The 2009 Pandemic Influenza A (H1N1) Infection: Renal Histopathology Findings in Two Infected Patients

Background: Acute kidney injury in the pandemic swine origin influenza A virus (H1N1) infection has been reported as coursing with severe illness, although renal pathogenic mechanisms and histologic features are still being characterised. Case Report: We present two patients admitted with H1N1 pneumonia, sepsis, acute respiratory distress syndrome and need for invasive mechanical ventilation who developed acute kidney injury and became dialysis-dependent. In both cases a kidney biopsy was performed to establish a definitive diagnosis. Severe acute tubular necrosis was identified, with no further abnormalities. Conclusion: This report seems to confirm that the acute kidney injury in H1N1 infection is focused on the tubular cells. Our cases corroborate the renal histopathologic findings of other studies, highlighting the central role of the tubular cell. We bring new evidence of the histopathology of AKI in H1N1 infection since our data were collected in living patients and not via post-mortem studies.

The Intensive Care Global Study on Severe Acute Respiratory Infection (IC-GLOSSARI): a Multicenter, Multinational, 14-Day Inception Cohort Study

PURPOSE: In this prospective, multicenter, 14-day inception cohort study, we investigated the epidemiology, patterns of infections, and outcome in patients admitted to the intensive care unit (ICU) as a result of severe acute respiratory infections (SARIs). METHODS: All patients admitted to one of 206 participating ICUs during two study weeks, one in November 2013 and the other in January 2014, were screened. SARI was defined as possible, probable, or microbiologically confirmed respiratory tract infection with recent onset dyspnea and/or fever. The primary outcome parameter was in-hospital mortality within 60 days of admission to the ICU. RESULTS: Among the 5550 patients admitted during the study periods, 663 (11.9 %) had SARI. On admission to the ICU, Gram-positive and Gram-negative bacteria were found in 29.6 and 26.2 % of SARI patients but rarely atypical bacteria (1.0 %); viruses were present in 7.7 % of patients. Organ failure occurred in 74.7 % of patients in the ICU, mostly respiratory (53.8 %), cardiovascular (44.5 %), and renal (44.6 %). ICU and in-hospital mortality rates in patients with SARI were 20.2 and 27.2 %, respectively. In multivariable analysis, older age, greater severity scores at ICU admission, and hematologic malignancy or liver disease were independently associated with an increased risk of in-hospital death, whereas influenza vaccination prior to ICU admission and adequate antibiotic administration on ICU admission were associated with a lower risk. CONCLUSIONS: Admission to the ICU for SARI is common and associated with high morbidity and mortality rates. We identified several risk factors for in-hospital death that may be useful for risk stratification in these patients.

Acute Sheehan's Syndrome Presenting as Central Diabetes Insipidus

Sheehan's syndrome occurs as a result of ischaemic pituitary necrosis due to severe postpartum haemorrhage. Improvements in obstetrical care have significantly reduced its incidence in developed countries, but postpartum pituitary infarction remains a common cause of hypopituitarism in developing countries. We report a case of severe postpartum haemorrhage followed by headache, central diabetes insipidus and failure to lactate, which prompted us to investigate and identify both anterior and posterior pituitary deficiency compatible with Sheehan's syndrome. A timely diagnosis allowed us to implement an adequate treatment and follow-up plan, which are known to improve clinical status and patient outcome.

Colestase Intra-Hepática da Gravidez: Fator de Risco para Síndrome de Dificuldade Respiratória Neonatal?

Introdução: A colestase intra-hepática da gravidez está associada a complicações fetais e neonatais graves, incluindo síndrome de dificuldade respiratória. Tem sido recomendada terapêutica materna com ácido ursodesoxicólico e antecipação do parto para reduzir o risco de complicações. Os objetivos foram determinar a associação entre colestase intra-hepática da gravidez e síndrome de dificuldade respiratória neonatal e avaliar a relação com níveis maternos de ácidos biliares e procedimentos perinatais. Metodologia: Estudo caso-controlo incluindo grávidas com colestase intra-hepática da gravidez e respetivos recém-nascidos (grupo colestase), com parto numa maternidade portuguesa de nível III entre 2006 e 2010. Os controlos foram emparelhados para idade gestacional e peso ao nascimento (1 caso para 2 controlos). Resultados: Foram incluídas 42 grávidas com colestase intra-hepática da gravidez (incidência 0,15%) e 53 recém- -nascidos. Dez recém-nascidos do grupo colestase (19,2%) e 14 controlos (13,7%) tiveram dificuldade respiratória(p=0,375). A FiO2 máxima foi superior no grupo colestase (mediana 34,0% vs. 25,0%; p=0,294), mas sem diferença quanto à ventilação mecânica. A idade gestacional ao diagnóstico de colestase materna foi menor nos recém-nascidos com dificuldade respiratória (mediana 30,5 vs 33,5 semanas; p=0,024). A taxa de parto desencadeado iatrogenicamente(69,8% vs. 40,6%; p=0,001; OR=3,4), cesariana (66,0% vs 44,3%; p=0,01; OR=2,4) e corticoterapia pré-natal (43,4% vs. 25,5%; p=0,022) foi significativamente maior no grupo colestase. Não se encontrou relação entre dificuldade respiratória neonatal e níveis maternos de ácidos biliares nem terapêutica materna com ácido ursodesoxicólico. Conclusão: A colestase intra-hepática da gravidez, sobretudo de início precoce, está tendencialmente associada a síndrome de dificuldade respiratória neonatal. A antecipação do parto traz riscos adicionais para os recém-nascidos. A corticoterapia pré-natal neste contexto pode ter mascarado a verdadeira incidência de dificuldade respiratória neonatal.

Mastocytosis: a Rare Case of Anaphylaxis in Paediatric Age and Literature Review

The term “mastocytosis” denotes a heterogeneous group of disorders characterised by abnormal growth and accumulation of mast cells (MC) in one or more organ systems. Symptoms result from MC chemical mediator’s release, pathologic infiltration of neoplastic MC in tissues or both. Multiple molecular, genetic and chromosomal defects seem to contribute to an autonomous growth, but somatic c-kit D816V mutation is more frequently encountered, especially in systemic disease. We present a literature review of mastocytosis and a rare case report of an 18 month-old-girl with a bullous dermatosis, respiratory distress and anaphylaxis, as clinical manifestations of mastocytosis. The developments of accepted classification systems and novel useful markers allowed a re-evaluation and updating of the classification of mastocytosis. In paediatric age cutaneous forms of disease prevail and may regress spontaneously. SM is more frequently diagnosed in adults and is a persistent(clonal) disease of bone marrow. The clinical course in these patients is variable.Today diagnostic criteria for each disease variant are reasonably well defined. There are, however, peculiarities, namely in paediatric age, that makes the diagnostic approach difficult. Systemic disease may pose differential diagnostic problems resulting from multiple organ systems involvement. Coversly, the “unexplained” appearance of those symptoms with no skin lesions should raise the suspicion of MC disease. This case is reported in order to stress the clinical severity and difficult diagnostic approach that paediatric mastocytosis may assume.

Validation of Two US Risk Scores for Percutaneous Coronary Intervention in a Single-Center Portuguese Population of Patients with Acute Coronary Syndrome

INTRODUCTION: New scores have been developed and validated in the US for in-hospital mortality risk stratification in patients undergoing coronary angioplasty: the National Cardiovascular Data Registry (NCDR) risk score and the Mayo Clinic Risk Score (MCRS). We sought to validate these scores in a European population with acute coronary syndrome (ACS) and to compare their predictive accuracy with that of the GRACE risk score. METHODS: In a single-center ACS registry of patients undergoing coronary angioplasty, we used the area under the receiver operating characteristic curve (AUC), a graphical representation of observed vs. expected mortality, and net reclassification improvement (NRI)/integrated discrimination improvement (IDI) analysis to compare the scores. RESULTS: A total of 2148 consecutive patients were included, mean age 63 years (SD 13), 74% male and 71% with ST-segment elevation ACS. In-hospital mortality was 4.5%. The GRACE score showed the best AUC (0.94, 95% CI 0.91-0.96) compared with NCDR (0.87, 95% CI 0.83-0.91, p=0.0003) and MCRS (0.85, 95% CI 0.81-0.90, p=0.0003). In model calibration analysis, GRACE showed the best predictive power. With GRACE, patients were more often correctly classified than with MCRS (NRI 78.7, 95% CI 59.6-97.7; IDI 0.136, 95% CI 0.073-0.199) or NCDR (NRI 79.2, 95% CI 60.2-98.2; IDI 0.148, 95% CI 0.087-0.209). CONCLUSION: The NCDR and Mayo Clinic risk scores are useful for risk stratification of in-hospital mortality in a European population of patients with ACS undergoing coronary angioplasty. However, the GRACE score is still to be preferred.

Candidemia in Acute Leukemia Patients

Fungal infections are an important cause of morbidity and mortality in patients with acute leukemia (AL). Candidemia, once rare, is now a common nosocomial infection because of the intensity of chemotherapy, prolonged neutropenia, administration of broad-spectrum antibiotics and use of central venous catheters (CVC). We retrospectively identified patients treated for AL from 6/86 to 6/95 who also had candidemia. We describe 28 patients (incidence 6.3%) with a median age of 39 years, 24 of whom were on remission induction and 4 on postremission chemotherapy. All patients had CVC and empiric antimicrobial therapy, 4 had been given prophylactic antifungal drugs, and 2 had parenteral nutrition. Neutropenia was profound (median leukocyte nadir 200/microliters, median duration 19 days). Candida was isolated in blood cultures 10 days (median) after the start of neutropenia. The clinical presentation included fever (100%), respiratory symptoms (71.4%), skin lesions (39.2%) and septic shock (17.8%). Amphotericin B was given to 17 patients and liposomal amphotericin to 5 patients. Infection resolved in 18 patients (64.2%). 10 of whom were in complete remission. Mortality from candidemia was 17.8% (5/28). In conclusion, fungal infections are responsible for death in a significant number of patients. In our series treatment success was related to its rapid onset and to the recovery of neutropenia.

Does Metabolic Syndrome Predict Significant Angiographic Coronary Artery Disease?

INTRODUCTION: Metabolic syndrome (MS) is an independent predictor of acute cardiovascular events. However, few studies have addressed the relationship between MS and stable angiographic coronary artery disease (CAD), which has a different pathophysiological mechanism. We aimed to study the independent predictors for significant CAD, and to analyze the impact of MS (by the AHA/NHLBI definition) on CAD. METHODS: We prospectively included 300 patients, mean age 64±9 years, 59% male, admitted for elective coronary angiography (suspected ischemic heart disease), excluding patients with known cardiac disease. All patients underwent assessment of demographic, anthropometric, and laboratory data and risk factors, and subsequently underwent coronary angiography. RESULTS: In the study population, 23.0% were diabetic, 40.5% had MS (and no diabetes) and 36.7% had neither diagnosis. Significant CAD was present in 51.3% of patients. CAD patients were older and more frequently male and diabetic, with increased triglycerides and glucose and lower HDL cholesterol. Abdominal obesity was also less prevalent. MS was not associated with the presence of CAD (OR 0.94, 95% CI 0.59-1.48, p=0.778). Of the MS components, the most important predictors of CAD were increased glucose and triglycerides. Abdominal obesity was associated with a lower risk of CAD. In a multivariate logistic regression model for CAD, independent predictors of CAD were age, male gender, glucose and triglycerides. Body mass index had a protective effect. CONCLUSIONS: Although MS is associated with cardiovascular events, the same was not found for stable angiographically proven CAD. Age, gender, diabetes and triglycerides are the most influential factors for CAD, with abdominal obesity as a protective factor.

Hyper-IgD and Periodic Fever Syndrome: a New MVK Mutation (p.R277G) Associated with a Severe Phenotype

Hyperimmunoglobulinemia D and periodic fever syndrome (HIDS; MIM#260920) is a rare recessively-inherited autoinflammatory condition caused bymutations in the MVK gene, which encodes for mevalonate kinase, an essential enzyme in the isoprenoid pathway. HIDS is clinically characterized by recurrent episodes of fever and inflammation. Herewe report on the case of a 2 year-old Portuguese boy with recurrent episodes of fever, malaise, massive cervical lymphadenopathy and hepatosplenomegaly since the age of 12 months. Rash, arthralgia, abdominal pain and diarrhea were also seen occasionally. During attacks a vigorous acute-phase response was detected, including elevated erythrocyte sedimentation rate, C-reactive protein, serum amyloid A and leukocytosis. Clinical and laboratory improvement was seen between attacks. Despite normal serum IgD level, HIDS was clinically suspected. Mutational MVK analysis revealed the homozygous genotype with the novel p.Arg277Gly (p.R277G) mutation, while the healthy non consanguineous parents were heterozygous. Short nonsteroidal anti-inflammatory drugs and corticosteroid courses were given during attacks with poor benefits, where as anakinra showed positive responses only at high doses. The p.R277Gmutation here described is a novel missense MVK mutation, and it has been detected in this casewith a severe HIDS phenotype. Further studies are needed to evaluate a co-relation genotype, enzyme activity and phenotype, and to define the best therapeutic strategies.

Economic Evaluation of Ticagrelor for Secondary Prevention Following Acute Coronary Syndromes

INTRODUCTION AND OBJECTIVES: To estimate the cost-effectiveness and cost-utility of ticagrelor in the treatment of patients with acute coronary syndromes (unstable angina or myocardial infarction with or without ST-segment elevation), including patients treated medically and those undergoing percutaneous coronary intervention or coronary artery bypass grafting. METHODS: A short-term decision tree and a long-term Markov model were used to simulate the evolution of patients' life-cycles. Clinical effectiveness data were collected from the PLATO trial and resource use data were obtained from the Hospital de Santa Marta database, disease-related group legislation and the literature. RESULTS: Ticagrelor provides increases of 0.1276 life years and 0.1106 quality-adjusted life years (QALYs) per patient. From a societal perspective these clinical gains entail an increase in expenditure of €610. Thus the incremental cost per life year saved is €4780 and the incremental cost per QALY is €5517. CONCLUSIONS: The simulation results show that ticagrelor reduces events compared to clopidogrel. The costs of ticagrelor are partially offset by lower costs arising from events prevented. The use of ticagrelor in clinical practice is therefore cost-effective compared to generic clopidogrel.

Hand, Foot, and Mouth Syndrome in an Immunocompetent Adult: a Case Report

BACKGROUND: Hand, foot, and mouth syndrome (HFMS) is a common acute illness. It is characterized by mild clinical symptoms including fever, blisters, and sores in the mouth and on the palms and soles following a 3- to 7-day incubation period. This syndrome is rarely seen in adults. CASE PRESENTATION: A 35-year-old male Caucasian patient had a history of multiple episodes of acute pharyngitis, hypertension, hypercholesterolemia, and occasional abdominal pain. He presented with polyarthralgia in the knees and hands and odynophagia, followed by fever, oral mucosal aphthous lesions, and vesicles on the palms and soles. Three weeks after presentation, he was admitted to the emergency room with acute myocarditis. The in-hospital evaluation revealed positive serology for coxsackie A9 (1:160), positive anti-transglutaminase and anti-gliadin antibodies, normal immunoglobulins, and human immunodeficiency virus negativity. CONCLUSION: We herein describe a case of HFMS that was associated with coxsackie A9 infection complicated by acute myocarditis. Although an association between celiac disease and HFMS has not been described, this patient's immunologic disruption could have favored the development of infection and ultimately HFMS.