Epidemiological and Clinical Aspects of Cutaneous and Mucosal Leishmaniases in Portugal: Retrospective Analysis of Cases Diagnosed in Public Hospitals and Reported in the Literature between 2010 and 2020.

Leishmania infantum, a zoonotic vector-born parasite, is endemic in the Mediterranean region, presenting mostly as visceral (VL), but also as cutaneous (CL) and mucosal leishmaniasis (ML). This study aimed to describe the epidemiological and clinical aspects of the CL and ML cases diagnosed in mainland Portugal between 2010 and 2020. Collaboration was requested from every hospital of the Portuguese National Health System. Cases were screened through a search of diagnostic discharge codes or positive laboratory results for Leishmania infection. Simultaneously, a comprehensive literature search was performed. Descriptive statistics and hypothesis testing were performed using IBM® SPSS® Statistics. A total of 43 CL and 7 ML cases were identified, with a predominance of autochthonous cases (86%). In CL, immunosuppressed individuals constituted a significant proportion of patients (48%), and in this group, disseminated CL (22%) and simultaneous VL (54%) were common. In autochthonous cases, lesions, mostly papules/nodules (62%), were frequently observed on the head (48%). The approach to treatment was very heterogeneous. ML cases were all autochthonous, were diagnosed primarily in older immunosuppressed individuals, and were generally treated with liposomal amphotericin B. The findings suggest a need for enhanced surveillance and reporting, clinical awareness, and diagnostic capacity of these forms of leishmaniasis to mitigate underdiagnosis and improve patient outcomes. A holistic One Health approach is advocated to address the multifaceted challenges posed by leishmaniases in Portugal and beyond.

Azacitidine-induced massive pericardial effusion in a child with myelodysplastic syndrome.

INTRODUCTION: Pericardial effusions are rare yet potentially fatal conditions in children. Azacitidine is a DNA-hypomethylating agent used in the treatment of myelodysplastic syndrome. Although seldomly described in adults, no cases of azacitidine-induced pericardial effusion have been reported in children. CASE REPORT: A 7-year-old boy with myelodysplastic syndrome presented with a large pericardial effusion with risk for cardiac tamponade after his first azacitidine cycle. MANAGEMENT & OUTCOME: The patient was admitted to a pediatric ICU, antibiotic and steroid therapy were initiated. Pericardiocentesis was done due to hemodynamic instability. Serum and pericardial fluid complementary evaluation excluded infectious and malignant causes. The pericardial effusion did not reappear and additional pleural and ascitic slight effusions responded well to diuretics. Follow-up azacitidine cycles were administered by tapering daily dosages and using adjunctive steroid therapy, with no additional adverse events. DISCUSSION: We report the first pediatric case of large pericardial effusion secondary to azacitidine therapy in a child with MDS. This adverse reaction has not been described in pediatric patients, in which this therapeutic option has been increasingly used. We seek to raise awareness on the potential life-threatening cardiotoxicity of azacitidine in pediatric patients.

Helicobacter pylori antimicrobial resistance in a pediatric population.

BACKGROUND: The increasing prevalence of Helicobacter pylori (H. pylori) antimicrobial resistance, primarily for clarithromycin decreases the success of treatment. The aim of this study is to determine the local pattern of first-line antimicrobials resistance and the eradication rate. MATERIAL AND METHODS: Prospective cohort study of H. pylori infected patients (positive histological or cultural exams) treated at Centro Materno-Infantil do Norte from January of 2013 to October of 2017. Susceptibility to 4 antibiotics: amoxicilin, metronidazole, clarithromycin, and levofloxacin were analyzed by E-test (phenotypic resistance). The E-test was chosen because it is simple and cost-effective for routine susceptibility testing. Point mutations that confer clarithromycin resistance were surveyed (genotypic resistance). Eradication of H. pylori infection was defined by a negative urea breath test or fecal antigen 6-8 weeks after the end of treatment. RESULTS: Of a total of 74 H. pylori infected patients, 16 were excluded because they had previous H. pylori treatment or severe systemic disease. Median age of infection cases was 15 years (3-17 years). Eradication regimen used in all patients combined the use of 3 antibiotics (amoxicillin and metronidazole or clarithromycin) and proton pump inibhitor for 14 days and was tailored according antimicrobial susceptibility. 79.5% of the patients completed the treatment. The resistance rate for metronidazole and clarithromycin was 3.3% and 23.3%, respectively. There was no resistance for amoxicilin and levofloxacin. The rate of genotypic resistance to clarithromycin was 37.2%. The eradication rate was 97.8%. CONCLUSIONS: The authors found a high resistance rate of H. pylori for clarithromycin in this northern portuguese pediatric center. This factor should determine a change in local current treatment, contraindicating the use of clarithromycin as a first-line treatment for H. pylori infection in children. The high eradication rate maybe explained for the eradication treatment tailored according antimicrobial susceptibility.

Performance of PRISM III and PELOD-2 scores in a pediatric intensive care unit.

UNLABELLED: The study aims were to compare two models (The Pediatric Risk of Mortality III (PRISM III) and Pediatric Logistic Organ Dysfunction (PELOD-2)) for prediction of mortality in a pediatric intensive care unit (PICU) and recalibrate PELOD-2 in a Portuguese population. To achieve the previous goal, a prospective cohort study to evaluate score performance (standardized mortality ratio, discrimination, and calibration) for both models was performed. A total of 556 patients consecutively admitted to our PICU between January 2011 and December 2012 were included in the analysis. The median age was 65 months, with an interquartile range of 1 month to 17 years. The male-to-female ratio was 1.5. The median length of PICU stay was 3 days. The overall predicted number of deaths using PRISM III score was 30.8 patients whereas that by PELOD-2 was 22.1 patients. The observed mortality was 29 patients. The area under the receiver operating characteristics curve for the two models was 0.92 and 0.94, respectively. The Hosmer and Lemeshow goodness-of-fit test showed a good calibration only for PRISM III (PRISM III: χ (2) = 3.820, p = 0.282; PELOD-2: χ (2) = 9.576, p = 0.022). CONCLUSIONS: Both scores had good discrimination. PELOD-2 needs recalibration to be a better reliable prediction tool. WHAT IS KNOWN: • PRISM III (Pediatric Risk of Mortality III) and PELOD (Pediatric Logistic Organ Dysfunction) scores are frequently used to assess the performance of intensive care units and also for mortality prediction in the pediatric population. • Pediatric Logistic Organ Dysfunction 2 is the newer version of PELOD and has recently been validated with good discrimination and calibration. What is New: • In our population, both scores had good discrimination. • PELOD-2 needs recalibration to be a better reliable prediction tool.

Serum uric acid and cardiovascular risk among Portuguese adolescents.

PURPOSE: The aim of the study was to investigate the association between serum uric acid (SUA) and cardiovascular risk classes (CRCs) in adolescents using a cluster-based approach. METHODS: A cross-sectional evaluation was carried out in the 2007-2008 school year, including adolescents born in 1990 and enrolled in the schools of Porto, Portugal. The analysis included 1,286 adolescents. To identify CRC, a normal mixture model was performed including several biological cardiovascular risk factors. A multinomial logistic regression model was applied to explore the association between SUA and each CRC. RESULTS: Three classes were extracted using model-based cluster analysis (low, medium, and high CRC). The high CRC accounted for the smallest proportion of participants (5.6%) and represented the adolescents with higher waist circumference, systolic and diastolic blood pressures, total cholesterol, triglycerides, and insulin levels. Adolescents at increased risk of cardiovascular disease had significantly higher mean concentrations of SUA compared with adolescents at low cardiovascular risk (55.0 vs. 51.5 mg/L in males and 41.9 vs. 37.6 mg/L in females). After adjustment and considering low CRC as reference, SUA was positively associated with high CRC in both sexes (odds ratio, 1.04; 95% confidence interval, 1.00-1.07 in males; and odds ratio, 1.04; 95% confidence interval, 1.01-1.07 in females). CONCLUSIONS: Among 17-year-old adolescents, SUA increases were positively associated with higher CRC.

[Provocative tests in the diagnosis of childhood onset growth hormone insufficiency]. / O Papel dos Testes de Estimulação Farmacológica no Diagnóstico da Deficiência de Hormona do Crescimento em Crianças e Adolescentes.

INTRODUCTION: The incidence of short stature associated with growth hormone deficiency has been estimated to be about 1:4000 to 1:10000. It is the main indication for treatment with recombinant growth hormone. OBJECTIVES: The aims of the study were to evaluate the results of growth hormone stimulation tests and identify the growth hormone deficiency predictors. MATERIAL AND METHODS: A cross-sectional, analytical and observational study was conducted. We studied all the children and adolescents submitted to growth hormone pharmacological stimulation tests between January 2008 and May 2012. Growth hormone deficiency diagnosis was confirmed by two negatives growth hormone stimulation tests (growth hormone peak < 7 ng/ml). The statistical analysis was performed using student t-test, chi-square, Pearson correlation and logistic regression. Statistical significance determined at the 5% level (p ≤ 0.05). RESULTS: Pharmacological stimulation tests were performed in 89 patients, with a median age of 10 [3-17] years. Clonidine (n = 85) and insulin tolerance test (n = 4) were the first growth hormone stimulation tests performed. Growth hormone deficiency was confirmed in 22 cases. In cases with two growth hormone stimulation tests, the growth hormone peak showed a moderate correlation (r = 0.593, p = 0.01). In logistic regression model height (z-score) and the growth hormone peak in first stimulation test were predictors of growth hormone deficiency diagnosis (each one unit increase in z-score decrease the growth hormone deficiency probability). DISCUSSION: Measurement of IGF-1 cannot be used in diagnosing growth hormone deficiency. CONCLUSION: Auxological criteria associated with a positive test seems to be a reliable diagnostic tool for growth hormone deficiency.

Introdução: A incidência da deficiência de hormona do crescimento é de 1:4000 a 1:10000, sendo a principal indicação para tratamento com hormona do crescimento recombinante.Objectivos: Avaliar os resultados dos testes de estimulação da hormona do crescimento e identificar factores preditivos para o diagnóstico da deficiência de hormona do crescimento.Material e Métodos: Estudo observacional, analítico e transversal. Foram analisados dados clínicos e auxológicos e os resultados dos exames de diagnóstico de crianças e adolescentes submetidos a testes de estimulação farmacológica da hormona do crescimento (01/01/2008 a 31/05/2012). O diagnóstico definitivo de deficiência de hormona do crescimento foi efectuado mediante dois testes com estímulos farmacológicos diferentes negativos (pico máximo da hormona do crescimento < 7 ng/mL) ou um teste negativo associado à presença de alterações anatómicas da região hipotálamo-hipofisária, observadas na ressonância magnética cerebral. Para análise estatística, foram realizados o testes de t student, do qui- quadrado, correlação de Pearson e a regressão logística. Foi considerado como nível de significância estatística (p) um valor igual ou menor que 0,05.Resultados: Realizaram-se testes de estimulação em 89 doentes, com mediana de idade igual a 10 [3-17] anos, 67% do sexo masculino e 77% pré-púberes. Os fármacos utilizados no primeiro teste de estimulação foram a clonidina (n = 85) e a insulina (n = 4). Foram diagnosticados 22 casos de deficiência de hormona do crescimento. Nos casos submetidos a dois testes, os valores máximos de hormona do crescimento apresentaram uma correlação moderada entre si (r = 0,593, p = 0,01). Verificou-se que as variáveis estatura (z-score) e pico máximo de hormona do crescimento obtido no primeiro teste têm valor preditivo no diagnóstico de deficiência de hormona do crescimento.Discussão: A determinação do IGF-1 não demonstrou ser preditor de deficiência de hormona do crescimento.Conclusão: Os testes de estimulação são uma ferramenta de diagnóstico da deficiência de hormona do crescimento e que devem ser enquadrados nos parâmetros clínicos e auxológicos.

[Fractional exhaled nitric oxide in monitoring and therapeutic management of asthma]. / Fração exalada de óxido nítrico no controlo e abordagem terapêutica da asma.

INTRODUCTION: Asthma is a chronic respiratory disease characterized by hyper-responsiveness and bronchial inflammation. The bronchial inflammation in these patients can be monitored by measuring the fractional exhaled nitric oxide. This study aims to determine fractional exhaled nitric oxide association with peak expiratory flow and with asthma control inferred by the Global Initiative for Asthma. MATERIAL AND METHODS: Observational, analytical and cross-sectional study of children with asthma, 6-12 years-old, followed in the Outpatient Respiratory Pathology of Braga Hospital. Sociodemographic and clinical information were collected through a questionnaire. fractional exhaled nitric oxide and peak expiratory flow were determined by portable analyzer Niox Mino® and flow meter, respectively. RESULTS: The sample is constituted by 101 asthmatic children, 63 (62.4%) of males and 38 (37.6%) females. The mean age of participants in the sample is 9.18 (1.99) years. The logistic regression performed with the cutoff value obtained by ROC curve, revealed that fractional exhaled nitric oxide (b(FENO classes) = 0.85; χ(2)Wald (1) = 8.71; OR = 2.33; p = 0.003) has a statistical significant effect on the probability of changing level of asthma control. The odds ratio of going from "controlled" to "partly controlled/uncontrolled" is 2.33 per each level of fractional exhaled nitric oxide. DISCUSSION: The probability of an asthmatic children change their level of asthma control, from 'controlled' to 'partly controlled/uncontrolled', taking into account a change in their fractional exhaled nitric oxide level, increases 133%.

Introdução: A asma é uma doença respiratória crónica caracterizada pela hiper-reactividade e inflamação brônquica. A inflamação brônquica destes doentes pode ser monitorizada através da medição da fração exalada de óxido nítrico. Este estudo tem por objetivo determinar a associação do valor da fração exalada de óxido nítrico com o débito expiratório máximo instantâneo e com o controlo da asma determinado pela Classificação da Iniciativa Global para a Asma.Material e Métodos: Estudo observacional, analítico e transversal de crianças com asma, 6-12 anos, seguidas na Consulta Externa de Patologia Respiratória do Hospital de Braga. Informação sociodemográfica e clínica colhida através de um questionário. Determinado o valor da fração exalada de óxido nítrico, através do analisador portátil Niox Mino®, e do débito expiratório máximo instantâneo,através do debitómetro.Resultados: A amostra é constituída por 101 crianças asmáticas, 63 (62,4%) do sexo masculino e 38 (37,6%) do sexo feminino. A idade média dos participantes na amostra é de 9,18 (1,99) anos. A regressão logística, realizada com o valor de cutoff obtido pela curva de ROC, revelou que a fração exalada de óxido nítrico tem um efeito estatisticamente significativo (bNíveis do FENO = 0,85; χ2Wald (1) = 8,71; OR = 2,33; p = 0,003) sobre a probabilidade de mudar de nível de controlo da asma. Por cada nível de fração exalada de óxido nítrico incrementado o odds de passar a não controlada é 2,33 vezes superior.Discussão e Conclusão: A probabilidade de uma criança asmática mudar o seu nível de controlo da asma, de 'controlada' para 'parcialmente controlada/não controlada', tendo em consideração uma alteração no seu nível da fração exalada de óxido nítrico, aumenta 133%.

Novel ABCA3 mutations as a cause of respiratory distress in a term newborn.

We report here the case of a term female newborn that developed severe respiratory distress soon after birth. She was found to be a compound heterozygote for both novel mutations in the ABCA3 gene. ABCA3 deficiency should be considered in mature babies who develop severe respiratory distress syndrome.

Short-time variation in serum uric acid concentrations in post-myocardial infarction patients.

BACKGROUND: Studies on SUA temporal profile in relation to acute myocardial infarction (AMI) are controversial. The aim of this study was to evaluate the SUA level variations following myocardial infarction. METHODS: We studied 222 patients more than 18 years old diagnosed with AMI. SUA was measured at baseline and on day 2 to 4 and day 5 to 8 after AMI. Within and between person variability of SUA following an AMI was estimated using intraclass correlation coefficients (ICC). The change in SUA between each assessment point was analyzed by repeated measures one-way analysis of variance. To evaluated.SUA variation post-myocardial infarction and its predictors we used generalized linear mixed-effects models. RESULTS: The mean plasma concentration of SUA was lower at baseline (58.5 +/- 18.9 mg/L). The ICC across the three time points was 0.75 (95% CI 0.70 - 0.80). SUA levels increased 1.33 mg/L per day after AMI (2.3 mg/L/day in women and 1.0 mg/L/day in men). Normouricemic patients had a 1.6 fold increase risk to change to hyperuricemic status per day after AMI (OR = 1.60, 95% CI: 1.27 - 2.00). CONCLUSIONS: Serum uric acid concentration is relatively stable over an eight-day post-myocardial infarction period. However, even a small increase of SUA per day after AMI is associated with a high probability of changing the classification of hyperuricemic status.

A novel de novo deletion of chromosome 7 [46,XX,del(7)(p14.2 p15.1)] in a child with feeding problems.

The phenotype and severity of symptoms associated with deletions on chromosome 7 are directly proportional to the size of the deleted segment. Distal and interstitial deletions have been described in 40 cases. In this report the authors aim to report a child with a novel de novo interstitial deletion on chromosome 7, with the following karyotype: 46,XX,del(7)(p14.2 p15.1). We described a female, born at 38 weeks with intrauterine growth restriction and feeding problems with episodes of cyanosis after feedings and failure to thrive. Physical examination showed low implantation of ears, hypertelorism, oblique palpebral fissures, retrognathia, and palate ogived, with insertion anomalies of the toes, poor facial expression and mild axial hypotonia. Transfontanelar ultrasound, magnetic resonance imaging, bronchofibroscopy and metabolic studies were normal. She was hospitalized until the 32nd day of life. She started speech therapy and presented improvements in swallowing. The percutaneous endoscopic gastrostomy was removed at 36 months. She had recurrent urinary tract infection with normal dimercaptosuccinic acid but with a vesicoureteral reflux (grade III). Imagiological studies revealed a bilateral osteonecrosis of femoral epiphysis (Legg-Calvé-Perthes disease). Currently (6years-old), she is being normally fed (body mass index=15.8kg/m(2)). Her weight is 16.4kg (3rd centile) and length is 105cm (3rd to 5th centiles). She has a mild delay of psychomotor development impairment and some speech problems. This is the first case report of a patient with this de novo small interstitial deletion on chromosome 7. This rare chromosomal abnormality was associated with severe feeding problems in the first years of life.

[The Alvarado score validation in diagnosing acute appendicitis in children at Braga Hospital]. / Validação do score de Alvarado no diagnóstico de apendicite aguda em crianças e adolescentes no Hospital de Braga.

INTRODUCTION: Acute appendicitis (AA) is the leading cause of emergency abdominal surgery in children. The diagnosis is essentially clinical, but some methodologies, such as Alvarado score (AS), have been developed in order to avoid non-therapeutic laparotomy (15-30%). AS ≥ 5 or 6 is compatible with AA and is an indication for the patient to remain on observations, if AS ≥ 7 a laparotomy procedure may be indicated. OBJECTIVE: To validate the AS for the AA diagnosis of children admitted at Braga Hospital. METHODS: A validation study of diagnostic method (AS) using the histological examination as a gold standard. The study population consisted of 192 children (4-17 years) with abdominal pain that underwent appendectomy in the last 20 months (December 2008 to July 2010). It was determined the values of sensitivity (S), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), likelihood ratio (LR) and the ROC curve for three different cut-off points (SA =5, 6 and 7). RESULTS: We found that as the cut-off point of AS decreases progressively the sensitivity and specificity increases and reduces the VPN and VPP. Assuming a cut-off value of 5, only 18 children would be false negatives, instead of the 67 children if the cut-off point was 7 points. The analysis of ROC curves demonstrated a greater area under the curve for a cut-off equal to or greater than 5 (AUC = 70%). DISCUSSION: We recommend using a cut-off value of 5 points, since only 18 children with AA were initially classified as appendicitis unlikely, this value would increase to 67 patients for the SA value of ≥ 7. The AS is a valuable tool in screening children with abdominal pain for the diagnosis of AA. Nonetheless the diagnosis and final decision must be based on clinical and systematic reassessment of patients.