Miracle-dz/UniFAR-FTUs huggingface dataset:
Small bowel villous atrophy: celiac disease and beyond

ABSTRACT Introduction: Small bowel villous atrophy can represent a diagnostic challenge for gastroenterologists and pathologists. In Western countries small bowel atrophy and mild non-atrophic alterations are frequently caused by celiac disease. However, other pathology can mimic celiac disease microscopically, widening the differential diagnosis. The several novelties on this topic and the introduction of the device-assisted enteroscopy in the diagnostic flowchart make an update of the literature necessary. Areas covered: In this review, a description of the different clinical scenarios when facing with small bowel mucosal damage, particularly small bowel atrophy, is described. The published literature on this subject has been summarized and reviewed. Expert commentary: When an intestinal mucosal alteration is histologically demonstrated, the pathology report forms part of a more complex workup including serological data, clinical presentation and clinical history. A multidisciplinary team, including pathologists and enteroscopy-devoted endoscopists, is frequently required to manage patients with small bowel alterations, especially in cases of severe malabsorption syndrome.
Neuroendocrine, goblet cell and mixed adeno-neuroendocrine tumours of the appendix: updates, clinical applications and the future

ABSTRACT Introduction: Appendiceal neuroendocrine neoplasms are rare, clinically challenging tumours that are typically incidentally diagnosed, have a poorly understood biology and have controversy surrounding their management. Most are adequately treated with appendectomy, and although distant metastases are rare, the threat of disease dissemination remains and current guidelines possess poor accuracy in terms of selecting patients requiring more extensive surgery, i.e. oncological right-hemicolectomy. Areas covered: In this article, we discuss the presentation and diagnostic work-up of patients with appendiceal neuroendocrine neoplasms, and also examine the evidence base for existing management strategies. We highlight controversies within the management of these tumours, and anticipate avenues for further progress. Although no longer classified as neuroendocrine neoplasms, we also discuss two related forms of tumours with neuroendocrine features – goblet cell cancers and mixed adeno-neuroendocrine carcinomas. Expert commentary: Existing guidelines for the treatment of appendiceal neuroendocrine neoplasms are derived from a limited evidence base and are unable to accurately predict which patients require extensive attempts at surgical disease control. Future advances in the field of improved patient selection for more extensive surgery may be possible with multi-factorial tumour assessment integrating morphological and molecular analyses.
Biomarkers as a diagnostic tool for irritable bowel syndrome: where are we?

ABSTRACT Introduction: Irritable bowel syndrome (IBS) is a common condition in clinical practice. There are currently no objective tests to rule in the disease, but rather tests to rule out other diseases. Biomarkers in IBS may provide the tools needed for diagnosis, prognosis and therapy. These include identification of differences in microbial composition, immune activation, bile acid composition, colonic transit, and alteration in sensation in subgroups of IBS patients. Areas covered: Studies included in our review were chosen based on a PubMed search for ‘biomarkers’ and ‘IBS’. We have reviewed the literature on biomarkers to appraise their accuracy, validity and whether they are actionable. We have not covered genetic associations as biomarkers in this review. Expert commentary: There is significant promise in the usefulness of biomarkers for IBS. The most promising actionable biomarkers are markers of changes in bile acid balance, such as elevated bile acid in the stool, and altered colonic transit. However, there is also potential for microbial studies and mucosal proteases as future actionable biomarkers.
Assessment of Myocardial Function and Injury by Echocardiography and Cardiac Biomarkers in African Children With Severe Plasmodium falciparum Malaria*

Objectives: Perturbed hemodynamic function complicates severe malaria. The Fluid Expansion as Supportive Therapy trial demonstrated that fluid resuscitation, involving children with severe malaria, was associated with increased mortality, primarily due to cardiovascular collapse, suggesting that myocardial dysfunction may have a role. The aim of this study was to characterize cardiac function in children with severe malaria. Design: A prospective observational study with clinical, laboratory, and echocardiographic data collected at presentation (T0) and 24 hours (T1) in children with severe malaria. Cardiac index and ejection fraction were calculated at T0 and T1. Cardiac troponin I and brain natriuretic peptide were measured at T0. We compared clinical and echocardiographic variables in children with and without severe malarial anemia (hemoglobin < 5 mg/dL) at T0 and T1. Setting: Mbale Regional Referral Hospital. Patients: Children 3 months to 12 years old with severe falciparum malaria. Interventions: Usual care. Measurements and Main Results: We enrolled 104 children, median age 23.3 months, including 61 children with severe malarial anemia. Cardiac troponin I levels were elevated (> 0.1 ng/mL) in n equals to 50, (48%), and median brain natriuretic peptide was within normal range (69.1 pg/mL; interquartile range, 48.4–90.8). At T0, median Cardiac index was significantly higher in the severe malarial anemia versus nonsevere malarial anemia group (6.89 vs 5.28 L/min/m2) (p = 0.001), which normalized in both groups at T1 (5.60 vs 5.13 L/min/m2) (p = 0.452). Cardiac index negatively correlated with hemoglobin, r equals to –0.380 (p < 0.001). Four patients (3.8%) had evidence of depressed cardiac systolic function (ejection fraction < 45%). Overall, six children died, none developed pulmonary edema, biventricular failure, or required diuretic treatment. Conclusions: Elevation of cardiac index, due to increased stroke volume, in severe malaria is a physiologic response to circulatory compromise and correlates with anemia. Following whole blood transfusion and antimalarial therapy, cardiac index in severe malarial anemia returns to normal. The majority (> 96%) of children with severe malaria have preserved myocardial systolic function. Although there is evidence for myocardial injury (elevated cardiac troponin I), this does not correlate with cardiac dysfunction.
The Pediatric Index of Mortality as a Trigger Tool for the Detection of Serious Errors and Adverse Events*

Objectives: To test the hypothesis that patients who die in a PICU despite a low predicted mortality at PICU admission are affected by serious errors and adverse events. Design: Retrospective cross-sectional review of medical records for serious errors and adverse events. Setting: Tertiary interdisciplinary neonatal PICU. Patients: All admissions to our PICU who died despite a low expected mortality (Pediatric Index of Mortality) of less than 10% (trigger-positive admissions). They were compared with a random sample of 100 PICU admissions with a Pediatric Index of Mortality of less than 10% who survived (trigger-negative admissions). Interventions: None. Measurements and Main Results: There were 7,383 admissions (91%) with a Pediatric Index of Mortality 2 below 10%. Seventy-two trigger-positive admissions and 100 trigger-negative admissions met the criteria for detailed chart review. Forty-five serious errors and adverse events were identified, 0.47 per trigger-positive admission and 0.11 per trigger-negative admission (p < 0.001). Nineteen serious errors and adverse events (42%) were related to clinical sepsis acquired during the PICU stay, 17 (89%) in trigger-positive admissions and two (11%) in trigger-negative admissions (p < 0.001). A further 18 serious errors and adverse events (40%) were intervention related, nine (50%) in trigger-positive admissions and nine (50%) in trigger-negative admissions (p = 0.46). Eight serious errors and adverse events (18%) were associated with medication use, all of which occurred in trigger-positive admissions (p = 0.001). The median (interquartile range) age for admissions with and without serious errors and adverse events was 0.3 months (0.0–4.6 mo) and 7.4 months (0.4–58.4 mo) (p < 0.001), and their median (interquartile range) duration of invasive ventilation was 140 hours (50–451 hr) and 2 hours (0–41 hr) (p < 0.001), respectively. Conclusions: The records of PICU patients with a low expected mortality at admission and death in PICU should be reviewed routinely and/or discussed at morbidity and mortality meetings. These patients may have experienced more in-hospital safety-related events compared with PICU patients with a low Pediatric Index of Mortality who survived. Such adverse events may be amenable to system changes, thus improving patient care.
Anticorpo contra o vírus C da hepatite em pacientes sob programa de hemodiálise em Salvador, BA, Brasil

Racional - A prevalencia da infeccao pelo virus da hepatite C em pacientes sob programa de hemodialise tem sido amplamente variavel. Objetivos ¾ Determinar a prevalencia do anticorpo contra o virus C da hepatite (anti-VHC) em pacientes sob hemodialise em Salvador, BA e sua associacao com transfusao de sangue, duracao de hemodialise e elevacao de alaninoaminotransferase. Metodos - Durante um periodo de 17 meses, foram avaliados todos os pacientes em programa de hemodialise, totalizando 395 individuos, que responderam a questionario e forneceram soro para analise laboratorial (alaninoaminotransferase serica e anti-VCH pelo ELISA II com confirmacao pelo Immunoblotting (RIBA III). Resultados - O anti-VHC foi positivo em 23,8% (94/395). A presenca de transfusao mostrou associacao com o anti-VHC e quanto maior o numero de transfusoes, mais frequente o anti-VHC. Dos pacientes que nunca foram transfundidos, 12,5% (6/48) foram anti-VHC positivos. A duracao do tratamento dialitico foi de 53,44 ± 36,45 meses no grupo anti-VHC positivo e de 22,10 ± 22,75 meses no grupo negativo. A elevacao de alaninoaminotransferase foi mais frequente no grupo positivo para o anti-VHC. A positividade para as fracoes do RIBA III foi de 79,8%, 100%, 80,9% e 52,1% para o c100-3, c33, c22 e NS5, respectivamente. O anti-NS5 foi ainda menos frequente no grupo com alaninoaminotransferase elevada. Conclusoes - A prevalencia do anti-VHC em pacientes sob hemodialise cronica de Salvador, BA e elevada e esta associada com transfusao de sangue, maior duracao de tratamento dialitico e elevacao de alaninoaminotransferase.
Effect of Progressive Muscle Relaxation Therapy on Stress and Anxiety of Patients from Traffic Accidents

Purpose: This study was to examine the effect of Progressive Muscle Relaxation Therapy on stress and anxiety of traffic accident patients. Method: Subjects of this study were 39 hospitalized patients at orthopedic ward. An experimental group received Progressive Muscle Relaxation Therapy five times each week for four weeks beginning from the fourth day following the injury, whereas a control group received regular care. A tape of Jacobson`s Progressive Muscle Relaxation Therapy recorded in Korean by the Rheumatoid Health Academic Society was used for relaxation therapy. Data were analyzed using SPSS 13.0 for Windows. Results: Patients who received Progressive Muscle Relaxation Therapy experienced lower level of stress (t
Infections as causative factors of epilepsy

Epilepsies bearing some relationship to infections or vaccinations are often encountered clinically. While the onset of epilepsy or aggravation of seizures may follow common infections or vaccinations, complete seizure control has also been observed after infections. However, the true mechanisms underlying the relationship between infections and epilepsies have not been fully elucidated. Recently, advances in immunology have contributed to the study of autoimmune mechanisms in Rasmussen’s syndrome, a prototype of autoimmune epilepsy related to infections. The roles of autoimmunity, including cytotoxic T cells and autoantibodies against neural molecules, have been demonstrated in Rasmussen’s syndrome. This review postulates the probable molecular mimicry of microbial and neural components in Rasmussen’s syndrome and proposes possible autoimmune mechanisms related to the development of symptomatic epilepsies.
Defibrotide for children and adults with hepatic veno-occlusive disease post hematopoietic cell transplantation

ABSTRACT Introduction: Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a complication that is typically associated with conditioning for hematopoietic stem cell transplantation (HSCT). In patients with concomitant multi-organ dysfunction, mortality may be >80%. Recently, the European Society for Blood and Marrow Transplantation established separate criteria for diagnosis and severity of VOD/SOS for adults and children, to better reflect current understanding of the disease. Areas covered: This review provides an overview of post-HSCT hepatic VOD/SOS and defibrotide, including its pharmacological, clinical, and regulatory profile. In children and adults following HSCT, defibrotide is approved for the treatment of hepatic VOD/SOS with concomitant renal or pulmonary dysfunction in the United States and for the treatment of severe hepatic VOD/SOS in the European Union. Day +100 survival rates with defibrotide are superior to those of historical controls receiving best supportive care only, and safety profiles are similar. Expert commentary: Defibrotide appears to act through multiple mechanisms to restore thrombo-fibrinolytic balance and protect endothelial cells, and there are promising data on the use of defibrotide for VOD/SOS prophylaxis in high-risk children undergoing HSCT. An ongoing randomized controlled trial in children and adults will better assess the clinical value of defibrotide as a preventive medication.
How to predict response to anti-tumour necrosis factor agents in inflammatory bowel disease

ABSTRACT Introduction: Anti-tumor necrosis factor (TNF) agents have changed the therapeutic approach to inflammatory bowel disease (IBD). However, a considerable proportion of patients either do not primarily respond or lose response to treatment. Despite the long-standing experience in the use of these drugs, still there is the need of identifying the possible predictors of efficacy. Areas covered: We critically review the current knowledge on predictors of response to anti-TNF therapy – both those available in clinical practice and those still under investigation. Multiple factors are involved in treatment success, including disease phenotype and severity, adherence to medications, and pharmacogenomic, pharmacokinetic, and immunologic factors. Literature search was conducted in PubMed using keywords ‘inflammatory bowel disease,’ ‘Crohn’s disease,’ and ‘ulcerative colitis,’ matched with ‘antitumor necrosis factor,’ ‘biologic therapy,’ ‘clinical response,’ ‘predictors,’ and ‘efficacy,’ Relevant articles were selected for review. Expert commentary: While the role of several factors in clinical practice is clearly established, other investigational markers have been proposed, mostly in small studies, yet for many of them little external validation exists. Therapeutic drug monitoring is emerging as a pivotal strategy to guide decisions in clinical practice. In the near future, novel markers could improve our ability to direct treatment and personalize therapy.
Interleukin-1 receptor antagonist intron 2 variable number of tandem repeats polymorphism and respiratory failure in children with community-acquired pneumonia*

Objective: To determine whether the variable nucleotide tandem repeat polymorphism in intron 2 of the interleukin-1 receptor antagonist gene is associated with lung injury in children with community-acquired pneumonia. Design: A prospective cohort of children diagnosed with community-acquired pneumonia. Setting: Two pediatric hospitals. Patients: Eight hundred fifty pediatric patients with community-acquired pneumonia were enrolled. Interventions: Genotyping of the variable nucleotide tandem repeat polymorphism in intron 2 of the interleukin-1 receptor antagonist gene was performed on DNA isolated from whole blood. Measurements and Main Results: The requirement for positive pressure ventilation or the diagnosis of acute lung injury or acute respiratory distress syndrome were the main outcomes of the study. Children (14 days–19 yrs) with community-acquired pneumonia (850) were enrolled; analysis was limited to African American (515) and Caucasian (232) patients. Of the 82 patients requiring positive pressure ventilation, 44 were diagnosed with acute lung injury or acute respiratory distress syndrome. Multivariate logistic regression analyses indicated that children without a copy of the A1 allele of the variable nucleotide tandem repeat polymorphism in intron 2 of the interleukin-1 receptor antagonist gene were more likely to need positive pressure ventilation compared to those with one or two copies of this allele (odds ratio = 2.65, confidence interval, 1.02–6.90). In addition, the absence of the A1 allele also appeared to be associated with the development of community-acquired pneumonia–induced acute lung injury/acute respiratory distress syndrome (odds ratio = 3.1, confidence interval, 0.99–9.67). Conclusions: In children with community-acquired pneumonia, absence of the A1 allele at the interleukin-1 receptor antagonist intron 2 polymorphic site is associated with increased risk for more severe lung injury, as measured by the need for positive pressure ventilation or the development of acute lung injury or acute respiratory distress syndrome. Conversely, presence of the A1 allele is associated with decreased risk for more severe lung injury in this patient population.
Diagnosing cystic fibrosis-related diabetes: current methods and challenges

ABSTRACT Introduction: Cystic fibrosis-related diabetes (CFRD) is the end-point of a spectrum of glucose abnormalities in cystic fibrosis that begins with early insulin deficiency and ultimately results in accelerated nutritional decline and loss of lung function. Current diagnostic and management regimens are unable to entirely reverse this clinical decline. Areas covered: This review summarises the current understanding of the pathophysiology of CFRD, the issues associated with using oral glucose tolerance tests in CF and the challenges faced in making the diagnosis of CFRD. Medline database searches were conducted using search terms “Cystic Fibrosis Related Diabetes”, “Cystic Fibrosis” AND “glucose”, “Cystic Fibrosis” AND “insulin”, “Cystic Fibrosis” AND “Diabetes”. Additionally, reference lists were studied. Expert commentary: Increasing evidence points to early glucose abnormalities being clinically relevant in cystic fibrosis and as such novel diagnostic methods such as continuous glucose monitoring or 30 minute sampled oral glucose tolerance test (OGTT) may play a key role in the future in the screening and diagnosis of early glucose abnormalities in CF.
Montelukast, current indications and prospective future applications

ABSTRACT Introduction: Montelukast is recommended for the treatment of asthma, exercise -induced bronchospasm and allergic rhinitis. Several trials demonstrated potential therapeutic effects in other respiratory conditions, and different animal-model-based studies explored potential pharmacological actions in non-respiratory conditions. Areas covered: Clinical investigations on the pharmacotherapeutic effects of montelukast, in addition to in-vivo studies on animal models of non-respiratory diseases. The data discussed in this review were mainly obtained from clinical randomized trials, real-life studies, and studies based on animal models as approve of concept. As a condition, all of the discussed articles were published in journals cited by Pubmed. Expert commentary: The current clinical data are in favor of montelukast use in the management of chronic asthma as an add-on or alternative therapy to the inhaled corticosteroids. Further clinical trials are required to confirm the effectiveness and feasibility of montelukast for the treatment of conditions other than the current clinical indications.
Differential expression of leukocyte functions associated antigen‐1 (LFA‐1) on peripheral blood mononuclear cells in patients with Crohn's disease

Background: The leukocyte function associated antigen‐1 (LFA‐1) intracellular adhesion molecule‐1 pathway is presumed to play a pivotal role in the perpetuation of inflammatory bowel disease. We aimed to elucidate the effect of 2 different therapies on LFA‐1 expression in patients with Crohn's disease (CD) and correlate LFA‐1 expression with disease activity. Methods: In all, 30 patients with active CD were recruited for the present investigation. Eleven patients were treated with infliximab and 19 patients with total parenteral nutrition. The clinical activity and the expression of LFA‐1 in peripheral blood mononuclear cells were assessed prior to and 4 weeks after treatment. Clinical activity was determined by measuring the Crohn's Disease Activity Index and LFA‐1 expression was measured by mean fluorescence intensity (MFI) under fluorescence‐activated cell sorter analysis. Results: In each treatment group the clinical disease activity index decreased significantly 4 weeks after treatment. In patients treated with infliximab, LFA‐1 expression decreased significantly (mean MFI decreased from 1983 to 1487, P < 0.05). However, LFA‐1 expression remained unchanged in the total parenteral nutrition group (mean MFI elevated from 1684 to 1902, P > 0.05). Conclusions: The mechanism of therapeutic action on CD is different between infliximab and total parenteral nutrition. (Inflamm Bowel Dis 2009;)
Avaliação clínica e hematológica de equinos submetidos ao modelo de laminite por oligofructose, tratados ou não com um agente antagonista de receptores CXCR1/2

Leucocytes recruitment to tissues is an essential part of the innate immune response and an unregulated process can result in tissue damage. Thus, leucocytes infiltration has been implicated in the pathogenesis of acute laminitis. The objectives of this stud were to determine the effect of an antagonist for CXCR1/2, a chemokine receptor for neutrophils attraction on clinical signs and hematological parameters in horses given oligofructose to induce laminitis. Twelve horses were given oligofructose (10g/kg bw PO) in time 0 and divided into two groups: one treated (30mg/kg bw. ICXCR1/2 IV, times 6, 12, 18 e 24 h) and the other not treated. Cardiac and respiratory frequency, rectal temperature, mucous membrane colour, digital pulse, hoof sensitivity and Obel's grade of lameness were recorded. Values for RBC, WBC and blood glucose, BUN, creatinin, ALT, AST, alkaline phosphatase, GGT, total bilirubin and serum protein concentrations were measured on times 0, 6, 12, 18, 24, 36, 48, 60 e 72 h. All the horses given oligofructose developed signs of endotoxemia like diarrhea, fever and leukocytosis and laminitis. Also, CXCR1/2 antagonist treatment did not cause any adverse effects. However, this substance when injected intravenously (30mg/kg) 6/6 hours in 4 applications, did not ameliorate clinical and hematological signs of endotoxemia.