Relation between Delay Time to Surgical Treatment of Prostate Cancer and Disease Recurrence Risk / Relação entre Tempo de Atraso no Tratamento Cirúrgico do Câncer de Próstata e Risco de Recorrência da Doença

De acordo com a literatura, não há consenso sobre um tempo de atraso razoável desde o diagnóstico até a operação da prostatectomia radical (PR) sem piora do prognóstico. Objetivo: Avaliar a influência desse tempo no risco de recorrência da doença em pacientes com adenocarcinoma acinar da próstata tratados com PR. Método: Quatrocentos e doze pacientes submetidos à PR foram avaliados retrospectivamente. Destes, 172 foram excluídos por dados incompletos e outros 28, por estadiamento pré- -operatório como câncer de próstata de alto risco (PSA > 10 ng/mL ou escore de Gleason na biópsia > 7). Os estadiamentos pré e pós-operatórios foram comparados, e a análise de sobrevida feita pelo método de Kaplan-Meier para examinar a influência do tempo na discordância entre os estadiamentos pré e pós-operatórios. Resultados: Para os 212 pacientes da amostra, o tempo médio desde o diagnóstico até a PR foi de 176,1 ± 120,2 dias (mediana de 145,5 dias), variando de 29 a um máximo de 798 dias. A curva de Kaplan-Meier indicou que o câncer piorava quanto maior o atraso entre o diagnóstico e a operação. Pacientes submetidos à cirurgia dentro de 60 dias tiveram cerca de 95% de probabilidade de não aumentarem o risco inicial de recorrência. Esse número caiu para 80%, 70% e 50% nos pacientes operados em até 100, 120 e 180 dias, respectivamente. Conclusão: O atraso na realização da PR representa risco contínuo de recorrência da neoplasia. O tempo ideal para PR é de até 60 dias a partir da biópsia da próstata, uma vez que a probabilidade de upstaging é inferior a 5% nesse período.

There is no consensus in the literature on a reasonable delay time from diagnosis to radical prostatectomy (RP) surgery, without worsening the prognosis. Objective: To evaluate the influence of the delay on the risk of disease recurrence in patients with acinar adenocarcinoma of the prostate treated with RP. Method: Four hundred and twelve patients undergoing RP were retrospectively evaluated. Of these, 172 were excluded due to incomplete data and another 28 due to preoperative staging as high-risk prostate cancer (PSA > 10 ng/mL or Gleason score on biopsy > 7). Pre-and postoperative stagings were compared and survival analysis was performed using the Kaplan-Meier method to investigate the influence of time on discordance between pre- and postoperative stagings. Results:For the 212 patients of the sample, the average time from diagnosis to RP was 176.1 ± 120.2 days (median 145.5 days), ranging from 29 to a maximum of 798 days. The Kaplan-Meier curve indicated that the cancer worsened the longer the delay between diagnosis and surgery. Patients undergoing surgery within 60 days had an approximately 95% probability of not increasing the initial risk of recurrence. This number fell to 80%, 70% and 50% in patients operated on up to 100, 120 and 180 days, respectively. Conclusion:Delay in performing RP represents a continuous risk of relapse. The ideal time for RP is up to 60 days from prostate biopsy, as the probability of upstaging is less than 5% in this period

Según la literatura, no existe consenso sobre un tiempo razonable de retraso desde el diagnóstico hasta la cirugía de prostatectomía radical (PR), sin empeorar el pronóstico. Objetivo: Evaluar la influencia de este tiempo sobre el riesgo de recurrencia de la enfermedad en pacientes con adenocarcinoma acinar de próstata tratados con PR. Método: Se evaluaron retrospectivamente 412 pacientes sometidos a PR. De ellos, 172 fueron excluidos por datos incompletos y otros 28 por estadificación preoperatoria como cáncer de próstata de alto riesgo (PSA > 10 ng/mL o puntuación de Gleason en la biopsia > 7). Se compararon las estadificaciones pre y posoperatorias y se realizó un análisis de supervivencia utilizando el método de Kaplan-Meier para examinar la influencia del tiempo en la discordancia entre las estadificaciones pre y posoperatorias. Resultados: Para los 212 pacientes de la muestra, el tiempo promedio desde el diagnóstico hasta la PR fue de 176,1 ± 120,2 días (mediana 145,5 días), oscilando entre 29 y 798 días. La curva de Kaplan-Meier indicó que el cáncer empeoraba cuanto mayor era el retraso entre el diagnóstico y la cirugía. Los pacientes sometidos a cirugía dentro de los 60 días tenían aproximadamente un 95% de probabilidad de no aumentar el riesgo inicial de recurrencia. Esta cifra cayó al 80%, 70% y 50% en los pacientes operados hasta 100, 120 y 180 días, respectivamente. Conclusión: El retraso en la realización de la PR representa un riesgo continuo de restablecimiento de la neoplasia. El momento ideal para la PR es hasta los 60 días desde la biopsia de próstata, ya que la probabilidad de upstaging es inferior al 5% en este periodo.

Vigilancia activa en cáncer de próstata en un grupo de pacientes asistidos en el Centro Docente Asociado de Oncología Médica Rivera: Cooperativa Médica de Rivera (COMERI) / Active surveillance in prostate cancer in a group of patients assisted at the Rivera Associated Teaching Center for Medical Oncology: Rivera Medical Cooperative (COMERI) / Vigilância ativa do câncer de próstata em um grupo de pacientes atendidos no Rivera Associated Teaching Center for Medical Oncology: Rivera Medical Cooperative (COMERI)

Introducción: En Uruguay el cáncer de próstata ocupa el primer lugar en incidencia y el tercer lugar en mortalidad en el hombre. La mayoría de estos cánceres se diagnostican en estadios precoces. Hoy en día, para pacientes con adenocarcinoma de muy bajo riesgo, bajo riesgo o riesgo intermedio favorable, la vigilancia activa es una opción adecuada. Objetivos: Describir una población de pacientes con cáncer de próstata de muy bajo riesgo, bajo riesgo o riesgo intermedio favorable, en vigilancia activa en COMERI. Material y métodos: Estudio descriptivo, observacional, retrospectivo. Se incluyeron pacientes con cáncer de próstata de muy bajo riesgo, bajo riesgo o riesgo intermedio favorable, tratados entre 2010 y 2018 en COMERI. Se recopilaron datos en el sistema de registro clínico electrónico. Resultados: Se incluyeron 33 pacientes, la mediana de edad al diagnóstico fue de 74 años. Todos los pacientes fueron sometidos a controles clínicos y determinación de PSA cada 3 meses. El tacto rectal se realizó en forma anual. El tiempo mediano de vigilancia activa fue de 33 meses. Durante el seguimiento, se observaron pocas variaciones en los valores de PSA. El 21% de los pacientes fue sometido a una nueva biopsia durante el seguimiento activo, y en todos los casos, el Gleason se mantuvo incambiado. Ningún paciente abandonó la modalidad de vigilancia activa. Conclusión: En nuestro entorno, la vigilancia activa se considera una opción terapéutica válida para pacientes altamente seleccionados con cáncer de próstata de muy bajo riesgo, bajo riesgo o riesgo intermedio favorable, y es bien aceptada por ellos.

Introduction: In Uruguay, prostate cancer ranks first in incidence and third in mortality among men. The majority of these cancers are diagnosed at early stages. Nowadays, active surveillance is an appropriate option for patients with adenocarcinoma of very low risk, low risk, or favorable intermediate risk. Objectives: To describe a population of patients with prostate cancer of very low risk, low risk, or favorable intermediate risk under active surveillance at COMERI. Materials and Methods: Descriptive, observational, retrospective study. Patients with prostate cancer of very low risk, low risk, or favorable intermediate risk treated between 2010 and 2018 at COMERI were included. Data were collected from the electronic clinical registry system. Results: Thirty-three patients were included, with a median age at diagnosis of 74 years. All patients underwent clinical monitoring and PSA determination every 3 months. Digital rectal examination was performed annually. The median time of active surveillance was 33 months. During follow-up, there were few variations in PSA values. 21% of patients underwent a repeat biopsy during active surveillance, and in all cases, the Gleason score remained unchanged. No patient discontinued active surveillance. Conclusion: In our setting, active surveillance is considered a valid therapeutic option for highly selected patients with prostate cancer of very low risk, low risk, or favorable intermediate risk, and it is well accepted by them.

Introdução: No Uruguai, o câncer de próstata ocupa o primeiro lugar em incidência e o terceiro lugar em mortalidade entre os homens. A maioria desses cânceres é diagnosticada em estágios precoces. Atualmente, para pacientes com adenocarcinoma de risco muito baixo, baixo risco ou risco intermediário favorável, a vigilância ativa é uma opção adequada. Objetivos: Descrever uma população de pacientes com câncer de próstata de risco muito baixo, baixo risco ou risco intermediário favorável sob vigilância ativa em COMERI. Material e métodos: Estudo descritivo, observacional, retrospectivo. Foram incluídos pacientes com câncer de próstata de risco muito baixo, baixo risco ou risco intermediário favorável, tratados entre 2010 e 2018 em COMERI. Os dados foram coletados no sistema de registro clínico eletrônico. Resultados: Foram incluídos 33 pacientes, com mediana de idade no diagnóstico de 74 anos. Todos os pacientes foram submetidos a controles clínicos e determinação de PSA a cada 3 meses. O toque retal foi realizado anualmente. O tempo médio de vigilância ativa foi de 33 meses. Durante o acompanhamento, houve poucas variações nos valores de PSA. 21% dos pacientes foram submetidos a uma nova biópsia durante a vigilância ativa, e em todos os casos, o Gleason permaneceu inalterado. Nenhum paciente abandonou a modalidade de vigilância ativa. Conclusão: Em nosso ambiente, a vigilância ativa é considerada uma opção terapêutica válida para pacientes altamente selecionados com câncer de próstata de risco muito baixo, baixo risco ou risco intermediário favorável, e é bem aceita por eles.

Aspects épidémiologiques, cliniques et évolutifs de la tuberculose multifocale à N'djamena / Epidemiology, Clinical Presentation and Outcome of Multifocal Tuberculosis in N'djamena

Introduction. La tuberculose est dite multifocale (TMF) lorsqu ́il y a l ́atteinte d ́au moins deux sites extra pulmonaires non contigus associée ou non à une atteinte pulmonaire. Cette étude avait pour but d'étudier les aspects épidémiologiques, diagnostics et évolutifs de la TMF au service de pneumo-phtisiologie du CHU-RN de N'Djamena. Matériels et méthode. Il s'agissait d'une étude rétrospective à visée descriptive de 5 ans allant de janvier 2018 à décembre 2022. Les variables étudiées étaient, épidémiologiques, cliniques et évolutives. Résultats. Au total, 185 patients étaient inclus sur 2001 cas de tuberculose, soit une fréquence de 9,24%. L'âge moyen était de 34,1 ans avec des extrêmes de 16 ans et 75 ans. Le sex-ratio était de 1,28. Les patients sans-emploi étaient majoritaire soit 47% des cas. La notion de contage tuberculeux représentait 13,5% des cas, et 66,5% des patients étaient vaccinés au BCG avec une séroprévalence VIH de 54,6%. Tous les signes habituels de la tuberculose étaient présents. La localisation pulmonaire était la plus représentée (66,2%) suivie de la localisation ganglionnaire (48,6%). Dans 80% des cas, la localisationétait bifocale. La mortalité était de 21,6% pour un séjour moyen d'hospitalisation de 20,26 jours. Conclusion. La tuberculose multifocale est une forme rare et grave, qui survient généralement chez les patients infectés par le VIH, mais le sujet immunocompétent peut être aussi touché. Un traitement antituberculeux doit être instauré le plus rapidement possible afind'éviter les complications

Introduction. Tuberculosisis called multifocal (TMF) when there is involvement of at least two non-contiguous extrapulmonary sites, whether or notassociated with pulmonary involvement. This study aimed to study the epidemiological, diagnostic and evolutionary aspects of FMT in the pneumo-phthisiology department of the CHU-RN of N'Djamena. Materials and method. This was a 5-year retrospective study with a descriptive aim from January 2018 to December 2022. The variables studied were epidemiological, clinical and progressive. Results. In total, 185 patients were included out of 2001 cases of tuberculosis, i.e. a frequency of 9.24%. The average age was 34.1 years with extremes of 16 and 75 years. The sex ratio was 1.28. Unemployed patients were the majority, i.e. 47% of cases. The notion of tuberculosis contagion represented 13.5% of cases, and 66.5% of patients were vaccinated with BCG with an HIV seroprevalence of 54.6%. All the usual signs of tuberculosis were present. The pulmonary location was the most represented (66.2%) followed by the lymph node location (48.6%). In 80% of cases, bifocal localization. Mortality was 21.6% for an average hospital stay of 20.26 days. Conclusion.Multifocal tuberculosis is a rare and serious form, which generally occurs in patients infected with HIV, but immunocompetent subjects can also be affected. Anti-tuberculosis treatment must be started as quickly as possible to avoid complications.

Prognostic awareness and prognostic information preferences among advanced cancer patients in Kenya

Background: Cancer is the third leading cause of death in Kenya. Yet, little is known about prognostic awareness and preferences for prognostic information. Aim: To assess the prevalence of prognostic awareness and preference for prognostic information among advanced cancer patients in Kenya. Setting: Outpatient medical oncology and palliative care clinics and inpatient medical and surgical wards of Moi Teaching and Referral Hospital (MTRH) in Eldoret, Kenya. Methods: The authors surveyed 207 adults with advanced solid cancers. The survey comprised validated measures developed for a multi-site study of end-of-life care in advanced cancer patients. Outcome variables included prognostic awareness and preference for prognostic information. Results: More than one-third of participants (36%) were unaware of their prognosis and most (67%) preferred not to receive prognostic information. Increased age (OR = 1.04, 95% CI: 1.02, 1.07) and education level (OR: 1.18, CI: 1.08, 1.30) were associated with a higher likelihood of preference to receive prognostic information, while increased symptom burden (OR= 0.94, CI: 0.90, 0.99) and higher perceived household income levels (lower-middle vs low: OR= 0.19; CI: 0.09, 0.44; and upper middle- or high vs low: OR= 0.22, CI: 0.09, 0.56) were associated with lower odds of preferring prognostic information. Conclusion: Results reveal low levels of prognostic awareness and little interest in receiving prognostic information among advanced cancer patients in Kenya. Contribution: Given the important role of prognostic awareness in providing patient-centred care, efforts to educate patients in Kenya on the value of this information should be a priority, especially among younger patients.

Absceso de Brodie en la clavícula: una forma poco frecuente de presentación / Brodie abscess in the clavicle: an uncommon presentation

La osteomielitis (OM) se define como la inflamación ósea de origen infeccioso. La forma aguda es frecuente en la edad pediátrica. El absceso de Brodie es un tipo de osteomielitis subaguda, históricamente con baja incidencia, pero que actualmente se presenta un aumento de la misma. De poca repercusión clínica, con pruebas de laboratorio inespecíficas y estudios radiológicos de difícil interpretación, es crucial la sospecha diagnóstica. Se asemeja a procesos neoplásicos, benignos o malignos. Recae en la experiencia del profesional realizar el diagnóstico adecuado. El tratamiento consiste en antibioticoterapia, tanto parenteral como por vía oral, y eventualmente drenaje quirúrgico. Presentamos una paciente sana que consultó por una tumoración en topografía de clavícula izquierda de 3 meses de evolución. Se realizó diagnóstico de absceso de Brodie, inició tratamiento y se obtuvo una buena respuesta. Resulta imprescindible tener un alto índice de sospecha de esta entidad para no someter al paciente a estudios, pruebas invasivas o tratamientos erróneos, y evitar secuelas a futuro.

Osteomyelitis is defined as an inflammation of the bone caused by infection. Acute osteomyelitis is common in pediatrics. A Brodie abscess is a type of subacute osteomyelitis, with a historically low incidence; however, its incidence is currently increasing. Given its little clinical impact, with non-specific laboratory tests and radiological studies of difficult interpretation, diagnostic suspicion is crucial. It resembles neoplasms, either benign or malignant. An adequate diagnosis falls on the health care provider's experience. Treatment consists of antibiotics, both parenteral and oral, with potential surgical drainage. Here we describe the case of a healthy female patient with a tumor found in the topography of the left clavicle 3 months before. She was diagnosed with Brodie abscess; treatment was started with a good response. A high index of suspicion of Brodie abscess is critical to avoid invasive tests and studies or inadequate treatments, and to prevent future sequelae.

Macrophage heterogeneity role in NAFLD and NASH disease progression / 中华肝脏病杂志

Nonalcoholic fatty liver disease (NAFLD) is a type of metabolic stress liver injury that is closely associated with insulin resistance and genetic susceptibility. The continuum of liver injury in NAFLD can range from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) and even lead to cirrhosis and liver cancer. The pathogenesis of NAFLD is complicated. Pro-inflammatory cytokines, lipotoxicity, and gut bacterial metabolites play a key role in activating liver-resident macrophages (Kupffer cells, KCs) and recruiting circulating monocyte-derived macrophages (MoDMacs) to deposit fat in the liver. With the application of single-cell RNA-sequencing, significant heterogeneity in hepatic macrophages has been revealed, suggesting that KCs and MoDMacs located in the liver exert distinct functions in regulating liver inflammation and NASH progression. This study focuses on the role of macrophage heterogeneity in the development and occurrence of NAFLD and NASH, in view of the fact that innate immunity plays a key role in the development of NAFLD.

Analysis of spontaneous nystagmus and the frequency characteristics of affected semicircular canals in patients with vestibular neuritis / 中华内科杂志

Objective: To investigate the spontaneous nystagmus (SN) and the frequency characteristics of affected semicircular canals in patients with vestibular neuritis (VN). Methods: This is a cross-sectional study. A total of 61 patients with VN admitted to the Department of Neurology of Shanxi Bethune Hospital from June 2020 to October 2021, 39 were male and 22 were female, with a mean age of (46±13) years old and male to female ratio of 1.77∶1. According to SN characteristics, 61 patients were divided into non-nystagmus group(nSN), horizontal nystagmus group(hSN) and horizontal-torsional nystagmus group (htSN). Clinical data were collected, and SN, unilateral weakness (UW), directional preponderance (DP), and video head impulse test (vHIT) gain were used as observation indicators. Statistical analysis by SPSS23.0 software. Normal distributed quantitative data (age, semicircular canal gain, SN intensity) were expressed by x¯±s, non-normal distributed quantitative data (disease course, UW, DP) were expressed by M(Q1,Q3), qualitative data were expressed by rate and composition ratio, difference analysis by one-way ANOVA, rank sum test, Chi-square test or Fisher's exact probability method, considered by P value<0.05. Results: (1)The disease course of nSN, hSN and htSN was 7.0 (4.0, 12.5), 6.0 (3.5, 11.5), and 3.0 (2.0, 6.5) days respectively, and there were statistical differences (χ2=7.31,P=0.026).(2)The horizontal nystagmus intensity of htSN was (16.8±8.6)°/s, which was significantly higher than that of (9.8±4.7)°/s in hSN (t=3.71, P<0.001). There was no significant difference in the positive rate of UW between the three groups (P=0.690), and there was a significant difference in the positive rate of DP in the three groups (χ2=12.23, P=0.002). The horizontal nystagmor intensity in the htSN was positively correlated with the vertical nystagmus intensity (r=0.59, P=0.001).(3)The gain of the affected horizontal canal of the three groups was statistically different (F=8.28, P=0.001), and the gain of the horizontal canal of hSN and htSN was significantly lower than that of nSN (t=2.74, P=0.008; t=4.05, P<0.001); The gain of the affected anterior canal in the three groups was statistically different (F=5.32, P=0.008). The gain of the anterior canal in both nSN and hSN was significantly higher than that in htSN (t=3.09, P=0.003; t=2.15, P=0.036). The horizontal canal gain of htSN is positively correlated with the anterior canal gain (r=0.74, P<0.001).(4)The affected semicircular canals in the two groups with no-vertical-component nystagmus (nSN and hSN) and the htSN were counted. The composition ratio of the affected semicircular canals in the two groups was different (χ2=8.34, P=0.015). Conclusion: The occurrence of SN in patients with VN is related to many factors, such as the disease course, low and high frequencies, and the severity of the condition in the affected semicircular canal.

Predictive factors for sequelae of bronchitis obliterans in refractory Mycoplasma pneumoniae pneumonia / 中华儿科杂志

Objective: To investigate the predictive factors for bronchitis obliterans in refractory Mycoplasma pneumoniae pneumonia (RMPP). Methods: A restrospective case summary was conducted 230 patients with RMPP admitted to the Department of No.2 Respiratory Medicine of Beijing Children's Hospital, Capital Medical University from January 2013 to June 2017 were recruited. Clinical data, laboratory results, imaging results and follow-up data were collected. Based on bronchoscopy and imaging findings 1 year after discharge, all patients were divided into two groups: one group had sequelae of bronchitis obliterans (sequelae group) and the other group had not bronchitis obliterans (control group), independent sample t-test and nonparametric test were used to compare the differences in clinical features between the two groups. Receiver operating characteristic (ROC) curve to explore the predictive value of Bronchitis Obliterans in RMPP. Results: Among 230 RMPP children, there were 115 males and 115 females, 95 cases had sequelae group, the age of disease onset was (7.1±2.8) years;135 cases had control group, the age of disease onset was (6.8±2.7) years. The duration of fever, C-reative protein (CRP) and lactate dehydrogenase (LDH) levels, the proportion of ≥2/3 lobe consolidation, pleural effusion and the proportion of airway mucus plug and mucosal necrosis were longer or higher in the sequelae group than those in the control group ((17±9) vs. (12±3) d, (193±59) vs. (98±42) mg/L,730 (660, 814) vs. 486 (452, 522) U/L, 89 cases (93.7%) vs. 73 cases (54.1%), 73 cases (76.8%) vs.59 cases (43.7%), 81 cases (85.3%) vs. 20 cases (14.8%), 67 cases (70.5%) vs. 9 cases (6.7%), t=5.76, 13.35, Z=-6.41, χ2=14.64, 25.04, 22.85, 102.78, all P<0.001). Multivariate Logistic regression analysis showed that the duration of fever ≥10 days (OR=1.200, 95%CI 1.014-1.419), CRP levels increased (OR=1.033, 95%CI 1.022-1.044) and LDH levels increased (OR=1.001, 95%CI 1.000-1.003) were the risk factors for sequelae of bronchitis obliterans in RMPP. ROC curve analysis showed that CRP 137 mg/L had a sensitivity of 82.1% and a specificity of 80.1%; LDH 471 U/L had a sensitivity of 62.7% and a specificity of 60.3% for predicting the development of bronchitis obliterans. Conclusions: The long duration of fever (≥10 d), CRP increase (≥137 mg/L) may be used to predict the occurrence of sequelae of bronchitis obliterans in RMPP. It is helpful for early recognition of risk children.

Discussion on how to optimize active surveillance for low-risk papillary thyroid microcarcinoma in China / 中华外科杂志

Active surveillance, as a first-line treatment strategy for low-risk papillary thyroid microcarcinoma, has been recommended by guidelines worldwide. However, active surveillance has not been widely accepted by doctors and patients in China. In view of the huge challenges faced by active surveillance, doctors should improve their understanding of the "low risk" of papillary thyroid micropapillary cancer, identify some intermediate or high-risk cases, be familiar with the criteria and methods of diagnosis for disease progression, and timely turn patients with disease progression into more active treatment strategies. By analyzing the long-term cost-effectiveness of active surveillance, it is clear that medical expense is only one cost form of medical activities, and the health cost (thyroid removal and surgical complications) paid by patients due to"over-diagnosis and over-treatment" is the most important. Moreover, the weakening of the patients' social function caused by surgical procedures is a more hidden and far-reaching cost. The formulation of health economic policies (including medical insurance) should promote the adjustment of diagnosis and treatment behavior to the direction which is conducive to the long-term life and treatment of patients, improving the overall health level of society and reducing the overall cost. At the same time, doctors should stimulate the subjective initiative of patients, help them fully understand the impact of various treatment methods on their psychological and physical status, support patients psychologically, and strengthen their confidence in implementing active surveillance. By strengthening multi-disciplinary treatment team and system support, doctors can achieve risk stratification of papillary thyroid microcarcinoma, accurate judgment of disease progress, timely counseling for psychological problems, and long-term adherence to active surveillance. Improving the treatment level of advanced thyroid cancer is the key point of improve the prognosis. It is important to promote the development of active surveillance for low-risk papillary thyroid microcarcinoma. In the future, it is necessary to carry out multi-center prospective research and accumulate research evidence for promoting the standardization process of active surveillance. Standardized active surveillance will certainly benefit specific papillary thyroid microcarcinoma patients.

Correlation between PAFAH1B3 Expression Level and Risk of Disease Progression After Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Patients / 中国实验血液学杂志

OBJECTIVE@#To investigate the association between the expression level of platelet-activating factor acetylhydrolase 1B3 (PAFAH1B3 ) gene in bone marrow CD138+ cells of patients with multiple myeloma (MM) treated with autologous hematopoietic stem cell transplantation (AHSCT) and the prognosis within 2 years.@*METHODS@#147 MM patients treated with AHSCT in The First and The Second Affiliated Hospital of Nantong University from May 2014 to May 2019 were included in the study. Expression level of PAFAH1B3 mRNA in bone marrow CD138+ cells of the patients was detected. Patients with disease progression or death during 2 years of follow-up were included in progression group, and the rest were included in good prognosis group. After comparing the clinical data and PAFAH1B3 mRNA expression levels of the two groups, the patients were divided into high PAFAH1B3 expression group and low PAFAH1B3 expression group based on the median PAFAH1B3 mRNA expression level of the enrolled patients. Progression-free survival rate (PFSR) between the two groups was compared by the Kaplan-Meier method. The related factors of prognosis within 2 years were analyzed by univariate analysis and multivariate COX regression analysis.@*RESULTS@#At the end of follow-up, there were 13 patients lost to follow-up. Finally, 44 patients were included in the progression group and 90 patients were included in the good prognosis group. Age in the progression group was higher than that in the good prognosis group, the proportion of patients with CR+VGPR after transplantation in the progression group was lower than that in the good prognosis group, and there was a statistical difference between two groups in the cases distribution of ISS stage (all P<0.05). PAFAH1B3 mRNA expression level and the proportion of patients with LDH>250U/L in the progression group were higher than those in the good prognosis group, and platelet count in the progression group was lower than that in the good prognosis group (all P<0.05). Compared with the low PAFAH1B3 expression group, the 2-year PFSR of the high PAFAH1B3 expression group was significantly lower (log-rank χ2=8.167, P=0.004). LDH>250U/L (HR=3.389, P=0.010), PAFAH1B3 mRNA expression (HR=50.561, P=0.001) and ISS stage Ⅲ(HR=1.000, P=0.003) were independent risk factors for prognosis in MM patients, and ISS stage Ⅰ (HR=0.133, P=0.001) was independent protective factor.@*CONCLUSION@#The expression level of PAFAH1B3 mRNA in bone marrow CD138+ cells is related to the prognosis of MM patients treated with AHSCT, and detecting PAFAH1B3 mRNA expression can bring some information for predicting PFSR and prognostic stratification of patients.

Investigation of androgen receptor-dependent alternative splicing has identified a unique subtype of lethal prostate cancer / 亚洲男科学杂志(英文版)

A complete proteomics study characterizing active androgen receptor (AR) complexes in prostate cancer (PCa) cells identified a diversity of protein interactors with tumorigenic annotations, including known RNA splicing factors. Thus, we chose to further investigate the functional role of AR-mediated alternative RNA splicing in PCa disease progression. We selected two AR-interacting RNA splicing factors, Src associated in mitosis of 68 kDa (SAM68) and DEAD (Asp-Glu-Ala-Asp) box helicase 5 (DDX5) to examine their associative roles in AR-dependent alternative RNA splicing. To assess the true physiological role of AR in alternative RNA splicing, we assessed splicing profiles of LNCaP PCa cells using exon microarrays and correlated the results to PCa clinical datasets. As a result, we were able to highlight alternative splicing events of clinical significance. Initial use of exon-mini gene cassettes illustrated hormone-dependent AR-mediated exon-inclusion splicing events with SAM68 or exon-exclusion splicing events with DDX5 overexpression. The physiological significance in PCa was investigated through the application of clinical exon array analysis, where we identified exon-gene sets that were able to delineate aggressive disease progression profiles and predict patient disease-free outcomes independently of pathological clinical criteria. Using a clinical dataset with patients categorized as prostate cancer-specific death (PCSD), these exon gene sets further identified a select group of patients with extremely poor disease-free outcomes. Overall, these results strongly suggest a nonclassical role of AR in mediating robust alternative RNA splicing in PCa. Moreover, AR-mediated alternative spicing contributes to aggressive PCa progression, where we identified a new subtype of lethal PCa defined by AR-dependent alternative splicing.

Distribution of monocyte subsets and their surface CD31 intensity are associated with disease course and severity of hemorrhagic fever with renal syndrome / 细胞与分子免疫学杂志

Objective To investigate the relationship between disease courses and severity and monocyte subsets distribution and surface CD31 intensity in patients of hemorrhagic fever with renal syndrome (HFRS). Methods Peripheral blood samples from 29 HFRS patients and 13 normal controls were collected. The dynamic changes of classical monocyte subsets (CD14++CD16-), intermediated monocyte subsets (CD14++CD16+) and non-classical monocyte subsets (CD14+CD16++) and the mean fluorescent intensity (MFI) of CD31 on monocyte subsets were detected by multiple-immunofluorescent staining and flow cytometry. Results In acute phase of HFRS, the ratio of classical monocyte subsets to total monocytes was dramatically decreased compared to convalescent phase and normal control. It was still much lower in convalescent phase compared to normal controls. The ratio of classical monocyte subsets to total monocytes were decreased in HFRS patients compared to that in normal control, whereas there was no difference between severe/critical groups and mild/moderate groups. On the contrary, the ratio of intermediate monocyte subsets to total monocytes in acute phase of HFRS was significantly increased compared to convalescent phase and normal control. The ratio of intermediate monocyte subsets to total monocytes were increased in HFRS patients compared to that in normal control, whereas no difference was found between severe/critical groups and mild/moderate groups. Phases or severity groups had no difference in ratio of non-classical monocyte subsets to total monocytes. Additionally, the ratio of classical monocyte subsets had a tendency to decline and that of intermediate monocyte subsets showed an increase both to total monocytes between the acute and convalescent phases in 11 HFRS patients with paired-samples. Moreover, in acute phase of HFRS, the mean fluorescent intensity (MFI) of CD31 on three monocyte subsets all decreased, specifically classical monocyte subsets showed the highest MFI of CD31 while the normal control reported the highest MFI of CD31 in non-classical monocyte subsets. In convalescent phase, the MFI of CD31 on classical and intermediated monocyte subsets were both lower than that of normal control, while MFI of CD31 was still significantly lower than normal control on non-classical monocyte subsets. Finally, MFI of CD31 on classical and intermediated monocyte subsets in severe/critical group were both lower than those in mild/moderate group, showing no statistical difference in MFI of CD31 on non-classical monocyte subset across groups of different disease severity. Conclusion The ratio of classical and intermediated monocyte subsets to total monocytes are correlated with the course of HFRS, and so are the surface intensity of CD31 on these monocyte subsets with the disease course and severity. The surface intensity of CD31 on non-classical monocyte subsets, however, is correlated only with the course of the disease. Together, the underlying mechanisms for the observed changes in monocyte subsets in HFRS patients should be further investigated.

Application of discrete event simulation model in analysis on cost-effectiveness of epidemiology screening / 中华流行病学杂志

Discrete event simulation (DES) model is based on individual data, by which discrete events over time are simulated to reflect disease progression. The effects of individual characteristics on disease progression could be considered in the DES model. Moreover, unlike state-transition models, DES model without setting of fixed cycle can contribute to more accurate estimation of event time, especially in the evaluation of the long-term effectiveness of screening strategies for complex diseases in which time dimension needs to be considered. This article introduces the general principles, construction steps, analytic methods and other relevant issues of the DES model. Based on a research case of estimating the cost-effectiveness of screening for abdominal aortic aneurysms in women aged 65 years and above in the United Kingdom, key points in applications of the DES model in analysis on effectiveness of complex disease screening are discussed in detail, including model construction and analysis and interpretation of the results. DES model can predict occurring time of discrete events accurately by establishing the distribution function of their occurring time and is increasingly used to evaluate the screening strategies for complex diseases in which time dimension needs to be considered. In the construction of DES model, it is necessary to pay close attention to the clear presentation of model structure and simulation process and follow the relevant reporting specification to conduct cost-effectiveness analysis to ensure the transparency and repeatability of the research.

Clinical characteristics and progression risk factors for patients with monoclonal gammopathy of undetermined significance / 中华血液学杂志

Objective: To analyze the clinical presentation and progression risk factors of patients with monoclonal gammopathy of undetermined significance (MGUS) in China. Methods: We retrospectively assessed the clinical features and disease progression of 1 037 patients with monoclonal gammopathy of undetermined significance between January 2004 and January 2022 at Peking Union Medical College Hospital. Results: A total of 1 037 patients were recruited in the study, including 636 males (63.6%) , with a median age of 58 (18-94) years. The median concentration of serum monoclonal protein was 2.7 (0-29.4) g/L. The monoclonal immunoglobulin type was IgG in 380 patients (59.7%) , IgA in 143 patients (22.5%) , IgM in 103 patients (16.2%) , IgD in 4 patients (0.6%) , and light chain in 6 patients (0.9%) . 171 patients (31.9%) had an abnormal serum-free light chain ratio (sFLCr) . According to the Mayo Clinic model for risk of progression, the proportion of patients in the low-risk, medium-low-risk, medium-high risk, and high-risk groups were 254 (59.5%) , 126 (29.5%) , 43 (10.1%) , and 4 (0.9%) , respectively. With a median follow-up of 47 (1-204) months, 34 of 795 patients (4.3%) had disease progression, and 22 (2.8%) died. The overall progression rate was 1.06 (0.99-1.13) /100 person-years. Patients with non-IgM MGUS have a markedly higher disease progression rate per 100 person-years than IgM-MGUS (2.87/100 person-years vs 0.99/100 person-years, P=0.002) . The disease progression rate per 100 person-years in non-IgM-MGUS patients of Mayo classification low-risk, medium-low risk and medium-high risk groups were 0.32 (0.25-0.39) /100 person-years, 1.82 (1.55-2.09) /100 person-years, and2.71 (1.93-3.49) /100 person-years, which had statistically difference (P=0.005) . Conclusion: In comparison to non-IgM-MGUS, IgM-MGUS has a greater risk of disease progression. The Mayo Clinic progression risk model applies to non-IgM-MGUS patients in China.

Osteonecrosis múltiple inducida por glucocorticoides / Multiple osteonecrosis induced bye glucocorticoids / Osteonecrose múltipla induzida por glicocorticóides

La osteonecrosis múltiple es una entidad poco frecuente que se define por el compromiso de al menos tres regiones diferentes. Es indispensable el abordaje multidisciplinario de los pacientes que la padecen tanto para el diagnóstico como el tratamiento oportuno. Presentamos el caso clínico de un paciente joven que presenta una osteonecrosis múltiple con compromiso de ambas caderas, hombros, rodillas, codo derecho y cuello de pie izquierdo. El principal factor de riesgo presente en nuestro caso es el consumo de glucocorticoides.

Multiple osteonecrosis is a rare entity that is defined by the involvement of at least three different regions. A multidisciplinary approach to patients who suffer from it is essential for both diagnosis and timely treatment. We present the clinical case of a young patient who presented multiple osteonecrosis with involvement of both hips, shoulders, knees, right elbow, and neck of the left foot. The main risk factor present in our case is the consumption of glucocorticoids.

A osteonecrose múltipla é uma entidade rara que se define pelo envolvimento de pelo menos três regiões diferentes. Uma abordagem multidisciplinar aos pacientes que sofrem com isso é essencial para o diagnóstico e tratamento oportuno. Apresentamos o caso clínico de um paciente jovem que apresenta osteonecrose múltipla envolvendo quadris, ombros, joelhos, cotovelo direito e pescoço do pé esquerdo. O principal fator de risco presente no nosso caso é o consumo de glicocorticóides.

Mapa de evidências sobre sequelas e reablitação da covid-19 pós-aguda: uma versão atualizada em julho de 2022 / Evidence map on post-acute COVID-19 sequelae and rehabilitation: Update as of July 2022 / Mapa de evidencia sobre las secuelas y la rehabilitación tras la COVID-19 aguda: versión actualizada en julio del 2022

RESUMO Objetivo. Atualizar o mapa de evidências sobre os efeitos de intervenções para reabilitação de covid-19 pós-aguda. Métodos. O escopo da busca foi definido conforme a população (pacientes que tiveram covid-19 sintomática e sequelas da doença pós-aguda), o contexto (intervenções para recuperação das sequelas) e o tipo de estudo (revisão sistemática, revisão sistemática rápida, revisão de escopo ou revisão de revisões). Após a busca na PubMed e na Biblioteca Virtual em Saúde, dois autores independentes selecionaram estudos de revisão. A atualização do mapa feita em 27 de julho de 2022 seguiu os mesmos procedimentos descritos anteriormente. Resultados. O mapa inicial de evidências continha 22 estudos (quatro revisões sistemáticas, quatro revisões rápidas, quatro revisões de estudos de caso, uma revisão de escopo e nove protocolos de revisão sistemática). Nesta atualização, outros 10 estudos foram incluídos. Foram identificados quatro grupos de intervenções (multimodal, terapêutica, terapias complementares e farmacológica) e sete grupos de desfechos (condições patológicas, doenças/transtornos respiratórios, dor, indicadores fisiológicos e metabólicos, saúde mental/qualidade de vida, funções sensoriais, mortalidade), totalizando 166 associações entre intervenções e desfechos. As terapias complementares tiveram mais associações com os desfechos (n = 94). Entre os desfechos, destacaram-se os indicadores fisiológicos e metabólicos, as condições patológicas e a saúde mental/qualidade de vida (44, 41 e 35 associações, respectivamente). Conclusões. Na atualização do mapa, analisaram-se 69 associações, com destaque para exercício (isolado, multicomponente ou intervenção multimodal, apresentando 23 efeitos positivos e quatro potencialmente positivos) e intervenções farmacológicas e terapias complementares para funções sensoriais (15 associações). O alto número de protocolos indica que a literatura permanece incipiente.

ABSTRACT Objective. To update the evidence map on the effects of interventions for post-acute COVID-19 rehabilitation. Method. The search scope was defined according to the population (patients with symptomatic COVID-19 and post-acute COVID sequelae), the context (interventions for rehabilitation), and the type of study (systematic reviews, rapid reviews, scoping reviews or overviews of reviews). Following a search in PubMed and the Virtual Health Library, two independent authors selected the articles for review. The map was updated on July 27, 2022, using the same procedures employed in the initial review. Results. The initial evidence map included 22 studies (four systematic reviews, four rapid reviews, four reviews of case reports, one scoping review, and nine systematic review protocols). In the present update, an additional 10 studies were included. The analysis revealed four groups of interventions (multimodal, therapeutic, complementary, and pharmacological) and seven groups of outcomes (pathological conditions, diseases/respiratory disorders, pain, physiological and metabolic markers, mental health/quality of life, sensory function, and mortality), totaling 166 associations between interventions and outcomes. The highest number of associations was observed for complementary therapies (n = 94). Among the outcomes, the highest number of associations was observed for physiological and metabolic markers, pathological conditions, and mental health/quality of life (44, 41, and 35 associations respectively). Conclusions. The map update involved the analysis of 69 associations, most notably exercise (isolated, multicomponent, or multimodal intervention), with 23 positive and four potentially positive effects) and pharmacologic and complementary therapies for sensorial functions (15 associations). The high number of systematic review protocols indicates that the literature is still incipient.

RESUMEN Objetivo. Actualizar el mapa de evidencia de los efectos de las intervenciones de rehabilitación tras la COVID-19 aguda. Métodos. El alcance de la búsqueda se definió en función de la población (pacientes que habían tenido COVID-19 sintomática y secuelas tras un cuadro agudo de la enfermedad), el contexto (intervenciones de recuperación de las secuelas) y el tipo de estudio (revisión sistemática, revisión sistemática rápida, revisión del alcance o revisión de revisiones). Después de realizar búsquedas en PubMed y en la Biblioteca Virtual de Salud, dos autores independientes seleccionaron los estudios de revisión. En la actualización del mapa realizada el 27 de julio del 2022 se siguieron los mismos procedimientos descritos anteriormente. Resultados. El mapa de evidencia inicial contenía 22 estudios (cuatro revisiones sistemáticas, cuatro revisiones rápidas, cuatro revisiones de estudios de casos, una revisión del alcance y nueve protocolos de revisión sistemática). En esta actualización se incluyeron otros 10 estudios. Se encontraron cuatro grupos de intervenciones (multimodales y terapéuticas, y tratamientos complementarios y farmacológicos) y siete grupos de resultados (afecciones patológicas, enfermedades y trastornos respiratorios, dolor, indicadores fisiológicos y metabólicos, salud mental/calidad de vida, funciones sensoriales y mortalidad), con un total de 166 asociaciones entre las intervenciones y los resultados. Los tratamientos complementarios presentaron más asociaciones con los resultados (n = 94). Entre los resultados, se destacaron los indicadores fisiológicos y metabólicos, las afecciones patológicas y la salud mental/calidad de vida (44, 41 y 35 asociaciones, respectivamente). Conclusiones. En la actualización del mapa, se analizaron 69 asociaciones entre las cuales se destacan el ejercicio (aislado o compuesto o una intervención multimodal, con 23 efectos positivos y cuatro potencialmente positivos) y las intervenciones farmacológicas y los tratamientos complementarios para las funciones sensoriales (15 asociaciones). El elevado número de protocolos indica que la bibliografía sigue siendo incipiente.

Value of baseline radiograph for COVID-19 infected patients

Introduction: A cluster of pneumonia cases of unknown origin was first reported in Wuhan China then the causative pathogen was identified and named severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) and the associated disease was named coronavirus disease 2019 (COVID-19). Chest radiograph has lower sensitivity for the detection of lung abnormalities but it has a role in disease progression and also in the late stages of COVID19. This study aims to evaluate the value of baseline radiographs in COVID-19-infected patients. Method: This is a retrospective study of COVID-19 patients with RT-PCR confirmation who were admitted to Eka Kotebe General Hospital and had baseline chest x-ray between April and May 2020. Baseline chest x-ray of all patients who have confirmed COVID-19 infection was reviewed and analyzed. Result: The study included 355 patients, 224 (63.1%) were male and 131 (36.9%) were female. Patient age ranged from 4 - 82 years with a mean age of 35. Two hundred twelve patients were symptomatic; the rest 143 were asymptomatic. Of the 355 baseline CXR, only 60 (16.9%) had abnormal radiographs and the rest 295 (83.1%) had normal radiographs. A combination of interstitial changes and GGO were the predominant descriptive finding accounting for 33.3% . Conclusion: Even if chest radiographs are important in the workup of patients with COVID-19 infection, the use of baseline radiographs in COVID-19 infection should not be a routine practice. Disease severity and timing of imaging appear to impact the rates of normal baseline imaging.

Potential biomarkers for diagnosis and disease evaluation of idiopathic pulmonary fibrosis / 中华医学杂志(英文版)

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease characterized by progressive lung fibrogenesis and histological features of usual interstitial pneumonia. IPF has a poor prognosis and presents a spectrum of disease courses ranging from slow evolving disease to rapid deterioration; thus, a differential diagnosis remains challenging. Several biomarkers have been identified to achieve a differential diagnosis; however, comprehensive reviews are lacking. This review summarizes over 100 biomarkers which can be divided into six categories according to their functions: differentially expressed biomarkers in the IPF compared to healthy controls; biomarkers distinguishing IPF from other types of interstitial lung disease; biomarkers differentiating acute exacerbation of IPF from stable disease; biomarkers predicting disease progression; biomarkers related to disease severity; and biomarkers related to treatment. Specimen used for the diagnosis of IPF included serum, bronchoalveolar lavage fluid, lung tissue, and sputum. IPF-specific biomarkers are of great clinical value for the differential diagnosis of IPF. Currently, the physiological measurements used to evaluate the occurrence of acute exacerbation, disease progression, and disease severity have limitations. Combining physiological measurements with biomarkers may increase the accuracy and sensitivity of diagnosis and disease evaluation of IPF. Most biomarkers described in this review are not routinely used in clinical practice. Future large-scale multicenter studies are required to design and validate suitable biomarker panels that have diagnostic utility for IPF.

Efficacy and clinical outcome of chemotherapy and endocrine therapy as first-line treatment in patients with hormone receptor-positive HER2-negative metastatic breast cancer / 中华医学杂志(英文版)

BACKGROUND@#Endocrine therapy (ET) and ET-based regimens are the preferred first-line treatment options for hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (HR+/HER2- MBC), while chemotherapy (CT) is commonly used in clinical practice. The aim of this study was to investigate the efficacy and clinical outcome of ET and CT as first-line treatment in Chinese patients with HR+/HER2- MBC.@*METHODS@#Patients diagnosed with HR+/HER2-MBC between January 1st, 1996 and September 30th, 2018 were screened from the Chinese Society of Clinical Oncology Breast Cancer database. The initial and maintenance first-line treatment, progression-free survival (PFS), and overall survival (OS) were analyzed.@*RESULTS@#Among the 1877 included patients, 1215 (64.7%) received CT and 662 (35.3%) received ET as initial first-line treatment. There were no statistically significant differences in PFS and OS between patients receiving ET and CT as initial first-line treatment in the total population (PFS: 12.0 vs. 11.0 months, P = 0.22; OS: 54.0 vs . 49.0 months, P =0.09) and propensity score matched population. For patients without disease progression after at least 3 months of initial therapy, maintenance ET following initial CT (CT-ET cohort, n = 449) and continuous schedule of ET (ET cohort, n = 527) had longer PFS than continuous schedule of CT (CT cohort, n = 406) in the total population (CT-ET cohort vs. CT cohort: 17.0 vs . 8.5 months; P <0.01; ET cohort vs . CT cohort: 14.0 vs . 8.5 months; P <0.01) and propensity score matched population. OS in the three cohorts yielded the same results as PFS.@*CONCLUSIONS@#ET was associated with similar clinical outcome to CT as initial first-line treatment. For patients without disease progression after initial CT, switching to maintenance ET showed superiority in clinical outcome over continuous schedule of CT.

Depressive symptoms are not associated with risks of rapid renal function decline or chronic kidney disease in middle-aged and elderly with normal kidney function: a longitudinal investigation / 南方医科大学学报

OBJECTIVE@#To explore the association between depressive symptoms and the risks of rapid decline in renal function and chronic kidney disease (CKD) in middle-aged and elderly with normal kidney function.@*METHODS@#The residents aged 40- 75 years with eGFR≥60 mL·min-1·1.73 m-2 without proteinuria in Lanzhou region, who participated in the "REACTION" study carried out in 2011, were selected and followed up in 2014. A total of 4961 individuals with complete and qualified data from the two surveys were included in the subsequent analysis. Based on PHQ-9 questionnaire scores, the baseline population was divided into two groups with and without depressive symptoms. Cox proportional hazard analysis was used to compare the incidences of rapid renal function decline and CKD between the two groups and study the association of depressive symptoms with the risk of these renal conditions.@*RESULTS@#PHQ-9 questionnaire scores were not found to correlate with baseline SCr, ALB, UACR or eGFR levels among the participarts (P>0.05). After a mean follow-up time of 3.4±0.6 years, 33.9% of the participants with depressive symptoms at baseline experienced a rapid decline in renal function and 3.6% progressed to CKD. During the follow-up, the incidence of rapid decline in renal function and the risk of developing CKD were not found to correlate with depressive symptoms in these participants (P>0.05) regardless of the type of the depressive syndromes.@*CONCLUSION@#Depressive symptoms are not associated with the risks of rapid renal function decline or progression to CKD in middle-aged and elderly with normal kidney function.