infection (0.17%±0.09) was significantly lower than those with negative H. pylori infection (0.21% ±0.10, P<0.05) and compared to the control group (0.27% ±0.11, P<0.05). Carotid intima media thickness level in patients with positive H. pylori infection (0.58±0.13 mm) was significantly higher than those with negative H. pylori infection (0.48±0.32 mm, P<0.05) and compared to the control group (0.36±0.44mm, P<0.05). The mean level of sICAM-1 in positive H. pylori infection group (352.16±7.54 pg/mL) was higher than negative H. pylori infection group (332.64±8.75 pg/mL =0.75) and compared to the control group (236.32±12.43 pg/mL, P<0.05). A direct relationship was revealed between flow-mediated dilation and carotid intima media thickness changes and between sICAM-1 and sVCAM-1 associated with the level of H. pylori IgG in chronic gastritis. CONCLUSION: The levels of flow-mediated dilation, carotid intima media thickness and sICAM-1 were higher among patients with positive H. pylori infection. Patients with chronic gastritis associated with H. pylori infection are at risk of endothelial dysfunction due to flow-mediated dilation and carotid intima media thickness abnormalities and increased level of sICAM-1 and sVCAM-1.

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RESUMO CONTEXTO: A disfunção endotelial é um dos estágios iniciais de doenças vasculares. OBJETIVO: O objetivo deste estudo foi investigar os marcadores de disfunção endotelial em pacientes com gastrite crônica associada com infecção por Helicobacter pylori (H. pylori). MÉTODOS: Através de estudo cruzado seccional, foram analisadas informações básicas e clínicas de 120 participantes (40 pacientes com infecção pelo H. pylori, 40 pacientes sem infecção pelo H. pylori e 40 pessoas saudáveis). A espessura da camada íntima-média da carótida e níveis de dilatação mediada por fluxo foram medidos em todos os pacientes e controles. A adesão da molécula-1 solúvel (sVCAM-1) à célula vascular e da molécula de adesão intercelular-1 (ICAM-1) foram medidas pelo método Elisa para todas os indivíduos. O nível de H. pylori IgG foi avaliado em pacientes de gastrite crônica. RESULTADOS: O nível de dilatação mediada por fluxo em pacientes com infecção positiva pelo H. pylori foi significativamente menor do que em aqueles com infecção negativa (0,17% ±0, 09) X (0,21% ±0,10) P<0,05 e em relação ao grupo controle (0,27% ±0,11) P<0,05). O nível da espessura da íntima-média da carótida em pacientes com infecção positiva pelo H. pylori foi significativamente maior (0,58±0,13 mm) do que aqueles com negativa (0,48±0,32 mm) P<0,05) e em relação ao grupo controle (0,36±0,44 mm) P<0,05). O nível médio de sICAM-1 grupo de infecção H. pylori positiva (352,16±7,54 pg/mL) foi maior do que o grupo de infecção negativa (332,64±8,75 pg/mL = 0,75) e em relação ao grupo controle (236,32±12,43 pg/mL) P<0,05). Revelou-se uma relação direta entre a dilatação mediada por fluxo e alterações da espessura da íntima-média da carótida e sICAM-1 e sVCAM-1, associada com o nível de H. pylori IgG em gastrite crônica. CONCLUSÃO: Os níveis de dilatação mediada por fluxo, da espessura da íntima-média da carótida e sICAM-1 foram maiores entre os pacientes com infecção positiva pelo H. pylori. Pacientes com gastrite crônica associada a infecção por H. pylori correm o risco de disfunção endotelial, devido à dilatação mediada por fluxo e anormalidades da espessura da íntima-média da carótida e aumento do nível de sICAM-1 e sVCAM-1.

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LOW PREVALENCE OF BARRETT’S ESOPHAGUS IN A RISK AREA FOR ESOPHAGEAL CANCER IN SOUTH OF BRAZIL

ABSTRACT BACKGROUND: Barrett's esophagus a complication of gastroesophageal reflux disease (GERD) is a precursor of esophageal adenocarcinoma. The incidence of esophageal adenocarcinoma has been increasing in most Western countries. Rio Grande do Sul (RS), the Southernmost state of Brazil has the highest rates of esophageal cancer with low prevalence of esophageal adenocarcinoma. OBJECTIVE: To investigate the prevalence of Barrett's esophagus among patients underwent to upper gastrointestinal endoscopy in the last 5 years. METHODS: The records of patients underwent upper gastrointestinal endoscopy between 2011 and 2015 were analyzed. Demographic data, GERD symptoms, endoscopic findings, extension and histological diagnosis of columnar epithelia of the esophagus were recorded. Significance among the variables was accessed by chi-square test and Fisher's exact test with 95% CI. RESULTS: A total of 5996 patients underwent to upper gastrointestinal endoscopy in the period were included. A total of 1769 (30%) patients with GERD symptoms or esophagitis and 107 (1.8%) with columnar lined esophagus were identified. Except for eight patients, the others with columnar lined esophagus had GERD symptoms or esophagitis. Barrett's esophagus defined by the presence of intestinal metaplasia occurred in 47 patients; 20 (43%) with segments over 3 cm and 27 (57%) with segments shorter than 3 cm. The global prevalence of Barrett's esophagus was 0.7% and in GERD patients 2.7%. The odds ratio for the occurrence of columnar lined esophagus in patients with GERD was 30 (95%CI=15.37-63.34). The odds ratio for the presence of intestinal metaplasia in long segments was 8 (95%CI=2.83-23.21). CONCLUSION: GERD patients had a risk 30-folds greater to present columnar lined esophagus than patients without GERD symptoms. Long segments of columnar lined esophagus, had a risk eight-folds higher to have Barrett's esophagus than short segments. Barrett's esophagus overall prevalence was 0.7%. In GERD patients, the prevalence was 2.7%. Long Barrett's esophagus represented globally 0.3% and 1.1% in GERD patients.

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RESUMO CONTEXTO: Esôfago de Barrett, complicação da doença do refluxo gastroesofágico (DRGE), é lesão precursora do adenocarcinoma esofágico. O adenocarcinoma esofágico apresenta incidência crescente principalmente no ocidente. O estado do Rio Grande do Sul apresenta as taxas mais altas de câncer esofágico no Brasil, porém com baixa prevalência de adenocarcinoma. OBJETIVO: Investigar a prevalência de esôfago de Barrett em pacientes submetidos a endoscopia digestiva alta nos últimos 5 anos. MÉTODOS: Revisão de prontuários dos pacientes submetidos a endoscopia digestiva alta entre 2011 e 2015. Registrados dados demográficos, sintomas de DRGE, achados endoscópicos, extensão e diagnóstico histológico de epitelização colunar do esôfago. A significância entre as variáveis foi acessada pelos testes do qui-quadrado e exato de Fisher com IC95%. RESULTADOS: Foram incluídos 5996 pacientes. Identificamos 1769 (30%) com sintomas de DRGE ou esofagite e 107 (1,8%) com epitelização colunar. À exceção de oito pacientes com epitelização colunar, os demais apresentavam sintomas de DRGE ou esofagite. Esôfago de Barrett definido pela presença de metaplasia intestinal ocorreu em 47 pacientes; 20 (43%) com segmentos acima de 3 cm e em 27 (57%) com segmentos menores. A prevalência global de esôfago de Barrett foi 0,7% e em pacientes com DRGE foi 2,7%. A razão de chances para a ocorrência de epitelização colunar em pacientes com DRGE foi 30 (IC95%=15,37-63,34) e para a ocorrência de metaplasia intestinal em segmentos longos foi 8 (IC95%=2,83-23,21). CONCLUSÃO: Pacientes com DRGE apresentaram risco 30 vezes maior que pacientes sem DRGE para a ocorrência de epitelização colunar. O risco de ocorrência de esôfago de Barrett em segmentos longos foi oito vezes maior. A prevalência global de esôfago de Barrett foi 0,7%. Em pacientes com DRGE a prevalência foi 2,7%. Segmentos longos de esôfago de Barrett representaram globalmente 0,3% e em pacientes com DRGE 1,1%.

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CHARACTERIZATION OF THE MUCIN PHENOTYPE CAN PREDICT GASTRIC CANCER RECURRENCE AFTER ENDOSCOPIC MUCOSAL RESECTION

ABSTRACT BACKGROUND: Endoscopic mucosal resection is still considered an accepted treatment for early gastric cancer for selected cases. Histopathologic criteria for curative endoscopic resection are intramucosal well-differentiated adenocarcinoma, lateral and deep margins free of tumor, no histological ulceration, and no venous or lymphatic embolism. A 5% local recurrence rate has been described even when all the above-mentioned criteria are met. On the other hand, antigen expression by tumoral cells has been related to the biological behavior of several tumors. OBJECTIVE: To evaluate whether early gastric cancer mucin immunoexpression, p53 and Ki-67, can predict recurrence after endoscopic mucosal resection, even when standard histopathologic criteria for curative measures have been attempted. METHODS: Twenty-two patients with early gastric cancer were considered to have been completely resected by endoscopic mucosal resection. Local recurrence occurred in 5/22 (22.7%). Immunohistochemical study was possible in 18 (81.8%) resected specimens. Patients were divided in two groups: those with and those without local recurrence. They were compared across demographic, endoscopic, histologic data, and immunohistochemical factors for MUC2, MUC5a, CD10, p53, and Ki-67. RESULTS: Mucin immunoexpression allowed a reclassification of gastric adenocarcinoma in intestinal (10), gastric (2), mixed (4), and null phenotypes (2). Mixed phenotype (positive for both MUC2 and MUC5a) was found in 80% of cases in the local recurrence group, while the intestinal type (positive MUC2 and negative MUC5a) was found in 76.9% of cases without local recurrence (P=0.004). Other observed features did not correlate with neoplastic recurrence. CONCLUSION: The mixed phenotype of early gastric adenocarcinoma is associated with a higher probability of local recurrence after endoscopic mucosal resection.

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RESUMO CONTEXTO: A ressecção endoscópica da mucosa é tratamento aceito para o tratamento do câncer gástrico precoce em casos selecionados. Os critérios histopatológicos favoráveis à ressecção endoscópica curativa são adenocarcinomas intramucosos, bem diferenciados, com margens lateral e profunda livres, ausência de ulceração ou de embolização angiolinfática. Taxas de recorrência local próximas a 5% têm sido descritas mesmo quando se cumprem tais critérios. Por outro lado, a expressão antigênica por células tumorais tem sido relacionada com o comportamento biológico de diversos tumores. OBJETIVO: Avaliar se a imunoexpressão de mucinas, p53 e Ki-67 podem predizer a recorrência tumoral após mucosectomia endoscópica no câncer gástrico precoce, mesmo se critérios de cura histopatológicos forem atingidos. MÉTODOS: Vinte e dois pacientes com critérios de cura para ressecção endoscópica e sumetidos a mucosectomia foram selecionados. A recorrência local ocorreu em 5/22 (22,7%). O estudo imunohistoquímico foi realizado em 18 (81,8%) espécimens. Os pacientes foram divididos em grupos com e sem recorrência local. Foram comparados quanto a dados demográficos, endoscópicos, histológicos e fatores imunohistoquímicos para MUC2, MUC5A, CD10, p53, e Ki-67. RESULTADOS: A imunoexpressão de mucinas permitiu a reclassificação dos adenocarcinomas gástricos em intestinal (10), gástrico (2), e de fenótipo misto (4) e nulo (2). Os fenótipos mistos (positivos tanto para MUC2 quanto para MUC5A) foram encontrados em 80% dos casos no grupo de recorrência local, enquanto tipos intestinais (MUC2 positivo e MUC5A negativo) foram identificados em 76,9% dos casos sem recorrência (P=0,004). Os outros fatores observados não se relacionaram com a recorrência tumoral. CONCLUSÃO: O fenótipo misto do câncer gástrico precoce está associado a maior probabilidade de recorrência local após a mucosectomia.

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ADENOMA DETECTION RATE EVALUATION AND QUALITY OF COLONOSCOPY IN THE CENTER-WEST REGION OF BRAZIL

ABSTRACT BACKGROUND: Colorectal cancer is the third commonest cancer in men and the second in women worldwide. Peculiarities of its evolution allow secondary prevention measures through colonoscopy, with high diagnostic and therapeutic capacity. In this context, the quality indicators of the procedure become important, among them the adenoma detection rate (ADR). OBJECTIVE: To relate the ADR in a medium risk population subjected to colonoscopy with sociodemographic, technical and histopathological indicators. METHODS: This was a descriptive, observational and retrospective study whose data were collected from medical records of colonoscopy exams with the indication of colorectal cancer screening or prevention in the period from August to October 2016. RESULTS: A total of 436 exams were included for analysis. Female sex represented 66.3% with 289 patients versus 33.7% for men. Patients aged between 50 and 59 years were 223 (51.1%) and those between 60 and 75 years were 213 (48.9%). In 99 exams (22.7%) chromoscopy was used, and 420 patients (96.3%) were adequately prepared. There were 118 patients with adenomas, resulting in an overall ADR of 27.1%. The ADR for men was 30.6% and 25.3% for women. Patients between 60 and 75 years old had a significantly higher ADR (31.9%, compared to 22.4% of the younger ones). Examinations in which chromoscopy was used also presented higher ADR. CONCLUSION: The ADR values found for the population of the studied region were compatible with internationally established goals. Continuous evaluation of the ADR may yield interventions aimed at improving quality standards for colonoscopy and promote better prevention of colorectal cancer.

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RESUMO CONTEXTO: O câncer colorretal é o terceiro câncer mais incidente em homens e o segundo em mulheres em todo o mundo. Peculiaridades de sua evolução permitem medidas de prevenção secundária através da colonoscopia, com alta capacidade diagnóstica e terapêutica. Nesse contexto os indicadores de qualidade se tornam importantes, dentre eles a taxa de detecção de adenomas (TDA). OBJETIVO: Avaliar a taxa de detecção de adenomas em uma população de médio risco submetida a colonoscopia, relacionando-a a indicadores sociodemográficos, técnicos e histopatológicos. MÉTODOS: Trata-se de estudo descritivo, observacional e retrospectivo cujos dados foram coletados de registros e prontuários médicos de exames de colonoscopia com indicação de rastreamento ou prevenção do câncer colorretal no período de agosto a outubro de 2016. RESULTADOS: Foram incluídos 436 laudos de exames para análise de dados. O sexo feminino representou 66,3% com 289 pacientes contra 33,7% de homens. Os pacientes entre 50 e 59 anos de idade foram 223 (51,1%) e 213 entre 60 a 75 anos (48,9%). Em 99 exames (22,7%) foi feito uso de cromoscopia e 420 exames (96,3%) tiveram preparo adequado. Cento e dezoito pacientes tiveram adenomas, resultando em uma TDA geral no serviço de 27,1%. A TDA para homens foi de 30,6% e 25,3% para mulheres. Os pacientes entre 60 e 75 anos tiveram uma TDA significativamente maior (31,9%, contra 22,4% dos mais jovens). Exames em que foi feito uso cromoscopia também apresentaram maior TDA. CONCLUSÃO: Os valores de TDA encontrados podem validar o uso de metas estabelecidas mundialmente para a população da região estudada e sua progressão temporal pode propor medidas para o aumento dessa taxa.

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ADALIMUMAB FOR ULCERATIVE COLITIS: RESULTS OF A BRAZILIAN MULTICENTER OBSERVATIONAL STUDY

ABSTRACT BACKGROUND: Adalimumab is a monoclonal antibody, tumor necrosis factor-alpha (TNFα) inhibitor that has efficacy for inducing and maintaining remission in moderate-to-severe ulcerative colitis. Real world studies with adalimumab in Latin American ulcerative colitis patients are scarce. OBJECTIVE: To assess the clinical remission rates in induction and maintenance with adalimumab therapy in ulcerative colitis. METHODS: Observational, multicenter and retrospective study on a case series of patients with moderate-to-severe ulcerative colitis under adalimumab therapy. The variables analyzed were: demographic data, previous infliximab status, concomitant drugs, the Montreal Classification, disease activity (Mayo score) at weeks 0, 8, 26 and 52, or until the last follow-up. Clinical remission was defined as a partial Mayo score ≤2 and Last observation carried forward (LOCF) and Non responder imputation (NRI) analysis were used. RESULTS: Thirty-six patients were included in the study. With LOCF analysis, remission rates at weeks 8, 26 e 52 were of 41.7%, 47.2% and 47.2%, respectively. With NRI analysis, remission rates at weeks 8, 26 and 52 were of 41.7%, 41.7% and 27.8%, respectively. CONCLUSION: Adalimumab was effective in the treatment of moderate-to-severe ulcerative colitis. Clinical remission was observed in approximately 40% of the patients at weeks 8 and 26, and in almost a quarter of the patients after 1 year of follow up.

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RESUMO CONTEXTO: O adalimumabe é um anticorpo monoclonal, inibidor do TNF alfa, que tem eficácia comprovada na indução e manutenção da remissão na retocolite ulcerativa inespecífica moderada à severa. Há escassez de dados sobre o uso do adalimumabe na retocolite ulcerativa inespecífica em pacientes latino-americanos. OBJETIVO: Analisar as taxas de remissão clínica na indução e manutenção do tratamento da retocolite ulcerativa inespecífica com adalimumabe. MÉTODOS: Estudo observacional, multicêntrico e retrospectivo de uma série de casos de portadores de retocolite ulcerativa inespecífica moderada à grave que utilizaram adalimumabe. Variáveis analisadas: dados demográficos, uso prévio de infliximabe, medicações concomitantes, Classificação de Montreal, atividade da doença (escore parcial de Mayo) nas semanas 0, 8, 26 e 52, ou até o maior tempo de seguimento atingido. Remissão clínica foi definida como escore parcial de Mayo ≤2 e foi avaliada pelos métodos. Abordagem com base na observação mais recente (LOCF) e Imputação de não respondedores (NRI). RESULTADOS: Trinta e seis pacientes foram incluídos no estudo. Pela análise LOCF, as taxas de remissão nas semanas 8, 26 e 52 foram de 41,7%, 47,2% e 47,2%, respectivamente. Pela análise NRI, as taxas nas semanas 8, 26 e 52 foram de 41,7%, 41,7% e 27,8%, respectivamente. CONCLUSÃO: Adalimumabe foi eficaz no manejo da retocolite ulcerativa inespecífica moderada a grave. A remissão clínica foi observada em cerca de 40% dos pacientes nas semanas 8 e 26, e em cerca de 1/4 dos pacientes após 1 ano de seguimento.

http://ift.tt/2ynGjYY

SAFETY PROFILE OF ANTI-TNF THERAPY IN CROHN’S DISEASE MANAGEMENT: A BRAZILIAN SINGLE-CENTER DIRECT RETROSPECTIVE COMPARISON BETWEEN INFLIXIMAB AND ADALIMUMAB

ABSTRACT BACKGROUND: Infliximab and adalimumab are considered effective drugs in the management of Crohn's disease. However, due to significant immunossupression, they can cause important adverse events, mostly infections. OBJECTIVE: The aim of this study was to quantify and describe adverse events derived from adalimumab and infliximab use in Crohn's disease patients, and to compare the safety profile between these two agents. METHODS: This was an observational, single-center, longitudinal, retrospective study with Crohn's disease patients under infliximab or adalimumab therapy. Variables analyzed: demographic characteristics (including the Montreal classification), type of agent used, concomitant immunomodulators, presence and types of adverse events observed. Patients were allocated in two groups (infliximab and adalimumab) and had their adverse events accessed and subsequently compared. RESULTS: A total of 130 patients were included (68 in infliximab and 62 in adalimumab groups, respectively). The groups were fully homogeneous in all baseline characteristics, with a median follow-up of 47.21±36.52 months in the infliximab group and 47.79±35.09 in the adalimumab group (P=0.512). Adverse events were found in 43/68 (63.2%) and 40/62 (64.5%) in each group, respectively (P=0.879). There were no differences between the groups regarding infections (P=0.094) or treatment interruption (P=0.091). There were higher rates of infusion reactions in the infliximab group (P=0.016). Cephalea and injection site reactions were more prevalent in adalimumab patients. CONCLUSION: Adverse events were found in approximately two thirds of Crohn's disease patients under anti-TNF therapy, and there were no significant differences between infliximab or adalimumab.

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RESUMO CONTEXTO: A utilização de inibidores do fator de necrose tumoral (TNF) alfa no manejo da doença de Crohn é cada vez mais frequente. Tanto o infliximabe quanto o adalimumabe são considerados medicamentos efetivos no controle da doença. Entretanto, por serem potentes imunossupressores, podem causar efeitos adversos importantes, principalmente infecções. OBJETIVO: O objetivo primário deste estudo foi analisar a presença de efeitos adversos dos anti-TNFs em portadores de doença de Crohn, comparando-se infliximabe e adalimumabe e individualizando-se o perfil de segurança de cada droga. MÉTODOS: Estudo observacional, longitudinal e retrospectivo, que incluiu portadores de doença de Crohn com uso de infliximabe ou adalimumabe de uma coorte de pacientes tratados em um único centro. Analisou-se características demográficas (incluindo-se a classificação de Montreal), tipo de agente utilizado, presença e tipo dos eventos adversos observados, entre outras variáveis. Os pacientes foram alocados em dois grupos (infliximabe e adalimumabe) e tiveram os efeitos adversos anotados e posteriormente comparados. RESULTADOS: Um total de 130 pacientes foram incluídos (68 com infliximabe e 62 com adalimumabe). Os grupos foram homogêneos em todas as variáveis analisadas, com tempo de seguimento médio de 47,21±36,52 meses no grupo infliximabe e 47,79±35,09 no grupo adalimumabe (P=0,512). Efeitos adversos foram encontrados em 43/68 (63,2%) e 40/62 (64,5%) nos dois grupos, respectivamente (P=0,879). Não houve diferença entre os grupos em relação a infecções (P=0,094) ou interrupção do tratamento (P=0,091). Houve maiores índices de reações infusionais no grupo infliximabe (P=0,016). Cefaleia e reações no local das injeções foram mais frequentes no grupo adalimumabe. CONCLUSÃO: Efeitos adversos foram encontrados em cerca de dois terços dos pacientes com doença de Crohn em uso de anti-TNF, não havendo maiores diferenças em relação ao uso de infliximabe ou adalimumabe.

http://ift.tt/2zwPpnw

IMPORTANCE OF MEASURING LEVELS OF INFLIXIMAB IN PATIENTS TREATING INFLAMMATORY BOWEL DISEASE IN A BRAZILIAN COHORT

ABSTRACT BACKGROUND: Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases. In such pathologies, there is an increased production of alpha tumor necrosis factor (TNF-α). Patients, in whom the conventional immunosuppressant treatment fails, require the use of immunobiological therapy, such as anti-TNF-α, a monoclonal antibody. Infliximab is an anti-TNF-α drug, a chimerical immunoglobulin, with a murine component, which is responsible for the generation of immunogenicity against the drug and formation of anti-TNF-α antibodies. The presence of anti-drug antibodies may be responsible for adverse events and reduction of the drug's effectiveness. Patients with inflammatory bowel diseases undergoing therapy with biological medication, such as infliximab, can relapse overtime and this may not be translated into clinical symptoms. Thus, there is a need for a method to evaluate the efficacy of the drug, through the measurement of serum infliximab levels, as well as antibodies research. OBJECTIVE: This study aimed to measure serum infliximab levels and anti-infliximab antibodies in patients with inflammatory bowel diseases post-induction phase and during maintenance therapy, and describe the therapeutic modifications that took place based on the serum levels results. METHODS: It was a retrospective study, that included forty-five patients, with a total of 63 samples of infliximab measurement. RESULTS: Twenty-one patients had an adequate infliximab serum level, 31 had subtherapeutic levels and 11 had supratherapeutic levels. Seven patients had their medication suspended due to therapeutic failure or high levels of antibodies to infliximab. CONCLUSION: In conclusion, only a third of the patients had adequate infliximab levels and 36% presented with subtherapeutic levels at the end of the induction phase. Therapy optimization occurred based in about 46% of the samples results, demonstrating the importance of having this tool to help the clinical handling of patients with inflammatory bowel diseases ongoing biologic therapy.

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RESUMO CONTEÚDO: Doença de Crohn e retocolite ulcerativa são doenças inflamatórias intestinais crônicas. Nelas, ocorre aumento da produção de fator de necrose tumoral alfa (TNF-α). Pacientes que falham no tratamento convencional imunossupressor, requerem uso de terapia imunobio­lógica, que são anticorpos monoclonais, principalmente os anti-TNF-α. O infliximabe é uma droga anti-TNF-α, uma imunoglobulina quimérica, com componente murino. Este é responsável pela imunogenicidade da droga e a formação de anticorpos. Presença de anticorpos antidroga pode ser responsável pelos eventos adversos e redução da eficácia da droga. Pacientes com doenças inflamatórias intestinais, em terapia imunossupressora com medicação biológica como o infliximabe, podem ter recaída da doença e muitas vezes isso não se relaciona com a sintomatologia do paciente. Por isso há a necessidade de um método de avaliação do efeito da droga como a dosagem do nivel sérico do infliximabe, bem como da pesquisa de anticorpos. OBJETIVO: O estudo tem como objetivo conhecer os níveis séricos do infliximabe e dos anticorpos anti-infliximabe em pacientes com doença inflamatória intestinal em terapia de manutenção ou pós-indução e descrever as condutas terapêuticas que foram modificadas em função dos níveis séricos de infliximabe e anticorpos para infliximabe. MÉTODOS: Trata-se de estudo restrospectivo, com análise da dosagem dos níveis séricos de infliximabe e anticorpos para Infliximabe. Foram incluídos 45 pacientes, num total de 63 coletas de dosagem de infliximabe. RESULTADOS: Vinte e um paciente estavam com o nível sérico de infliximabe adequado, níveis subterapêuticos em 31 pacientes e níveis supraterapêuticos em 11 pacientes. Sete pacientes tiveram a medicação suspensa por falha terapêutica ou altos níveis de anticorpos para infliximabe. CONCLUSÃO: Apenas um terço dos pacientes apresentavam níveis adequados de infliximabe e 36% dos pacientes apresentavam níveis subterapêuticos ao término da indução. Em cerca de 46% das amostras a conduta adotada se baseou nos níveis de infliximabe e anticorpos para infliximabe demonstrando a importância de se ter esta ferramenta para auxílio no manejo clínico dos pacientes portadores de doenças inflamatórias intestinais em terapia biológica.

http://ift.tt/2ymUOMw

ALCOHOL DEPENDENCE IN GASTROENTEROLOGY OUTPATIENT ON A PUBLIC HOSPITAL

ABSTRACT BACKGROUND: Alcoholism and alcoholic liver disease are both considered worldwide health problems. OBJECTIVE: The prevalence of alcohol dependence, the associated risk factors and the concordance between the prevalence found and the data collected during the medical visit were evaluated. METHODS: A prospective study evaluating gastroenterology outpatients at a public tertiary hospital was conducted. Two specific questionnaires to assess alcohol dependence were applied: Cut down, Annoyed by criticism, Guilty, Eye-opener (CAGE) and The Alcohol Use Disorder Identification Test (AUDIT). Data on comorbidities, clinical diagnosis and assessment of alcohol consumption by the attending physician were collected through medical records. RESULTS: One hundred and seventy eight patients were interviewed, of which 119 (66.9%) were women and 59 (33.1%) were men, with mean age of 57 years. Thirty-three (18.5%) of the 178 patients were considered alcohol-dependent by the CAGE questionnaire. Thirteen (7.3%) patients scored 8 points or more on the AUDIT questionnaire. The agreement (kappa) between these questionnaires was 0.37 (P<0.001). The most consumed drink was beer. The median daily consumption of dependent patients was 64 g. None of the patients were undergoing treatment in a specific treatment center, and 14/33 (42.4%) patients considered themselves alcoholics. Only in 17/33 (51.5%) there was information about alcoholism in their respective medical records. In the bivariate analysis, male gender (P<0.001), onset of alcohol consumption before the age of 15 (P=0.003), daily alcohol consumption in the last 12 months (P<0.001) and smoking (P<0.001) were identified as risk factors. After multivariate analysis, only male gender (P=0.009) and smoking (P=0.001) were associated with alcoholism. CONCLUSION: The present study demonstrated a high prevalence of alcohol dependence in the gastroenterology outpatient clinic, being predominantly associated with male gender and smoking. It is worth noting that approximately half of the dependents were not identified as such in the medical appointment, evidencing the importance of the diagnostic approach in the alcoholic outpatient.

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RESUMO CONTEXTO: O alcoolismo e a doença hepática alcoólica são considerados problemas de saúde de relevância mundial. OBJETIVO: Avaliar a prevalência de dependência alcoólica, os fatores de risco associados e a concordância entre a prevalência encontrada e os dados coletados na consulta médica. MÉTODOS: Estudo prospectivo, avaliando pacientes de ambulatório de gastroenterologia de um hospital terciário, composto por um questionário geral e dois específicos para avaliar a dependência de álcool: Cut down, Annoyed by criticism, Guilty, Eye-openner (CAGE) e o Alcohol Use Disorder Identification Test (AUDIT). Dados sobre comorbidades, diagnóstico clínico e aferição sobre o consumo de álcool pelo médico assistente, foram coletados através de revisão de prontuário. RESULTADOS: Foram entrevistados 178 pacientes, 119 (66,9%) mulheres e 59 (33,1%) homens com média de idade de 57 anos. Trinta e três (18,5%) dos 178 pacientes foram considerados dependentes alcoólicos pelo questionário CAGE. Treze (7,3%) pacientes fizeram oito ou mais pontos no questionário AUDIT. A concordância (kappa) entre os testes foi 0,37 (P<0,001). A bebida mais consumida foi a cerveja. A mediana de consumo diário dos pacientes dependentes foi de 64 g, nenhum destes estava em tratamento em centro específico, 14/33 (42,4%) pacientes seconsideravam alcoolistas e em apenas 17/33 (51,5%) havia registro no prontuário sobre alcoolismo. Na análise bivariada, gênero masculino (P<0,001), início de consumo de álcool antes dos 15 anos (P=0,003), consumo diário de bebida alcoólica nos últimos 12 meses (P<0,001) e tabagismo (P<0,001) foram identificados como fatores de risco. Após análise multivariada, permaneceram associados: gênero masculino (P=0,009) e tabagismo (P=0,001). CONCLUSÃO: O presente estudo demonstrou alta prevalência de dependência alcoólica no ambulatório geral de gastroenterologia, estando associada predominantemente ao gênero masculino e ao tabagismo. Ressalta-se que aproximadamente metade dos dependentes não foram identificados como tal na consulta médica, evidenciando a importância da abordagem diagnóstica no paciente alcoolista.

http://ift.tt/2zxCiCs

PSYCHOMETRIC PROPERTY OF FATIGUE SEVERITY SCALE AND CORRELATION WITH DEPRESSION AND QUALITY OF LIFE IN CIRRHOTICS

ABSTRACT BACKGROUND: Fatigue is a common complaint in cirrhotic patients and may be considered a debilitating symptom with negative impact on quality of life. Research on its etiology and treatment has been hampered by the lack of relevant and reproducible measures of fatigue. OBJECTIVE: To evaluate the psychometric properties of the Fatigue Severity Scale (FSS) in cirrhotic patients and to correlate with depressive symptomatology and quality of life. METHODS: Cross-sectional study with a convenience sample of 106 cirrhotic patients, aged between 18 and 70 years, both genders, literate, pre and post liver transplantation in outpatient follow-up. Internal consistency, reproducibility, discriminant validity, criterion validity, construct validity, responsiveness criterion, depressive symptomatology and quality of life were evaluated through questionnaires between January and October 2015. RESULTS: The mean age was 54.75±9.9 years, 65.1% male and 32.1% of the sample had cirrhosis due to hepatitis C virus. The mean FSS score was 4.74±1.64. Cronbach's alpha was 0.93, and the Intraclass Correlation Coefficient was 0.905 (95% CI: 0.813-0.952). For discriminant validity, FSS differentiated scores from different groups (P=0.009) and presented a correlation with the Modified Fatigue Impact Scale (r=0.606, P=0.002). FSS correlated significantly and positively with depressive symptomatology and correlated negatively with the SF-36 domains for construct validity. For responsiveness, no significant changes were observed in the fatigue scores in the pre and post-liver transplantation periods (P=0.327). CONCLUSION: FSS showed good psychometric performance in the evaluation of fatigue in patients with cirrhosis. Fatigue presented a strong correlation with depressive symptomatology and quality of life.

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RESUMO CONTEXTO: A fadiga é uma queixa comum em pacientes cirróticos e pode ser considerada um sintoma debilitante com impacto negativo na qualidade de vida. A investigação sobre a sua etiologia e tratamento tem sido dificultada pela falta de medidas relevantes e reprodutíveis da fadiga. OBJETIVO: Avaliar as propriedades psicométricas da Escala de Gravidade da Fadiga (FSS) em pacientes cirróticos e correlacionar com sintomatologia depressiva e qualidade de vida. MÉTODOS: Estudo transversal com amostra de conveniência de 106 pacientes cirróticos, com idade entre 18 e 70 anos, ambos os sexos, alfabetizados, pré e pós-transplante hepático em acompanhamento ambulatorial. Foram avaliados: consistência interna, reprodutibilidade, validade discriminante, validade de critério, validade de construto, critério de responsividade, sintomatologia depressiva e qualidade de vida através de questionários, entre janeiro e outubro de 2015. RESULTADOS: A média de idade foi 54,75±9,9 anos, 65,1% do sexo masculino e 32,1% da amostra apresentava cirrose pelo vírus da hepatite C. O escore médio no FSS foi de 4,74±1,64. O alfa de Cronbach foi de 0,93, e o coeficiente de correlação intraclasse foi de 0,905 (IC 95%: 0,813-0,952). Para validade discriminante, o FSS diferenciou escores de grupos distintos (P=0,009) e apresentou correlação com a Escala de Impacto de Fadiga Modificada (r=0,606, P=0,002). O FSS se correlacionou significativamente e positivamente com sintomatologia depressiva e, negativamente com os domínios SF-36 para a validade de construto. Para responsividade, não foram observadas alterações significativas nos escores de fadiga nos períodos de transplante pré e pós-fígado (P=0,327). CONCLUSÃO: O FSS mostrou bom desempenho psicométrico na avaliação da fadiga em pacientes com cirrose. A fadiga apresentou forte correlação com sintomatologia depressiva e qualidade de vida.

http://ift.tt/2ylJyA1

VARICEAL BLEEDING: UPDATE OF RECOMMENDATIONS FROM THE BRAZILIAN ASSOCIATION OF HEPATOLOGY

ABSTRACT Since the publication of the Brazilian Association of Hepatology recommendations for the prevention and treatment of variceal bleeding in 2010, new evidence-based data were reported in the literature. This has changed our current management for portal hypertension. This review updates the previous recommendations. It takes the new prognostic staging of cirrhosis into account allowing tailored treatment for advanced fibrosis, compensated or decompensated cirrhosis. An organizing panel of five experts reviewed all recommendations according to available data, which were subsequently scrutinized by all members of the Brazilian Association of Hepatology using a web-based approach. The accepted recommendations are presented in this manuscript.

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RESUMO Desde a publicação em 2010 das recomendações da Sociedade Brasileira de Hepatologia sobre a prevenção e tratamento do sangramento varicoso, novos dados baseados em evidências científicas foram publicados na literatura, mudando o manejo atual da hipertensão portal. O objetivo deste manuscrito foi atualizar as recomendações prévias da SBH, levando em consideração o novo conceito de estadiamento prognóstico da cirrose individualizando seu manejo de acordo com a presença de fibrose avançada, cirrose compensada ou descompensada. Um grupo de cinco experts revisou todas as recomendações de acordo com os dados publicados na literatura e elaborou um manuscrito submetido subsequentemente à apreciação e revisão de todos os membros da Sociedade Brasileira de Hepatologia via homepage da sociedade. As recomendações finais revisadas foram condensadas no presente documento.

http://ift.tt/2zwPh7w

Hepatitis B status in hemodialysis patients

ABSTRACT BACKGROUND: Patients on chronic dialysis present a high prevalence of hepatitis B virus infection. Despite infection-control practices, surveillance of serological markers, and hepatitis B vaccination, there are still outbreaks of the disease in dialysis centers. OBJECTIVE: This study aims to assess the serologic and vaccination status for hepatitis B in hemodialysis patients. METHODS: This cross-sectional study assessed serologic markers and hepatitis B vaccination status of chronic kidney disease patients on regular dialysis program in São Carlos, SP, Brazil. Patients without information about hepatitis B status (anti-HBc, HBsAg and anti-HBs) were referred for testing. Individuals with uncertain or incomplete immunization status and without serological conversion (anti-HBs <10mIU/mL) were referred to vaccination, with adverse effects monitored. RESULTS: The study included 130 from a total of 181 dialysis patients. The majority were male (63.8%), mean age 53.9 years. All patients were already screened and negative for HBsAg, and 73.8% were vaccinated against hepatitis B (59.2% complete and 14.6% incomplete schedule), with a seroconversion rate of 75.3%. Only 11 (8.5%) patients had prior dosage of anti-HBc (negative). Among the 47 patients referred for anti-HBc testing, four were anti-HBc positive and one indeterminate. Of the total of patients referred to immunization, 34 have actually received HBV vaccine; among them five had mild adverse effects. CONCLUSION: Despite the benefit of dosing of anti-HBc and anti-HBs before admission to dialysis, economic constraints have reduced the screening to only HBsAg. Since occult HBV infection has already been demonstrated in hemodialysis patients, the measure of anti-HBc should be encouraged.

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RESUMO CONTEXTO: Pacientes cronicamente em diálise apresentam alta prevalência de infecção por vírus da hepatite B. Apesar de práticas de controle de infecção, vigilância de marcadores sorológicos e vacinação contra a hepatite B, ainda há surtos da doença em centros de diálise. OBJETIVO: Este estudo tem como objetivo avaliar o estado sorológico e a vacinação contra hepatite B em pacientes em hemodiálise. MÉTODOS: Estudo transversal avaliando marcadores sorológicos e vacinação contra a hepatite B em pacientes com doença renal crônica em programa regular de hemodiálise em São Carlos, SP, Brasil. Pacientes sem marcadores sorológicos para hepatite B disponíveis (anti-HBc, HBsAg e anti-HBs) foram encaminhados para testagem. Em caso de situação vacinal desconhecida, incompleta ou sem resposta vacinal (anti-HBs <10mIU/mL), os pacientes foram encaminhados para vacinação, sendo os efeitos adversos monitorados. RESULTADOS: O estudo incluiu 130 de um total de 181 pacientes em diálise. A maioria era do sexo masculino (63,8%), com idade média de 53,9 anos. Todos os pacientes já haviam sido rastreados e eram negativos para HBsAg, e 73,8% foram vacinados contra a hepatite B (59,2% esquema completo e 14,6% esquema incompleto), com uma taxa de soroconversão de 75,3%. Apenas 11 (8,5%) pacientes dispunham de dosagem prévia de anti-HBc (negativo). Entre os 47 pacientes encaminhados para testagem anti-HBc, quatro eram anti-HBc reagentes e um indeterminado. Do total de pacientes encaminhados à imunização, 34 receberam efetivamente a vacina contra o HBV; entre eles, cinco tiveram efeitos adversos leves. CONCLUSÃO: Apesar do benefício da dosagem de anti-HBc e anti-HBs antes da admissão à diálise, restrições econômicas reduziram o rastreio apenas à dosagem de HBsAg. Como a infecção oculta por HBV já foi demonstrada em pacientes em hemodiálise, a dosagem de anti-HBc deve ser incentivada.

http://ift.tt/2yonBjT

IVIG-Associated Maternal Pancytopenia during Treatment for Neonatal Alloimmune Thrombocytopenia

AJP Rep 2017; 07: e197-e200
DOI: 10.1055/s-0037-1607055

Background Treatment for neonatal alloimmune thrombocytopenia (NAIT) primarily involves maternal administration of intravenous immunoglobulin (IVIG) therapy and prednisone according to protocols based on risk stratification. While IVIG is generally well tolerated, hematologic side effects are a potential complication. Case We present the successful management of a rare complication of maternal pancytopenia following standard IVIG treatment. Diagnosis was made during routine obstetric exams. Management included reducing IVIG dosage and adding daily prednisone. Additionally, infusion Lots possibly associated with the event were identified and avoided. Interventions resulted in the resolution of pancytopenia and the birth of a healthy infant without thrombocytopenia. Conclusion Pancytopenia is a rare complication of IVIG treatment in women with pregnancies complicated by NAIT. Serial complete blood counts at the time of treatment would allow for early detection and timely management of the patient. Additionally, limiting the number of infusion Lots may decrease the chance of the described complications.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
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Microorganisms Identified in the Maternal Bladder: Discovery of the Maternal Bladder Microbiota

AJP Rep 2017; 07: e188-e196
DOI: 10.1055/s-0037-1606860

Objective The objective of this study was to characterize the bladder microbiota in pregnancy. Methods A prospective observational study of 51 pregnant women, admitted to a tertiary care hospital, who underwent straight catheterization urine collection or transurethral Foley catheter placement. 16S rRNA gene sequencing and enhanced quantitative urine culture assessed the maternal bladder microbiota with comparisons made to standard urine culture results. Results Enhanced quantitative urine culture and 16S rRNA gene sequencing detected bacteria in the majority of participants. Lactobacillus and Gardnerella were the most commonly detected microbes. In contrast, standard urine culture had a 100% false-negative rate and failed to detect several known or emerging urinary pathogens. Conclusion There are live bacteria in the bladders of most pregnant women. This challenges the definition of asymptomatic bacteriuria.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
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Neonatal Graves' Disease with Maternal Hypothyroidism

AJP Rep 2017; 07: e181-e184
DOI: 10.1055/s-0037-1606365

Neonatal Graves' disease presenting as conjugated hyperbilirubinemia is a diagnostic challenge because the differential includes a gamut of liver and systemic diseases. We present a unique case of neonatal Graves' disease in a premature infant with conjugated hyperbilirubinemia born to a mother with hypothyroidism during pregnancy and remote history of Graves' disease. Infant was treated with a combination of methimazole, propranolol, and potassium iodide for 4 weeks. Thyroid function improved after 8 weeks of treatment with full recovery of thyroid function, disappearance of thyroid-stimulating antibodies, and resolution of failure to thrive and conjugated hyperbilirubinemia. This case provides several clinical vignettes as it is a rare, severe, presentation of an uncommon neonatal disease, signs, symptoms, and clinical history presented a diagnostic challenge for neonatologists and endocrinologists, normal newborn screen was misleading, and yet timely treatment led to a full recovery.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  open access Full text

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A novel germline mutation in CDK4 codon 24 associated to familial melanoma

http://ift.tt/2zwcXsV

Lignin degradation: microorganisms, enzymes involved, genomes analysis and evolution

Abstract

Extensive research efforts have been dedicated to describing degradation of wood, which is a complex process; hence, microorganisms have evolved different enzymatic and non-enzymatic strategies to utilize this plentiful plant material. This review describes a number of fungal and bacterial organisms which have developed both competitive and mutualistic strategies for the decomposition of wood and to thrive in different ecological niches. Through the analysis of the enzymatic machinery engaged in wood degradation, it was possible to elucidate different strategies of wood decomposition which often depend on ecological niches inhabited by given organism. Moreover, a detailed description of low molecular weight compounds is presented, which gives these organisms not only an advantage in wood degradation processes, but seems rather to be a new evolutionatory alternative to enzymatic combustion. Through analysis of genomics and secretomic data, it was possible to underline the probable importance of certain wood-degrading enzymes produced by different fungal organisms, potentially giving them advantage in their ecological niches. The paper highlights different fungal strategies of wood degradation, which possibly correlates to the number of genes coding for secretory enzymes. Furthermore, investigation of the evolution of wood-degrading organisms has been described.

http://ift.tt/2mfbSTp

Light-controlled motility in prokaryotes and the problem of directional light perception

Abstract

The natural light environment is important to many prokaryotes. Most obviously, phototrophic prokaryotes need to acclimate their photosynthetic apparatus to the prevailing light conditions, and such acclimation is frequently complemented by motility to enable cells to relocate in search of more favorable illumination conditions. Non-phototrophic prokaryotes may also seek to avoid light at damaging intensities and wavelengths, and many prokaryotes with diverse lifestyles could potentially exploit light signals as a rich source of information about their surroundings and a cue for acclimation and behavior. Here we discuss our current understanding of the ways in which bacteria can perceive the intensity, wavelength and direction of illumination, and the signal transduction networks that link light perception to the control of motile behavior. We discuss the problems of light perception at the prokaryotic scale, and the challenge of directional light perception in small bacterial cells. We explain the peculiarities and the common features of light-controlled motility systems in prokaryotes as diverse as cyanobacteria, purple photosynthetic bacteria, chemoheterotrophic bacteria and haloarchaea.

http://ift.tt/2yMJePk

The role of toxins in Clostridium difficile infection

Abstract

Clostridium difficile is a bacterial pathogen that is the leading cause of nosocomial antibiotic-associated diarrhea and pseudomembranous colitis worldwide. The incidence, severity, mortality and healthcare costs associated with C. difficile infection (CDI) are rising, making C. difficile a major threat to public health. Traditional treatments for CDI involve use of antibiotics such as metronidazole and vancomycin, but disease recurrence occurs in about 30% of patients, highlighting the need for new therapies. The pathogenesis of C. difficile is primarily mediated by the actions of two large clostridial glucosylating toxins, toxin A (TcdA) and toxin B (TcdB). Some strains produce a third toxin, the binary toxin C. difficile transferase, which can also contribute to C. difficile virulence and disease. These toxins act on the colonic epithelium and immune cells and induce a complex cascade of cellular events that result in fluid secretion, inflammation and tissue damage, which are the hallmark features of the disease. In this review, we summarize our current understanding of the structure and mechanism of action of the C. difficile toxins and their role in disease.

http://ift.tt/2mbxYpx

Repetitive sequences in malaria parasite proteins

Abstract

Five species of parasite cause malaria in humans with the most severe disease caused by Plasmodium falciparum. Many of the proteins encoded in the P. falciparum genome are unusually enriched in repetitive low-complexity sequences containing a limited repertoire of amino acids. These repetitive sequences expand and contract dynamically and are among the most rapidly changing sequences in the genome. The simplest repetitive sequences consist of single amino acid repeats such as poly-asparagine tracts that are found in approximately 25% of P. falciparum proteins. More complex repeats of two or more amino acids are also common in diverse parasite protein families. There is no universal explanation for the occurrence of repetitive sequences and it is possible that many confer no function to the encoded protein and no selective advantage or disadvantage to the parasite. However, there are increasing numbers of examples where repetitive sequences are important for parasite protein function. We discuss the diverse roles of low-complexity repetitive sequences throughout the parasite life cycle, from mediating protein–protein interactions to enabling the parasite to evade the host immune system.

http://ift.tt/2yN1rw5

A visual review of the human pathogen Streptococcus pneumoniae

Abstract

Being the principal causative agent of bacterial pneumonia, otitis media, meningitis and septicemia, the bacterium Streptococcus pneumoniae is a major global health problem. To highlight the molecular basis of this problem, we have portrayed essential biological processes of the pneumococcal life cycle in eight watercolor paintings. The paintings are done to a consistent nanometer scale based on currently available data from structural biology and proteomics. In this review article, the paintings are used to provide a visual review of protein synthesis, carbohydrate metabolism, cell wall synthesis, cell division, teichoic acid synthesis, virulence, transformation and pilus synthesis based on the available scientific literature within the field of pneumococcal biology. Visualization of the molecular details of these processes reveals several scientific questions about how molecular components of the pneumococcal cell are organized to allow biological function to take place. By the presentation of this visual review, we intend to stimulate scientific discussion, aid in the generation of scientific hypotheses and increase public awareness. A narrated video describing the biological processes in the context of a whole-cell illustration accompany this article.

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Beyond the bulk: disclosing the life of single microbial cells

Abstract

Microbial single cell analysis has led to discoveries that are beyond what can be resolved with population-based studies. It provides a pristine view of the mechanisms that organize cellular physiology, unbiased by population heterogeneity or uncontrollable environmental impacts. A holistic description of cellular functions at the single cell level requires analytical concepts beyond the miniaturization of existing technologies, defined but uncontrolled by the biological system itself. This review provides an overview of the latest advances in single cell technologies and demonstrates their potential. Opportunities and limitations of single cell microbiology are discussed using selected application-related examples.

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Diversity and regulation of intrinsic β-lactamases from non-fermenting and other Gram-negative opportunistic pathogens

Abstract

This review deeply addresses for the first time the diversity, regulation and mechanisms leading to mutational overexpression of intrinsic β-lactamases from non-fermenting and other non-Enterobacteriaceae Gram-negative opportunistic pathogens. After a general overview of the intrinsic β-lactamases described so far in these microorganisms, including circa. 60 species and 100 different enzymes, we review the wide array of regulatory pathways of these β-lactamases. They include diverse LysR-type regulators, which control the expression of β-lactamases from relevant nosocomial pathogens such as Pseudomonas aeruginosa or Stenothrophomonas maltophilia or two-component regulators, with special relevance in Aeromonas spp., along with other pathways. Likewise, the multiple mutational mechanisms leading to β-lactamase overexpression and β-lactam resistance development, including AmpD (N-acetyl-muramyl-L-alanine amidase), DacB (PBP4), MrcA (PPBP1A) and other PBPs, BlrAB (two-component regulator) or several lytic transglycosylases among others, are also described. Moreover, we address the growing evidence of a major interplay between β-lactamase regulation, peptidoglycan metabolism and virulence. Finally, we analyse recent works showing that blocking of peptidoglycan recycling (such as inhibition of NagZ or AmpG) might be useful to prevent and revert β-lactam resistance. Altogether, the provided information and the identified gaps should be valuable for guiding future strategies for combating multidrug-resistant Gram-negative pathogens.

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Strategies and ecological roles of algicidal bacteria

Abstract

In both freshwater and marine ecosystems, phytoplankton are the most dominant primary producers, contributing substantially to aquatic food webs. Algicidal bacteria that can associate to microalgae from the phytoplankton have the capability to control the proliferation and even to lyse them. These bacteria thus play an important role in shaping species composition in pelagic environments. In this review, we discuss and categorise strategies used by algicidal bacteria for the attack on microalgae. We highlight the complex regulation of algicidal activity and defence responses that govern alga–bacteria interactions. We also discuss how algicidal bacteria impact algal physiology and metabolism and survey the existing algicidal metabolites and enzymes. The review illustrates that the ecological role of algicidal bacteria is not yet fully understood and critically discusses the challenges in obtaining ecologically relevant data.

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Functional insights into pathogen biology from 3D electron microscopy

Abstract

In recent years, novel imaging approaches revolutionised our understanding of the cellular and molecular biology of microorganisms. These include advances in fluorescent probes, dynamic live cell imaging, superresolution light and electron microscopy. Currently, a major transition in the experimental approach shifts electron microscopy studies from a complementary technique to a method of choice for structural and functional analysis. Here we review functional insights into the molecular architecture of viruses, bacteria and parasites as well as interactions with their respective host cells gained from studies using cryogenic electron tomography and related methodologies.

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Transmission as a basic process in microbial biology. Lwoff Award Prize Lecture

Abstract

Transmission is a basic process in biology and evolution, as it communicates different biological entities within and across hierarchical levels (from genes to holobionts) both in time and space. Vertical descent, replication, is transmission of information across generations (in the time dimension), and horizontal descent is transmission of information across compartments (in the space dimension). Transmission is essentially a communication process that can be studied by analogy of the classic information theory, based on 'emitters', 'messages' and 'receivers'. The analogy can be easily extended to the triad 'emigration', 'migration' and 'immigration'. A number of causes (forces) determine the emission, and another set of causes (energies) assures the reception. The message in fact is essentially constituted by 'meaningful' biological entities. A DNA sequence, a cell and a population have a semiotic dimension, are 'signs' that are eventually recognized (decoded) and integrated by receiver biological entities. In cis-acting or unenclosed transmission, the emitters and receivers correspond to separated entities of the same hierarchical level; in trans-acting or embedded transmission, the information flows between different, but frequently nested, hierarchical levels. The result (as in introgressive events) is constantly producing innovation and feeding natural selection, influencing also the evolution of transmission processes. This review is based on the concepts presented at the André Lwoff Award Lecture in the FEMS Microbiology Congress in Maastricht in 2015.

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