Immunohistochemical evidence of melatonin protection on lung tissue during chemotherapy / Evidencia inmunohistoquímica de la protección de la melatonina en el tejido pulmonar durante la quimioterapia

SUMMARY: The present study investigated the possible protective effects of melatonin on Bleomycin, Cisplatin and etoposide (BEP) chemotherapy regimens using immunohistochemistry. Forty male Wistar rats were divided into four groups of ten as; group 1 as untreated control; group 2 as BEP group which received the three cycles of 21 days' regimen each of 0.5¥ dose levels ofBEP (bleomycin 0.75 mg/kg, etoposide 7.5 mg/kg and cisplatin 1.5 mg/kg). Rats in the group 3 (MEL group) received 10 mg/kg/day melatonin once daily. Group 4 received the melatonin (30 min before the BEP injections) and BEP as in groups 2. Proliferating cell nuclear antigen (PCNA) staining was used to detect cell proliferation and caspase-3, caspase-9 and Caspase-8 were detected to investigate apoptosis. PCNA immunostaining in alveolar epithelium, alveolar macrophages and bronchus was weak to moderate in BEP group. However, diffuse and strong caspase immunoreactions for caspase-3, caspase 8- and caspase-9 were detected in the bronchioles epithelium, vascular endothelium, alveolar luminal macrophages in the BEP group. PCNA and caspase immunoreactivities in MEL and Mel + BEP groups were close to the control one. The surface are in the BEP group was significantly reduced as compared to the control one ((P0.05). It can be concluded that BEP regimen can affects negatively on lung tissue and melatonin inhibits lung tissue injuries during BEP chemotherapy.

El presente estudio investigó los posibles efectos protectores de la melatonina en los regímenes de quimioterapia con bleomicina, etopósido y cisplatino (BEP) mediante inmunohistoquímica. Cuarenta ratas Wistar macho se dividieron en cuatro grupos de diez: grupo 1, control sin tratar; grupo 2, quimioterapia con una dosis de 0,5x de BEP (0,75 mg/kg de bleomicina, 7,5 mg/ kg de etopósido y 1,5 mg/kg de cisplatino) con tres ciclos de 21 días cada uno. Las ratas del grupo 3 (grupo MEL) recibieron 10 mg/kg/día de melatonina una vez al día. El grupo 4 (Mel + BEP) recibió melatonina (30 minutos antes de las inyecciones de BEP) y BEP, como en los grupos 2. Se usó la tinción del antígeno nuclear de células en proliferación (PCNA) para detectar la proliferación celular y, caspasa- 3, caspasa-9 y caspasa-8 para investigar apoptosis. La inmunotinción de PCNA en el epitelio alveolar, los macrófagos alveolares y los bronquios varió de débil a moderada en el grupo BEP. Sin embargo, se detectaron inmunorreacciones difusas y fuertes para caspasa-3, caspasa 8- y caspasa-9 en el epitelio de los bronquiolos, endotelio vascular y macrófagos luminales alveolares. Las inmunorreactividades de PCNA y caspasa en los grupos MEL y Mel + BEP fueron similares a las del control. El área de superficie en el grupo BEP se redujo significativamente en comparación con el control (P0,05). Se puede concluir que la quimioterapia con BEP puede afectar negativamente al tejido pulmonar y la melatonina inhibe las lesiones durante la quimioterapia.

Analysis of the prevalence and social security situation of pneumoconiosis in non-coal mine industry in Jiangsu Province / 中华劳动卫生职业病杂志

Objective: To understand the social security situation of current cases of pneumoconiosis in non-coal mine industries in Jiangsu Province, and to provide reference for the treatment and security work of pneumoconiosis patients. Methods: From January to October 2020, a follow-up survey was conducted on 4038 cases of pneumoconiosis in non-coal mine industries of the province from October 1949 to December 2019. The age, type of pneumoconiosis, industry type, and social security status of the patients were collected. Namely, work-related injury insurance, employer compensation, basic medical insurance for urban and rural residents, major illness insurance, etc. SPSS 19.0 was used for statistical description and analysis. Results: The cases of pneumoconiosis in non-coal mine industries in Jiangsu Province ranged in age from 36 to 105 (70.78±8.43) years old, and had been exposed to dust for 1 to 55 (19.27±9.29) years. Silicosis was the main form (3875 cases, 95.96%), and non-metallic mining and dressing industry was the main form (2618 cases, 64.83%). A total of 3991 cases (98.84%) of pneumoconiosis patients enjoyed social security, most of them were urban and rural residents with basic medical insurance (3624 cases, 89.75%), but there were still 47 patients without any social security. 15 cases (0.37%) enjoyed the subsistence allowance, with the monthly allowance amount ranging from 104 to 3960 yuan, with the average amount of 954.87 yuan/month. Conclusion: In Jiangsu Province, the proportion of pneumoconiosis patients in non-coal mine industries enjoying social security is relatively high, but there are still patients who do not enjoy any social security, and the difference in the amount of subsistence allowance is slightly larger. It is necessary to further improve the medical security of pneumoconiosis patients and improve their quality of life.

Analysis of 7 cases of pediatric acute myeloid leukemia with DEK-NUP214 fusion gene / 中华儿科杂志

Objective: To investigate the clinical features, treatment regime, and outcome of pediatric acute myeloid leukemia (AML) with DEK-NUP214 fusion gene. Methods: The clinical data, genetic and molecular results, treatment process and survival status of 7 cases of DEK-NUP214 fusion gene positive AML children admitted to the Pediatric Blood Diseases Center of Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2015 to February 2022 were analyzed retrospectively. Results: DEK-NUP214 fusion gene positive AML accounted for 1.02% (7/683) of pediatric AML diagnosed in the same period, with 4 males and 3 females. The age of disease onset was 8.2 (7.5, 9.5) years. The blast percentage in bone marrow was 0.275 (0.225, 0.480), and 6 cases were M5 by FAB classification. Pathological hematopoiesis was observed in all cases except for one whose bone marrow morphology was unknown. Three cases carried FLT3-ITD mutations, 4 cases carried NRAS mutations, and 2 cases carried KRAS mutations. After diagnosis, 4 cases received IAE induction regimen (idarubicin, cytarabine and etoposide), 1 case received MAE induction regimen (mitoxantrone, cytarabine and etoposide), 1 case received DAH induction regimen (daunorubicin, cytarabine and homoharringtonine) and 1 case received DAE induction regimen (daunorubicin, cytarabine and etoposide). Complete remission was achieved in 3 cases after one course of induction. Four cases who did not achieved complete remission received CAG (aclarubicin, cytarabine and granulocyte colony-stimulating factor), IAH (idarubicin, cytarabine and homoharringtonine), CAG combined with cladribine, and HAG (homoharringtonine, cytarabine and granulocyte colony-stimulating factor) combined with cladribine reinduction therapy, respectively, all 4 cases reached complete remission. Six patients received hematopoietic stem cell transplantation (HSCT) after 1-2 sessions of intensive consolidation treatment, except that one case was lost to follow-up after complete remission. The time from diagnosis to HSCT was 143 (121, 174) days. Before HSCT, one case was positive for flow cytometry minimal residual disease and 3 cases were positive for DEK-NUP214 fusion gene. Three cases accepted haploid donors, 2 cases accepted unrelated cord blood donors, and 1 case accepted matched sibling donor. The follow-up time was 20.4 (12.9, 53.1) months, the overall survival and event free survival rates were all 100%. Conclusions: Pediatric AML with DEK-NUP214 fusion gene is a unique and rare subtype, often diagnosed in relatively older children. The disease is characterized with a low blast percentage in bone marrow, significant pathological hematopoiesis and a high mutation rate in FLT3-ITD and RAS genes. Low remission rate by chemotherapy only and very high recurrence rate indicate its high malignancy and poor prognosis. Early HSCT after the first complete remission can improve its prognosis.

Clinical Anslysis of Primary Adrenal NK/T-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics, diagnosis, and treatment of one patient with primary adrenal natural killer/T-cell lymphoma (PANKTCL), and to strengthen the understanding of this rare type of lymphoma.@*METHODS@#The clinical manifestations, diagnosis and treatment process, and prognosis of the patient admitted in our hospital were retrospectively analyzed.@*RESULTS@#Combined with pathology, imaging, bone marrow examination， etc, the patient was diagnosed with PANKTCL (CA stage, stage II; PINK-E score 3, high-risk group). Six cycles of "P-GemOx+VP-16" regimen（gemcitabine 1 g/m2 d1 + oxaliplatin 100 mg/m2 d 1 + etoposide 60 mg/m2 d 2-4 + polyethylene glycol conjugated asparaginase 3 750 IU d 5） was performed, and complete response was assessed in 4 cycles. Maintenance therapy with sintilimab was administered after the completion of chemotherapy. Eight months after the complete response, the patient experienced disease recurrence and underwent a total of four courses of chemotherapy, during which hemophagocytic syndrome occurred. The patient died of disease progression 1 month later.@*CONCLUSION@#PANKTCL is rare, relapses easily, and has a worse prognosis. The choice of the "P-GemOx+VP-16" regimen combined with sintilimab help to improve the survival prognosis of patient with non-upper aerodigestive tract natural killer /T-cell lymphoma.

Matrix stiffening related lncRNA SNHG8 regulates chemosensitivity of ovarian cancer / 生物医学工程学杂志

Extracellular matrix (ECM) has been implicated in tumor progress and chemosensitivity. Ovarian cancer brings a great threat to the health of women with a significant feature of high mortality and poor prognosis. However, the potential significance of matrix stiffness in the pattern of long non-coding RNAs (lncRNAs) expression and ovarian cancer drug sensitivity is still largely unkown. Here, based on RNA-seq data of ovarian cancer cell cultured on substrates with different stiffness, we found that a great amount of lncRNAs were upregulated in stiff group, whereas SNHG8 was significantly downregulated, which was further verified in ovarian cancer cells cultured on polydimethylsiloxane (PDMS) hydrogel. Knockdown of SNHG8 led to an impaired efficiency of homologous repair, and decreased cellular sensitivity to both etoposide and cisplatin. Meanwhile, the results of the GEPIA analysis indicated that the expression of SNHG8 was significantly decreased in ovarian cancer tissues, which was negatively correlated with the overall survival of patients with ovarian cancer. In conclusion, matrix stiffening related lncRNA SNHG8 is closely related to chemosensitivity and prognosis of ovarian cancer, which might be a novel molecular marker for chemotherapy drug instruction and prognosis prediction.

Dose-adjusted EPOCH-R vs. R-CHOP in frontline management of Waldeyer's ring diffuse large B-cell lymphoma: a retrospective study from a single institution / 中华医学杂志(英文版)

BACKGROUND@#To compare the efficacy and safety of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in Waldeyer's ring diffuse large B-cell lymphoma (WR-DLBCL) at a single institution.@*METHODS@#This retrospective study included 115 newly diagnosed patients with WR-DLBCL, of whom 68 patients received R-CHOP, and 47 patients received DA-EPOCH-R as their first-line treatment. The baseline features of the two groups were well balanced using a 1:1 propensity score matching method, and a total of 84 cases were obtained, including respective 42 cases in the R-CHOP and DA-EPOCH-R groups, for further survival and prognosis analysis. The primary objectives included progression-free survival (PFS) and overall survival (OS).@*RESULTS@#During a median follow-up of 45 months, there were nine (21.4%) deaths in the R-CHOP group and two (4.8%) in the DA-EPOCH-R group. Kaplan-Meier analysis showed statistically significant improvements in PFS and OS in patients with DA-EPOCH-R compared with those treated with R-CHOP (log-rank test, P  = 0.025 and P  = 0.035, respectively). The 2-year PFS and OS rates in the DA-EPOCH-R group were 90.1% (95% confidence interval [CI]: 81.4-99.8%) and 95.2% (95% CI: 89.0-100.0%), respectively, and 80.5% (95% CI: 69.3-93.6%) and 90.5% (95% CI: 52.8-99.8%) in the R-CHOP group. Patients without B symptoms and elevated lactate dehydrogenase levels had a higher PFS in the DA-EPOCH-R group, with P values of 0.038 (hazard ratio [HR]: 0.11; 95% CI: 0.01-0.88) and 0.042 (HR: 0.19; 95% CI: 0.04-0.94), respectively. There were no statistically significant differences in clinical responses and treatment-related toxicities between the two groups.@*CONCLUSION@#Compared with patients received R-CHOP, those treated by DA-EPOCH-R had superior PFS, OS, and controlled toxicity in patients with WR-DLBCL.

Pathological characteristics and clinical prognosis of nodular sclerosis grade 2 of classic Hodgkin's lymphoma / 中华肿瘤杂志

Objective: To investigate the pathological characteristics and clinical prognosis of nodular sclerosis grade 2 of classic Hodgkin's lymphoma (cHL-NS2) in our cancer center. Methods: A retrospective collection of 23 cases of cHL-NS2 admitted in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from July 2008 to April 2019 was performed. Fifty-five cases of nodular sclerosis grade 1 of classical Hodgkin's lymphoma (cHL-NS1) during the same period were selected as control group. Survival curves were plotted using the Kaplan-Meier method, and Cox regression model was used to analyze the influencing factors for survival. Results: The median age of 23 cases of cHL-NS2 was 30 years old. Five cases had extra nodal invasion, and 19 cases were Ⅰ-Ⅱ stage based on Ann Arbor system. The pathological morphology of cHL-NS2 showed that the lymph node structure was completely destroyed and was divided into nodules by thick collagen. The tumor cells in the nodules were abundant and proliferated in sheets. The boundaries between the tumor cells were not clear. The incidence of tumor necrosis in cHL-NS2 was 43.5% (10/23), which was significantly higher than 18.2% (10/55) in cHL-NS1 (P=0.040). The 3-year progression-free survival (PFS) rate of patients in the cHL-NS2 group was 58.1%, which was significantly lower than 89.7% in the cHL-NS1 group (P=0.002). In all of 78 cases, the 3-year PFS rate of patients who did not obtain complete response (CR) was 67.1%, which was significantly lower than 92.2% in patients who achieved CR (P=0.030). Multivariate Cox regression analysis demonstrated that both cHL-NS2 and failure to obtain CR by first-line treatment were independent indicators for short PFS time (P<0.05). Conclusions: In cHL-NS2, the morphology of tumor cells are diverse, and tumor necrosis can be easily found. Under the current first-line treatments of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), cHL-NS2 is an independent indicator for worse PFS.

Uterine rescue in high-risk gestational trophoblastic neoplasia treated with ema-co by uterine arteries embolization due to arteriovenous malformations / Resgate uterino em neoplasia trofoblástica gestacional de alto risco tratada com EMA-CO por embolização de artérias uterinas devido a malformações arteriovenosas

Abstract Complete hydatidiform mole (CHM) is a rare type of pregnancy, in which 15 to 20% of the cases may develop into gestational trophoblastic neoplasia (GTN). The diagnostic of GTN must be done as early as possible through weekly surveillance of serum hCG after uterine evacuation.We report the case of 23-year-old primigravida, with CHM but without surveillance of hCG after uterine evacuation. Two months later, the patient presented to the emergency with vaginal bleeding and was referred to the Centro de Doenças Trofoblásticas do Hospital São Paulo. She was diagnosed with high risk GTN stage/score III:7 as per The International Federation of Gynecology and Obstetrics/World Health Organization (FIGO/WHO). The sonographic examination revealed enlarged uterus with a heterogeneous mass constituted of multiple large vessels invading and causing disarrangement of the myometrium. The patient evolved with progressive worsening of vaginal bleeding after chemotherapy with etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA-CO) regimen. She underwent blood transfusion and embolization of uterine arteries due to severe vaginal hemorrhage episodes, with complete control of bleeding. The hCG reached a negative value after the third cycle, and there was a complete regression of the anomalous vascularization of the uterus as well as full recovery of the uterine anatomy. The treatment in a reference center was essential for the appropriate management, especially regarding the uterine arteries embolization trough percutaneous femoral

Resumo Mola hidatiforme completa (MHC) é um tipo raro de gravidez, na qual 15 a 20% dos casos podem desenvolver neoplasia trofoblástica gestacional (NTG). O diagnóstico de NTG deve ser feito o mais cedo possível, pelo monitoramento semanal do hCG sérico após esvaziamento uterino. Relatamos o caso de uma paciente primigesta, de 23 anos de idade, com MHC, sem vigilância de hCG após esvaziamento uterino. Dois meses depois, a paciente compareceu na emergência com sangramento vaginal, sendo encaminhada ao Centro de Doenças Trofoblásticas do Hospital São Paulo, onde foi diagnosticada com NTG de alto risco, estádio e score de risco III:7 de acordo com a The International Federation of Gynecology and Obstetrics/Organização Mundial de Saúde (FIGO/OMS). O exame ultrassonográfico revelou útero aumentado com uma massa heterogênea constituída pormúltiplos vasos volumosos invadindo e desestruturando o miométrio. A paciente evoluiu com piora progressiva do sangramento vaginal após quimioterapia com o regime etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA-CO). Ela foi submetida a transfusão de sangue e embolização das artérias uterinas devido aos episódios graves de hemorragia vaginal, com completo controle do sangramento. O hCG atingiu valor negativo após o terceiro ciclo, havendo regressão completa da vascularização uterina anômala, assim como recuperação da anatomia uterina. O tratamento em um centro de referência permitiu o manejo adequado, principalmente no que se refere à embolização das artérias uterinas através da punção percutânea da artéria femoral, que foi crucial para evitar a histerectomia, permitindo a cura da NTG e a manutenção da vida reprodutiva.

MDT Treatment of Small Cell Lung Cancer Complicated with Adenocarcinoma: A Case Report and Literature Review / 中国肺癌杂志

Small cell lung cancer (SCLC) is the most malignant lung cancer with the highest mortality. At present, the first-line standard treatment is still based on Etoposide and Platinum chemotherapy. However, for SCLC that progresses after first-line therapy, the treatment options are still very limited. Since the molecular mechanism of first-line drug resistance of SCLC is still unclear, and the precision medicine strategy after first-line drug resistance is still in the pre-clinical stage. The proportion of secondary biopsy and genetic testing is very low after the progress of first-line treatment of SCLC. In this study, we report a case of a middle-aged woman who was first diagnosed with SCLC. Adenocarcinoma with sensitive gene mutations and repeated changes of small cell carcinoma were detected by multiple biopsies during the course of the disease, suggesting that the patient may be a special subtype of SCLC - mixed SCLC (M-SCLC). In this case, the patient has been treated with radiotherapy and chemotherapy, immunotherapy and targeted therapy successively, and the survival time has reached 2 years and 8 months. Through the case report and literature review retrospectively, this study aimed to explore the part patients may start to present hybrid histopathologic types or tissue type change after treatment of SCLC. Biopsy pathologic histology and genetic testing is necessary after disease progression to look for potential therapeutic targets, so as to give precise treatment based on molecular markers detection results and provide the patient with the benefit of survival for as long as possible.
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Effect of Etoposide on Elimination of Chronic Myeloid Leukemia Stem Cells by Imatinib in Vivo / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of etoposide (ETO) on elimination of chronic myeloid leukemia (CML) stem cells by imatinib mesylate(IM) in vivo.@*METHODS@#SCL-tTA/BCR-ABL mice were used as CML animal model. Flow cytometry was used to assess the effect of ETO alone or in combination with IM on the number of leukemia stem cell （LSC） in bone marrow and spleen, and peripheral blood neutrophils in CML mice and normal control FVB mice.@*RESULTS@#The results showed that in CML mice, the number and proportion of LSC in bone marrow and the proportion of neutrophils in peripheral blood decreased significantly after ETO and IM combined treatment, and the degree of decrease was more significant than that of both alone. While in wild type FVB mice, the combination of ETO and IM showed no significant effect on the number and proportion of LSK cells in bone marrow and the proportion of neutrophils in spleen.@*CONCLUSION@#ETO can selectively enhance elimination of CML LSC by IM in vivo.

Clinical Characteristics for Cutaneous Involvement in Diffuse Large B-Cell Lymphoma and Hemophagocytic Syndrome patients with First Presentation of Dermatomyositis / 中国实验血液学杂志

OBJECTIVE@#To present one patient initially diagnosed with dermatomyositis(DM) who was eventually revealed to be diffuse large B-cell lymphoma(DLBCL) complicated with hemophagocytic syndrome(HPS), and to improve the understanding of the disease.@*METHODS@#The clinical characteristics, diagnostic approach, treatment of the patient were retrospectively analyzed, and some related literatures were reviewed.@*RESULTS@#A 52-year-old female patient suffered from muscle weakness, elevated serum creatine kinase activity, electromyography changes and characteristic skin rashes and diagnosed as DM. The patient was treated with glucocorticoid therapy and the muscle strength, skin rashes, and creatine kinas index turns into remission. Subsequently, subcutaneous nodules appeared during treatment, and the patient was confirmed as DLBCL based on pathological biopsy; And the patient was considered HPS because of presenting with repeated fever, splenomegaly, cytopenias, hypofibrinogenemia, hypertriglyceridemia, hyperferritinemia, high levels of sCD25, low NK-cell activity and hemophagocytosis in bone marrow. But the patient refused chemotherapy, and only treated with "DXM+VP-16" to control hemophagocytic syndrome, and unfortunately died due to the disease progression.@*CONCLUSION@#Cutaneous involvement in diffuse large B-cell lymphoma and hemophagocytic syndrome patients with first presentation of dermatomyositis is relatively rare. Malignacy screening should be performed as soon as possible after newly diagnosed DM, so that the patient can get early diagnosis and effective treatment to improve survival rate.

Linfohistiocitosis hemofagocítica secundaria a infección crónica activa por virus de Epstein-Barr en un hospital pediátrico en México: series de casos y revisión de la literatura / Hemophagocytic lymphohistiocytosis secondary to chronic active Epstein-Barr virus infection in a pediatric hospital in Mexico: case series and literature review

INTRODUCCIÓN: La linfohistiocitosis hemofagocitica (HLH) secundario está asociada a enfermedades malignas, genéticas o autoinmunes, pero también a infecciones principalmente EBV hasta en un 70%, sin embargo hay poca información. Esta entidad se caracteriza por un curso variable y recurrente que conlleva a una alta morbimortalidad con complicaciones potencialmente mortales. OBJETIVO: Describir las características clínicas y evolución de los pacientes pediátricos con diagnóstico de HLH secundario a CAEBV. RESULTADOS: Se incluyeron 7 pacientes, edad media al diagnóstico fue 52 meses con predilección al sexo masculino. Todos los pacientes fueron tratados con un régimen quimioterapéutico multiagente, que incluye corticosteroide, etopósido y Ciclosporina. Después del tratamiento 6 pacientes presentaron remisión y uno de ellos reactivación. La media de seguimiento fue 19 meses y la supervivencia libre de enfermedad (SLE) 16 meses. CONCLUSIÓN: Podemos observar que el curso clínico es variable en ocasiones fulminantes y con pobre respuesta al tratamiento. Un diagnóstico temprano, así como detectar los factores pronóstico podría ayudar a adaptar estrategias de tratamiento que cambiaría la evolución clínica.

INTRODUCTION: Secondary hemophagocytic lymphohistiocytosis (HLH) is associated with malignant, genetic or autoimmune diseases but also with infections mainly EBV in up to 70%, however there is little information. This entity is characterized by a variable and recurrent course that leads to high morbidty and mortality with life-threatening complications. OBJECTIVE: To describe the clinical characteristics and evolution of pediatric patients with a diagnosis of HLH secondary to CAEBV. RESULTS: 7 patients were included, mean age at diagnosis was 52 months with a predilection for males. All patients were treated with a multiagent chemotherapeutic regimen, including corticosteroid, etoposide, and cyclosporine. After treatment, 6 patients presented remission and one of them had reactivation. The mean follow-up was 19 months and disease-free survival (DFS) 16 months. CONCLUSION: We can observe that the clinical course is variable, sometimes fulminant and with poor response to treatment. An early diagnosis as well as detecting prognostic factors could help to adapt treatment strategies that would change the clinical course.

Informe diário de evidências COVID-19: busca realizada em 4 de agosto de 2020 / COVID-19 daily evidence report: search conducted on August 4, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 16 artigos e 13 protocolos.

Pancreatitis aguda en carcinoma de célula pequeña de pulmón (CPCP) resuelta con quimioterapia / Acute pancreatitis in small-cell lung carcinoma (SCLC) resolved with chemotherapy

Resumen El carcinoma de célula pequeña (CPCP) o microcítico de pulmón es un subtipo de cáncer de pulmón que típicamente se ha asociado al tabaquismo y que se caracteriza por su agresividad y mal pronóstico a corto plazo. Como entidad, puede metastatizar en cualquier órgano, siendo las metástasis pancreáticas raras y la mayoría de las veces asintomáticas. Por ello, la presencia de una pancreatitis neoplásica, como en el caso presentado, es excepcional, y aún más cuando presenta refractariedad al tratamiento médico convencional y responde al tratamiento citotóxico sistémico. Por todo ello, se expone esta experiencia clínica y se debate la presencia de esta rara entidad y su manejo.

Abstract Small-cell lung carcinoma is a subtype of neoplasm that has been typically associated with smoking; it is characterized by its aggressiveness and poor prognosis in the short term. As an entity, it can metastasize in any organ, but pancreatic metastases are rare and most of the time asymptomatic. Therefore, the presence of neoplastic pancreatitis as in our case is exceptional; even more when it presents refractoriness to conventional medical treatment, responding instead to systemic cytotoxic treatment. Therefore, we expose our clinical experience and discuss the presence of this rare entity and its management.

Comparison of the clinical response of high-risk and ultra high-risk gestational trophoblastic neoplasia to etoposide- methotrexate-actinomycin-cyclosphosphamide-vincristine: Experience at the Philippine General Hospital / Philippine Journal of Obstetrics and Gynecology

Background@#Recent studies have shown poorer outcomes for patients with prognostic score above 12. Authors have proposed categorizing these patients as ultra high-risk to emphasize the need for a different treatment regimen.@*Objectives@#This study was conducted to compare the clinical response of high-risk and ultra high-risk Gestational Trophoblastic Neoplasia (GTN) patients who were managed at the Philippine General Hospital, from January 1, 2010 to December 31, 2015, after receiving the EMACO regimen as first line treatment.@*Methods@#All patients diagnosed with metastatic high-risk GTN who were managed at the Philippine General Hospital from January 1, 2010 to December 31, 2015 and given the EMACO regimen as first-line treatment were included in the study. Patients were divided into high-risk disease or patients with a WHO prognostic score of 7-11 and ultra high-risk disease or patients with WHO prognostic score of 12 and above. Using the Z-test on two proportion, treatment outcome between the two groups were compared.@*Results@#A total of 57 patients diagnosed with metastatic high-risk GTN were included in the study. Of these, 35 or 61% were classified as high-risk while 22 or 39% were ultra high-risk. The primary remission rate of the high-risk group was 89% compared to 77% for the ultra high-risk group. The difference was not statistically significant (p=0.2542). Out of the 57 patients included in the study, 48 patients achieved remission after being treated with EMACO. An additional 4 patients achieved remission after being shifted to EPEMA due to resistance to the first line agent. All patients were alive after one year of follow-up, giving a one-year survival rate of 91.2%.@*Conclusion@#The result of this study showed a relatively higher remission rate for high-risk (89%) than ultra highrisk GTN (77%) with EMACO as first line chemotherapy regimen, but statistical analysis revealed no significant difference. This finding suggests that EMACO may still be used as first line regimen for ultra high-risk GTN to attain remission.

Analysis of Relevant Factors of Refractory and Relapse DLBCL Treated by Rituximab Combined with CHOP/EPOCH Regimen / 中国实验血液学杂志

OBJECTIVE@#To analyze the efficacy of rituximab combined with CHOP/EPOCH regimen for treatment of diffuse large B-cell lymphoma（DLBCL） patients, and to explore the high risk factors of refractory and relapsed patients.@*METHODS@#The clinical data of 72 patients with de novo DLBCL from December 2012 to December 2018 in the Department of Hematology, Zhongda Hospital Affiliated to Southeast University were retrospectively analyzed. The remission rate of DLBCL patients treated by rituximab combined with CHOP/EPOCH was analyzed, and survival analysis was conducted to explore the risk factors influencing refractory recurrence.@*RESULTS@#45 cases among 72 patients achieved complete remission (CR), 11 cases achieved partial remission (PR), the total remission rate was 77.78%. 25 cases (34.2%) refractory and relapsed. Single factor analysis showed that the B symptoms, low Hb, high NLR, low MLR, high β@*CONCLUSION@#The remission rate of DLBCL patients treated by rituximab combined with CHOP/EPOCH regimen is high, but about one third of the patients still show refractory and relapsed. B Symptoms, anemia, high β

Adenovirus pneumonia with hemophagocytic lymphohistiocytosis in children: a clinical analysis of 7 children / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features of children with adenovirus pneumonia and hemophagocytic lymphohistiocytosis (HLH).@*METHODS@#A retrospective analysis was performed on the mediacal data of 7 children with adenovirus pneumonia and HLH from March to September, 2019.@*RESULTS@#The age of these children ranged from 11 months to 5 years, and among these children, 5 were aged <2 years and 5 were boys. None of these children had underlying diseases. All children were hospitalized due to persistent high fever and cough, and the peak temperature of fever was 39°C to 41°C. With disease progression, 7 children developed hepatomegaly and 6 developed splenomegaly. Routine blood test results showed reductions in two or three lineages of blood cells, with increases in serum ferritin (SF), C-reactive protein (CRP), procalcitonin (PCT), and lactate dehydrogenase (LDH). Phagocytosis of blood cells was observed in 6 children. Radiological examination of lungs showed pneumonia changes. All 7 children were diagnosed with human adenovirus type 7 infection based on pathogenic metagenome detection. No abnormality was found by HLH gene detection and the children were diagnosed with secondary HLH. All children received intravenous immunoglobulin. Among these children, 4 received dexamethasone and etoposide chemotherapy, 3 received dexamethasone alone, and 4 received plasma exchange. Of the 7 children, 2 died and 5 were recovered. Compared with those who survived, the children who died had significantly greater reductions in the three lineages of blood cells and significantly greater increases in serum levels of CRP, PCT, SF, and LDH.@*CONCLUSIONS@#The children with adenovirus pneumonia and HLH have main clinical features of persistent high fever, progressive reductions in two or three lineages of peripheral blood cells, and involvement of other organ systems, including hepatosplenomegaly. Significant increases in serum levels of CRP, PCT, SF, and LDH may suggest a poor prognosis.

Evolución de un linfoma no Hodgkin "triple expresor" en un paciente trasplantado renal con quimioterapia DA-R-EPOCH. Caso clínico / Triple expressor lymphoma in a kidney transplant patient

Patients transplanted from solid organs have an increased risk of cancer, especially lymphomas. Lymphomas correspond to 4 to 5% of malignant neoplasms in the general population and in solid organ transplant patients it reaches an incidence of 21%. The incidence of non-Hodgkin lymphomas is 10 times higher than in the non-transplanted population. We report the case of a 68-year-old man with a kidney transplant who 6 years after transplantation, developed a non-Hodgkin diffuse large cells B lymphoma with lymph node and pulmonary involvement, with markers of very poor prognosis (triple MYC expressor, BCL2 and BCL6). and its evolution with chemotherapy with DA R EPOCH.

First - line, non - cryopreserved autologous stem cell transplant for poor - risk germ - cell tumors: Experience in a developing country

ABSTRACT Purpose: The current first - line treatment for non - seminomatous germ cell tumor (NSGCT) consists of four cycles of cisplatin, etoposide, and bleomycin (BEP), which results in 5 - year overall survival < 60% in patients with poor - risk features. Autologous hematopoietic stem cell transplantation (auto - HSCT) as a method for overcoming high toxicity after high dose chemotherapy (HDC) has been explored in different solid tumors, but has remained standard practice only for NSGCT. Our objective was to describe outcomes of patients with poor - risk NSGCT who underwent first - line autologous HSCT in a tertiary center in Mexico. Patients and Methods: Twenty nine consecutive patients with NSGCT who received first - line, non - cryopreserved autologous HSCT at the National Institute of Medical Sciences and Nutrition Salvador Zubiran in Mexico City, Mexico, from November 1998 to June 2016, were retrospectively analyzed. Results: The median age at transplantation was 23 (15 - 39) years. Most patients (n = 18, 62%) had testicular primary tumor, and 23 had metastases (79%). Complete response after auto - HSCT was observed in 45%. Non - relapse mortality was 0. Five - year relapse / progression free and overall survival were 67% and 69%, respectively. Conclusions: This small single limited - resource institution study demonstrated that patients with poor - risk NSGCT are curable by first - line HDC plus autologous HSCT and that this procedure is feasible and affordable to perform using non - cryopreserved hematopoietic stem cells.

Randomized Phase III Trial of Irinotecan Plus Cisplatin versus Etoposide Plus Cisplatin in Chemotherapy-Naïve Korean Patients with Extensive-Disease Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This randomized phase III study was designed to compare the efficacy and safety of irinotecan plus cisplatin (IP) over etoposide plus cisplatin (EP) in Korean patients with extensive-disease small-cell lung cancer (SCLC). MATERIALS AND METHODS: Patients were randomly assigned to receive IP, composed of irinotecan 65 mg/m2 intravenously on days 1 and 8+cisplatin 70 mg/m2 intravenously on day 1 every 3 weeks, or EP, composed of etoposide 100 mg/m2 intravenously on days 1, 2, 3+cisplatin 70 mg/m2 intravenously on day 1, every 3 weeks for a maximum of six cycles, until disease progression, or until unacceptable toxicity occurred. The primary endpoint was overall survival. RESULTS: A total of 362 patients were randomized to IP (n=173) and EP (n=189) arms. There were no significant differences between IP and EP arms for the median overall survival (10.9 months vs. 10.3 months, p=0.120) and the median progression-free survival (6.5 months vs. 5.8 months, p=0.115). However, there was a significant difference in response rate (62.4% vs. 48.2%, p=0.006). The pre-planned subgroup analyses showed that IP was associated with longer overall survival in male (11.3 months vs. 10.1 months, p=0.036), < 65 years old (12.7 months vs. 11.3 months, p=0.024), and Eastern Cooperative Oncology Group performance status 0/1 (12.4 months vs. 10.9 months, p=0.040) patient groups. The severity of treatment-related adverse events such as grade 3/4 anemia, nausea and diarrhea was more frequent in patients treated with IP. CONCLUSION: The IP chemotherapy did not significantly improve the survival compared with EP chemotherapy in Korean patients with extensive-disease SCLC.