Catch-up growth in term and preterm infants after surgical closure of ventricular septal defect in the first year of life.

UNLABELLED: Growth impairment in infants with unrestrictive ventricular septal defects (VSD) is common, and normalisation of growth has been reported after surgical correction. Literature is inconsistent about growth velocity after surgery in term and preterm infants. We aimed to establish the pattern of catch-up growth in term and preterm infants submitted to VSD surgical correction before 1 year of age. Fifty-two infants (41 term, 11 preterm) were studied. Anthropometric data at birth, surgery and 3, 6, 12 and 24 months after surgery were collected retrospectively. Statistic analyses were performed in SPSS® version 21. At the time of surgery, growth was severely impaired in term and preterm infants. Term infants underwent a period of fast growth within the first 6 months after surgery, achieving posteriorly a normal growth pattern, as both weight and height were not significantly different from the reference population at 24 months after surgery. Preterms caught-up later than term infants but with a significant weight gain within 3 months after surgery. CONCLUSION: Early surgical repair of VSD leads to a significant acceleration of growth within 3 to 6 months after surgery, for both groups. WHAT IS KNOWN: • Growth impairment in infants with unrestrictive ventricular septal defects is well documented in literature. • Surgical correction in the first months of life is the current option for most ventricular septal defects, leading to a more favourable growth pattern. • Rapid growth during infancy may be associated with the development of insulin resistance, metabolic syndrome, obesity and cardiovascular disease later in life. What is New: • Literature is inconsistent about catch-up growth velocities after ventricular correction for term infants. • Preterm infants have never been enrolled in previous studies that aimed to establish a pattern of growth after surgery. • This group of children, who underwent a rapid post-surgery catch-up growth that follows a period of failure to thrive, may be at a higher risk of insulin resistance, metabolic syndrome, obesity and cardiovascular disease.

Sialyl LewisX/A and Cytokeratin Crosstalk in Triple Negative Breast Cancer.

Triple-negative breast cancer (TNBC) encompasses multiple entities and is generally highly aggressive and metastatic. We aimed to determine the clinical and biological relevance of Sialyl-Lewis X and A (sLeX/A)-a fucosylated glycan involved in metastasis-in TNBC. Here, we studied tissues from 50 TNBC patients, transcripts from a TNBC dataset from The Cancer Genome Atlas (TCGA) database, and a primary breast cancer cell line. All 50 TNBC tissue samples analysed expressed sLeX/A. Patients with high expression of sLeX/A had 3 years less disease-free survival than patients with lower expression. In tissue, sLeX/A negatively correlated with cytokeratins 5/6 (CK5/6, which was corroborated by the inverse correlation between fucosyltransferases and CK5/6 genes. Our observations were confirmed in vitro when inhibition of sLeX/A remarkably increased expression of CK5/6, followed by a decreased proliferation and invasion capacity. Among the reported glycoproteins bearing sLeX/A and based on the STRING tool, α6 integrin showed the highest interaction score with CK5/6. This is the first report on the sLeX/A expression in TNBC, highlighting its association with lower disease-free survival and its inverse crosstalk with CK5/6 with α6 integrin as a mediator. All in all, sLeX/A is critical for TNBC malignancy and a potential prognosis biomarker and therapeutic target.

BRCA1 VUS: A functional analysis to differentiate pathogenic from benign variants identified in clinical diagnostic panels for breast cancer.

Genetic testing for susceptibility genes through next­generation sequencing (NGS) has become a widely used technique. Using this, a number of genetic variants have been identified, several of which are variants of unknown significance (VUS). These VUS can either be pathogenic or benign. However, since their biological effect remains unclear, functional assays are required to classify their functional nature. As the use of NGS becomes more mainstream as a diagnostic tool in clinical practice, the number of VUS is expected to increase. This necessitates their biological and functional classification. In the present study, a VUS was identified in the BRCA1 gene (NM_007294.3:c.1067A>G) in two women at risk for breast cancer, for which no functional data has been reported. Therefore, peripheral lymphocytes were isolated from the two women and also from two women without the VUS. DNA from all samples were sequenced by NGS of a breast cancer clinical panel. Since the BRCA1 gene is involved in DNA repair and apoptosis, the functional assays chromosomal aberrations, cytokinesis­blocked micronucleus, comet, γH2AX, caspase and TUNEL assays were then conducted on these lymphocytes after a genotoxic challenge by ionizing radiation or doxorubicin to assess the functional role of this VUS. The micronucleus and TUNEL assays revealed a lower degree of DNA induced­damage in the VUS group compared with those without the VUS. The other assays showed no significant differences between the groups. These results suggested that this BRCA1 VUS is likely benign, since the VUS carriers were apparently protected from deleterious chromosomal rearrangements, subsequent genomic instability and activation of apoptosis.

Statin Therapy Among Bariatric Patients: The Impact on Metabolic Outcomes and Diabetes Status.

INTRODUCTION: Statin therapy is associated with an increased risk of developing diabetes. Among bariatric patients, the influence of this therapy on various metabolic outcomes, such as diabetes status and its remission, is largely unknown. METHODS: This was a retrospective study of 1710 patients who underwent bariatric surgery at our hospital between January/2010 and June/2017. We compared patients with and without statin therapy at baseline, 12 and 24 months after surgery regarding statin use and its impact on several clinical and analytical parameters. Multiple linear regression was performed, adjusting differences for age, sex, surgery type, antidiabetic drugs at baseline, hypertension at baseline, LDL cholesterol ˃ 130 mg/dL, weight variation one year after surgery, and age of obesity onset. RESULTS: The overall prevalence of statin use was 20.2% before, 13.6% 12 months after surgery, and 15.0% 24 months after surgery. There was a larger reduction in fasting glucose and HbA1c at 12 and 24 months after surgery among statin-treated patients, with the opposite trend for weight reduction and BMI. Statin-treated patients with diabetes had lower diabetes remission rates (45.3 vs 68.5%) 12 months after surgery, with the highest reduction in HbA1c (1.3±1.3 vs -1.1±1.2%; p=0.042), fasting glucose (-40.8±48.8 vs -30.9±41.6 mg/dL; p=0.028), and insulin (-21.7±28.2 vs -13.4±14.2 mIU/L; p=0.039). The proportion of new-onset cases of diabetes was equal between statin-treated vs non-treated individuals at 12 months (1.9%) and 24 months (1.0%) after surgery. CONCLUSION: Bariatric surgery seems to lead to diabetes remission more frequently in patients not treated with statins. A larger reduction was observed in fasting glucose and HbA1c among statin-treated patients. Statin did not contribute to an increased proportion of new-onset diabetes after surgery.

Assessment of the Safety and Therapeutic Benefits of Convalescent Plasma in COVID-19 Treatment: A Systematic Review and Meta-Analysis.

Background: The coronavirus disease (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), prompted a global health crisis, with no available specific treatments. Convalescent plasma (CP) with neutralizing antibodies could be a promising therapeutic approach to reduce mortality. Objectives: To evaluate the therapeutic potential of CP for COVID-19 and to assess its safety and efficacy in reducing the patients' mortality. Methods: We retrieved clinical trial references from multiple Databases (e.g., PubMed, B-On, SCOPUS), for complete studies until November 26th 2020. We included Randomized controlled trials (RCT) and controlled non-randomized trials (CNRT), that assessed the efficacy of CP to treat hospitalized COVID-19 patients. Trials were included regardless of concomitant medications in the intervention's arms. Eleven trials met our eligibility criteria. This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We defined a methodological protocol to extract and evaluate all pertinent baseline demographics and interventions' characteristics from trials. The primary outcomes were the safety profile of CP, measured by the type, frequency and severity of adverse events, and CP effectiveness in reducing mortality, measured by the number of deaths registered for this therapy. Results: We assessed 11 trials (5 RCT and 6 CNRT) with 3,098 participants, of whom 923 patients were treated with CP. Only 32 (3.5%) of the treated patients suffered adverse events (from which 9.4% serious transfusion-related adverse events). The overall mortality rates were significantly decreased by CP administration {risk ratio (RR) 0.71, p = 0.005, 95% confidence interval (Cl) [0.57-0.90]}, with low heterogeneity. In the sub-analysis by period of transfusion, CP transfusion within a week of hospitalization contributed to diminished mortality rate (RR = 0.71, p = 0.03, 95%Cl [0.53-0.96]). CP therapy also led to significantly reduced viral loads at 72 h after transfusion (RR = 0.61, p = 0.04, 95%Cl [0.38-0.98]), despite high heterogeneity due to disease severity. Conclusion: This meta-analysis established CP as a safe and potentially effective therapy for COVID-19, decreasing the mortality rates and promoting a swift viral clearance. Further studies are necessary to provide stronger evidence.

Beta Cell Function as a Baseline Predictor of Weight Loss After Bariatric Surgery.

Background: Obesity is a multifactorial disease, which is strongly associated to other metabolic disorders. Bariatric surgery is the most effective treatment of morbid obesity. The role of beta cell function in weight loss after bariatric surgery is uncertain. Aim: To evaluate the association between beta cell function and percentage of total body weight loss (TBWL%) 1, 2, 3, and 4 years after bariatric surgery in patients with morbid obesity. Methods: Retrospective longitudinal study in patients with morbid obesity followed in our center between January 2010 and July 2018. Patients were excluded if they had diabetes at baseline or missing data on the needed parameters. We evaluated baseline Homeostatic Model Assessment of IR, Homeostatic Model Assessment of ß-cell function (HOMA-beta), Quantitative Insulin Sensitivity Check Index, and Matsuda and DeFronzo index, and TBWL% at years 1 to 4. Linear regression models were used to evaluate the association of indexes of insulin resistance with TBWL% (unadjusted and adjusted for age, sex, BMI, and type of surgery). Results: There were 1,561 patients included in this analysis. HOMA-beta was negatively associated with TBWL% at second, third, and fourth years post-surgery (ß = -1.04 [-1.82 to -0.26], p<0.01; ß = -1.16 [-2.13 to -0.19], p=0.02; ß = -1.29 [-2.64 to 0.06], p=0.061, respectively). This was not observed in the first year post-surgery nor for the other indexes. Glycemia at baseline was positively associated to EWL% at second and third years post-surgery. Conclusion: ß-cell function at baseline seems to be associated to long-term weight loss, explicitly after the first year post bariatric surgery. This might be a helpful predictor of weight loss in clinical practice.

Secondary Hyperparathyroidism Among Bariatric Patients: Unraveling the Prevalence of an Overlooked Foe.

INTRODUCTION: Bariatric surgery (BS) is the most effective therapeutic approach to obesity. It is associated with great gastrointestinal anatomic changes, predisposing the patients to altered nutrient absorption that impacts phosphocalcium metabolism. This study aimed to clarify the prevalence of secondary hyperparathyroidism (SHPT) and its predictors in patients submitted to BS. METHODS: Retrospective study of 1431 patients who underwent metabolic surgery between January 2010 and June 2017 and who were followed for at least 1 year. We compared the clinical and biochemical characteristics of patients with and without secondary hyperparathyroidism (considering SHPT a PTH ˃ 69 pg/mL). Two different analyses were performed: (1) paired analysis of participants before and 1 year after surgery (N = 441); (2) Cross sectional analysis of participants submitted to bariatric surgery before (N = 441), 1 year after (N = 1431) and 4 years after surgery (N = 333). Multiple logistic regression models were used to evaluate possible predictors of SHPT after BS. RESULTS: The overall prevalence of SHPT was 24.9% before surgery, 11.2% 1 year after surgery and 21.3% 4 years after surgery. Patients submitted to LAGB had the highest prevalence of SHPT 1 year after surgery (19.4%; vs RYGB, 12.8%, vs SG, 5.3%). Four years after surgery, RYGB had the highest prevalence of SHPT (27.0%), followed by LAGB (13.2%) and SG (6.9%). Higher body mass index and age, decreased levels of vitamin D and RYGB seem to be independent predictors of SHPT 1 year after surgery. The only independent predictor of SHPT 4 years after surgery was RYGB. CONCLUSION: The prevalence of SHPT is higher before and 4 years after BS than 1 year after surgery. This fact raises some questions about the efficacy of the implemented follow-up plans of vitamin D supplementation on the long term, mainly among patients submitted to RYGB.

The Impact of Vitamin D in Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study in Patients with Morbid Obesity.

PURPOSE: We aimed to evaluate the association between vitamin D status and hepatic function parameters and scores: Fatty Liver Index (FLI, predictor of hepatic steatosis) and BARD (BMI, AST/ALT ratio and DM, predictor of hepatic fibrosis) in patients with morbid obesity. PATIENTS AND METHODS: Cross-sectional study including patients with morbid obesity followed in our centre between January 2010 and July 2018. Patients with missing vitamin D levels or hepatic profile parameters were excluded. We divided the population according to two cut-offs of vitamin D levels (12ng/mL and 20ng/mL). RESULTS: The included population (n=1124) had an average age of 43.3±10.7 years and 84.3% were female. Seventy-point eight percent of the population had vitamin D levels lower than 20ng/mL and 34.8% lower than 12ng/dL. Patients with lower vitamin D levels (<12ng/mL) had higher BMI, hip and waist circumferences and higher prevalence of hypertension. Higher FLI scores [OR= 0.77 (0.07), p<0.01] and ALP levels [ß= -0.03 (-0.06, -0.01), p<0.01] associated to lower vitamin D levels. CONCLUSION: Vitamin D deficiency is associated with a higher risk of hepatic steatosis in individuals with morbid obesity. Correction of vitamin D deficiency may have a beneficial role in the management of NAFLD in patients with morbid obesity.

The Impact of Bariatric Surgery on Hepatic Function and Predictors of Liver Steatosis and Fibrosis.

PURPOSE: To evaluate the variation in parameters of hepatic function and in the scores Fatty Liver Index (FLI; predictor of hepatic steatosis) and BARD (BMI, AST/ALT ratio and DM, predictor of hepatic fibrosis), 1 year after bariatric surgery. MATERIAL AND METHODS: This is a observational retrospective cohort study in patients with morbid obesity that underwent bariatric surgery in our centre. We used two linear regression models: (1) unadjusted and (2) adjusted for surgery type, sex, age, body mass index, diabetes, and dyslipidaemia. RESULTS: The included population (n = 1955) had an average age of 43.1 ± 10 years and 85.8% were female. Diabetes was present in 32.4% of the patients, 45.1% had dyslipidaemia, and 62.2% had hypertension. Twelve percent were submitted to gastric band, 29.6% to sleeve gastrectomy, and 58.4% to gastric bypass. We observed a relevant decrease in transaminases and gamma-glutamyltransferase, and an increase in alkaline phosphatase and total bilirubin. Both FLI and BARD markedly decrease 1 year after surgery (p < 0.01). Comparing the surgical procedures, sleeve gastrectomy was associated with a greater reduction of hepatic enzymes and of both FLI and BARD compared with gastric band. Comparing with gastric bypass, sleeve was associated with a greater reduction of transaminases and alkaline phosphatase, but a smaller reduction of FLI and BARD. CONCLUSION: Bariatric surgery is associated with a reduction of the hepatic enzymes and an improvement of FLI and BARD. It may represent an effective therapeutic approach for NAFLD.

Thyroid Function and the Risk of Non-Alcoholic Fatty Liver Disease in Morbid Obesity.

Background: An association between hypothyroidism and the risk of Non-alcoholic Fatty Liver Disease (NAFLD) has been suggested. This association remains to be elucidated in patients with morbid obesity. Aim: To evaluate the association between thyroid function and parameters of liver function and hepatic scores in patients with morbid obesity. Methods: Patients with morbid obesity followed in our center between January 2010 and July 2018 were included. The ones without evaluation of liver and thyroid functions were excluded. Fatty Liver Index (FLI) and BARD scores were used as predictors of hepatic steatosis and fibrosis, respectively. Results: We observed a positive association between TSH and both BARD (OR 1.14; p = 0.035) and FLI (OR 1.19; p = 0.010) in the unadjusted analysis. We found a negative association between free triiodothyronine levels and BARD (OR 0.70; p<0.01) and a positive association between free triiodothyronine levels and FLI (OR 1.48; p = 0.022). Concerning liver function, we found a positive association between total bilirubin and free thyroxine levels (ß = 0.18 [0.02 to 0.35]; p = 0.033) and a negative association between total bilirubin and free triiodothyronine levels (ß = -0.07 [-0.14 to -0.002]; p = 0.042). Conclusion: Higher levels of TSH and free triiodothyronine may be associated with a higher risk of NAFLD, particularly steatosis, in patients with morbid obesity.

Surgery in Pediatric Crohn Disease: Case Series from a Single Tertiary Referral Center.

INTRODUCTION: There is a recognized increase of lifelong surgery risk in Crohn disease (CD). Outcome data concerning surgery in children, particularly in the biological era, are limited. AIM: To characterize the clinical profile and the clinical outcome in children and adolescents with CD who underwent surgical intervention, in a single tertiary referral center. METHODS: Retrospective, cross-sectional study, including pediatric patients with CD undergoing intra-abdominal surgery in the last 11 years. RESULTS: Included eight of 50 CD total patients (16%); six female; median age at CD diagnosis of 12.0 years; Paris classification: (a) location: ileocolonic (5), colonic (1), upper disease (1), ileocolonic/upper disease (1); (b) behavior: stricturing (4), nonstricturing nonpenetrating (2), penetrating (1), both penetrating and stricturing disease (1); growth delay (2). Six children received thiopurines, five mesalazine, three corticosteroids and four anti-TNF therapy, preoperatively. Surgery followed diagnosis by a median of 2.9 years. Median PCDAI at the time of surgery was 35.0. Elective surgery was performed in six patients and emergency surgery in two, without major complications. Five children received anti-TNF and three thiopurines post-operatively. Within the follow-up period (median 1.7 years), relapse occurred in one child (3.2 years after intervention); the remaining seven patients persist in clinical remission. Median PCDAI in the last evaluation was 6.3. Weight and height recovery was observed in seven patients, at last follow-up. CONCLUSION: Surgical treatment of CD is a valid alternative in selected cases, contributing to the resolution of acute complications and maintenance of remission, allowing disease-free interval and nutritional recovery.

INTRODUÇÃO: É reconhecido o risco aumentado de cirurgia ao longo da vida na população com doença de Crohn (DC). Contudo os estudos publicados em idade pediátrica são ainda escassos, particularmente na era dos biológicos. OBJETIVOS: Caraterizar o perfil evolutivo da população pediátrica com DC submetida a cirurgia num centro de referência. MÉTODOS: Estudo retrospetivo, transversal, doentes pediátricos com DC submetidos a cirurgia intra-abdominal no período de 11 anos. RESULTADOS: 8/50 doentes com DC (16%); seis raparigas; idade mediana ao diagnóstico 12,0 anos; Classificação de Paris: a) localização: ileocólica (5), cólica (1), proximal (1); ileocólica e proximal (1); b) comportamento: estenosante (4), não estenosante não penetrante (2), penetrante (1), estenosante e penetrante (1); atraso de crescimento (2); terapêutica pré-cirurgia: tiopurinas (6), mesalazina (5), corticóides (3) e agentes biológicos (4). Mediana do PCDAI à data da cirurgia 35,0. O timing cirúrgico mediano foi 2,9 anos após o diagnóstico. Foram efetuadas cirurgias eletivas em seis doentes e de emergência em dois, sem complicações. No período após cirurgia, a terapêutica de manutenção incluiu: biológicos (5) e tiopurinas (3). No período de seguimento (mediana 1,7 anos), ocorreu recidiva numa criança (3,2 anos após a intervenção); as restantes persistiram em remissão clínica; PCDAI mediano na última avaliação 6,3. Observou-se recuperação ponderal e estatural em sete doentes, na última avaliação. CONCLUSÃO: O tratamento cirúrgico da DC representa uma alternativa válida em casos selecionados, contribuindo para a resolução de complicações agudas e manutenção da remissão, permitindo um intervalo livre de doença e recuperação nutricional.

Neonatal McCune-Albright syndrome with systemic involvement: a case report.

INTRODUCTION: McCune-Albright syndrome is a rare sporadic disease characterized by fibrous bone dysplasia, café-au-lait skin spots and variable hyperfunctional endocrinopathies. McCune-Albright syndrome is caused by somatic postzygotic activating mutations in the GNAS gene that produce a broad spectrum of effects. CASE PRESENTATION: We report a case of McCune-Albright syndrome with multi-organ manifestations in the neonatal period. A newborn preterm black girl was referred to our Neonatal Intensive Care Unit at the age of 17 days for suspected extrahepatic cholestasis. On clinical examination she presented failure to thrive, jaundice, hypertension, marked hypotonia and café-au-lait spots on her back and lower limbs. An abdominal ultrasound excluded extrahepatic causes of cholestasis but revealed bilateral serpiginous adrenal hyperplasia. These clinical findings suggested a diagnosis of McCune-Albright syndrome with multi-organ involvement. Laboratory data confirmed adrenocorticotropic hormone-independent Cushing's syndrome, hyperthyroidism, cholestasis and elevated transaminases. Ventricular hypertrophy was demonstrated by echocardiography. The baby girl underwent medical treatment of Cushing's syndrome with metyrapone which was followed by a rapid recovery. A mosaic activating GNAS gene mutation was found on DNA extracted from a buccal swab sample. However, she died at 4 months due to a respiratory infection. CONCLUSION: In the neonatal period the diagnosis of McCune-Albright syndrome depends on having a high index of suspicion and café-au-lait spots may be the clue for the diagnosis.

Transient neonatal diabetes due to a missense mutation (E227K) in the gene encoding the ATP-sensitive potassium channel (KCNJ11).

Neonatal diabetes is a monogenic form of diabetes. Herein, we report on a newborn presenting diabetic ketoacidosis at 17 days of life. A KCNJ11 mutation was identified. In such cases, insulin can be replaced by sulfonylurea with a successful metabolic control, as an example of how molecular diagnosis may influence the clinical management of the disorder.

Surto de shigelose em missäo operativa da marinha do Brasil / Shigelosis outbreak in a operative mission of Brasilian marine

Os autores descrevem um surto de shigelose em uma populaçäo militar durante operaçäo na Restinga da Marambaia, RJ, em maio de 1989, na qual 101 dos 418 militares apresentaram diarréia. Shigella flexneri foi isolada em coprocultura de 7 pacientes, examinados na fase aguda da doença; 5 deles foram tratados com ampicilina e após 10 dias, nenhum apresentou mais cultura positiva para shigella. A dor abdominal e a febre foram os dados mais freqüentes. Os 94 pacientes restantes foram examinados 4 semanas após a fase aguda de diarréia, näo sendo isolada shigella nas coprocultruas deste grupo

Discussäo sobre o risco das interaçöes de agrotóxicos na dieta brasileira / Discussion about the risk of pesticides interactions in the Brazilian diet

Objetivo. Estudar os riscos à saúde humana da interaçäo de resíduos de agrotóxicos em alimentos consumidos pelos brasileiros. Material e Método. Com base na legislaçäo brasileira sobre Limite Máximo de Resíduo (LMR), Ingestäo Diária Aceitável (IDA) dos agrotóxicos e com alguns dados da dieta do brasileiro (IBGE/POF) foram estudados três alimentos (tomate, maçä e banana) de relevante consumo e uso de agrotóxicos. Estes dados foram tabulados individualmente para cada alimento e foram a base para cálculo do índice de risco e para o estudo das interaçöes. Resultados. Os agrotóxicos de menos toxidade no grupo químico dos organofosforados e carbamatos (OP/CP) mostraram-se dentro do aceitável para tomate, banana-maçä, banana-dÆágua e maçä; e acima do aceitável para banana-prata. Para agrotóxicos de maior toxicidade neste grupo, constatou-se que o mesmo índice estava dentro do aceitável para banana-maçä , banana-dÆágua e maçä; e acima do aceitável para banana-prata e tomate. No grupo químico dos organoclorados e piretróides (OC/PY), os agrotóxicos de menor toxicidade apresentaram-se dentro do aceitável apenas para as bananas ficando o tomate e a maçä acima do aceitável. Para agrotóxicos de maior toxicidade, este índice foi considerado aceitável para tomate, banana-maçä, banana-dÆágua e maçä; e acima do aceitável apenas para banana-prata. Conclusäo. Os índices de risco à saúde humana devido ao consumo de alimentos com resíduos de agrotóxicos podem diferir quando as análises consideram os agrotóxicos individualmente ou levam em consideraçäo as suas interaçöes.