R-CHOP and consolidation radiotherapy for limited-stage and low-IPI high-grade b-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements: A single-center case series and review of literature

@#High-Grade B-Cell Lymphoma (HGBCL) with gene rearrangements in MYC and BCL2 and/or BCL6 is an aggressive malignancy usually presenting in advanced stages. Current recommendations suggest the use of regimens more intensive than R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone), which are based on retrospective studies and single-arm prospective trials that included patients who are mostly in the advanced stage, and did not receive consolidation radiotherapy. The optimal approach and treatment of HGBCL, whether limited-stage (LS) or advanced-stage, remains to be determined. Here we describe the promising outcomes of three patients with LS and low IPI HGBCL with the use of R-CHOP as induction chemotherapy regimen, which was followed by consolidation radiotherapy. Three women, 54-, 60-, and 64-years of age diagnosed to have HGBCL with MYC, and BCL2 and/or BCL6 rearrangements, with Ann Arbor stages I-IIE were included in this case series. All three patients had complete metabolic response to 6 cycles of R-CHOP and was subsequently treated with consolidation involved site radiotherapy (ISRT; total dose 30-36 Gy). Chemotherapy and radiotherapy were tolerated very well. All patients remain to be in remission, with the longest being at 23 months. Outcomes of patients with HGBCL generally remain to be poor, but this may not be the case for patients with limited-stage disease and favorable clinicopathologic risk profile. Nevertheless, the treatment of HGBCL is currently evolving and more studies are needed to determine the ideal approach and preferred chemotherapy regimen. Also, more studies are needed to elucidate the potential role of consolidation radiotherapy in patients with limited-stage HGBCL to improve survival outcomes. Findings of this case series suggest that patients with LS HGBCL may still derive benefit from R-CHOP followed by consolidation ISRT, but prospective trials are needed to confirm this.

Visualizing Regional Disparities in Cardiovascular Surgery, Suggestions to Advance the Careers of Young Surgeon by Decentralizing to Rural Areas / 日本心臓血管外科学会雑誌

It is the most important for young cardiovascular surgeon that ensure the number of cases to obtain and renew the specialties qualifications. Regional disparities such as concentration of facilities in urban areas and shortage of physicians in rural areas, may be affecting the lack of cases. I compared the population of each medical region with the number of cardiac surgery training facilities to examine regional disparities in cardiovascular surgery. As one way to solve the regional disparity problem, I make a suggestion to decentralize young doctors from urban areas to rural areas.

Humeral shaft fracture with an intact wedge fragment: mipo vs conventional plating / Fraturas diafisárias de úmero com cunha intacta: mipo x estabilidade absoluta com placa

ABSTRACT Objectives: Evaluate bone healing time, consolidation, and the complication rate between the minimally invasive plate osteosynthesis and open reduction with plate osteosynthesis in humeral diaphyseal fractures with an intact wedge (AO 12B2). Methods: A retrospective study was carried out between 2016 and 2020. The medical records and radiographs of 18 patients were analyzed, and data were collected regarding the time of consolidation, age, sex, plate size, number of screws, complications such as iatrogenic injury damage to the radial nerve, material failure, and postoperative infection. Results: No statistically significant differences were observed in the variables of age, sex, plate size, and number of screws used or in the RUSHU index (Radiographic Union Score for Humeral fractures). There were no postoperative infections, material failure, or need for reoperation, nor cases of secondary radial nerve injury. After one year, all patients had a consolidation index analyzed by RUSHU >11. Conclusion: both techniques showed similar results, with a high consolidation rate and low rates of complications or iatrogenic damage to the radial nerve. Evidence level III; Retrospective comparative study .

RESUMO Objetivos: Comparar o tempo de consolidação e o índice de complicações entre os métodos de osteossíntese com placa minimamente invasiva e estabilidade absoluta através da placa nas fraturas diafisárias do úmero com cunha intacta (AO 12B2). Métodos: Foi realizado um estudo retrospectivo entre os anos de 2016 e 2020. Foram analisados os prontuários e radiografias de 18 pacientes e coletados dados referentes a: tempo de consolidação, idade, sexo, tamanho da placa, número de parafusos, presença de complicações como lesão iatrogênica do nervo radial, falha do material e infecção pós operatória. Resultados: Não foram observadas diferenças estatisticamente significativas nas variáveis de idade, sexo, tamanho da placa e número de parafusos utilizados, ou no índice de RUSHU (Radiographic Union Score for Humeral fractures). Não houve casos de infecção pós-operatória, falha do material ou necessidade de reoperação, nem casos de lesão secundária do nervo radial. Após 1 ano todos os pacientes tiveram índice de consolidação analisado pelo RUSHU >11. Conclusão: Ambas as técnicas se mostraram com resultados similares, com alta taxa de consolidação e baixas taxas de complicações ou lesão iatrogênica do nervo radial. Nível de evidência III; Estudo retrospectivo comparativo .

Desarrollo y validación de una tarea experimental de Memoria Episódica verbal en español / Development and validation of an experimental verbal Episodic Memory task in Spanish

RESUMEN Propósito Elaborar y validar una tarea experimental de memoria episódica verbal en español. Método Se elaboraron seis bloques de codificación: tres profundos y tres superficiales, cado uno con distintas demandas de esfuerzo cognitivo. Los bloques fueron revisados por cuatro jueces expertos y examinados en una aplicación piloto. Se evaluó la concordancia respecto a si la tarea permitía manipular combinadamente el nivel de procesamiento y el esfuerzo cognitivo durante la codificación incidental de palabras, así como la claridad de las instrucciones, ejemplos y dinámica de trabajo. Resultados Variables como la disponibilidad léxica, metría y fuerza de asociación fueron útiles para diferenciar el esfuerzo cognitivo entre cada bloque. Los jueces concordaron que los bloques de procesamiento admiten una manipulación combinada del nivel de procesamiento y esfuerzo cognitivo y que las instrucciones son precisas. Luego del pilotaje, los participantes concordaron que las instrucciones, ejemplos y forma de trabajo eran fácil de comprender y realizar. Conclusión Los resultados proporcionan evidencia de validez relacionada con el contenido para la tarea experimental propuesta, transformándose con ello en una alternativa viable de considerar en investigaciones orientadas a identificar factores ambientales que contribuyan a compensar los defectos que muestra la memoria episódica con la edad.

ABSTRACT Purpose To develop and validate an experimental verbal episodic memory task in Spanish. Methods Six encoding blocks were elaborated, three deep and three superficial, each one with different demands of cognitive effort. The blocks were reviewed by four expert judges and tested in a pilot application. The agreement was assessed on whether the task allowed combined processing level and cognitive effort to be manipulated during incidental encoding of words, as well as clarity of instructions, examples, and workflow. Results Variables such as lexical availability, metrics, and strength of association were useful to differentiate the cognitive effort between each block. The judges agreed that the processing blocks allowed a combined manipulation of the level of processing and cognitive effort and that the instructions are precise. After the pilot, the participants agreed that the instructions, examples, and way of working were easy to understand and perform. Conclusion The results provide evidence of validity related to the content for the proposed experimental task, thus becoming a viable alternative to consider in research aimed at identifying environmental factors that contribute to compensating the defects shown by episodic memory with age.

Fijadores externos para tratar fractura mandibular causada por herida de arma de fuego. Reporte de caso / External fxators as treatment for mandibular fracture caused by gunshot wound. Case report

Introducción: las heridas por proyectil de arma de fuego en la región craneofacial provocan daños funcionales devastadoras y deformidades estéticas, que se suman al trauma psicológico al momento del regreso a la vida cotidiana de un paciente. Por esta razón, la reconstrucción adecuada es esencial para una rehabilitación integral. La fijación externa es un método de reducción cerrada de fracturas que implica el uso de tornillos para manipular segmentos sueltos de hueso, que luego se fijan mediante conexiones externas. Es importante recalcar que las fracturas mandibulares causadas por proyectil de arma de fuego son un reto para este tipo de tratamiento. Objetivo: presentar el caso de un paciente con fractura mandibular por proyectil de arma de fuego tratado con fijadores externos y revisión de la literatura sobre este tipo de tratamiento. Caso clínico: paciente masculino de 19 años que presentó fractura de rama mandibular izquierda causado por proyectil de arma de fuego; la fractura se manejó mediante la colocación de fijación intermaxilar con arcos barra tipo Erich y fijación externa durante 3 meses. Como parte del resultado, el paciente presentó una correcta oclusión dentaria y mantiene sus movimientos mandibulares sin ninguna limitación. Esto demuestra que la reducción cerrada y fijación externa debe mantenerse en el arsenal terapéutico debido a sus adecuados resultados comprobados en la literatura y en este caso. Ahora bien, aunque la reducción abierta y fijación interna con material de osteosíntesis hace parte del manejo idóneo para todo tipo de fractura, todos los casos requieren ser individualizados.

Background: wounds from a frearm projectile in the craniofacial region cause devastating functional damage and aesthetic deformities, along with psychological trauma when returning to daily life. This is why proper reconstruction is essential for comprehensive rehabilitation. External fxation is a method of closed fracture reduction that involves the use of screws to manipulate loose segments of bone that are then fxed using external connections. Objective: to present the case of a patient with a mandibular fracture caused by a frearm projectile treated with external fixators and review the literature. Clinical case: a 19-year-old male patient who presented a fracture of the left mandibular ramus caused by a frearm projectile, the fracture was managed by placing intermaxillary fxation with Erich-type bar arches and external fixation for 3 months. The patient presented a correct dental occlusion and maintains his mandibular movements without any limitation. Conclusion: mandibular fractures caused by frearm projectiles are a challenge for treatment. Open reduction and internal fixation with osteosynthesis material is the ideal management for all types of fractures, however, all cases must be individualized, and it must be considered that closed reduction and external fxation must remain in our therapeutic arsenal due to their adequate results verifed in the literature and in our case.

Construction of a predictive model for performing bronchoalveolar lavage in children with Mycoplasma pneumoniae pneumonia and pulmonary consolidation / 中国当代儿科杂志

OBJECTIVES@#To investigate the risk factors for performing bronchoalveolar lavage (BAL) in children with Mycoplasma pneumoniae pneumonia (MPP) and pulmonary consolidation, and to construct a predictive model for performing BAL in these children.@*METHODS@#A retrospective analysis was performed for the clinical data of 202 children with MPP who were hospitalized in the Department of Pediatrics, Changzhou No. 2 People's Hospital Affiliated to Nanjing Medical University, from August 2019 to September 2022. According to whether BAL was performed, they were divided into BAL group with 100 children and non-BAL group with 102 children. A multivariate logistic regression analysis was used to identify the risk factors for performing BAL in MPP children with pulmonary consolidation. Rstudio software (R4.2.3) was used to establish a predictive model for performing BAL, and the receiver operator characteristic (ROC) curve, C-index, and calibration curve were used to assess the predictive performance of the model.@*RESULTS@#The multivariate logistic regression analysis demonstrated that the fever duration, C-reactive protein levels, D-dimer levels, and presence of pleural effusion were risk factors for performing BAL in MPP children with pulmonary consolidation (P<0.05). A nomogram predictive model was established based on the results of the multivariate logistic regression analysis. In the training set, this model had an area under the ROC curve of 0.915 (95%CI: 0.827-0.938), with a sensitivity of 0.826 and a specificity of 0.875, while in the validation set, it had an area under the ROC curve of 0.983 (95%CI: 0.912-0.996), with a sensitivity of 0.879 and a specificity of 1.000. The Bootstrap-corrected C-index was 0.952 (95%CI: 0.901-0.986), and the calibration curve demonstrated good consistency between the predicted probability of the model and the actual probability of occurrence.@*CONCLUSIONS@#The predictive model established in this study can be used to assess the likelihood of performing BAL in MPP children with pulmonary consolidation, based on factors such as fever duration, C-reactive protein levels, D-dimer levels, and the presence of pleural effusion. Additionally, the model demonstrates good predictive performance.

Impacto del diámetro del clavo endomedular en la consolidación de fracturas diafisarias de tibia. Análisis retrospectivo sobre 96 pacientes / Impact of the nail diameter on consolidation of tibial diaphyseal fractures. Retrospective analysis of 96 patients

Resumen: Introducción: el estándar de oro de tratamiento para la mayoría de las fracturas diafisarias de tibia está representado por el clavo endomedular (CEM). El objetivo de este estudio fue analizar la importancia del diámetro del CEM sobre la consolidación de fracturas diafisarias de tibia. Material y métodos: se realizó un estudio retrospectivo en pacientes con fracturas cerradas de tibia 42 OTA/AO, tratados con un CEM fresado y acerrojado, entre Enero de 2014 y Diciembre de 2020. Las variables analizadas fueron género, edad, comorbilidades, cantidad de cerrojos utilizados, relación clavo/canal (diferencia entre el diámetro del canal medular y clavo), el índice clavo/canal (razón entre diámetro del clavo y el canal medular), en relación con la tasa de consolidación y falla (retardo de consolidación y seudoartrosis). Resultados: la serie final se conformó por 96 pacientes y la tasa de consolidación fue de 91.7% (n = 88). Se observó un diámetro de clavo significativamente mayor en los pacientes que consolidaron respecto a los que fallaron (p = 0.0014), incrementando la posibilidad de consolidación 5.30 (p = 0.04) veces, por cada milímetro que el clavo aumentó su diámetro. Se observó un incremento de probabilidad de consolidación de 13.56 (p = 0.018) veces utilizando un clavo > 10 mm de diámetro. El índice clavo/canal ≥ 0.80 aumentó la posibilidad de consolidación 23.33 veces (p = 0.005). Conclusión: nuestros hallazgos sugieren que los CEM fresados y acerrojados en fracturas diafisarias de tibia deben colocarse del mayor diámetro posible (> 10 mm y con un índice clavo/canal ≥ 0.80) para favorecer la consolidación.

Abstract: Introduction: the gold standard for tibial diaphyseal fracture treatment is represented by the intramedullary nail (IMN). This study aimed to assess the relevance of nail diameter in bone healing of tibial diaphyseal fractures. Material and methods: a retrospective study was conducted analyzing patients with closed 42 OTA/AO tibial fractures, treated with a reamed and locked IMN between January 2014 and December 2020. The variables assessed were gender, age, comorbidities, number of bolts used, canal/nail index (difference between the diameter of the medullary canal and nail), nail/canal ratio (ratio between nail diameter and medullary canal), related to consolidation and failure rates (delay - and non-union). Results: 96 patients were included. The consolidation rate was 91.7% (n = 88). Patients with consolidation had a significantly larger nail diameter than those who failed (p = 0.0014), increasing the chance of consolidation 5.30 (p = 0.04) times for each millimeter that the nail increased its diameter. Using a nail > 10 mm increased the chance of consolidation 13.56 times (p = 0.018). A nail/canal ratio ≥ 0.80 increased the chance of consolidation 23.33 times (p = 0.005). Conclusion: our findings suggested that reamed and locked IMN in tibial diaphyseal fractures should be implanted with the largest possible diameter (> 10 mm and with a nail-to-canal ratio ≥ 0.80) to promote bone healing.

Consolidation chemoradiation (cCTRT) improves survival in responders to first?line chemotherapy (CT) in locally advanced gallbladder cancer (LA?GBC): A new standard of Care?

Introduction: Chemotherapy (CT) is the standard of care in advanced gallbladder cancer (GBC). Should locally advanced GBC (LA-GBC) with response to CT and good performance status (PS) be offered as consolidation chemoradiation (cCTRT) to delay progression and improve survival? There is a scarcity of literature on this approach in the English literature. We present our experience with this approach in LA-GBC. Materials and Methods: After obtaining ethics approval, we reviewed the records of consecutive GBC patients from 2014 to 2016. Out of 550 patients, 145 were LA-GBC who were initiated on chemotherapy. A contrast-enhanced computed tomography (CECT) abdomen was done to evaluate the response to treatment, according to the RECIST (Response Evaluation Criteria in Solid Tumors) criteria. All responders to CT (PR and SD) with good PS but unresectable were treated with cCTRT. Radiotherapy was given to GB bed, periportal, common hepatic, coeliac, superior mesenteric, and para-aortic lymph nodes up to a dose of 45 to 54 Gy in 25 to 28 fractions along with concurrent capecitabine at the rate of 1,250 mg/m2. Treatment toxicity, overall survival (OS), and factors affecting OS were computed based on Kaplan–Meier and Cox regression analysis. Results: The median age of patients was 50 years (interquartile range [IQR] = 43–56 years), and men to women ratio was 1:3. A total of 65% and 35% patients received CT and CT followed by cCTRT, respectively. The incidence of Grade 3 gastritis and diarrhea was 10% and 5%, respectively. Responses were partial response (PR; 65%), stable disease (SD; 12%), progressive disease (PD; 10%), and nonevaluable (NE; 13%) because they did not complete six cycles of CT or were lost to follow-up. Among PR, 10 patients underwent radical surgery (six after CT and four after cCTRT). At a median follow-up of 8 months, the median OS was 7 months with CT and 14 months with cCTRT (P = 0.04). The median OS was 57 months, 12 months, 7 months, and 5 months for complete response (CR) (resected), PR/SD, PD, and NE (P = 0.008), respectively. OS was 10 months and 5 months for Karnofsky performance status (KPS) >80 and <80 (P = 0.008), respectively. PS (hazard ratio [HR] = 0.5), stage (HR = 0.41), and response to treatment (HR = 0.05) were retained as independent prognostic factors.

Challenges in Management of Tracheobronchial Foreign Bodies with Delayed Presentation: An Institutional Experience

Abstract Introduction Airway foreign bodies are emergencies involving multidisciplinary departments like Pediatrics, Aneasthesiology and Otorhinolaryngology. It is always a challenge to diagnose and manage patients who present late to our emergencies. Objective In the present study, we aim to analyze the various challenges faced during the management of tracheobronchial foreign bodies with delayed presentation. Methods A retrospective hospital record-based analysis of patients who presented to us with tracheobronchial foreign bodies from January 2017 to February 2020 was performed. All patients until the age of 16 years old were included in the present study. We assessed the demographics, preoperative, intraoperative and postoperative data of the patients. Results Seventeen patients were analyzed in the study. Among these, 44.4% of the patients had delayed presentation (> 1 month). The majority of the patients had an organic foreign body (Supari or betel nut). All patients underwent rigid bronchoscopy, followed by optical forceps-assisted removal of the foreign body. A total of 82% of the patients had granulations around the foreign body. Conclusion Management of delayed presentation tracheobronchial foreign body is a big challenge for Otorhinolaryngologists. The key factors for preventing complications in the definitive management of tracheobronchial foreign bodies are preoperative planning, multi-discipline teamwork, surgeon expertise and technique.

Effects of dexmedetomidine on enhancement of fear memory by propofol in rats with post-traumatic stress disorder / 中华麻醉学杂志

Objective:To evaluate the effects of dexmedetomidine on the enhancement of fear memory by propofol in rats with post-traumatic stress disorder (PTSD).Methods:Two hundred and twenty clean-grade healthy male Sprague-Dawley rats, weighing 300-400 g, aged 12-16 weeks, underwent conditioned fear memory training, and PTSD model was developed.One hundred and twenty rats were divided into 6 groups ( n=20 each) by a random number table method: control group (C group), PTSD group, propofol group (P1 group), and propofol + different doses of dexmedetomidine groups (P1+ DEX10 group, P1+ DEX20 group and P1+ DEX40 group). In group C, only sound was played and no electric shock was given during conditioned fear memory training.After conditioned fear memory training, sesame oil 1 ml/kg was intraperitoneally injected in PTSD group, propofol 1 ml/kg was intraperitoneally injected in group P1, and dexmedetomidine 10, 20 and 40 μg/kg were intraperitoneally injected in P1+ DEX10, P1+ DEX20 and P1+ DEX40 groups, respectively.After drug administration, conditioned fear memory test was performed to record the time of rigid behavior within 90 s, and the percentage of time of rigid behavior was calculated.The development of SpO 2<90% was recorded during administration.One hundred Sprague-Dawley rats were divided into 5 groups ( n=20 each) by the random number table method: propofol group (P2 group), and propofol+ dexmedetomidine given at different timings groups (P2+ DEX T0 group, P2+ DEX T30 group, P2+ DEX T60 group and P2+ DEX T90 group). After the conditioned fear memory training, propofol 1 ml/kg was intraperitoneally injected in 5 groups, an then dexmedetomidine 20 μg/kg was intraperitoneally injected at 0, 30, 60 and 90 min after propofol administration in P2+ DEX T0, P2+ DEX T30, P2+ DEX T60 and P2+ DEX T90 groups, respectively.Conditioned fear memory test was performed after drug administration to record the time of rigid behavior within 90 s, and the percentage of time of rigid behavior was calculated. Results:Only 6 rats developed SpO 2<90% during the administration period in P1+ DEX40 group.Compared with C group, the percentage of time of rigid behavior was significantly increased in PTSD group ( P<0.05). Compared with PTSD group, the percentage of time of rigid behavior was significantly increased in P1 group ( P<0.05). Compared with P1 group, the percentage of time of rigid behavior was significantly decreased in P1+ DEX20 and P1+ DEX40 groups ( P<0.05), and no significant change was found in the percentage of time of rigid behavior in P1+ DEX10 group ( P>0.05). Compared with P2 group, the percentage of time of rigid behavior was significantly decreased in P2+ DEX T0 and P2+ DEX T30 groups ( P<0.05), and no significant change was found in the percentage of time of rigid behavior in P2+ DEX T60 and P2+ DEX T90 groups ( P>0.05). Conclusions:Dexmedetomidine can attenuate propofol-induced enhancement of fear memory in a rat model of PTSD, and the best effect is achieved in early administration of moderate dose (20 μg/kg, within 30 min after propofol administration).

Clinical Study of Jiawei Xiaochaihutang Combined with Microwave Ablation in Treatment of Primary Hepatocellular Carcinoma / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of Jiawei Xiaochaihutang combined with microwave ablation （MWA） in the treatment of primary hepatocellular carcinoma （HCC） and its influence on tumor microenvironment. MethodA total of 128 patients were randomly divided into control group （64 cases： 2 cases of dropout，2 cases of elimination，and 60 cases of completion） and observation group （64 cases： 3 cases of dropout，2 cases of elimination，and 59 cases of completion）. Both groups were given comprehensive treatment after MWA surgery. Patients in control group took Biejiajian Wan orally （3 g/time，3 times/d）， and those in observation group took Jiawei Xiaochaihutang （1 dose/d）. The treatment lasted for 3 consecutive months. The size of solid tumor before and after treatment was evaluated to record the progression-free survival （PFS）. The alpha-fetoprotein-L13 （AFP-L3），des-γ-carboxy prothrombin （DCP），Golgi protein 73 （GP73），tumor necrosis factor-α （TNF-α），transforming growth factor-β （TGF-β），vascular endothelial growth factor （VEGF） and matrix metalloproteinase-2 （MMP-2） levels，as well as performance status （PS），liver function and syndrome of liver depression and Qi stagnation scores were also detected before and after treatment. In addition， the incidence of side effects of grade Ⅲ and above was compared. ResultThe total effective rate of solid tumor in observation group was 91.53% （54/59），higher than that （76.67%， 46/60） in control group（χ2=4.895，P<0.05）. The PFS in observation group was （7.16±0.95） months， longer than that （6.24±0.89 months） in control group （P<0.01）. The effective rate of traditional Chinese medicine （TCM） syndrome in observation and control groups were 88.14% （52/59）and 70.00% （42/60）， respectively （χ2=5.897，P<0.05）. The observation group （57.63%，34/59） had higher marked effective rate of TCM syndrome than control group （31.67%，19/60） （χ2=8.116，P<0.01）. The AFP-13，DCP，GP73，TNF-α，TGF-β，VEGF and MMP-2 levels and the PS，liver function and syndrome of liver depression and Qi stagnation scores in observation group were lower than those in control group （both P<0.01）. The cumulative incidence of side effects of grade Ⅲ and above in observation and control groups was 16.95% and 33.33%， respectively（χ2=4.261，P<0.05）. ConclusionConsolidation treatment of HCC after MWA surgery with Jiawei Xiaochaihutang relieved symptoms and side effects，improved PS and liver function，regulated tumor microenvironment，inhibited tumor markers and prolonged survival time. The clinical effect was better than that of Biejia decoction pill， and thus it was worthy of clinical use.

Cost-utility analysis of durvalumab for consolidation therapy after chemoradiotherapy for stage Ⅲ non-small cell lung cancer / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer from the perspective of the Chinese health care system. METHODS A Markov model was developed by using updated four-year survival data from the PACIFIC trial in May 2021 and relevant literature. The cost-effectiveness of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer was evaluated by using quality-adjusted life years （QALYs）as health output index with 20-year simulation time frame and a 2-week cycling period. The costs and health output were discounted using discount rate of 5％；one-way sensitivity analysis and probabilistic sensitivity analysis were used to examine the robustness of the model simulation results. RESULTS The results of the base analysis showed that compared with placebo group ，durvalumab resulted in 0.73 QALYs at an incremental cost of 1 076 062.86 yuan and an incremental cost-utility ratio （ICER）of 1 467 546.54 yuan/QALY，which was much higher than 3-fold per capita gross domestic products （GDP）in 2020（217 713 yuan）as willingness-to-pay （WTP）threshold. The results of one-way sensitivity analysis showed that the price of durvalumab and discount rate had a great impact on ICER. Probabilistic sensitivity analysis showed no cost-effective advantage for durvalumab when the WTP threshold was three times of GDP per capita in 2020 （217 713 yuan）. CONCLUSIONS From the perspective of Chinese health care system ，there is no cost-effective advantage to the use of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer when the WTP threshold was three times of GDP per capita in 2020.

Harder maintained than achieved: Challenges of maintaining malaria-free in China / 中国血吸虫病防治杂志

On June 2021, China was certified malaria-free by WHO. However, the global number and death of malaria cases have recently increased, and the malaria vectors will continue to inhabit in China, resulting in a high difficulty in consolidation of malaria elimination achievements. Hereby, we analyze the current challenges and propose the future priority of the national malaria control program in China, in order to provide insights into prevention of re-establishment of imported malaria in the country.

The role of nocturnal sleep on the retention, adaptability, and relearning rate of a motor skill

Abstract Aim: The influence of sleep on the adaptability and relearning rate during learning of complex motor skills is still unknown, limiting the comprehension of the sleep role in motor memory consolidation. Thus, we aimed to investigate the nocturnal sleep influence on retention, adaptability, and relearning rate of the dart-throwing task. Methods: Sixty healthy adults were divided into two groups: SLEEP and WAKE. Both groups practiced an under-arm dart-throwing task. However, WAKE practiced in the morning and performed a retention phase in the evening, and SLEEP practiced in the evening and performed a retention phase in the morning of the next day. The practice and retention phases were separated by 12 h in both groups. There were analyses regarding retention (retention test), adaptability (delayed transfer test), and relearning rate (savings). Results: Both groups improved their performance across the acquisition phase and maintained it in the retention test. The groups did not demonstrate adaptability and did not demonstrate a significant difference in relearning rate. Conclusion: We conclude that nocturnal sleep did not modulate the consolidation of motor memories related to ballistic discrete motor skills.

Consolidação de atos normativos: a especificidade da técnica legislativa e a consolidação do Sistema Único de Saúde / Consolidation of enacted statutes: the specificity of the legislative technique and the consolidation of the Unified Health System / Consolidación de actos normativos: la especificidad de la técnica legislativa y la consolidación del Sistema Único de Salud

Objetivo: o objetivo central do artigo é o de identificar a função e o regime jurídico específico da consolidação de atos normativos, enquanto instituição de direito público, tendo por base a experiência consolidadora modelar do Sistema Único de Saúde (SUS). Metodologia: a interpretação dos diplomas normativos pertinentes à elaboração, redação, alteração e consolidação de atos normativos obedeceu à hermenêutica prescritiva ou metodológica, aplicando-se os cânones da autonomia hermenêutica do objeto, expressa na máxima sensus non est inferendus sed efferendus; da coerência de sentido ou princípio da integralidade; da atualidade da compreensão; e da correspondência hermenêutica de sentido ou harmonização, tomando-se por tipos ideais os constructos da garantia institucional, do neoinstitucionalismo jurídico e das normas de ocorrência singular, e por pressuposto a objetividade da interpretação de E. D. Hirsch. Resultados: a função da consolidação é tanto de momento de ajuste de técnica legislativa, quanto, principalmente, de garantia institucional do princípio da segurança jurídica, revelada por suas características de norma singular de atualização contínua e permanente de sistemas normativos e de reestruturação orgânica neoinstitucional de diplomas normativos esparsos. O diferencial funcional da categoria jurídica da consolidação, por sua vez, impõe um regime jurídico distinto daquele aplicado às categorias normativas ordinárias, configurando-se em etapa processual legislativa ou normativa alheia à inovação e imune a exigências formais de numeração sequencial e vigência diferida. Conclusão: a interpretação das normas sobre elaboração, redação, alteração e consolidação das normas federais vigentes no Brasil, bem como o uso do parâmetro teórico do neoinstitucionalismo jurídico, evidenciaram a distinção funcional e de regime jurídico da consolidação frente às categorias normativas ordinárias presentes no ordenamento jurídico brasileiro.

Objetive: to identify the legal regime and legal functions of normative consolidations as public law institutions, taking into consideration the recent approval of the Brazilian Unified Health System consolidation. Methodology: based on prescriptive or methodologicalhermeneutics, this article applies Betti's canons of (i) the hermeneutical autonomy of the object, expressed in the maxim sensus non est inferendus sed efferendus, (ii) the coherence of meaning or principle of totality, (iii) the actuality of understanding, and (iv) the hermeneutical correspondence of meaning or harmonization. It also adopts as ideal-types, the legal constructs of institutional guarantees, neoinstitutionalism and nonsequential statutes, based on the assumption of Hirsch's objectivity of interpretation. Results: consolidation, as a legal institution, plays two main roles: (i) It fosters a juridical-technical harmonization of the norm in itself and in relation with the other norms on related topics; (ii) It presents itself as an institutionalguarantee of the principle of legal certainty, due to its features of continuous renewal of the normative content and neoinstitutional reengineering of sparsely positioned norms in an organic set of interrelated legal content. The legal institution of theconsolidation is characterized by a specific legal regime: (i) Firstly, it figures as a normative procedural step that avoid innovation; (ii) Secondly, it is exempted of the sequential numbering of the norms and several rules pertaining entry into force. Conclusion: the interpretation of federal acts in Brazil on legal drafting, writing, changing and consolidation, and the use of neoinstitutional underpinnings brings to light the specific role played by the consolidation and the unique functional and legalregime when compared to the ordinary normative categories in the Brazilian Law.

Objetivo: identificar el régimen y las funciones legalesde las consolidaciones normativas como instituciones de derecho público, tomando en consideración la reciente aprobación de la consolidación del Sistema Único de Salud Brasileño. Metodología: basado en la hermenéutica prescriptiva o metodológica, este artículo aplica los cánones de Betti de (i) la autonomía hermenéutica del objeto, expresada en la máxima sensus non est inferendus sed efferendus, (ii) la coherencia de significado o principio de la totalidad, (iii) ) la actualidad del entendimiento, y (iv) la correspondencia hermenéutica de significado o armonización. También adopta como tipos ideales, las construcciones legales de las garantías institucionales, el neoinstitucionalismo y las normas de ocurrencia singular, basado en el supuesto de la objetividad de interpretación de Hirsch. Resultados: la consolidación, como institución jurídica, juega dos roles principales: (i) fomenta una armonización jurídico-técnica de la norma en sí misma y en relación con las demás normas en temas relacionados; (ii) se presenta como garantía institucional del principio de seguridad jurídica, por sus características de renovación continua del contenido normativo y reingeniería neoinstitucional de normas escasamente posicionadas en un conjunto orgánico de contenido jurídicointerrelacionado. La institución jurídica de la consolidación se caracteriza por un régimen jurídico específico: (i) en primer lugar, figura como un paso procesal normativo no inovador; y (ii) en segundo lugar, se exime de la numeración secuencial de las normas y de reglas básicas a la entrada en vigorde la norma. Conclusión: la interpretación de las leyes federales en Brasil sobre redacción, cambio y consolidación legal, y el uso de fundamentos neoinstitucionales, pone de manifiesto el papel específico que juega la consolidación y su régimen funcional y legal único en comparación con las categorías normativas ordinarias en la ley brasileña.

Evolución histórica de la osteosíntesis de huesos largos I: Fijación con placa y tornillos / Historical Evolution of Long Bone Osteosynthesis I: Fixation with Plate and Screws

Introducción: El hombre ha actuado sobre las fracturas óseas de los miembros desde tiempos ancestrales, confirmando a la inmovilización (reducción-estabilidad) como la forma básica de tratar la afección, que se le presenta con la tríada: trauma, dolor e impotencia funcional. Objetivo: El objetivo de este trabajo fue organizar la presentación de los cambios que ocurrían con las innovaciones tecnológicas que se incorporaban en el tratamiento de las fracturas. Métodos: Se presenta una revisión de artículos sobre fracturas publicados en revistas indizadas por el CITMA, libros de autores reconocidos, notas personales de eventos y actividades quirúrgicas, con el fin de analizar las variables seleccionadas y sus vínculos históricos con las distintas etapas que marcaron las nuevas concepciones y modificaciones, surgidas en la aplicación de este tipo de osteosíntesis, lo que nominamos Generaciones. Las variables seleccionadas para el análisis fueron: la reducción de la fractura, la vía de acceso para la colocación de la placa, el procedimiento quirúrgico, los nuevos diseños de implantes, el instrumental, la metalurgia de los implantes y la consolidación curativa. Elementos constitutivos del procedimiento quirúrgico de la osteosíntesis. Relacionando los resultados obtenidos y las fechas de su puesta en práctica, con momentos históricos y la inclusión de Innovaciones Tecnológicas de relevancia, llegamos a reconocer tres etapas o Generaciones donde la influencia de las mismas, explican los adelantos en las concepciones actuales de este proceder. Primera Generación: Clásica, a principios del siglo XX. Segunda Generación: de Compresión, Post Segunda Guerra Mundial. Tercera Generación: Actual, Funcional, y Biológica. Conclusiones: Relacionando los resultados obtenidos y las fechas de su puesta en práctica, con momentos históricos e inclusión de innovaciones tecnológicas de relevancia, llegamos a reconocer tres etapas o Generaciones donde su influencia explica los adelantos en las concepciones actuales de este proceder. Primera Generación o Clásica: a principios del siglo XX. Segunda Generación: de Compresión, Post Segunda Guerra Mundial. Tercera Generación: Actual, Funcional y Biológica(AU)

Introduction: Man has acted on bone fractures of the limbs since ancient times, confirming immobilization (reduction-stability) as the basic way of treating the condition, which is presented with the triad of trauma, pain and functional impotence. Objective: The objective of this paper was to organize the presentation of the changes occurred with technological innovations, integrated in the treatment of fractures. Methods: A literature review on fractures is presented here. Articles published in journals indexed by CITMA, books by well-known authors, personal notes of events and surgical activities were reviewed, in order to analyze the selected variables and their historical links with the different stages that marked the new conceptions and modifications, arisen in the use of this type of osteosynthesis we call generations. Variables selected for analysis were fracture reduction, access route for plate placement, surgical procedure, new implant designs, instrumentation, implant metallurgy, and healing consolidation. Constitutive elements of the osteosynthesis surgical procedure: By relating the results obtained and the dates of their implementation, with historical moments and the inclusion of relevant technological innovations, we come to recognize three stages or generations and their influence explains the advances in the current conceptions of this approach. First generation: classic, early 20th century. Second generation: compression, post-World War II. Third generation: current, functional, and biological. Conclusions: By relating the results obtained and the dates of their implementation, with historical moments and the inclusion of relevant technological innovations, we come to recognize three stages or generations whose influence explains the advances in the current conceptions of this procedure. First generation or classic: at the beginning of the 20th century. Second generation: compression, post-World War II. Third generation: current, functional and biological(AU)

Uso de los factores de crecimiento presentes en el plasma rico en plaquetas como un tratamiento alternativo de lesiones músculo esqueléticas en animales / Use of growth factors present in platelet-rich plasma as an alternative treatment for musculoskeletal lesions in animals / Uso de fatores de crescimento presentes no plasma rico em plaquetas como tratamento alternativo para lesões musculo esqueléticas em animais

Resumen Se realizó una revisión sistemática del uso de plasma rico en plaquetas (PRP) en animales, seleccionando 105 artículos de referencia, publicados en los últimos 8 años (2012 a 2020) de las revistas Veterinary Medicine International, Scientific Reports, BMC Veterinary Research, Platelets, Biomedicine and Pharmacotherapy entre otras y validadas en las siguientes bases de datos: Pubmed, Web of Science, Sciencedirect, Scielo, Medline, Embase y Scopus. Limitando solo las revistas con altos rankings ayudados con las clasificaciones de revistas por scimago journal. Solo 35 artículos cumplieron los criterios de selección; articulándolo con necesidades actuales en la medicina veterinaria, buscando una nueva biotecnología y proyectándose hacia la medicina regenerativa, basándose en reconstrucción de tejidos vivos para contrarrestar daño o remplazo de función de órganos lesionados. Una de estas herramientas es el plasma rico en plaquetas (PRP) con sus factores de crecimiento (FC) Transformante ß (TGF ß), fibroblástico básico (FGFb), derivado de plaquetas (PDGF), del endotelio vascular (VEGF), tejido conectivo (CTGF) y epidérmico (EGF). Actualmente el (PRP) es un bioestimulante tomado como base por estudios en medicina humana y medicina veterinaria, observando su efectividad en el proceso de consolidación ósea en pacientes clínicos. Se recogieron evidencias científicas presentadas en literatura médica con respecto al PRP como una alternativa de tratamiento en el manejo de fracturas y lesiones músculo esqueléticas, con ello se logra determinar la importancia de la estandarización del procedimiento (PRP) en uso, preparación, almacenamiento y administración.

Abstract A systematic review of platelet-rich plasma (PRP) use in animals was carried out by taking 105 reference articles published during the last 8 years (2012 to 2020) in Veterinary Medicine International, Scientific Reports, BMC Veterinary Research, Platelets, Biomedicine and Pharmacotherapy; they were validated in the following databases: PubMed, Web of Science, ScienceDirect, SciELO, Medline, Embase and Scopus. The search was limited to just journals having a high impact factor; the SCImago journal rank (SJR) indicator (i.e. a sophisticated citation analysis algorithm) was also used. Only 35 of these articles met the selection criteria: i.e. coordinating content with current needs in veterinary medicine, seeking new biotechnological approaches and promoting regenerative medicine based on reconstructing living tissue to counteract damage or replace injured organs' function. One such tool is platelet-rich plasma (PRP) with its derivative growth factors (GF): transforming growth factor-ß (TGF-ß), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), connective tissue growth factor (CTGF) and epidermal growth factor (EGF). PRP is currently used as a biostimulant, acting as the basis for human and veterinary medicine studies; its effectiveness regarding bone/fracture healing/regeneration in clinical patients has been observed. Scientific evidence in the pertinent medical literature regarding PRP as an alternative treatment for managing fractures and musculoskeletal injuries was collected, thereby determining the importance of standardising the PRP procedure regarding its use, preparation, storage and administration.

Resumo Foi realizada uma revisão sistemática da utilização de plasma rico em plaquetas (PRP) em animais, com 105 artigos de referência, publicados nos últimos 8 anos (2012 a 2020) das revistas Veterinary Medicine International, Scientific Reports, BMC Veterinary Research, Platelets, Biomedicina e Farmacoterapia entre outros e validados nas seguintes bases de dados: Pubmed, Web of Science, Sciencedirect, Scielo, Medline, Embase e Scopus. Limitar apenas os periódicos com classificações altas ajudou com as classificações de periódicos pelo jornal scimago. Dos quais apenas 35 artigos atenderam aos critérios de seleção; articulando-se com as necessidades atuais da medicina veterinária, buscando uma nova biotecnologia e projetando-se na medicina regenerativa, baseada na reconstrução de tecidos vivos para neutralizar danos ou substituição de função de órgãos lesados. Uma dessas ferramentas é o plasma rico em plaquetas (PRP) com seus fatores de crescimento (FC) ß transformador (TGF ß), fibroblasto básico (FGFb), derivado de plaquetas (PDGF), endotelial vascular (VEGF), tecido conjuntivo (CTGF) e epidérmico (EGF). Atualmente (PRP) é um bioestimulante tomado como base para estudos em medicina humana e veterinária, observando sua eficácia no processo de consolidação óssea em pacientes clínicos. Foram coletadas evidências científicas apresentadas na literatura médica a respeito do PRP como alternativa de tratamento no manejo de fraturas e lesões musculoesqueléticas, determinando a importância da padronização do procedimento (PRP) no uso, preparo, armazenamento e administração.

Humeral fracture repair using a robust fixation in an adult Giant Anteater (Myrmecophaga tridactyla): case report / [Reparo de fratura umeral usando uma fixação robusta em um tamanduá-bandeira adulto (Myrmecophaga tridactyla): relato de caso]

The treatment of fractures from the thoracic limb in giant anteaters is extremely challenging. Unfamiliar and peculiar anatomical characteristics, robust musculature and the imminent need for an early return to limb function highlight such challenges. The objective of this report was to describe the successful use of anatomical osteosynthesis with a robust locking compression plate in a humeral fracture of an adult giant anteater. The patient was rescued on the highway after being run over and presented for treatment at the Veterinary Teaching Hospital. Surgical stabilization was performed using a craniomedial approach to the humerus, using a customized broad 3.5mm locking compression plate. The patient presented early limb support at 24 hours postoperatively. Radiographic monitoring was performed at 30, 60 and 90 days postoperatively, and bone healing was observed without any complications. It is concluded that the treatment of humerus fractures in giant anteaters requires robust fixation. The use of a reinforced locking compression plate system proved to be effective and adequate to the mechanical load that an adult individual of this species needs for early use of the thoracic limb and, at the same time, efficient in controlling interfragmentary movement, which allowed fracture consolidation.(AU)

O tratamento das fraturas do membro torácico dos tamanduás-bandeira (Myrmecophaga tridactyla) é extremamente desafiador. Características anatômicas pouco familiares e peculiares, musculatura muito desenvolvida e necessidade iminente de retorno precoce à função do membro destacam tais desafios. Objetivou-se, neste relato, descrever a utilização com sucesso da osteossíntese anatômica com placa bloqueada robusta em fratura umeral de um tamanduá-bandeira. O paciente foi resgatado em rodovia após atropelamento e atendido no Hospital Veterinário Universitário. Após sedação e avaliação física completa, foi realizado exame radiográfico, o qual revelou fratura completa oblíqua curta em diáfise média de úmero esquerdo. A estabilização cirúrgica foi realizada por abordagem craniomedial ao úmero, utilizando-se placa bloqueada (LCP) do sistema 3,5mm customizada. O paciente apresentou apoio precoce do membro com 24 horas de pós-operatório. Realizou-se acompanhamento radiográfico aos 30, 60 e 90 dias, sendo observada união clínica sem quaisquer complicações. Conclui-se que o tratamento das fraturas do úmero em tamanduás-bandeira exige robustez na fixação. A utilização de sistema reforçado de placa bloqueada mostrou-se efetiva e adequada à carga mecânica de que um indivíduo adulto dessa espécie necessita para uso precoce do membro torácico e, ao mesmo tempo, eficiente no controle da movimentação interfragmentária, o qual permitiu consolidação da fratura.(AU)

Evaluación de los resultados en el tratamiento de los pacientes con fracturas de pilón tibial / Outcomes assessment in the treatment of patients with tibial pylon fractures

RESUMEN Introducción: las fracturas de pilón tibial son un desafío para el cirujano y actualmente existe controversia en cuanto a su tratamiento. Objetivo: evaluar los resultados del tratamiento aplicado. Materiales y métodos: se realizó un estudio observacional, descriptivo, longitudinal, con el universo de estudio de todos los pacientes que fueron atendidos y tratados con fractura de pilón tibial desde el 1 de enero de 2015 al 31 de diciembre de 2016. Se seleccionó una muestra de 27 pacientes. Resultados: hubo un predominio del sexo masculino (78 %), y del grupo de edades de 40 a 49 años para ambos sexos (37 %). Prevalecieron las fracturas producidas por accidentes de tránsito, con 59 %. Las fracturas cerradas fueron las más representadas, con 78 %. El 67 % de los pacientes no presentaron lesiones asociadas y predominaron las fracturas tipo II en el 55 % del total. Se aplicó tratamiento quirúrgico a un 74 % y se logró la consolidación en un 78 % de los casos antes de las 16 semanas. Antes de las 20 semanas se le indicó el apoyo al 78 % de los casos. Se complicaron 13 pacientes, para un 48 % del total. A pesar de ello, como resultado final, fueron evaluados de excelente y bien el 63 % de los pacientes. Conclusiones: la fractura de pilón tibial constituye una lesión de muy difícil manejo para el cirujano traumatólogo de hoy (AU).

ABSTRACT Introduction: tibial pylon fractures are a challenge for the surgeon surgery and currently there is a controversy regarding their treatment. Objective: to assess the outcomes of the applied treatment. Materials and methods: an observational, descriptive, longitudinal study was carried out with the study universe of all the patients who were attended and treated with tibial pylon fracture from January 1st, 2015 to December 31st, 2016. A sample composed by 27 patients was chosen. Results: male sex (78 %) and both-sexes 40-49 age group (37 %) predominated. There was a predominance of fractures caused by traffic accidents with 59 %, being closed fractures the most represented ones, with 78 %. 67 % of the patients did not present associated injuries, being type II fractures predominant in 55 % of the total. 74 % of the cases underwent surgery, achieving consolidation in 78 % of the cases before 16 weeks. Before 20 weeks, 78 % of the cases were indicated to set on their foot, and 13 patients had complications, representing 48 % of the total. In spite of this, 63 % of the patients were evaluated as excellent and well as final outcome. Conclusions: the tibial pylon fracture is an injury of very difficult handling for the today's orthopedic surgeon (AU).

Effect and underlying mechanism of obstructive sleep apnea on memory consolidation / 四川精神卫生

The purpose of this paper is to review the research progress on the effects of obstructive sleep apnea （OSA） on memory consolidation， and to speculate on possible mechanisms underlying these effects， so as to inform the exploration of effective therapeutic measures for impaired memory consolidation. Previous studies have shown that mild OSA may impair different types of memory consolidation， and the impairments are closely related to certain indices of polysomnography （such as sleep microstructure， apnea hypopnea index， arousal index， etc）. Therefore， it is hypothesized that disruption of sleep architecture and damage to brain regions and neural pathways associated with sleep-dependent memory consolidation due to intermittent hypoxia may trigger a decline in memory consolidation. Meantime， long-term continuous positive airway pressure can alleviate the impairment of memory consolidation induced by OSA， but whether other interventions can mitigate the damage remains unclear.