An Uncommon Cause of Recurrent Dysphagia and Chest Pain in an Adolescent Boy.

An 11-year-old boy was brought to the emergency department with a week-long history of widespread pain in his upper abdomen that worsened with deep breathing and eating, sialorrhea, food impaction sensation, and a recent fever. Ten months prior, he had similar symptoms and was diagnosed with a pharyngeal phlegmon. He was treated with antibiotics and dexamethasone. In the current episode, he presented with mild elevation of inflammatory markers, a slight deviation of the trachea on chest X-ray, and a tubular esophageal duplication was identified on a thoracic CT, with its opening observed during the endoscopic study. The patient was admitted for further treatment with fluids, analgesia, and antibiotics, and showed improvement over the next seven days with no significant incidents. Esophageal duplications are a rare congenital anomaly and their exact cause is unknown. Typically found in the posterior mediastinum and lower esophagus, they can cause symptoms such as pain, dysphagia, regurgitation, and malnutrition. Surgical or endoscopic resection can be a treatment option for these malformations.

Curva de Aprendizagem da Mortalidade Hospitalar da Substituição da Válvula Aórtica Transcateter: Insights do Registro Nacional Brasileiro / Learning Curve for In-Hospital Mortality of Transcatheter Aortic Valve Replacement: Insights from the Brazilian National Registry

Resumo Fundamento Dados robustos sobre a curva de aprendizagem (LC) da substituição da válvula aórtica transcateter (TAVR) são escassos nos países em desenvolvimento. Objetivo Avaliar a LC da TAVR no Brasil ao longo do tempo. Métodos Analisamos dados do registro brasileiro de TAVR de 2008 a 2023. Pacientes de cada centro foram numerados cronologicamente em número sequencial de caso (NSC). A LC foi realizada usando um spline cúbico restrito ajustado para o EuroSCORE-II e o uso de próteses de nova geração. Ainda, os desfechos hospitalares foram comparados entre grupos definidos de acordo com o nível de experiência, com base no NSC: 1º ao 40º caso (experiência inicial), 41º ao 80º caso (experiência básica), 81º ao 120º caso (experiência intermediária) e 121º caso em diante (experiência alta). Análises adicionais foram conduzidas de acordo com o número de casos tratados antes de 2014 (>40 e ≤40 procedimentos). O nível de significância adotado foi p <0,05. Resultados Foram incluídos 3194 pacientes de 25 centros. A idade média foi 80,7±8,1 anos e o EuroSCORE II médio foi 7±7,1. A análise da LC demonstrou uma queda na mortalidade hospitalar ajustada após o tratamento de 40 pacientes. Um patamar de nivelamento na curva foi observado após o caso 118. A mortalidade hospitalar entre os grupos foi 8,6%, 7,7%, 5,9%, e 3,7% para experiência inicial, básica, intermediária e alta, respectivamente (p<0,001). A experiência alta foi preditora independente de mortalidade mais baixa (OR 0,57, p=0,013 vs. experiência inicial). Centros com baixo volume de casos antes de 2014 não mostraram uma redução significativa na probabilidade de morte com o ganho de experiência, enquanto centros com alto volume de casos antes de 2014 apresentaram uma melhora contínua após o caso de número 10. Conclusão Observou-se um fenômeno de LC para a mortalidade hospitalar do TAVR no Brasil. Esse efeito foi mais pronunciado em centros que trataram seus 40 primeiros casos antes de 2014 que naqueles que o fizeram após 2014.

Abstract Background Robust data on the learning curve (LC) of transcatheter aortic valve replacement (TAVR) are lacking in developing countries. Objective To assess TAVR's LC in Brazil over time. Methods We analyzed data from the Brazilian TAVR registry from 2008 to 2023. Patients from each center were numbered chronologically in case sequence numbers (CSNs). LC was performed using restricted cubic splines adjusted for EuroSCORE-II and the use of new-generation prostheses. Also, in-hospital outcomes were compared between groups defined according to the level of experience based on the CSN: 1st to 40th (initial-experience), 41st to 80th (early-experience), 81st to 120th (intermediate-experience), and over 121st (high-experience). Additional analysis was performed grouping hospitals according to the number of cases treated before 2014 (>40 and ≤40 procedures). The level of significance adopted was <0.05. Results A total of 3,194 patients from 25 centers were included. Mean age and EuroSCORE II were 80.7±8.1 years and 7±7.1, respectively. LC analysis demonstrated a drop in adjusted in-hospital mortality after treating 40 patients. A leveling off of the curve was observed after case #118. In-hospital mortality across the groups was 8.6%, 7.7%, 5.9%, and 3.7% for initial-, early-, intermediate-, and high-experience, respectively (p<0.001). High experience independently predicted lower mortality (OR 0.57, p=0.013 vs. initial experience). Low-volume centers before 2014 showed no significant decrease in the likelihood of death with gained experience, whereas high-volume centers had a continuous improvement after case #10. Conclusion A TAVR LC phenomenon was observed for in-hospital mortality in Brazil. This effect was more pronounced in centers that treated their first 40 cases before 2014 than those that reached this milestone after 2014.

Effect of Personalized Sodium Replacement on Fluid and Sodium Balance and Thermophysiological Strain During and After Ultraendurance Running in the Heat.

PURPOSE: To investigate the effect of personalized sweat sodium replacement on drinking behavior, sodium and water balance, and thermophysiological responses during and after ultraendurance running in hot conditions. METHODS: Nine participants (7 male, 2 female) completed two 5-hour treadmill runs (60% maximum oxygen uptake, 30°C ambient temperature), in a double-blind randomized crossover design, consuming sodium chloride (SODIUM) capsules to replace 100% of previously assessed losses or placebo (PLACEBO). Fluid was consumed ad libitum. RESULTS: No effect of SODIUM was observed for ad libitum fluid intake or net fluid balance (P > .05). Plasma sodium concentration increased in both trials, but to a greater extent in SODIUM at 2.5 hours (mean [SD]: 4 [4] mmol·L-1 vs 1 [5] mmol·L-1; P < .05) and postexercise (4 [3] mmol·L-1 vs 1 [5] mmol·L-1; P < .05). Plasma volume change was not different between trials (P > .05) but was strongly correlated with sodium balance in SODIUM (r = .880, P < .01). No effect of sodium replacement was observed for heart rate, rectal temperature, thermal comfort, perceived exertion, or physiological strain index. During the 24 hours postexercise, ad libitum fluid intake was greater following SODIUM (2541 [711] mL vs 1998 [727] mL; P = .04), as was urinary sodium excretion (NaCl: 66 [35] mmol, Pl: 21 [12] mmol; P < .01). CONCLUSIONS: Personalized sweat sodium replacement during ultraendurance running in hot conditions, with ad libitum fluid intake, exacerbated the rise in plasma sodium concentration compared to no sodium replacement but did not substantially influence overall body-water balance or thermophysiological strain. A large sodium deficit incurred during exercise leads to substantial renal sodium conservation postexercise.

Leprosy in children under fifteen years of age in the most hyperendemic municipality in Brazil / Hanseníase em menores de quinze anos no município mais hiperendêmico do Brasil

ABSTRACT Objective: To describe leprosy involvement and physical disability profiles in children and adolescents under 15 years old. Methods: Ecological time series study, based on data from the Brazilian Notifiable Diseases Information System, including new cases of leprosy residing in Palmas (TO), from 2001 to 2020. Results: A total of 471 notified cases in children and adolescents under 15 years of age were evaluated, resulting in a detection coefficient of 26.5 per 100,000 inhabitants. Of these, 52% (n=243) were women, 5% (n=24) corresponded to grade two disability, and 36% (n=168) were diagnosed through spontaneous demand. The temporal trend analysis showed a 0.5% reduction in the detection coefficient. There was a significant decrease in the diagnosis of the undetermined and tuberculoid clinical forms and a significant increase in the dimorphous form. Diagnosis through contact examination increased significantly by 13.1% and that through spontaneous demand decreased by 4.9%. The detection coefficient of cases with grade two disability reduced significantly by 7.4% while those with grade one increased by 16.8%. Conclusions: Despite the downward trend in the detection coefficient in children and adolescents under 15 years of age and in cases with grade two disability, other factors indicate failure in the adequate management of leprosy in Palmas.

RESUMO Objetivo: Descrever os perfis de acometimento de hanseníase e incapacidade física em menores de 15 anos. Métodos: Estudo ecológico de série temporal, baseado em dados do Sistema Nacional de Agravos de Notificação, incluindo casos novos de hanseníase residentes em Palmas (TO), no período de 2001 a 2020. Resultados: Foram avaliados 471 casos notificados em crianças e adolescentes menores de 15 anos, resultando em um coeficiente de detecção de 26,5 por cem mil habitantes. Destes, 52% (n=243) eram do gênero feminino, 5% (n=24) correspondiam ao grau dois de incapacidade física, e 36% (n=168) foram diagnosticados por demanda espontânea. A análise de tendência temporal mostrou queda do coeficiente de detecção em 0,5%. Houve queda significativa no diagnóstico das formas clínicas indeterminada e tuberculoide e aumento significativo da dimorfa. O diagnóstico por exame de contato teve um aumento significativo de 13,1% e o por demanda espontânea, queda significativa de 4,9%. O coeficiente de detecção de casos com grau dois de incapacidade apresentou uma queda significativa de 7,4%, enquanto o de casos com grau um, apresentou um aumento de 16,8%. Conclusões: Apesar da tendência de queda do coeficiente de detecção em menores de 15 anos e do coeficiente de detecção de casos com grau dois de incapacidade, outros fatores indicam falha no manejo adequado da hanseníase em Palmas.

Pediatric COVID-19: clinical and epidemiological data of 1303 cases in a general hospital in Brazil / COVID-19 pediátrico: dados clínicos e epidemiológicos de 1303 casos em um hospital geral no Brasil

ABSTRACT Objective: This study aimed to describe the clinical characteristics of the pediatric population with COVID-19 in an Emergency Department (ED) of a Brazilian general hospital. Methods: Epidemiological and clinical data of patients younger than 20 years old were collected from patients' medical records from February 2020 to July 2021. Most of the epidemiological data described pertains to hospitalized patients. We also reviewed coinfections, treatment, and outcomes and compared the first and second waves of COVID-19. Results: We identified a total of 1303 episodes of SARS-CoV-2 infection. The median time from symptom onset to diagnosis was three days. Symptoms were present in 92.3% of the patients. The most common symptoms were fever (45.2%), nasal congestion/discharge (44.2%), and cough (39.4%). Chest radiography and tomography were performed in 7.7 and 3.3% of cases, with abnormal findings in 29.7 and 53.4%, respectively. Hospital admissions occurred in 3.5% of patients, mainly in the presence of comorbidities, in children under five years old and in those who presented to the ED during the first wave of COVID-19. Coinfection with a viral agent was identified in 20% of the 71 cases tested in this study, and a positive rapid test for Streptococcus pyogenes was found in 8% of the 174 cases tested, with no impact of these coinfections on hospitalization. Conclusions: We found that COVID-19 was a mild disease in most children in our study population, with most hospitalizations and readmissions occurring during the first wave of COVID-19.

RESUMO Objetivo: Este estudo teve como objetivo descrever as características clínicas da população pediátrica com COVID-19 no setor de emergência de um hospital geral brasileiro. Métodos: Os dados epidemiológicos e clínicos de pacientes idade inferior a 20 anos foram coletados dos prontuários dos pacientes de fevereiro de 2020 a julho de 2021. A maior parte dos dados epidemiológicos descritos refere-se a pacientes hospitalizados. Também foram revisados as coinfecções, o tratamento e os desfechos de internação e comparadas a primeira e a segunda ondas de COVID-19. Resultados: Foi identificado o total de 1.303 episódios de infecção por SARS-CoV-2. A mediana de tempo desde o início dos sintomas até o diagnóstico foi de três dias. Os sintomas estiveram presentes em 92,3% dos pacientes. Os sintomas mais comuns foram febre (45,2%), congestão/secreção nasal (44,2%) e tosse (39,4%). Radiografia e tomografia de tórax foram realizadas em 7,7 e 3,3% dos casos, com achados anormais em 29,7 e 53,4%, respectivamente. As internações hospitalares ocorreram em 3,5% dos pacientes, principalmente na presença de comorbidades, em crianças menores de cinco anos e naqueles que se apresentaram no pronto-socorro durante a primeira onda de COVID-19. Foi identificada coinfecção viral em 20% dos 71 casos testados e teste rápido positivo para Streptococcus pyogenes em 8% dos 174 casos testados, não havendo impacto dessas coinfecções quanto à internação hospitalar. Conclusões: Observamos que a COVID-19 foi uma doença leve na maioria das crianças de nossa população, com a maior parte das hospitalizações e readmissões ocorrendo durante a primeira onda de COVID-19.

A Cohort Study of the Antitumor Efficacy and Toxicity Profile of Alpelisib for Metastatic or Locally Advanced HR+, HER2- Breast Cancer: A Single-Institution Experience.

INTRODUCTION: Alpelisib is approved in combination with endocrine therapy (ET) to treat patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) progressive metastatic breast cancer (MBC). The SOLAR-1 trial demonstrated the efficacy of this oral agent and showed that, while alpelisib improves outcomes compared to placebo, it is also associated with clinically relevant adverse events (AEs). There is a pressing need for improved knowledge on the effectiveness and tolerability of this agent in real-world patient populations. METHODS: We conducted a retrospective cohort study of patients with HR+, HER2- MBC treated with alpelisib and ET. We assessed the safety, tolerability, and effectiveness of alpelisib in a real-world population. Deidentified patient-, tumor-, and outcome-related data, including AEs, were collected and summarized. Kaplan-Meier methods were applied for survival analyses, and stratified analyses of interest were conducted. A p value <0.05 was considered statistically significant. RESULTS: A total of 76 women treated with alpelisib + ET were included in our cohort. Most had been previously treated with cyclin-dependent kinase (CDK) 4/6 inhibitors and chemotherapy for MBC. The estimated median progression-free survival was 5.2 months (95% CI, 4.1-8.0). The median overall survival was longer among patients without prior everolimus therapy (hazard ratio, 4.28 [95% CI, 1.64-11.16]; p = 0.0012), and no significant outcome differences were observed between patients treated with different starting doses of alpelisib. Approximately 31.6% of patients permanently discontinued alpelisib due to AEs, and 32.9% had at least one dose reduction. The most common grade 3/4 AEs were hyperglycemia (21%), fatigue (13.2%), and diarrhea (10.5%). CONCLUSIONS: For progressive HR+, HER2- MBC, alpelisib + ET showed effectiveness in a real-world patient population that was comparable to published clinical trial data, regardless of starting dose. However, the effectiveness of alpelisib following previous everolimus exposure may be limited and, hence, should be a consideration to decide sequencing of therapy in these patients. Patients treated with alpelisib are at risk for clinically relevant AEs and require close monitoring.

Retrospective Study of Treatment Patterns and Natural History of Patients with T1a/b N0 Triple-Negative Breast Cancers: A Single-Institution Experience.

INTRODUCTION: T1a/b, node-negative (node-), triple-negative breast cancers (TNBCs) are underrepresented in randomized drug-approving clinical trials. Given their low incidence, the clinicopathological features, natural history, and treatment patterns of these tumors remain insufficiently understood. METHODS: We conducted a single-institution retrospective cohort study of patients with T1a/b, N0, M0 TNBCs. Deidentified patient- and tumor-related data were collected and summarized. Kruskal-Wallis, χ2, or Fisher exact tests were used to evaluate associations of interest. Kaplan-Meier methods, log-rank tests, and Cox's proportional hazards models were applied for survival analyses. RESULTS: Of 108 cases of node- TNBCs measuring ≤2 cm, 34 node- T1a/b tumors were included in our analysis. All cases had an intermediate to high histological grade, and most had a Ki-67 score of ≥20%. All patients received adjuvant chemotherapy, and many underwent mastectomy (47%). Docetaxel combined with cyclophosphamide was the most common adjuvant chemotherapy regimen (75%). We did not observe significant associations between improved outcomes and treatment with anthracycline-containing regimens. Among patients with node- pT1a/b tumors, the estimated 3-year recurrence-free survival (RFS) and distant RFS rates were both 96.3% (95% CI: 76.5-99.5), and the overall survival rate was estimated to be 100% (95% CI: 100-100). There were no cases of local recurrences observed. CONCLUSIONS: In our cohort, all patients with T1a/b node- TNBCs were treated with adjuvant chemotherapy and had favorable outcomes even when treated with anthracycline-sparing regimens.

Sarcopenia in Children With Wilms Tumor: A Marker of Undernutrition Which May Impact Adversely on Clinical Outcomes.

The therapeutic approach to Wilms tumor (WT) is multidisciplinary and leads to significant patient impairment, increasing the risk of nutritional compromise and malnutrition. Children with cancer are vulnerable to sarcopenia which has been recognized as a negative impact of anticancer therapy. Recent studies have highlighted the reduction in the total psoas muscle area (TPMA) to be associated with a poor prognosis in many pediatric diseases, including cancer. This study aims to evaluate changes in the TPMA compartment during the treatment of children with WT. An observational, longitudinal, and retrospective study was undertaken in a single institution evaluating children (1 to 14 y, n=38) with WT between 2014 and 2020. TPMA was assessed by the analysis of previously collected, electronically stored computed tomography images of the abdomen obtained at 3 time points: diagnosis, preoperatively, and 1 year after surgery. For all patients, TPMA/age were calculated with a specific online calculator. Our data show a high incidence of sarcopenia (55.3%) at diagnosis which increased after 4 to 6 weeks of neoadjuvant chemotherapy (73.7%) and remained high (78.9%) 1 year after the surgical procedure. Using TPMA/age Z-score curves we have found significant and rapid muscle loss in children with WT, with little or no recovery in the study period.

Early-Stage Triple-Negative Breast Cancer Journey: Beginning, End, and Everything in Between.

Triple-negative breast cancer (TNBC) is a very heterogeneous and aggressive breast cancer subtype with a high risk of mortality, even if diagnosed early. The mainstay of early-stage breast cancer includes systemic chemotherapy and surgery, with or without radiation therapy. More recently, immunotherapy is approved to treat TNBC, but managing immune-rated adverse events while balancing efficacy is a challenge. The purpose of this review is to highlight the current treatment recommendations for early-stage TNBC and the management of immunotherapy toxicities.

Spectrochemical analysis of seasonal and sexual variation of antioxidants in Corema album (L.) D. Don leaf extracts.

Bioactive phytoconstituents have been increasingly investigated for their potential human health benefits. Corema album (L.) D. Don, an Ericaceae, reportedly has antioxidant, antimicrobial and anticancer properties. Aiming at enhancing its nutraceutical potential, we performed a spectrochemical analysis of hydroethanolic extracts from C. album leaves. We report on changes in the antioxidant activity of the extracts, as well as in the accumulation of key phytoconstituents (namely phenolic compounds), in female and male samples, throughout three harvesting seasons (February, July, and October). For each extract, the antioxidant activity was assessed by different spectrophotometric methods. Simultaneously, attenuated total reflectance Fourier transform mid-infrared spectroscopy (FTIR-ATR), and high-performance liquid chromatography - electrospray ionisation - quadrupole time-of-flight mass spectrometry (HPLC-ESI-Q-TOF-MS), were used to identify and monitor variations in the composition of phenolic compounds in the extracts. The main compounds identified were epicatechin, laricitrin-O-hexoside isomers, and myricetin-O-hexoside isomers. Significant differences were found in the composition and relative abundance of the compounds of interest, according to sex and season. Overall, a trend was observed whereby phenolic content and antioxidant activities were higher in males and increased between the earlier and the latest harvests. Based on these results, we may conclude that late summer or early autumn harvests are preferable when aiming at the highest yearly content of bioactive compounds. Additionally, it should be considered that extracts from male individuals typically display higher antioxidant activities. Ultimately, our understanding of C. album in the context of nutraceutical applications is benefited from the quantitative and qualitative portrait provided here, thus promoting its relevance as a source of bioactive compounds.

Ioxaglate Versus IoDixanol for the Prevention of Contrast-Induced Nephropathy: The IDPC Trial.

BACKGROUND: Despite the potential benefits of percutaneous procedures for the assessment and treatment of coronary artery disease, these interventions require the use of iodine contrast, which might lead to contrast-induced nephropathy (CIN) and increased risk of dialysis and major adverse cardiac events (MACE). AIMS: We sought to compare two different iodine contrasts (low vs. iso-osmolar) for the prevention of CIN among high-risk patients. METHODS: This is a single-center, randomized (1:1) trial comparing consecutive patients at high risk for CIN referred to percutaneous coronary diagnostic and/or therapeutic procedures with low (ioxaglate) vs. iso-osmolarity (iodixanol) iodine contrast. High risk was defined by the presence of at least one of the following conditions: age >70 years, diabetes mellitus, non-dialytic chronic kidney disease, chronic heart failure, cardiogenic shock, and acute coronary syndrome (ACS). The primary endpoint was the occurrence of CIN, defined as a >25% relative increase and/or >0.5 mg/dL absolute increase in creatinine (Cr) levels compared with baseline between the 2nd and 5th day after contrast media administration. RESULTS: A total of 2,268 patients were enrolled. Mean age was 67 years. Diabetes mellitus (53%), non-dialytic chronic kidney disease (31%), and ACS (39%) were highly prevalent. The mean volume of contrast media was 89 ml ± 48.6. CIN occurred in 15% of all patients, with no significant difference regarding the type of contrast used (iso = 15.2% vs. low = 15.1%, P>.99). Differences were not observed in specific subgroups such as diabetics, elderly, and ACS patients. At 30-day follow-up, 13 patients in the iso-osmolarity group and 11 in low-osmolarity group required dialysis (P =.8). There were 37 (3.3%) deaths in the iso-osmolarity cohort vs. 29 (2.6%) in the low-osmolarity group (P =.4). CONCLUSION: Among patients at high risk for CIN, the incidence of this complication was 15%, and independent of the use of low- or iso-osmolar contrast.

Oncolytic T-VEC virotherapy plus neoadjuvant chemotherapy in nonmetastatic triple-negative breast cancer: a phase 2 trial.

Talimogene laherparepvec (T-VEC) is an oncolytic virus hypothesized to enhance triple-negative breast cancer (TNBC) responses to neoadjuvant chemotherapy (NAC). This article describes the phase 2 trial of T-VEC plus NAC (ClinicalTrials.gov ID: NCT02779855 ). Patients with stage 2-3 TNBC received five intratumoral T-VEC injections with paclitaxel followed by doxorubicin and cyclophosphamide and surgery to assess residual cancer burden index (RCB). The primary end point was RCB0 rate. Secondary end points were RCB0-1 rate, recurrence rate, toxicity and immune correlates. Thirty-seven patients were evaluated. Common T-VEC toxicities were fevers, chills, headache, fatigue and injection site pain. NAC toxicities were as expected. Four thromboembolic events occurred. The primary end point was met with an estimated RCB0 rate = 45.9% and RCB0-1 descriptive rate = 65%. The 2-year disease-free rate is equal to 89% with no recurrences in RCB0-1 patients. Immune activation during treatment correlated with response. T-VEC plus NAC in TNBC may increase RCB0-1 rates. These results support continued investigation of T-VEC plus NAC for TNBC.

Clinical and Prognostic Impact of the Warburg Effect in Esophageal Carcinoma: Monocarboxylate Transporters as Candidates for Therapeutic Targeting.

INTRODUCTION: Esophageal cancer (EC) seems to display increased glycolytic activity, but clinical studies on the expression/prognostic significance of glycometabolism-related proteins, as well as functional assays, are missing. METHODS: Expression of 10 glycolytic biomarkers was evaluated by immunohistochemistry in tissue sections from 95 patients. Two esophageal squamous cell carcinoma (ESCC) cell lines were used to assess the effect of monocarboxylate transporter (MCT) downregulation on cell viability and extracellular lactate/glucose accumulation. RESULTS: Expression of MCT1, MCT4, CD147, and GLUT1 was significantly associated with an ESCC histopathology, while a poor clinicopathological profile was seen in GLUT1- and LDHA-positive EC cases. In the ESCC group, MCT1 immunoreactivity is associated with high TNM stage and metastasis. The 3-year overall survival (OS) rate was significantly influenced by MCT4 and CAIX positivity and HKII negativity. Those biomarkers were considered independent prognostic factors of OS in multivariate analysis. Dual inhibition of MCT1/4 expression decreased cell viability and extracellular lactate accumulation in ESCC cells. CONCLUSION: Elevated glycolytic rates correlate with a poor clinicopathological profile in EC patients. MCT4 and CAIX positivity independently predict a worse prognosis. Due to the lack of information on treatment modalities, we could not further infer the role of these biomarkers in predicting response to therapy, which needs to be assessed in future studies. In addition, MCT1/4 targeting should be performed both "in vitro" and "in vivo" to further explore its impact on tumor growth and response to classical therapies. HKII expression and function, particularly in the tumor stroma, should be investigated.

A Real-World Data Retrospective Cohort Study of HER2-positive, Early-Stage Breast Cancer in Patients 70 Years of Age or Older: Natural History, Treatment Patterns, and Outcomes.

PURPOSE: Early-stage human epidermal growth factor receptor 2-positive (HER2-positive) breast cancers (BCs) are routinely treated with intense perioperative chemotherapy combined with HER2-targeted agents. There is thus an unmet need for knowledge about treatment patterns and outcomes among patients 70 years of age or older, as this is an under-represented subset of patients in large clinical trials. METHODS: We used a deidentified cohort derived from a nationwide electronic health record database to conduct a retrospective cohort study of patients with HER2-positive BCs. Descriptive statistics were used to evaluate tumor characteristics, treatment patterns across age groups, and pathologic complete response rates. We used Kaplan-Meier survival curves to estimate recurrence-free and overall survivals; Cox proportional methods were used for adjustments with covariates of interest, including age as a categorical variable. RESULTS: We included 395 patients with HER2-positive stage I to III BCs who were 70 years of age or older. Most patients had tumors with high nuclear-grade T2 tumors, and received surgical treatment first. Most patients (61.7%) who received HER2 therapies underwent treatment in the adjuvant setting; paclitaxel and trastuzumab combination was the most commonly used adjuvant regimen. Older age was associated with increased hazard of recurrence or death. We did not detect significant evidence of decline in performance status, but there was modest weight drop after perioperative HER2 treatments. CONCLUSION: Findings suggest that patients in this older-age cohort were treated with de-escalated perioperative strategies and had poorer outcomes; our findings should be validated in future studies.

Acute Hepatitis of Unknown Origin in Children: Two Cases in a Portuguese Hospital.

Several cases of paediatric acute hepatitis of an unknown aetiology have been described in these last few months and in several countries worldwide. We present two patients, a 7-month-old girl and an 8-year-old boy, with gastrointestinal symptoms and lethargy, associated with elevation of transaminase levels. Serologies for hepatitis A-E virus and PCR test to SARS-CoV-2 were all negative. In the first case, an adenovirus serotype C could be isolated in a respiratory sample as well as cytomegalovirus (CMV) in the blood (100 copies/mL). In both children, there was a progressive decrease in the hepatic markers and symptomatic resolution, compatible with a good prognosis, also seen globally in most cases. To date, infection remains the most plausible cause to consider, especially when it is presumed to be linked to adenovirus. Other potential agents and causes are still being evaluated, thus emphasizing the importance of continuous epidemiological surveillance, notification, and detailed study of all hepatitis cases.

Evaluation of the Efficacy of Paracetamol in the Control of Pain After Adenotonsillectomy in the Pediatric Population.

Introduction Adenotonsillectomy is a common surgical procedure in otolaryngology. Over the years, several techniques have been developed and modified in order to reduce mortality and morbidity. Postoperative pain control remains controversial. The aim of this study was to evaluate the efficacy of paracetamol alone in the control of postoperative pain. Methods A prospective study was conducted between May 2018 and February 2019, including 76 pediatric patients (age < 18 years), who underwent adenotonsillectomy. The surgeries were performed by the lead author with the same surgical technique. Patients were evaluated one week and one month after surgery through the application of the visual analog pain scale and the number of days of pain was assessed by the need for medication. Results Seventy-six total adenotonsillectomy were performed, with a total of 152 tonsils removed. The majority of patients were male (n=39, 51.3%), with an average age of 6.9 years (min 5, max 15 years). The most frequent surgical indication was sleep breathing disorders, present in 86.9% of the cases. The average duration of postoperative pain was 3 days, with no significant difference between groups (p>0.05). The average intensity of postoperative pain was 3.36 and was higher in patients with infectious criteria as surgical indications (p<0.05). Postoperative bleeding occurred in 3.9% (n=3) of the children, self-limited, without the need for readmission or surgical revision. Conclusion Pain after adenotonsillectomy was more intense in patients undergoing surgery for infectious criteria. Paracetamol used in monotherapy has shown safety and efficacy in controlling postoperative pain.

Pharyngoplasty for obstructive sleep apnea: The influence of surgical technique.

INTRODUCTION AND OBJECTIVES: Obstructive sleep apnea is the most frequent sleep disorder worldwide, with rising incidence. Pharyngoplasty is an alternative treatment in patients not suitable to continuous positive airway pressure devices (CPAP). The aim of this study is to compare different surgical techniques of pharyngoplasty for treatment of obstructive sleep apnea and evaluate its influence in surgical success. MATERIAL AND METHODS: Retrospective study of 92 patients that underwent pharyngoplasty for treatment of obstructive sleep apnea from 2001 to 2020. Included patients performed classic uvulopalatopharyngoplasty (UPPP), radiofrequency assisted uvulopalatopharyngoplasty (RF-UPPP) or barbed reposition pharyngoplasty (BRP). Surgical success was defined and outcomes and complications assessed for each procedure. RESULTS: Most patients were male, with a mean age of 49.36±9.6 years and a mean apnea hypopnea index (AHI) of 29.14±2.94events/h. Thirty-six patients performed classic UPPP, thirty-one underwent RF-UPPP and the remaining twenty-five performed BRP. BRP achieved the highest success rate (66%) in comparison with UPPP (57%) and RF-UPPP (54%) (p=0.032). Mean relative AHI reduction after surgery was not statistically different between three procedures (p=0.098), although there was a tendency for greater reduction with BRP. Most symptoms improved after surgery and snoring was the most recurrent symptom. BRP had less foreign body sensation after surgery, however, it was the procedure with highest rate of post-operative tonsillar bleeding. CONCLUSIONS: In our department, the introduction of recent techniques of velopharyngeal surgery, focused in functional and lateral muscular collapse, has translated into an increase in success rate after surgery. The relative ease of the procedure and reduction of long term complications make BRP an attractive alternative option for CPAP in OSA, in carefully selected patients.

Predictive factors for repeated tympanostomy tube placement in children.

OBJECTIVES: To determine the rate and risk factors for additional tympanostomy tube (TT) placement after first set of TT extrusion in children. MATERIALS AND METHODS: Single-centre cohort study. Clinical records of children undergoing TT placement from January 2015 to December 2017 were reviewed and factors related to the need for subsequent TT were evaluated. RESULTS: A total of 183 children were included, with a mean age of 5.45±2.672 years old. All surgeries were performed simultaneously with adenoidectomy and 64.3% with tonsillectomy. The mean TT retention time was 12.13±6.033 months and the rate of second TT insertion was 21.9%. The TT retention time was significantly lower in children who needed a second TT (8.97±3.962 vs 13.05±6.229, p<.001). Other factors significantly associated with the need for a second TT in the univariate analysis were the presence of otorrhoea and snoring after TT placement (p=.042 and p=.02), RAOM (p=.016), passive smoking (p=.038) and rhinorrhoea (p=.008). However, on multivariate analysis only TT retention time (OR=.831, 95% CI: .727-.950) and RAOM as an indication for surgery (OR: 5.767; 95% CI: 1.696-19.603) were predictors of a second TT. Gender, age, asthma, prematurity, and low birth weight were not significantly associated with a second TT. CONCLUSIONS: RAOM and a short TT retention time were significantly associated with additional TT placement, enhancing the need for and importance of follow up of these children after TT extrusion.