Asociación entre metaplasia, displasia y cáncer de vesícula biliar en una EPS de Bogotá, Colombia / Association between metaplasia, dysplasia and gallbladder cancer in an EPS in Bogotá, Colombia

Introducción. El cáncer de vesícula biliar es el más común en el tracto biliopancreático y una importante causa de mortalidad. La metaplasia y la displasia han sido mencionados como probables precursores relacionados con la secuencia metaplasia-displasia-cáncer. El objetivo de este estudio fue establecer las posibles asociaciones entre estas alteraciones histopatológicas y su relación con la edad y el sexo de los pacientes. Métodos. Estudio observacional retrospectivo descriptivo, con un componente analítico de corte transversal. Se incluyeron los informes de patología de pacientes llevados a colecistectomía laparoscópica electiva y ambulatoria, entre enero de 2015 y diciembre de 2020, con colecistitis crónica, colelitiasis o pólipos vesiculares, mayores de 18 años. Se describieron las características demográficas por sexo y edad utilizando medias, desviaciones estándar y porcentajes. Se emplearon la prueba de chi cuadrado y la prueba exacta de Fisher para evaluar la asociación entre las variables cualitativas. Resultados. Se incluyeron 4871 informes de patología. En esta cohorte se encontró asociación estadísticamente significativa entre metaplasia, displasia y cáncer de vesícula (p<0,05), al igual que con el sexo y la edad de los pacientes. Conclusiones. Los resultados sugieren una asociación entre metaplasia, displasia y cáncer de vesícula biliar en la población estudiada. Se recomienda la realización de investigaciones complementarias para definir la posible causalidad entre metaplasia, displasia y cáncer de vesícula biliar en una población más heterogénea.

Introduction. Gallbladder cancer is the most common cancer in the biliopancreatic tract and an important cause of mortality. Metaplasia and dysplasia have been mentioned as probable precursors related to the metaplasia-dysplasia-cancer sequence. The objective of this study was to establish the possible associations between these histopathological alterations and their relationship with the age and sex of the patients. Methods. Descriptive retrospective observational study, with a cross-sectional analytical component. Pathology reports of patients undergoing elective and outpatient laparoscopic cholecystectomy were included between January 2015 and December 2020, with chronic cholecystitis, cholelithiasis, or gallbladder polyps, over 18 years of age. Demographic characteristics by sex and age was performed using means, standard deviations, and percentages. The chi2 test and Fisher's exact test were used to evaluate the association between the qualitative variables. Results. 4871 pathology reports were included. In this cohort, a statistically significant association was found between metaplasia, dysplasia, and gallbladder cancer (p<0.05), as well as with the sex and age of the patients. Conclusions. The results suggest an association between metaplasia, dysplasia and gallbladder cancer in the study population. Additional research is recommended to define the possible causality between metaplasia, dysplasia, and gallbladder cancer in a more heterogeneous population.

Predictive Value of Peripheral Blood Biomarkers in the Treatment of Lung Cancer Patients with Anti PD-1 Immunotherapy / 中国肺癌杂志

BACKGROUND@#The application of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies has greatly improved the clinical outcomes of lung cancer patients. Here, we retrospectively analyzed the efficacy of PD-1 antibody therapy in locally advanced non-surgical or metastatic lung cancer patients, and preliminarily explored the correlation between peripheral blood biomarkers and clinical responses.@*METHODS@#We conducted a single center study that included 61 IIIA-IV lung cancer patients who received PD-1 antibody treatment from March 2020 to December 2021, and collected the medical record data on PD-1 antibody first-line or second-line treatment. The levels of multiple Th1 and Th2 cytokines in the patient's peripheral blood serum, as well as the phenotype of peripheral blood T cells, were detected and analyzed.@*RESULTS@#All the patients completed at least 2 cycles of PD-1 monoclonal antibody treatment. Among them, 42 patients (68.9%) achieved partial response (PR); 7 patients (11.5%) had stable disease (SD); and 12 patients (19.7%) had progressive disease (PD). The levels of peripheral blood interferon gamma (IFN-γ) (P=0.023), tumor necrosis factor α (TNF-α) (P=0.007) and interleukin 5 (IL-5) (P=0.002) before treatment were higher in patients of the disease control rate (DCR) (PR+SD) group than in the PD group. In addition, the decrease in absolute peripheral blood lymphocyte count after PD-1 antibody treatment was associated with disease progression (P=0.023). Moreover, the levels of IL-5 (P=0.0027) and IL-10 (P=0.0208) in the blood serum after immunotherapy were significantly increased compared to baseline.@*CONCLUSIONS@#Peripheral blood serum IFN-γ, TNF-α and IL-5 in lung cancer patients have certain roles in predicting the clinical efficacy of anti-PD-1 therapy. The decrease in absolute peripheral blood lymphocyte count in lung cancer patients is related to disease progression, but large-scale prospective studies are needed to further elucidate the value of these biomarkers.

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.

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.

Analysis of pregnancy outcomes, disease progression, and risk factors in patients with undifferentiated connective tissue disease / 北京大学学报(医学版)

OBJECTIVE@#To investigate the fetal and maternal outcomes, risk factors of disease progression and adverse pregnancy outcomes (APOs) in patients with undifferentiated connective tissue disease (UCTD).@*METHODS@#This retrospective study described the outcomes of 106 pregnancies in patients with UCTD. The patients were divided into APOs group (n=53) and non-APOs group (n=53). The APOs were defined as miscarriage, premature birth, pre-eclampsia, premature rupture of membranes (PROM), intrauterine growth restriction (IUGR), postpartum hemorrhage (PPH), and stillbirth, small for gestational age infant (SGA), low birth weight infant (LBW) and birth defects. The differences in clinical manifestations, laboratory data and pregnancy outcomes between the two groups were compared. Logistic regression analysis was performed to analyze the risk factors for APOs and the progression of UCTD to definitive CTD.@*RESULTS@#There were 99 (93.39%) live births, 4 (3.77%) stillbirths and 3 (2.83%) miscarriage, 20 (18.86%) preterm delivery, 6 (5.66%) SGA, 17 (16.03%) LBW, 11 (10.37%) pre-eclampsia, 7 (6.60%) cases IUGR, 19 (17.92%) cases PROM, 10 (9.43%) cases PPH. Compared with the patients without APOs, the patients with APOs had a higher positive rate of anti-SSA antibodies (73.58% vs. 54.71%, P=0.036), higher rate of leukopenia (15.09% vs. 3.77%, P=0.046), lower haemoglobin level [109.00 (99.50, 118.00) g/L vs. 124.00 (111.50, 132.00) g/L, P < 0.001].Multivariate Logistic regression analysis showed that leucopenia (OR=0.82, 95%CI: 0.688-0.994) was an independent risk factors for APOs in UCTD (P=0.042). Within a mean follow-up time of 5.00 (3.00, 7.00) years, the rate of disease progression to a definite CTD was 14.15%, including 8 (7.54%) Sjögren's syndrome, 4 (3.77%) systemic lupus erythematosus (SLE), 4 (3.77%) rheumatoid arthritis and 1 (0.94%) mixed connective tissue disease. Multivariate Cox proportional risk regression analysis showed that Raynaud phenomenon (HR=40.157, 95%CI: 3.172-508.326) was an independent risk factor for progression to SLE.@*CONCLUSION@#Leukopenia is an independent risk factor for the development of APOs in patients with UCTD. Raynaud's phenmon is a risk factor for the progression of SLE. Tight disease monitoring and regular follow-up are the key measures to prevent adverse pregnancy outcomes and predict disease progression in UCTD patients with pregnancy.

Research Progress of Iron Metabolism in Disease Progression and Drug Resistance of Multiple Myeloma--Review / 中国实验血液学杂志

Iron metabolism is involved in the development and drug resistance of many malignancies, including multiple myeloma (MM). Based on recent studies on iron metabolism and MM, this paper reviews the relationship between iron metabolism and disease process of MM in terms of iron overload leading to ferroptosis in MM cells, the role of iron deficiency in oxidative respiration and proliferation of MM cells, and the interaction between ferroptosis and autophagy in the disease process. The mechanisms by which iron metabolism-related substances lead to MM cells' resistance to proteasome inhibitors (PI) through inducing redox imbalance and M2 macrophage polarization are also briefly described, aiming to provide a theoretical basis for the application of iron metabolism-related drugs to the clinical treatment of MM patients.

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.

Does the 2017 global initiative for chronic obstructive lung disease revision really improve the assessment of Chinese chronic obstructive pulmonary disease patients? A multicenter prospective study for more than 5 years / 中华医学杂志(英文版)

BACKGROUND@#The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 proposed a new classification that reclassified many chronic obstructive pulmonary disease (COPD) patients from group D to B. However, there is a paucity of data related to the comparison between reclassified and non-reclassified COPD patients in terms of long-term prognosis. This study aimed to investigate long-term outcomes of them and determine whether the GOLD 2017 revision improved the assessment of COPD patients.@*METHODS@#This observational, multicenter, prospective study recruited outpatients at 12 tertiary hospitals in China from November 2016 to February 2018 and followed them up until February 2022. All enrolled patients were classified into groups A to D based on GOLD 2017, and the subjects in group B included patients reclassified from group D to B (group DB) and those remaining in group B (group BB). Incidence rates and hazard ratios (HRs) were calculated for the exacerbation of COPD and hospitalization in each group.@*RESULTS@#We included and followed up 845 patients. During the first year of follow-up, the GOLD 2017 classification had a better discrimination ability for different risks of COPD exacerbation and hospitalization than GOLD 2013. Group DB was associated with a higher risk of moderate-to-severe exacerbation (HR = 1.88, 95% confidence interval [CI] = 1.37-2.59, P  <0.001) and hospitalization for COPD exacerbation (HR = 2.23, 95% CI = 1.29-3.85, P  = 0.004) than group BB. However, during the last year of follow-up, the differences in the risks of frequent exacerbations and hospitalizations between group DB and BB were not statistically significant (frequent exacerbations: HR = 1.02, 95% CI = 0.51-2.03, P  = 0.955; frequent hospitalizations: HR = 1.66, 95% CI = 0.58-4.78, P  = 0.348). The mortality rates of the two groups were both approximately 9.0% during the entire follow-up period.@*CONCLUSIONS@#The long-term prognosis of patients reclassified into group B and of those remaining in group B was similar, although patients reclassified from group D to group B had worse short-term outcomes. The GOLD 2017 revision could improve the assessment of Chinese COPD patients in terms of long-term prognosis.

Clinical and molecular biological characterization of patients with accelerated chronic lymphocytic leukemia / 中华血液学杂志

Objective: To investigate the clinical and molecular biological characteristics of patients with accelerated chronic lymphocytic leukemia (aCLL) . Methods: From January 2020 to October 2022, the data of 13 patients diagnosed with aCLL at The First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed to explore the clinical and molecular biological characteristics of aCLL. Results: The median age of the patients was 54 (35-72) years. Prior to aCLL, five patients received no treatment for CLL/small lymphocytic lymphoma (SLL), while the other patients received treatment, predominantly with BTK inhibitors. The patients were diagnosed with aCLL through pathological confirmation upon disease progression. Six patients exhibited bulky disease (lesions with a maximum diameter ≥5 cm). Positron emission tomography (PET) -computed tomography (CT) images revealed metabolic heterogeneity, both between and within lesions, and the median maximum standardized uptake value (SUVmax) of the lesion with the most elevated metabolic activity was 6.96 (2.51-11.90). Patients with unmutated IGHV CLL accounted for 76.9% (10/13), and the most frequent genetic and molecular aberrations included +12 [3/7 (42.9% ) ], ATM mutation [6/12 (50% ) ], and NOTCH1 mutation [6/12 (50% ) ]. Twelve patients received subsequent treatment. The overall response rate was 91.7%, and the complete response rate was 58.3%. Five patients experienced disease progression, among which two patients developed Richter transformation. Patients with aCLL with KRAS mutation had worse progression-free survival (7.0 month vs 26.3 months, P=0.015) . Conclusion: Patients with aCLL exhibited a clinically aggressive course, often accompanied by unfavorable prognostic factors, including unmutated IGHV, +12, ATM mutation, and NOTCH1 mutation. Patients with CLL/SLL with clinical suspicion of disease progression, especially those with bulky disease and PET-CT SUVmax ≥5, should undergo biopsy at the site of highest metabolic uptake to establish a definitive pathological diagnosis.

Typical hemophagocytic syndrome associated with cytomegalovirus infection in an immunocompetent patient: a case report and literature review / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Cytomegalovirus (CMV) infection is currently prevalent in populations throughout the world, and 56%‍-94% of the global population is seropositive for CMV. CMV infection mainly affects immunocompromised hosts. In these cases, it can cause significant symptoms, tissue-invasive disease, and many sequelae including death (Dioverti and Razonable, 2016). The vast majority of healthy adults with CMV infection experience an asymptomatic course; when symptomatic, it manifests as a mononucleosis-like syndrome in approximately 10% of patients (Sridhar et al., 2018). The gastrointestinal tract and central nervous system appear to be the most frequent sites of severe CMV infection in immunocompetent individuals (Rafailidis et al., 2008). However, CMV infection is relatively rarely recorded in immunocompetent hosts.

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.