Bula gigante secundaria a neumonía adquirida en la comunidad en niños / Giant Bulla Secondary to Community-Acquired Pneumonia in Children

Introducción: Los neumatoceles y las bulas pulmonares son lesiones que se observan en los niños casi siempre asociadas a neumonías infecciosas, aunque sus causas pueden ser diversas. La importancia clínica de estos procesos radica en el peligro de crecimiento progresivo, que puede comprometer las funciones respiratoria y cardiovascular. Objetivo: Describir las experiencias derivadas del proceso de diagnóstico por imágenes y del tratamiento invasivo de casos atendidos. Presentación de los casos: Desde finales de 2021 y durante un período de un año, se atendieron, en la unidad de cuidados intensivos pediátricos del Hospital Pediátrico Universitario de Cienfuegos, cinco niños con neumonías extensas, que desarrollaron bulas de gran tamaño varios días después del tratamiento antimicrobiano adecuado. Estas necesitaron drenaje y aspiración percutáneos debido a su magnitud y a la presencia de síntomas cardiovasculares. Conclusiones: Las bulas que aparecieron como complicación de la neumonía en el niño pueden presentarse con una frecuencia no despreciable, y hay que mantenerse atentos a su evolución, porque, a diferencia de los neumatoceles, pueden crecer progresivamente y comprometer las funciones respiratoria y cardiovascular. El drenaje percutáneo y aspiración continua por cinco días resultó un método seguro y eficaz para tratar estos procesos(AU)

Introduction: Pneumoatoceles and pulmonary bullae are lesions that are observed in children almost always associated with infectious pneumonia, although their causes may be diverse. The clinical importance of these processes lies in the danger of progressive growth, which can compromise respiratory and cardiovascular functions. Objective: To describe the experiences derived from the imaging process and the invasive treatment of treated cases. Presentation of the cases: Since the end of 2021 and for a period of one year, five children with extensive pneumonia were treated in the pediatric intensive care unit of the University Pediatric Hospital of Cienfuegos, who developed large bullae several days after appropriate antimicrobial treatment. The bullae required percutaneous drainage and aspiration due to their magnitude and the presence of cardiovascular symptoms. Conclusions: The bulla that appeared as a complication of pneumonia in the child can occur with a not negligible frequency, and it is necessary to be attentive to their evolution, because, unlike pneumoatoceles, can grow progressively and compromise respiratory and cardiovascular functions. Percutaneous drainage and continuous aspiration for five days was a safe and effective method to treat these processes(AU)

Intoxication par tortue de mer vue au Centre Hospitalier Universitaire Antanambao, Toliara, Madagascar / Poisoning by sea turtle at the Antanambao University Hospital, Toliara, Madagasca

Le chélonitoxisme est une intoxication collective par consommation de la chair, de la peau et des viscères de la tortue marine. Elle est peu fréquente. Notre objectif était de décrire l'aspect épidémio-clinique et thérapeutique de l'intoxication par tortue de mer. Méthodes : Il s'agit d'un rapport de cas effectué au Centre Hospitalier Universitaire (CHU) Antanambao Toliara, Madagascar après une intoxication collective dans la commune rurale de Soalara Sud, Toliara. Résultats : Nous avons colligé 70 patients qui ont ingéré une tortue adulte du genre Eretmochelys imbricata. Les signes cliniques étaient du type chélonitoxisme. Parmi les 70 cas, 8 patients ont été hospitalisés. L'âge des patients intoxiqués variait de 2 ans à 65 ans avec un âge moyen de 20 ± 14 ans. La tranche d'âge entre 10-20 ans était la plus touchée (44%). Les hommes représentaient 54% des patients avec un sex ratio de 1,18. Cinquante-huit pourcent ont eu leurs premiers signes 24 heures après l'intoxication et 81% des patients ont été vus au CHU entre 24 et 48 heures. Les signes cliniques du chélonitoxisme sont polymorphes : 86% ont présenté une asthénie, 91% des nausées, 25% des vomissements, 71% des céphalées et 21% des stomatites. A l'issue de l'hospitalisation, 99% des malades ont été guéris et un patient est décédé. Les traitements étaient symptomatiques. Conclusion : L'intoxication par tortue de mer est généralement bénigne. La prise en charge est symptomatique.

Riscos da suplementação com doses excessivas de vitamina D / Risks of Supplementation with Excessive Doses of Vitamin D

A intoxicação por vitamina D era pouco frequente no Brasil até seu crescente uso na última década. Neste artigo relatamos um caso de intoxicação por vitamina D em que houve a prescrição intencional de dose muito superior ao recomendado pela literatura, com a finalidade de prevenir doenças via "modulação hormonal". A paciente em questão, idosa, previamente hígida, foi submetida a um tratamento não regulamentado e sem respaldo científico, que culminou em sintomas como náuseas e vômitos, além de perda de peso, inapetência, poliúria e astenia ao longo dos meses. Através da história e exames laboratoriais foi diagnosticada intoxicação por vitamina D e lesão renal aguda. Após o tratamento houve remissão completa dos sintomas. A "modulação hormonal" é uma prática condenada pelos Conselhos Federais de Medicina e Odontologia e pela Sociedade Brasileira de Endocrinologia e Metabologia. O ato de prescrever é de grande responsabilidade ética e técnica e deve ser embasado em evidências científicas, oferecendo o melhor tratamento possível aos pacientes, seja ele preventivo ou curativo, minimizando riscos e danos, respeitando as recomendações das autoridades competentes. (AU)

Vitamin D poisoning was not frequent in Brazil until its increasing use in the last decade. In this article, we report a case of intoxication by intentional prescription of vitamin D in a much higher dose than the literature recommends, in order to prevent diseases via "hormonal modulation". The case described in this report was an elderly woman, previously healthy patient that was submitted to an unregulated treatment without scientific support, leading to symptoms such as nausea and vomiting, in addition to weight loss, lack of appetite, polyuria and asthenia over the months. Through the history and laboratory testing, vitamin D intoxication and acute kidney injury were diagnosed. After treatment, there was a complete remission of the symptoms. "Hormonal modulation" is a practice condemned by the Federal Councils of Medicine and Dentistry and by the Brazilian Society of Endocrinology and Metabology. The act of prescribing is of great ethical and technical responsibility and it must be based on scientific evidence. Thus, the patient can receive the best possible treatment, for either preventive or curative nature, by respecting the recommendations of the competent authorities and, therefore, minimizing risks and damages to patients. (AU)

Comportamento clínico dos pacientes com asma durante a pandemia de COVID-19 / Clinical behavior of patients with asthma during the COVID-19 pandemic

Introdução: A asma é uma doença respiratória crônica e os vírus respiratórios são gatilhos bem conhecidos das suas exacerbações. O coronavírus pode se manifestar com sintomas pulmonares. Objetivo: Avaliar o comportamento clínico dos pacientes com asma durante a pandemia de COVID-19. Métodos: Estudo retrospectivo de prontuário eletrônico de pacientes adultos asmáticos, em acompanhamento em serviço terciário e que receberam ligações telefônicas para reagendamento, nos meses iniciais da pandemia de COVID-19. Foram analisados dados demográficos, sintomas de asma, atopia, comorbidades e sintomas relacionados à infecção pelo coronavírus. Os pacientes foram classificados conforme a história de crise de asma, como também steps de tratamento da asma. Resultados: Foram incluídos 207 pacientes, sendo 79,7% do sexo feminino, com média de idade de 53,3 anos e tempo de asma de 35 anos, sendo 81,7% atópicos. As principais comorbidades foram obesidade (32,9%), hipertensão arterial (47,3%), diabetes mellitus (17,4%) e estresse emocional (68,1%). Do total, 87 pacientes (40,1%) apresentaram sintomas agudos, sendo que 20 (9,7%) procuraram pronto atendimento, e 15 (7,2%) foram investigados para COVID-19, todos negativos. Apenas 7 pacientes (3,4%) exacerbaram e necessitaram de corticoide sistêmico. Dentre os pacientes com sintomas respiratórios agudos, os sintomas mais frequentes sugestivos de COVID-19 foram dispneia, tosse, astenia e cefaleia, quando comparados com os pacientes que não apresentaram sintomas agudos de asma (p < 0,05). Conclusão: Este estudo observou que os pacientes asmáticos apresentaram baixa prevalência de exacerbação da asma no período da pandemia pelo coronavírus. Os pacientes com sintomas agudos podem ter sido subdiagnosticados para COVID- 19, devido à baixa procura ao pronto atendimento. Antecedente de atopia pode funcionar como fator protetor para COVID-19 em pacientes asmáticos.

Introduction: Asthma is a chronic respiratory disease, and respiratory viruses are well-known triggers for asthma exacerbations. Patients with coronavirus disease 2019 (COVID-19) can present with pulmonary symptoms. Objective: To evaluate the clinical behavior of patients with asthma during the COVID- 19 pandemic. Methods: A retrospective study of electronic medical records of adult asthmatic patients being followed up in a tertiary care service and who received telephone calls for rescheduling during the COVID-19 pandemic. Demographic data, asthma symptoms, atopy, comorbidities, and symptoms related to coronavirus infection were analyzed. Patients were classified according to their history of asthma attacks. Results: In total, 207 patients were included; 79.7% were female, mean age was 53.3 years, mean asthma duration was 35 years, and 81.7% were atopic. The main comorbidities were obesity (32.9%), high blood pressure (47.3%), diabetes mellitus (17.4%), and emotional stress (68.1%). Eighty-seven patients (40.1%) had acute symptoms, of which 20 (9.7%) sought emergency care and 15 (7.2%) were investigated for COVID-19, all of which were negative. Only 7 patients (3.4%) had exacerbations and required systemic corticosteroids. Among patients with acute respiratory symptoms, dyspnea, cough, asthenia, and headache were the most frequent complaints suggestive of COVID-19 when compared to those without an asthma attack (p < 0.05). Conclusion: This study found that asthmatic patients had a low prevalence of asthma exacerbation during the coronavirus pandemic. Patients with acute symptoms may have been underdiagnosed for COVID-19 in view of the low demand for emergency care. Previous atopy may act as a protective factor for COVID-19 in asthmatic patients.

COVID-19 en la terapia intensiva: Análisis de la experiencia durante el primer mes de la pandemia / COVID-19 in the intensive care unit. Analysis of the experience during the first month of pandemic

Se trata de un análisis de características clínicas, hallazgos radiológicos, variables de laboratorio y mecánica respiratoria en pacientes con enfermedad por coronavirus 2019 (COVID-19) durante el primer mes de la pandemia en Buenos Aires. Es un estudio descriptivo de casos, de un solo centro. Se incluyeron todos los casos confirmados de COVID-19 internados en la unidad de terapia intensiva de adultos (UTIA) del Hospital Italiano de Buenos Aires. Todos los casos se confirmaron por reacción en cadena de la polimerasa con transcriptasa inversa. Un total de 7 pacientes con COVID-19 fueron atendidos en la UTIA. La mediana de edad fue de 71 años (intervalos intercuartílicos: 52-75), 4 hombres y 3 mujeres. Las manifestaciones clínicas más comunes fueron fiebre (7), tos (5), astenia (4) y disnea (3). Entre los hallazgos radiológicos, cinco de ellos mostraron opacidades intersticiales y un paciente consolidación pulmonar bilateral. Cinco requirieron ventilación mecánica invasiva y múltiples sesiones de decúbito prono. Ninguno murió durante la hospitalización, aunque aún tres permanecen en UCI.

This is an analysis of clinical characteristics, images findings, laboratory variables and respiratory mechanics in patients with coronavirus disease 2019 (COVID-19) during the first month of the pandemic outbreak in Buenos Aires. In this descriptive case study of a single-centre, we included all confirmed cases of COVID-19 hospitalized in intensive care unit (ICU). All cases were confirmed by reverse transcription polymerase chain reaction. A total of 7 patients with confirmed COVID-19 were referred to out ICU. The median age was 71 years (interquartile range 52-75), including 4 men and 3 women. Patients most common clinical manifestations were fever (7), cough (5), asthenia (4) and shortness of breath (3). Among the radiological findings, five of them showed interstitial opacities and one patient had bilateral pulmonary consolidation. Five required invasive mechanical ventilation and multiple prone sessions. None died during hospitalization, although three still remain in the ICU. According to imaging examination, 71.4% showed interstitial opacities and one patient bilateral consolidation. Five patients required invasive mechanical ventilation and multiple prone sessions. None of them died during hospitalization, although three still remain in the ICU.

Pneumonia por toxoplasmose em paciente imunocompetente / Toxoplasma pneumonia in an immunocompetent patient: case repor

Com grande distribuição mundial e incidência significativa, a toxoplamose é uma doença comum em mamíferos e pássaros, causada pelo protozoário Toxoplasma gondii. No homem, o parasitismo na fase proliferativa intracelular pode se apresentar sem sintomas, ou causar clínica transitória caracterizada por febre, fadiga e linfadenopatia. Por se tratar de patologia com sintomas inespecíficos e comuns a muitas outras, é fundamental a correta pesquisa de diagnósticos diferenciais, como citomegalovírus e Epstein-Barr. Relatamos o caso de um jovem e hígido, que desenvolveu pneumonia e, após confirmação sorológica para toxoplasmose e o tratamento adequado, apresentou melhora clínica.

With great worldwide distribution and significant incidence, toxoplamosis is a common disease in mammals and birds, caused by the protozoan Toxoplasma gondii. In humans, the parasitism in its intracellular proliferative phase may present no symptoms, or cause a transient condition characterized by fever, fatigue, and lymphadenopathy. Because it is a pathology with nonspecific symptoms that are common to many other conditions, it is fundamental to find the correct research of differential diagnoses, such as for Cytomegalovirus and Epstein Barr. We report a case of a young and healthy man who developed pneumonia and, after serological confirmation for toxoplasmosis and the appropriate treatment, presented clinical improvement

Síndrome de Gitelman / Gitelman syndrome

El síndrome de Gitelman forma parte de las denominadas tubulopatías perdedoras de sal. El bloqueo parcial de la reabsorción de sodio en el túbulo contorneado distal determina la aparición de hipokalemia e hipomagnesemia. Se realizó un estudio descriptivo de una serie de cinco casos de síndrome de Gitelman (4 mujeres, de 28 a 85 años de edad) atendidos en nuestra institución entre los años 2004 y 2015. La forma de diagnóstico más frecuente en nuestra serie fue por hallazgo de laboratorio. El único síntoma clínico manifestado en forma espontánea fue astenia. En cuanto a los valores de laboratorio, la potasemia fue 2.5 ± 0.5 mmol/l, con un valor mínimo de 2.1. Adicionalmente, el valor de magnesio en sangre fue 1.3 ± 0.3 mg/dl. Como conclusión, observamos que las formas de presentación consisten en alteraciones bioquímicas con o sin manifestaciones inespecíficas, lo que representa actualmente la mayor dificultad diagnóstica y refuerza la importancia de lograr un diagnóstico oportuno, en especial en pacientes jóvenes y con valores críticos de potasio sérico.

Gitelman syndrome is one of the salt losing tubulopathies. Hypokalemia and hypomagnesemia appear in the setting of the partial blockade of salt absorption in the distal tubule. We conducted a descriptive study of a case series of five patients with Gitelman syndrome (4 women, from 28 to 85 years) in our institution, between the years 2004 and 2015. The most frequent form of diagnosis in our series was by laboratory finding. The only acknowledged clinical symptom was malaise. Regarding laboratory findings, the mean potassemia was of 2.5 ± 0.5 mmol/l, with a minimum value of 2.1 mmol/l. Additionally, the serum magnesium value was of 1.3 ± 0.3 mg/dl. In conclusion, we observed that the forms of presentation consist of biochemical alterations with or without nonspecific manifestations, which currently represents the greatest diagnostic difficulty and reinforces the importance to achieve a timely diagnosis, especially in young patients with critical serum potassium values.

Caracterización de los pacientes con leucemia aguda en un hospital de tercer nivel de Quito - Ecuador / Characterization of patients with acute leukemia in a third level hospital from Quito - Ecuador

INTRODUCCIÓN. Las leucemias agudas son neoplasias hematológicas primarias, carac-terizadas por la proliferación anormal de células inmaduras en la médula ósea. OBJETI-VO. Definir las características clínicas, demográficas, de laboratorio y citogenéticas de los pacientes diagnosticados con leucemias agudas; además sus complicaciones durante la inducción a la remisión. MATERIALES Y MÉTODOS. Estudio descriptivo, retrospectivo. La población fue de 191 pacientes con diagnóstico de leucemia aguda en la Unidad Téc-nica de Hematología del Hospital de Especialidades Carlos Andrade Marín entre enero 2016 y octubre 2018. Los datos fueron tomados de la Historia Clínica documentada en el sistema AS-400, el análisis descriptivo se realizó con el programa estadístico International Business Machines Statistical Package for the Social Sciences, Versión 25.0. RESULTA-DOS. La leucemia mieloide aguda fue diagnosticada en el 62,30% (118; 191), seguida de la leucemia linfoide aguda en el 34,00% (64; 191). La leucemia aguda fue más común en hombres en un 54,45% (103; 191) que en mujeres. Las alteraciones de laboratorio más frecuentes fueron la hiperleucocitosis, anemia y trombocitopenia. En el 37,50% (69; 184) de los casos se determinó un cariotipo normal, la alteración numérica más frecuente fue la hipoploidía. La complicación más constante durante la inducción fueron las infecciones; el microorganismo hallado en más del 80,00% de los cultivos fueron las bacterias. CON-CLUSIÓN. La leucemia mieloide aguda fue el tipo más común en la población adulta, posterior a la inducción existió alto porcentaje de mortalidad y bajo de remisión completa

INTRODUCTION. Acute leukemias are primary hematologic malignancies, characterized by abnormal proliferation of immature cells in the bone marrow. OBJECTIVE. Define the clinical, demographic, laboratory and cytogenetic characteristics of the patients diagnosed with acute leukemias; also its complications during induction to remission. MATERIALS AND METHODS. Descriptive, retrospective study. The population was 191 patients diag-nosed with acute leukemia in the Technical Unit of Hematology of the Carlos Andrade Marín Specialty Hospital between january 2016 and october 2018. Data were taken from the Clinical History documented in the AS-400 system, the descriptive analysis was perfor-med with the International Business Machines Statistical Package for the Social Sciences, Version 25.0. RESULTS. Acute myeloid leukemia was diagnosed in 62,30% (118; 191), followed by acute lymphoid leukemia at 34,00% (64; 191). Acute leukemia was more com-mon in men in 54,45% (103; 191) than in women. The most common laboratory disorders were hyperleukocytosis, anemia and thrombocytopenia. In 37,50% (69; 184) of cases, a normal karyotype was determined, the most frequent numerical alteration was hypoploidy. The most constant complication during induction were infections; the microorganism found in more than 80,00% of the cultures were bacteria. CONCLUSION. Acute myeloid leuke-mia was the most common type in the adult population, after induction there was a high percentage of mortality and a low rate of complete remission.

Doença de Addison e esclerose múltipla: relato de caso / Addison's disease and multiple sclerosis: case report

A doença de Addison é uma endocrinopatia rara, de etiologia autoimune. É caracterizada por défice na secreção de glicocorticoides e mineralocorticoides. A esclerose múltipla consiste em patologia neurológica, de origem autoimune, que resulta na desmielinização da bainha de mielina. O objetivo deste relato foi demonstrar a associação rara entre essas duas patologias e suas possíveis relações imunológicas. A paciente analisada é do sexo feminino, 41 anos, portadora de esclerose múltipla, que posteriormente foi diagnosticada com insuficiência adrenal primária. (AU)

Addison's disease is a rare endocrinopathy of autoimmune etiology. It is characterized by a secretion's deficit of glucocorticoids and mineralocorticoids. Multiple sclerosis is a neurological pathology of autoimmune origin, which results in demyelination of the myelin sheath. The purpose of this report is to demonstrate the uncommon association between these two pathologies and their possible immunological relationships. The analyzed patient is a woman, 41 years old, with multiple sclerosis, who was later diagnosed with primary adrenal insufficiency. (AU)

Early Injection Laryngoplasty With a Long-Lasting Material in Patients With Potentially Recoverable Unilateral Vocal Fold Paralysis

OBJECTIVES: Injection laryngoplasty (IL) is one of the major options for treatment of unilateral vocal fold paralysis (UVFP). Early IL in patients with abrupt-onset UVFP can reduce hoarseness and aspiration-related discomfort and complications. Temporary or short-lasting materials are recommended for the early IL since permanent or long-lasting materials may negatively affect the voice quality when vocal fold motion is spontaneously recovered. METHODS: Patients who received IL with a long-lasting material (ArteSense) within 1 month following development of postoperative UVFP were enrolled for this study. They were categorized into a spontaneously recovered group (n=30) and unrecovered group (n=276) from UVFP. The subjective and objective voice parameters were collected before and 6 months after IL. Patients' demographics and collected voice parameters were compared between the two groups. RESULTS: Age and sex distributions were not different between the two groups. Aspiration symptom, maximum phonation time (MPT), jitter, shimmer, noise to harmonic ratio (NHR), overall grade (G) and breathiness (B) of GRBAS (grade of dysphonia, roughness, breathiness, asthenia, strain) scale score, and voice handicap index (VHI) were significantly improved after IL in both groups. The amounts of improvement in MPT, jitter, shimmer, NHR and VHI were significantly greater in the recovered group. There was no IL-related complication including granuloma formation, hypersensitivity to injection material, or worsening of hoarseness. CONCLUSION: Early IL with a long-lasting material can be safely performed to improve voice quality and to reduce aspiration episode for the patients with postoperative UVFP, regardless of recovery from the paralysis. The amounts of improvement in the subjective and objective voice parameters were significantly greater in patients who showed spontaneous recovery from UVFP when compared with those in patients who did not.

Perceptual and Acoustic Outcomes of Early-Stage Glottic Cancer After Laser Surgery or Radiotherapy: A Meta-Analysis

Laser surgery (LS) or radiotherapy (RT) is normally recommended in early glottic cancer. The objective of this study was to perform a comprehensive meta-analysis of acoustic and perceptual outcomes to compare voice quality of LS or RT in early-stage glottic cancer. Data sources were obtained after searching PubMed, Google Scholar, EBSCO, and RISS using the following search terms: glottic cancer, glottic carcinoma, endoscopic surgery, laser surgery, radiotherapy, radiation, voice, voice quality, and grade, roughness, breathiness, asthenia, and strain (GRBAS) scale. Articles that compared voice outcomes between LS and RT were identified. This meta-analysis included 15 articles with 744 patients, including 400 in the LS group and 344 in the RT group. Random effects models were selected. Forest plots included standardized mean differences, standard errors, variance, 95% confidence intervals (lower limit to upper limit), z-values, and P-values. In perceptual analysis, grade (G) and asthenia (A) of RT were significantly better than LS. There was no statistically significant difference in roughness (R), breath (B), or strain (S) between LS and RT groups. Jitter, shimmer, and noise to harmonic ratio measurements showed significant differences, resulting in enhanced posttreatment effect of RT compared to LS. Results of our meta-analysis suggested that RT might lead to superior voice quality than LS in early glottic cancer.

The Evaluation of the Short-Term Voice Outcome of Injection Laryngoplasty Using Two Types of Calcium Hydroxylapatite (Radiesse versus Facetem) / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Radiesse® is a widely used calcium hydroxyapatite (CaHA) injection material used for vocal fold injection. Recently, a new CaHA injection material (Facetem ®) which complements the structural disadvantages of Radiesse has been developed and released in the market. The aim of this study is to compare the efficacy and short-term voice outcome of these two CaHA materials. SUBJECTS AND METHOD: A retrospective analysis was performed for 70 patients with unilateral vocal fold paralysis who underwent vocal fold injection using CaHA materials. Acoustic voice analysis, maximal phonation time (MPT), voice handicap index (VHI), and Grade, Roughness, Breathiness, Asthenia, Strain (GRBAS) scale were evaluated between Radiesse and Facetem injection group. RESULTS: Both groups showed a signifcant improvement of MPT, VHI, and G, B, A scale after injection. The Facetem group showed similar voice improvement as the Radiesse group, where pre- and postoperatively objective and subjective voice evaluation results were compared. CONCLUSION: Our study reveals that there is no significant difference in efficacy and nor any short-term vocal improvement between Radiesse and Facetem. Therefore, the use of Facetem as CaHA injection material could be considered as an alternative material for patients with unilateral vocal cord paralysis.

Safety Results and Analysis of Eribulin Efficacy according to Previous Microtubules-Inhibitors Sensitivity in the French Prospective Expanded Access Program for Heavily Pre-treated Metastatic Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Eribulin is approved for advanced breast cancers refractory to anthracyclines and taxanes. Efficacy according to sensitivity to previous therapies has been poorly explored. MATERIALS AND METHODS: Safety data were collected prospectively and we retrospectively collected efficacy data from the five French centres that participated in the Eribulin E7389-G000-398 expanded access program. Our main objectives were exploration of safety and analysis of eribulin efficacy (progression-free survival [PFS] and overall survival [OS]) according to sensitivity to the last microtubule-inhibiting agent administered. RESULTS: Median eribulin treatment duration was 3.3 months for the 250 patients included in this prospective single-arm study. Two hundreds and thirty-nine patients (95.6%) experienced an adverse event (AE) related to treatment including 129 (51.6%) with grade ≥ 3 AEs. The most frequently observed toxicities were cytopenias (59.6% of included patients), gastro-intestinal disorders (59.2%), and asthenia (56.4%). The most frequent grade 3-4 AE was neutropenia (37.2% with 4.8% febrile neutropenia). Median PFS and OS were 4.6 and 11.8 months, respectively. Patients classified as responders to the last microtubule-inhibiting therapy had a longer OS (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.51 to 0.94; p=0.017), and tended to display a better PFS (HR, 0.78; 95% CI, 0.58 to 1.04; p=0.086). OS improvement was still significant in multivariate analysis (adjusted HR, 0.53; 95% CI, 0.35 to 0.79; p=0.002). CONCLUSION: This work based on a prospective study suggests that identification of patients likely to be more sensitive to eribulin could be based on their previous response to microtubules inhibitors.

TAK-264 (MLN0264) in Previously Treated Asian Patients with Advanced Gastrointestinal Carcinoma Expressing Guanylyl Cyclase C: Results from an Open-Label, Non-randomized Phase 1 Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This phase 1 dose-escalation portion of the study evaluated the safety, pharmacokinetics (PK), and antitumor activity of TAK-264 in Asian patients with advanced gastrointestinal (GI) carcinoma or metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma expressing guanylyl cyclase C (GCC). MATERIALS AND METHODS: Adult patients with advanced GI malignancies expressing GCC (H-score ≥ 10) received TAK-264 on day 1 of 3-week cycles as 30-minute intravenous infusions for up to 1 year or until disease progression or unacceptable toxicity. The primary objectives were to evaluate the safety profile including dose-limiting toxicities (DLTs) during cycle 1, determine the maximum tolerated dose (MTD), and characterize the PK profile of TAK-264. RESULTS: Twelve patients were enrolled and treated with 1.2 mg/kg (n=3), 1.5 mg/kg (n=3), or 1.8 mg/kg TAK-264 (n=6). Median number of treatment cycles received was two (range, 1 to 10). None of the patients experienced a DLT and the MTD was not determined. Ten patients (83%) experienced adverse events (AEs). The most common were neutropenia, anorexia, and nausea (each reported by four patients). Five patients (42%) experienced grade ≥ 3 AEs consisting of tumor hemorrhage and hypertension, ascites, adrenal insufficiency, neutropenia and asthenia. Serum exposure to TAK-264 increased proportionally with the dose and the median half-life was approximately 5.5-6.6 days. No patients experienced an objective response. CONCLUSION: TAK-264 demonstrated a manageable safety profile with limited antitumor activity consistent with studies conducted in Western patients with advanced GI malignancies. TAK-264 exposure increased proportionally with the dose.

Signs and symptoms of rheumatic diseases as first manifestation of pediatric cancer: diagnosis and prognosis implications / Sinais e sintomas sugestivos de doenças reumáticas como primeira manifestação de doenças neoplásicas na infância: implicações no diagnóstico e prognóstico

ABSTRACT Objective: To assess the prevalence and describe the clinical, laboratory and radiological findings, treatment and outcome of children with cancer initially referred to a tertiary outpatient pediatric rheumatology clinic. Methods: Retrospective analysis of medical records from patients identified in a list of 250 new patients attending the tertiary Pediatric Rheumatology Clinic, Ribeirão Preto Medical School hospital, University of São Paulo, from July 2013 to July 2015, whose final diagnosis was cancer. Results: Of 250 patients seen during the study period, 5 (2%) had a cancer diagnosis. Among them, 80% had constitutional symptoms, especially weight loss and asthenia, and 60% had arthritis. Initially, all patients had at least one alteration in their blood count, lactate dehydrogenase was increased in 80% and a bone marrow smear was conclusive in 60% of patients. Bone and intestine biopsies were necessary for the diagnosis in 2 patients. JIA was the most common initial diagnosis. The definitive diagnosis was acute lymphoblastic leukemia (2 patients), M3 acute myeloid leukemia, lymphoma, and neuroblastoma (one case each). Of 5 patients studied, 3 (60%) are in remission and 2 (40%) died, one of them with prior use of steroids. Conclusion: The constitutional and musculoskeletal symptoms common to rheumatic and neoplastic diseases can delay the diagnosis and consequently worsen the prognosis of neoplasms. Initial blood count and bone marrow smear may be normal in the initial framework of neoplasms. Thus, the clinical follow-up of these cases becomes imperative and the treatment, mainly with corticosteroids, should be delayed until diagnostic definition.

RESUMO Objetivo: Avaliar a prevalência e descrever as principais manifestações clínicas, os exames complementares, o tratamento e a evolução de crianças com doenças neoplásicas atendidas inicialmente em um serviço terciário de reumatologia pediátrica. Métodos: Analisamos retrospectivamente o prontuário médico de pacientes com diagnóstico definitivo de neoplasia, identificados entre 250 casos novos atendidos no ambulatório de reumatologia pediátrica do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto-USP, de julho de 2013 a julho de 2015. Resultados: Dos 250 pacientes, cinco (2%) tiveram diagnóstico de neoplasia. Desses, 80% apresentavam sintomas constitucionais, principalmente perda de peso e astenia e 60% artrite. Inicialmente, todos apresentavam pelo menos uma série alterada no hemograma, 80% aumento da desidrogenase lática (LDH) e 60% mielograma confirmatório. Dois pacientes necessitaram de biópsia, óssea e de intestino, para o diagnóstico final. Artrite idiopática juvenil foi o diagnóstico inicial mais frequente. Os diagnósticos definitivos foram leucemia linfoide aguda (dois casos), leucemia mieloide aguda-M3, neuroblastoma e linfoma (um caso cada). Dos pacientes estudados, três (60%) estão em remissão. Dois pacientes foram a óbito (40%), um deles com uso prévio de corticoide. Conclusão: Os sintomas constitucionais e musculoesqueléticos comuns às doenças reumáticas e neoplásicas podem retardar o diagnóstico e consequentemente agravar o prognóstico das neoplasias. O hemograma inicial, assim como o mielograma, podem estar normais no quadro inicial das neoplasias. Dessa forma, o seguimento clínico evolutivo desses casos torna-se imperativo e o tratamento, principalmente com corticoides, deve ser retardado até definição diagnóstica.

Relationship between Voice Fatigue and Voice Assessment in Patients with Voice Disorders and Applicability of Voice Fatigue Index in Korean Version / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Vocal fatigue is a symptom and a term that has been frequently used in the clinical study. Although a recently developed vocal fatigue index (VFI), a self-report questionnaire that reliably identifies vocal fatigue patients, provides detailed characteristics of the symptom, there has been no study about the association between VFI and other voice assessment parameters. This study aimed to investigate whether there is a relationship between VFI and the established voice assessment in Korean patients. SUBJECTS AND METHOD: Two hundred fifty-seven patients with voice disorders (mean age, 49.48±14.34; 145 male and 112 female) undertook the voice assessment that consisting of perceptual judgment [Grade, Roughness, Breathiness, Asthenia, Strain (GRBAS) Scale], acoustic and aerodynamic analysis, and voice handicap index (VHI) questionnaire. All patients validated using VFI. Correlation analysis between each voice assessment and VFI was conducted. RESULTS: There were statistical significances between items of voice assessment and VFI. Among the GRBAS Scale, G, B, A, S and a number of acoustic measures were associated with vocal fatigue. In particular, these features were prominent in men. As the score of VFI increased, the sound pressure level during voicing and the phonation time from aerodynamic measures were decreased while the mean pitch was increased. In addition, VFI was closely correlated with pre-existing self-report questionnaire and VHI in both gender. CONCLUSION: These findings suggest that VFI has a significant association with pre-established voice assessment. Therefore, VFI can be used as a reliable tool for identifying and validating vocal fatigue in Korean.

Phase II Study of Irinotecan and Cisplatin Combination Chemotherapy in Metastatic, Unresectable Esophageal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The objective of this multicenter phase II study was to evaluate the efficacy and safety of irinotecan and cisplatin combination chemotherapy in metastatic, unresectable esophageal cancer. MATERIALS AND METHODS: Patients were treated with irinotecan 65 mg/m² and cisplatin 30 mg/m² on days 1 and 8 of each 21-day treatment cycle. The primary endpoint was response rate, and secondary endpoints were survival, duration of response, initial metabolic response rate, and toxicity. RESULTS: A total of 27 patients with squamous cell histology were enrolled in the study. The median age of the patients was 61 years. The objective response rate of the 20 patients in the perprotocol group was 30.0% (90% confidence interval [CI], 13.2 to 46.9). The median follow-up duration was 10.0 months, and the median progression-free survival and overall survival were 4.5 months (95% CI, 1.6 to 6.2) and 8.8 months (95% CI, 4.7 to 10.5), respectively. Four of 13 patients (30.8%) evaluated showed initial metabolic response. The median duration of response for partial responders was 5.0 months (range, 3.4 to 8.0 months). The following grade 3/4 treatment-related hematologic toxicities were reported: neutropenia (40.7%), anaemia (22.2%), and thrombocytopenia (7.4%). Two patients experienced febrile neutropenia. The most common grade 3/4 non-hematologic toxicities were asthenia (14.8%) and diarrhoea (11.1%). CONCLUSION: Irinotecan and cisplatin combination chemotherapy showed modest anti-tumour activity and manageable toxicity for patients with metastatic, unresectable esophageal cancer.

Lead Poisoning at an Indoor Firing Range

In March 2014, a 39-year-old Korean male presented with a 6-month history of various nonspecific symptoms including dizziness, fatigue, asthenia, irritability, elevated blood pressure, palpitation, eyestrain, and tinnitus. His occupational history revealed that he had been working as an indoor firing range manager for 13 months; therefore, he was subjected to a blood lead level (BLL) test. The test results showed a BLL of 64 µg/dL; hence, he was diagnosed with lead poisoning and immediately withdrawn from work. As evident from the workplace environmental monitoring, the level of lead exposure in the air exceeded its limit (0.015–0.387 mg/m³). He received chelation treatment with calcium-disodium ethylenediaminetetraacetic acid (1 g/day) for 5 days without any adverse effects. In the follow-up results after 2 months, the BLL had decreased to 9.7 µg/dL and the symptoms resolved. This report represents the first occupational case of lead poisoning in firing ranges in Korea, and this necessitates institutional management to prevent the recurrence of poisoning through this route. Workplace environmental monitoring should be implemented for indoor firing ranges, and the workers should undergo regularly scheduled special health examinations. In clinical practice, it is essential to question the patient about his occupational history.

Minimally Invasive Stereotactical Radio-ablation of Adrenal Metastases as an Alternative to Surgery / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to study the clinical outcome for patients with metastases of the adrenal gland treated with stereotactic body radiation therapy. MATERIALS AND METHODS: Forty-six patients were studied retrospectively. The dose prescription was 40 Gy in four fractions. Dosimetric analysis was performed using the dose volume histograms while clinical outcome was assessed using actuarial analysis with determination of the overall survival (OS) and local control (LC) rates. RESULTS: The planning objectives were met for all patients. With a median follow-up period of 7.6 months, at the last follow-up 42 patients (91.3%) were alive and four had died because of distant progression. The actuarial mean OS was 28.5±1.6 months, the median was not reached. One-year and 2-year OS were 87.6±6.1%. None of the risk factors was significant in univariate analysis. Actuarial mean LC was 14.6±1.8 months (95% confidence interval [CI], 11.0 to 18.2) and median LC was 14.5±2.0 months (95% CI, 10.5 to 18.5). One-year and 2-year LC were 65.5±11.9% and 40.7±15.8%, respectively. A mild profile of toxicity was observed in the cohort of patients. Forty patients (86.9%) showed no complication (grade 0); two patients reported asthenia, six patients (13.1%) reported either pain, nausea, or vomiting. Of these six patients, five patients (10.9%) were scored as grade 1 toxicity while one patient (2.2%) was scored as grade 2. CONCLUSION: Stereotactic body radiation therapy treatment provided an adequate clinical response in the management of adrenal gland metastases.