Childhood-onset systemic lupus erythematosus (cSLE) and malignancy: a nationwide multicentre series review

Abstract Background Increased malignancy frequency is well documented in adult-systemic lupus erythematosus (SLE), but with limited reports in childhood-onset SLE (cSLE) series. We explored the frequency of malignancy associated with cSLE, describing clinical and demographic characteristics, disease activity and cumulative damage, by the time of malignancy diagnosis. Method A retrospective case-notes review, in a nationwide cohort from 27 Pediatric Rheumatology centres, with descriptive biopsy-proven malignancy, disease activity/damage accrual, and immunosuppressive treatment were compiled in each participating centre, using a standard protocol. Results Of the 1757 cSLE cases in the updated cohort, 12 (0.7%) developed malignancy with median time 10 years after cSLE diagnosis. There were 91% females, median age at cSLE diagnosis 12 years, median age at malignancy diagnosis 23 years. Of all diagnosed malignancies, 11 were single-site, and a single case with concomitant multiple sites; four had haematological (0.22%) and 8 solid malignancy (0.45%). Median (min-max) SLEDAI-2 K scores were 9 (0-38), median (min-max) SLICC/ACR-DI (SDI) score were 1 (1-5) Histopathology defined 1 Hodgkin's lymphoma, 2 non-Hodgkin's lymphoma, 1 acute lymphoblastic leukaemia; 4 gastrointestinal carcinoma, 1 squamous cell carcinoma of the tongue and 1 anal carcinoma; 1 had sigmoid adenocarcinoma and 1 stomach carcinoid; 3 had genital malignancy, being 1 vulvae, 1 cervix and 1 vulvae and cervix carcinomas; 1 had central nervous system oligodendroglioma; and 1 testicle germ cell teratoma. Conclusion Estimated malignancy frequency of 0.7% was reported during cSLE follow up in a multicentric series. Median disease activity and cumulative damage scores, by the time of malignancy diagnoses, were high; considering that reported in adult series.

Improved efficiency in the management of newborns with infectious risk factors by the sepsis risk calculator and clinical observation

Abstract Objective To evaluate the efficiency of the sepsis risk calculator and the serial clinical observation in the management of late preterm and term newborns with infectious risk factors. Method Single-center, observational, two-phase cohort study comparing the rates of neonates born ≥35 weeks' gestation, ≥2000 g birthweight, and without major congenital anomalies, who were screened and/or received antibiotics for early-onset neonatal sepsis risk at our center during two periods, before (January/2018-June/2019) and after (July/2019-December/2020) the implementation of the sepsis risk calculator. Results A total of 1796 (Period 1) and 1867 (Period 2) patients with infectious risk factors were included. During the second period, tests to rule out sepsis were reduced by 34.0 % (RR, 95 %CI): 0.66 (0.61, 0.71), blood cultures by 13.1 %: 0.87 (0.77, 0.98), hospital admissions by 13.5 %: 0.86 (0.76, 0.98) and antibiotic administration by 45.9 %: 0.54 (0.47, 0.63). Three cases of early-onset neonatal sepsis occurred in the first period and two in the second. Clinical serial evaluation would have detected all true cases. Conclusions The implementation of a sepsis risk calculator in the management of newborns ≥35 weeks GA, ≥2000 g birthweight, without major congenital anomalies, with infectious risk factors is safe and adequate to reduce laboratory tests, blood cultures, hospital admissions, and antibiotics administration. Serial clinical observation, in addition, could be instrumental to achieve or even improve this goal.

The Prevention and Treatment of Pulmonary Nodules “Nodule-cancer Transformation” Based on the View of “Disease with Latent Pathogen Induced by a New Pathogen” / 中医杂志

As one of the pathogenic mechanisms contained in The Inner Canon of Yellow Emperor （《黄帝内经》）， “disease with latent pathogen induced by a new pathogen” means that the induced new pathogen resulted to a combination of the latent previous pathogen and the new pathogen， which caused the disease. Based on this， it is believed that the change of “nodule-cancer transformation” of pulmonary nodules is actually based on the deficiency of original qi， and the new pathogen induces the latent pathogens like phlegm coagulation， qi stagnation， blood stasis， toxicity， so healthy qi can not drive the pathogens out， and the long-time detention generated into cancerous turbidity， and deve-loped into cancerous tumour at the end. Therefore， based on the three-stage treatment of unformed cancer， dense cancerous toxin， and developed cancer， the clinical practice applied six methods of clearing， expelling， dissipating， tonifying， harmonizing， and transforming， taking into account both the manifestation and root cause， moving the treatment window of pulmonary nodules forward， attacking the pathogens when the toxin was not yet overbearing， supporting the healthy qi before declining， delaying the process of nodules-cancer transformation， and providing ideas for the prevention and treatment of pulmonary nodules “nodule-cancer transformation” in traditional Chinese medicine.

Relationship between age and the histopathological features to chemotherapy response in colorectal cancer patients: a prospective observational study

Introduction: Chemotherapy response in early age-onset colorectal cancer patients is still controversial, and the results of chemotherapy response are unknown. Therefore, the purpose of this study is to determine the relationship between the age of colorectal cancer patients and histopathological features and chemotherapy response. Methods: This is a prospective observational study. The subjects in this study were colorectal cancer patients in the Digestive Surgery division at Tertiary Hospital in West Java from September 2021 to September 2022. Results: There were 86 subjects who underwent chemotherapy in accordance with the inclusion and exclusion criteria. Consisting of 39 patients of early age onset and 44 female patients. The most common histopathological feature in early age onset (EAO) and late age onset (LAO) was adenocarcinoma (25% and 46%, respectively). Stage III colorectal cancer affected 38 patients, while stage IV affected 48 patients. There was a significant relationship between early age onset and late age onset with histological features (p < 0.001). The patients with the highest chemotherapy response had stable diseases in EAO (17 patients) and LAO (20 patients). There was no statistically significant relationship between age, histological features, and stage of colorectal cancer and chemotherapy response (p > 0.05). The results of the ordinal logistic regression test showed no systematic relationship between chemotherapy response and age, histopathological features, gender, or cancer stage (p > 0.05). Conclusion: There was no association between age and histopathologic features with chemotherapy response and there is no difference in chemotherapy response between early and late age onset. (AU)

Características clínicas de pacientes con Lupus Eritematoso Sistémico, al debut y en recaídas

Introducción. Las formas clínicas de presentación del lupus eritematoso sistémico (LES) son variadas, así como las recaídas que ocurren en el curso de la enfermedad. Objetivo. Describir las formas de presentación del debut y las recaídas de pacientes con LES. Metodología. Estudio observacional, descriptivo, de corte transversal, de pacientes con LES, que acudieron al Hospital Nacional, durante el periodo 2022 a 2023. Las variables analizadas fueron las variables sociodemográficas, clínicas y de laboratorio, al debut y durante las recaídas. Resultados. Se incluyeron 47 pacientes, entre 14 y 68 años de edad (media: 29,6 ±12 años), 91,5% del sexo femenino, 59,5% del interior del país, con educación secundaria (68,1%) y ocupación ama de casa (55,3%). El tiempo de enfermedad fue en promedio 48,7 ±37.1 meses. La forma más frecuente de debut fue la poli-artralgia (55,3%), seguido de nefritis (27,7%). En la recaída, la nefritis fue más frecuente (44,7%), seguida de dolor poliarticular (40,4%). La causa de recaída más frecuente fue el abandono del tratamiento (34,0%). Conclusión. La mayoría de las pacientes eran mujeres jóvenes que debutaron la enfermedad con artralgias, seguida de la afectación renal. Las recaídas se presentaron con nefritis. La causa principal de las recaídas fue el abandono del tratamiento.

Introduction: The clinical forms of presentation of systemic lupus erythematosus (SLE) are varied, as well are the relapses that occur in the course of the disease. Objective: To describe the onset and relapses in a cohort of patients with SLE. Methodology. Observational, descriptive, cross-sectional study of patients with SLE who attended the National Hospital, during the period 2022 to 2023. The variables analyzed were sociodemographic, forms of onset and relapses. Results: 47 patients between 14 and 68 years of age (mean: 29.6 ±12 years) were included in the study, 91.5% female, 59.5% from the interior of the country, with secondary education (68.1%) and housewife occupation (55.3%). The duration of illness was on average 48.7 ±37.1 months. The most common form of onset was polyarthralgia (55.3%), followed by nephritis (27.7%). In relapse, nephritis was more frequent (44.7%), followed by polyarticular pain (40.4%). The most frequent cause of relapse was treatment abandonment (34.0%). Conclusion: The majority of patients were young women who presented the disease with arthralgia, followed by kidney involvement. Relapses presented with nephritis. The main cause of relapses were treatment abandonment.

Câncer colorretal de início precoce: uma análise de onze anos das características clinicopatológicas em um centro de saúde terciário / Early-onset colorectal cancer: an eleven-year analysis of clinicopathological characteristics at a tertiary healthcare center

ABSTRACT Background: Early-onset colorectal cancer (EO-CRC) incidence has increased significantly worldwide in recent years, and these individuals frequently have advanced disease at the time of diagnosis. This study examines the clinicopathological characteristics of EO-CRC cases diagnosed at an academic healthcare center in Spain. Methods: A retrospective record review study of patients diagnosed with EO-CRC from 2010 to 2021 was performed. Clinical and pathological data were collected. Results: A total of 101 patients were included. The majority of cases (75.3%) were diagnosed in the age group between 40 and 49 years, specifically within the subgroup of 46-49 years. A family history of colorectal cancer was found in 23% of patients. Left-sided tumors were more common (43.6%), and most patients were diagnosed at advanced stages (34.7% at stage III and 32.7% at stage IV). The majority of patients (94.1%) were symptomatic, with rectal bleeding being the most prevalent clinical presentation. The most frequent histological type was moderately differentiated adenocarcinoma (44.6%). KRAS mutant tumors were found in 18.8% and BRAF mutant tumors in 11.9%. 67.3% had microsatellite stability. Tumor recurrence occurred in 24.8% of the patients, while 27.7% of the patients died. Conclusion: From 2010 to 2021, EO-CRC accounted for 3% of all colorectal cancer cases. To improve early diagnosis and treatment, physicians should maintain a high suspicion of red flag symptoms in young patients. To decrease EO-CRC morbidity and mortality, starting diagnostic screening tests at age 45 should be considered.

RESUMO Contexto: A incidência de câncer colorretal de início precoce (CCR-IP) tem aumentado significativamente em todo o mundo nos últimos anos, e esses indivíduos frequentemente apresentam doença avançada no momento do diagnóstico. Este estudo examina as características clinicopatológicas dos casos de CCR-IP diagnosticados em um centro de saúde acadêmico na Espanha. Métodos: Realizado um estudo retrospectivo de revisão de prontuários de pacientes diagnosticados com CCR-IP de 2010 a 2021. Dados clínicos e patológicos foram coletados. Resultados: Foram incluídos um total de 101 pacientes. A maioria dos casos (75,3%) foi diagnosticada na faixa etária entre 40 e 49 anos, especificamente dentro do subgrupo de 46 a 49 anos. Histórico familiar de câncer colorretal foi encontrado em 23% dos pacientes. Tumores do lado esquerdo foram mais comuns (43,6%), e a maioria dos pacientes foi diagnosticada em estágios avançados (34,7% no estágio III e 32,7% no estágio IV). A maioria dos pacientes (94,1%) apresentava sintomas, sendo o sangramento retal a apresentação clínica mais prevalente. O tipo histológico mais frequente foi adenocarcinoma moderadamente diferenciado (44,6%). Tumores com mutação KRAS foram encontrados em 18,8% e tumores com mutação BRAF em 11,9%. 67,3% apresentavam estabilidade de microssatélites. A recorrência do tumor ocorreu em 24,8% dos pacientes, enquanto 27,7% dos pacientes morreram. Conclusão: De 2010 a 2021, o CCR-IP representou 3% de todos os casos de câncer colorretal. Para melhorar o diagnóstico precoce e o tratamento, os médicos devem manter uma alta suspeita de sintomas de alerta em pacientes jovens. Para diminuir a morbidade e a mortalidade do CCR-IP, a consideração de iniciar exames de triagem diagnóstica aos 45 anos deve ser considerada.

Clinical and metabolic characteristics of males with early-onset androgenetic alopecia

Background: Men with early-onset androgenetic alopecia (AGA) often have an abnormal hormonal milieu. Objective: To ascertain the clinico-phenotypic characteristics and the prevalence of hormonal and metabolic changes in men with early-onset AGA. Methods: Consecutive male patients less than 30 years of age with a Norwood-Hamilton grade ?3 AGA were recruited in this comparative cross-sectional study. After endocrine evaluation they were classified into two groups, that is, Group A consisting of subjects with an altered hormonal profile and Group B with normal hormonal profiles. The groups were assessed for differences in disease phenotype and severity (Norwood-Hamilton grade), insulin resistance and parameters of metabolic syndrome (ATP III guidelines). Results: Altered hormonal profiles were seen in 34 of the 100 subjects with AGA, while insulin resistance and metabolic syndrome were noted in 44 and 26 respectively. Altered hormonal profiles were significantly associated with insulin resistance and severe alopecia (grade 4 and above Hamilton-Norwood Scale). Insulin resistant Group A patients had a significantly higher prevalence of severe alopecia (>grade 4) (P = 0.0036). The prevalence of metabolic syndrome was similar in both groups. Limitation: The cross sectional study design was a drawback of this study. Further, a control arm without AGA was not included and the sample size of 100 was selected arbitrarily. Conclusion: An altered hormonal profile and insulin resistance was noted in a third of the males with early-onset AGA. Subjects with altered hormonal profiles had a higher prevalence of insulin resistance and were likely to have severe grades of AGA

Hernia diafragmática congénita de presentación tardía Reporte de caso con revisión de literatura / Late Presentation Congenital Diaphragmatic Hernia: Case Report with Literature Review

Resumen Una hernia diafragmática congénita ocurre cuando existe un defecto estructural en el diafragma que permite la migración de los órganos abdominales a la cavidad torácica. Se considera de presentación tardía cuando se diagnostica después de los 30 días de vida extrauterina. Más del 60% de los pacientes con hernia diafragmática congénita cuentan con un diagnóstico erróneo al momento del nacimiento, encontrándose dentro de los diagnósticos más frecuentes al derrame pleural, neumonía, neumotórax, neumatocele y absceso pulmonar. Presentamos el caso de una paciente del sexo femenino de 3 años que acudió a urgencias por dolor abdominal, náuseas, vómito, intolerancia a la vía oral y dificultad respiratoria. La radiografía de tórax evidenció migración de la cámara gástrica hacia el tórax, dessplazamiento de la silueta cardiaca y las estructuras del mediastino hacia la derecha con la punta de la sonda nasogástrica ubicada en el hemitórax izquierdo. Se concluyó el diagnóstico de hernia diafragmática de presentación tardía. La paciente recibió tratamiento quirúrgico, el cual fue exitoso. Este trabajo destaca la importancia de sospechar el diagnóstico de hernia diafragmática congénita de presentación tardía cuando se abordan pacientes pediátricos con dificultad respiratoria sin otra causa aparente, dolor abdominal, náuseas y vómito.

Abstract A congenital diaphragmatic hernia occurs when the diaphragm has a structural defect that allows the migration of abdominal organs into the chest cavity. It is called late presentation when its diagnosis does after 30 days of life. More than 60% of patients with congenital diaphragmatic hernia are misdiagnosed. The most common misdiagnoses are pleural effusion, pneumonia, pneumothorax, pneuma tocele, and lung abscess. We present a case of a 3-year-old female who attended the emergency room due to abdominal pain, nausea, vomiting, intolerance to the oral route, and respiratory distress. The chest X-ray showed migration of the gastric chamber towards the thorax, displacement of the cardiac silhouette and the mediastinal structures to the right, and the tip of the nasogastric tube located in the left hemithorax. The doctors concluded a late presentation diaphragmatic hernia. The patient received surgical treatment, which was successful. This paper highlights the importance of suspecting the diagnosis of late-onset congenital diaphragmatic hernia when treating pediatric patients with respiratory distress without another apparent cause, abdominal pain, nausea, and vomiting.

New-onset Geriatric Epilepsy in a Latin American Country: A Multi-centric Study from Mexico

ABSTRACT Background: In Latin America, epilepsy in the elderly is a neglected issue that has never been studied. The epidemiological transition has significantly altered the demographics of epilepsy, and therefore, we would like to draw attention to this topic. Objective: We require local real-world evidence, as the literature often depicts a different scenario, including pharmacological management. Methods: From 2007 to 2018, we recruited all patients with new-onset geriatric epilepsy (first seizure after the age of 60) tracked from ten Mexican hospitals, adding them to patients with similar characteristics from a previously published study. The diagnosis was confirmed in all patients by a certified neurologist, and they were also studied using a conventional electroencephalogram and imaging workup. Results: A diagnosis of new-onset geriatric epilepsy (Elderly patients was established in 100 cases. No specific cause was found in 26% of patients, while 42% had a stroke and 10% had neurocysticercosis (NCC). Monotherapy was the choice in 83 patients, and phenytoin was the most used drug (50%), followed by carbamazepine (25%). Conclusion: NCC remains a frequent cause of new-onset geriatric epilepsy. This distribution is not seen in the literature, mainly representing patients from wealthy economies. In our setting, financial constraints influence the choice of the drug, and newer antiepileptic drugs should be made more affordable to this population with economic and physical frailty.

Prevalencia de sepsis neonatal confirmada microbiológicamente en una maternidad de la Ciudad Autó noma de Buenos Aires / Prevalence of microbiologically confirmed neonatal sepsis at a maternity center in the City of Buenos Aires

Introducción. En neonatos internados es frecuente sospechar sepsis neonatal, pero solo en el 25 % al 30 % se confirma con cultivos positivos. La selección del esquema antibiótico basándose en la epidemiología local favorece el uso racional y minimiza sus efectos colaterales. Objetivo primario. Describir la prevalencia de sepsis precoz y tardía con rescate microbiológico y sus características clínicas. Población y método. Estudio transversal retrospectivo, realizado del 1 de enero de 2013 al 31 de diciembre de 2017, en una maternidad pública de Argentina, que incluyó todos los recién nacidos internados en la unidad con diagnóstico de sepsis precoz y tardía con rescate microbiológico, y aquellos reingresados dentro del mes de vida. Resultados. Ingresaron 3322 recién nacidos, 1296 evaluados por sospecha de sepsis precoz, cultivos positivos en 25 (1,9 %; tasa: 0,86 ‰). El 52 % eran menores de 33 semanas de edad gestacional. Microorganismos: Escherichia coli 5, Listeria monocytogenes 4, Streptococcus agalactiae (SGB) 3, Streptococcus pneumoniae 3. Sepsis tardía (tasa 8,73 ‰), el 68 % ocurridas en menores de 33 semanas. Microorganismos intrahospitalarios: Staphylococcus coagulasa negativos 115, Staphylococcus aureus 47, Escherichia coli 30, Cándida spp. 16, Enterococcus faecalis 13, Klebsiella pneumoniae 11 y Streptococcus agalactiae 10. En los reingresos: E. coli 11, S. aureus 12, SGB 3 y Haemophilus influenzae 3. Conclusiones. Se observa en el período estudiado una frecuencia de sepsis precoz similar a los reportes internacionales, con predominio de E. coli y L. monocytogenes. La tasa de sepsis tardía presentó una tendencia descendente en los años analizados, con predominio de los cocos grampositivos

Introduction. Neonatal sepsis is often suspected in hospitalized newborn infants, but only in 25­30% of cases it is confirmed via a positive culture. Selecting the antibiotics based on local epidemiology favors their rational use and minimizes their side effects. Primary objective. To describe the prevalence of early- and late-onset sepsis with microorganism isolation and their clinical characteristics. Population and method. Retrospective, cross-sectional study conducted between 01-01-2013 and 12-31-2017 in a public maternity center of Argentina in all hospitalized newborn infants with a diagnosis of early- and late-onset sepsis with microorganism isolation, and those re-admitted in their first month of life. Results. A total of 3322 newborn infants were admitted; 1296 were assessed for suspected early- onset sepsis; 25 had a positive culture (1.9%; rate: 0.86‰). Of these, 52% were born before 33 weeks of gestation. Microorganisms: Escherichia coli 5, Listeria monocytogenes 4, Streptococcus agalactiae (SGB) 3, Streptococcus pneumoniae 3. Also, 68% of late-onset sepsis cases (rate: 8.73‰) occurred in infants born before 33 weeks of gestation. Hospital-acquired microorganisms: coagulase-negative Staphylococcus 115, Staphylococcus aureus 47, Escherichia coli 30, Candida spp. 16, Enterococcus faecalis 13, Klebsiella pneumoniae 11, and Streptococcus agalactiae 10. In re-admissions: E. coli 11, S. aureus 12, SGB 3, and Haemophilus influenzae 3. Conclusions. During the study period, the frequency of early-onset sepsis was similar to international reports, with a predominance of E. coli and L. monocytogenes. The rate of late-onset sepsis showed a downward trend in the analyzed years, with a predominance of Gram-positive cocci.

Guía práctica para el uso de clozapina en niños/as y adolescentes / Practical guidelines for the use of clozapine in children and adolescents

El uso de clozapina (CZP) en niños/as y adolescentes ha estado históricamente limitado, debido a los efectos adversos y riesgos médicos asociados al fármaco, a pesar de ser una herramienta farmacológica de gran efectividad en la psiquiatría general. A continuación, se presenta una guía clínica con los siguientes objetivos: 1) identificar los criterios de indicación de CZP en niños, niñas y adolescentes (NNA) según la evidencia disponible; 2) entregar algunas directrices a los clínicos y profesionales de salud respecto a la prescripción de CZP y precauciones a tener en consideración en esta población y; 3) entregar algunos datos comparativos del uso de CZP entre población infantojuvenil y población adulta. Todo lo anterior tiene como finalidad poder entregar la información necesaria para que los clínicos no limiten el uso de este fármaco y puedan prescribirlo de acuerdo con la evidencia científica disponible.

The use of clozapine (CZP) in children and adolescents has historically been limited due to the adverse effects and medical risks commonly associated with the drug, despite being a highly effective pharmacological tool in general psychiatry. Below we developed a clinical guideline with the following objectives: 1) identify the indication criteria for CZP in children and adolescents (NNA) according to the available evidence; 2) provide some guidelines to clinicians and health professionals regarding the prescription of CZP and precautions to be taken into account in this population and; 3) provide some comparative data on the use of CZP between the pediatric and adult population. The purpose of the guideline is to provide the necessary information so that clinicians do not limit the use of CLZ when needed and can prescribe it safely and according to the available scientific evidence.

Analysis on the trends of incidence and age change for global female breast cancer / 中华肿瘤杂志

Objective: To analyze the trends of incidence and age change for global female breast cancer in different regions of the world according to the database from Cancer Incidence in Five Continents Time Trends (CI5plus) published by the International Association of Cancer Registries (IACR). Methods: The recorded annual female breast cancer (ICD-10: C50) incidence data and corresponding population at-risk data (1998-2012) were extracted from CI5plus published by IACR. The annual change percentage and average annual change percentage (AAPC) were calculated to examine the trends of incidence. The age-standardized mean age at diagnosis and proportion of incidence cases by age were calculated to analyze the relationship between incidence and age. Results: For crude incidence, except in Northern America, all other regions showed an upward trend, with Asia showing the most obvious upward trend (AAPC: 4.1%, 95% CI: 3.9%, 4.3%). For age-standardized incidence, in Asia, Latin America and Europe, the rising trends had slowed down, in Oceania and Africa, the trends began to be stable, and in Northern America, the trend showed a downward trend (APPC: -0.6%; 95% CI: -1.0%, -0.1%). The mean age at diagnosis were increased from 1998 to 2012 in Asia, Latin America, Oceania and Europe, with an annual increase of 0.12 years, 0.09 years, 0.04 years and 0.03 years, respectively. But after age-standardized, only Europe still kept increasing year by year, with an annual increase of 0.02 years, while Northern America showed a decreasing trend, with an annual decrease of about 0.03 years. Conclusions: From 1998 to 2012, the trends of incidence and age change for global female breast cancer vary in different regions of the world, and the global population aging is widespread, which affects the trend of the actual age change. Prevention and control strategies should be targeted at different age groups in different regions.

Research on the average age of onset of endometrial cancer based on data mining / 中国医师杂志

Objective:To explore the average age at onset of endometrial cancer (EC) and the differences between domestic and international factors.Methods:Pubmed, Wanfang Database, VIP Information Resource System, and China National Knowledge Infrastructure (CNKI) were selected to extract clinical research data related to EC. Through data mining methods such as frequency analysis and cluster analysis, we compared the differences in the average age of onset of EC between domestic and foreign countries.Results:A total of 280 articles that met the inclusion criteria were selected, and frequency analysis found that the average age of onset of EC in the Chinese population was mostly concentrated under 57 years old, while in European and American countries, it was mainly concentrated above 57 years old. Through cluster analysis, it was found that the average age of onset in China was clustered in one category with most Asian countries, while European and American countries and Australian countries were clustered in another category. Through analysis of domestic and foreign articles, it was found that the average age of onset of EC did not show a significant upward or downward trend with years.Conclusions:There are differences in the average onset age of EC among different countries and regions. The onset age of EC in Asian populations is significantly earlier than that in European and American populations. The average onset age of EC in Chinese populations is 54 years old, and there is no trend towards a younger onset of EC.

The speed-limiting role in the onset of antidepres-sants:the re-establishment of the excitation/inhibi-tion(E/I)function balance in the mPFC of rats / 中国药理学与毒理学杂志

OBJECTIVE There are serious hazards in depression,and the precise mechanism underlying the delayed onset of clinical antidepressants remains unclear.The purpose of this study was to investigate the regular pattern of the speed-limiting role of excitation/inhibition(E/I)function balance in the mechanism of antidepressant action.METHODS Based on the previous study,we focused on glutamatergic pyramidal neurons in the medial prefrontal cortex(mPFC)here and used its excitability to represent the establishment of a new E/I functional balance.We studied the changes in the firing activity of glutamatergic pyramidal neuron in the mPFC at different administration times for five types of antidepressants that act on different pharmacological targets and different onset times,including fluoxetine(SSRI),duloxetine(SNRI),vilazodone[serotonin 1A receptor(5-HT1A)ago-nist and SSRI],ketamine[N-methyl-D-aspartate(NMDA)receptor antagonist],and hypidone hydrochloride(YL-0919,new antidepressant with sigma-1 receptor ago-nist and SSRI).We first examined the initial onset time of activation of pyramidal neurons using multichannel elec-trophysiological recordings and tested the antidepressant behavioral effects using the FST.We then selected three antidepressants(fluoxetine,ketamine,and vilazodone)to explore its effects on the BDNF-mTOR pathway by West-ern blotting.In addition,we disrupted the E/I function bal-ance using chemogenetics to investigate the antidepres-sant-like effects of YL-0919 and ketamine in the FST and TST.RESULTS We found that treatment with fluoxetine for 17 days significantly increased the firing activity of pyramidal neurons and decreased the immobility duration in the FST.Similarly,it took duloxetine for 10 d,vilazodone for 4 d,YL-0919 for 3 d and ketamine for 24 h,to exert such effects.Meanwhile,Western blotting results sug-gested that the expression of BDNF and phosphorylation of mTOR in the mPFC significantly increased.How-ever,haloperidol,a classic antipsychotic(without antide-pressant effects),exerted no such effects on the firing activities of pyramidal neurons.In addition,disrupting the E/I function balance(via activating the GABA neurons and inhibiting the glutamate neurons)blocks out the antidepressant-like effects of YL-0919 and ketamine in the FST and TST.CONCLUSION Taken together,our findings suggest that the commencement of antide-pressant effects may be accompanied by the increase in the firing activity of pyramidal neurons and the activation of the BDNF-mTOR pathway,which may be a necessary and rate-limiting process.The re-establishment of the E/I balance may be a landmark event for the onset of antide-pressant effects.

Differences of resting-state brain functional connectivity in patients with early-onset and late-onset obsessive compulsive disorder and their correlation with cognitive flexibility / 中华行为医学与脑科学杂志

Objective:To explore the differences of the resting-state functional connectivity(FC) between goal-directed network and habituation networks in patients with early- and late-onset obsessive compulsive disorder (OCD) and the correlation between the strength of FC in the differential brain regions and cognitive flexibility.Methods:From October 2019 to April 2021, 40 patients with OCD were included in this study, including 22 patients with early-onset OCD and 18 patients with late-onset OCD.The cognitive flexibility of all subjects was assessed using the Wisconsin card sorting test (WCST), the Stroop task and the trail making test (TMT). The brain regions which were associated with goal-directed network(caudate, orbitofrontal cortex, ventromedial prefrontal cortex, and anterior cingulate cortex) and the brain regions which were associated with habituation network(putamen, supplementary motor area and insula) were selected as FC regions of interest (ROI). The DPABI and SPM12 plug-ins in the matlab2011a platform were used for whole brain FC analysis to compare the difference of FC between patients with early-onset OCD and patients with late-onset OCD on the two networks.The data were analyzed by SPSS 25.0 with χ2 test, independent samples t-test, and Pearson correlation analysis. Results:Compared with patients with early-onset OCD, patients with late-onset OCD had significantly enhanced FC of the left supplementary motor area with the left putamen and left insula.The total number of persistent errors of WCST in patients with late-onset OCD was greater than that in patients with early-onset OCD ((20.61±11.30), (14.95±8.94), P<0.05). The FC of the left putamen-left supplementary motor area was significantly and positively correlated with the total number of sustained responses ( r=0.678, P=0.003) and the total number of incorrect responses ( r=0.590, P=0.013) in patients with late-onset OCD.The FC of the left supplementary motor area-left insula was significantly positively correlated with the number of responses required to complete the first classification in patients with late-onset OCD ( r=0.485, P=0.049). Conclusion:Patients with late-onset OCD have stronger habituation network FC than patients with early-onset OCD, and the enhanced FC correlates with patients' cognitive flexibility performance, while late-onset OCD has more impaired cognitive flexibility than early-onset OCD.

Prevalence trend of hand-foot-mouth disease in children and its correlation with meteorological factors in Kaizhou District, Chongqing in 2018 - 2021 / 公共卫生与预防医学

Objective To analyze the incidence trend of hand-foot-mouth disease (HFMD) and its correlation with meteorological factors in Children in Kaizhou District, Chongqing from 2018 to 2021, and to provide a theoretical basis for the diagnosis and treatment of HFMD in children. Methods The HFMD epidemic information was collected from 2018 to 2021 in Kaizhou District of Chongqing by using the China Disease Surveillance Information and Report Management System. The epidemiological characteristics of HFMD were descriptively analyzed, and the correlation between HFMD incidence and meteorological factors was analyzed by multiple regression. Results A total of 5 121 HFMD cases were reported in Kaizhou District of Chongqing from 2018 to 2021, with an average annual incidence of 143.30/100 000. The incidence of HFMD fluctuated from 120.87/100,000 to 159.78/100,000 from 2018 to 2021, showing a downward trend year by year. There were 2929 males and 2192 females with HFMD. The incidence of HFMD was the highest in early childhood (70.13/100 000), followed by pre-school age (43.06/100 000). There was significant difference in the incidence of HFMD among different age groups (χ2=53.497, P<0.05). The cases were mainly scattered children (3127 cases, 61.06%). The second was nursery children (1627 cases, 31.77%). In addition, there were 289 cases of students (5.64%). There were 1084 laboratory-confirmed cases in Kaizhou District of Chongqing from 2018 to 2021, including 269 (24.82%) children with EV71 infection, 178 (16.42%) children with Cox A16 infection, and 637 (58.76%) children with other enterovirus infections. There were significant differences in pathogen composition among different years (Z=32.75, P<0.05). From 2018 to 2021, the proportion of EV71 increased year by year, while COX16 and other enterovirus infections showed a downward trend year by year. Average daily temperature (OR=1.873) and average daily pressure (OR=-1.498) were independent risk factors for HFMD in Kaizhou District of Chongqing (P<0.05). Conclusion The reported incidence of HFMD in Kaizhou District of Chongqing shows a decreasing trend, and the incidence is closely related to temperature and atmospheric pressure. It is still necessary to strictly implement the prevention and control measures in key population in the season of high incidence. The main virus is EV71, which can be vaccinated with EV71 HFMD vaccine to reduce the occurrence of severe cases.

J-shaped association between dietary zinc intake and new-onset hypertension: a nationwide cohort study in China / 医学前沿

We aimed to investigate the relationship of dietary zinc intake with new-onset hypertension among Chinese adults. A total of 12,177 participants who were free of hypertension at baseline from the China Health and Nutrition Survey were included. Dietary intake was assessed by three consecutive 24-h dietary recalls combined with a household food inventory. Participants with systolic blood pressure ≽ 140 mmHg or diastolic blood pressure ≽ 90 mmHg or diagnosed by a physician or under antihypertensive treatment during the follow-up were defined as having new-onset hypertension. During a median follow-up duration of 6.1 years, 4269 participants developed new-onset hypertension. Overall, the association between dietary zinc intake and new-onset hypertension followed a J-shape (P for non-linearity < 0.001). The risk of new-onset hypertension significantly decreased with the increment of dietary zinc intake (per mg/day: hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.88-0.98) in participants with zinc intake < 10.9 mg/day, and increased with the increment of zinc intake (per mg/day: HR 1.14; 95% CI 1.11-1.16) in participants with zinc intake ≽ 10.9 mg/day. In conclusion, there was a J-shaped association between dietary zinc intake and new-onset hypertension in general Chinese adults, with an inflection point at about 10.9 mg/day.

Genotypes and phenotypes of hereditary eye diseases associated with early-onset high myopia / 中华实验眼科杂志

Objective:To analyze the genotype of hereditary eye diseases with early-onset high myopia (eoHM) and its relationship with phenotype.Methods:The families with eoHM were collected in Ningxia Eye Hospital from January 2019 to June 2020.The medical records of the probands and their family members were inquired and recorded in detail, and the relevant ocular examinations were performed.Peripheral venous blood samples were collected from patients and their family members, and whole-genome DNA was extracted.Sequence capture sequencing technology was applied to screen for disease-causing gene mutations in probands.The detected suspected pathogenic variants were verified by Sanger sequencing and were analyzed by family cosegregation analysis.According to ACMG guidelines, the pathogenicity of novel variants was evaluated.The original literature about hereditary eye diseases with eoHM was searched to analyze the relationship between mutated genes and clinical phenotype.This study protocol adhered to the Declaration of Helsinki.All subjects or their guardians were informed of the purpose and procedure of the study and signed the informed consent form.The study protocol was approved by the Ethics Committee of the People's Hospital of Ningxia Hui Autonomous Region (No.2016018).Results:A total of 20 eoHM families were collected, among which pathogenic variants associated with inherited eye diseases were detected in 8 families.Of the 8 probands, two were diagnosed with familial exudative vitreoretinopathy, one with X-linked retinitis pigmentosa, one with congenital stationary nightblindness, one with Stickler syndrome, one with achromatopsia, one with Leber congenital amaurosis, and one with gyrate atrophy of the choroid and retina.The first diagnosis age of the 8 probands was 4-7 years old, and they were all diagnosed as high myopia, with a refractive status ≤-6.00 DS.Genetic tests showed that the 8 probands carried a heterozygous variant c. 313A>G (p.M105Val) in FZD4 gene, a heterozygous variant c. 14_15insAAGA (p.Asp5fs *) in TSPAN12 gene, a heterozygous frameshift variant c. 2234_2237del (p.Arg745fs) in RPGR gene, a compound heterozygous variant of c. 481C>T (p.Gln161Ter *) and c. 355>T (p.Arg119Cys *) in GPR179 gene, a frameshift variant c. 1659_1660insACGGTGACCCTGGCCGTCCTGG (p.Pro554fs *) in COL2A1 gene, a compound heterozygous variant of c. 1811C>T (p.Thr604Ile *) and c. 967G>A (p.Gly323Ser) in PDE6B gene, a compound heterozygous variant of c. 604_619delTCCACGGCACTCAGGG (p.Ser202fs *) and c. 995G>C (p.Arg332Pro) in GUCY2D gene, a homozygous variant c. 772C>T (p.Pro241Leu) in OAT gene.Seven of them were novel variants.Compared with the previous literature, the clinical and gene phenotypes of the 8 families were analyzed in detail in this study, which provided the basis for the diagnosis of hereditary eye diseases with eoHM. Conclusions:EoHM is closely related to some hereditary eye diseases, which may be the reason for the early diagnosis of children and an important clue for clinicians to detect potential hereditary eye diseases.Further clinical evaluations of ocular structure and function as well as genetic screening in children with eoHM are recommended.

Changes of peripheral perfusion index in very low birth weight infants with late-onset sepsis / 中国小儿急救医学

Objective:To analyze the changes of peripheral perfusion index (PPI) with late-onset sepsis (LOS) in very low birth weight infants during hospitalization.Methods:Very low birth weight infants admitted to the neonatal intensive care unit of Children′s Hospital of Fudan University from August 1, 2021 to August 31, 2022 were consecutively included.Infants with admission age ≥three days and unstable circulation, or positive blood culture within three days after birth were excluded.From the day of admission, the PPI values of the right hand and either foot of the infants were measured with Masimo SET Radical-7 everyday while whether LOS occurred during hospitalization was observed.The mean PPI curve of very and extremely low birth weight infants without LOS was plotted.For those with LOS confirmed by blood culture, the PPI change trajectory three days before and after the occurrence of LOS was drawn, and the change trend of PPI before the occurrence of LOS was analyzed by trend chi-square test.Non-parametric test was used to analyze the effect of LOS on pre- and post-ductal PPI values.Results:A total of 107 very low birth weight infants were included in the final analysis.Among them, there were 11 infants confirmed as LOS by blood culture, 37 infants diagnosed as clinical LOS, and 59 infants without LOS.Pre-and post-ductal PPI values of very low birth weight infants without LOS were 2.06±1.30 and 1.72±0.92, respectively; those with clinical LOS were 1.90±0.94 and 1.58±0.83, respectively; those with LOS confirmed by blood culture were 1.92±1.11 and 1.62±0.82, respectively.For infants with LOS confirmed by blood culture, the pre-and post-ductal PPI values showed a continuous downward trend during three days before the onset of disease, with the lowest PPI values on the first day before the diagnosis of blood culture.The downtrend of pre-ductal PPI was statistically significant ( χtrend2=5.57, P<0.05). Conclusion:The PPI value of very low birth weight infants show a downward trend when LOS occurs.It should be observed dynamically in clinical practice, which is helpful to suspect or identify LOS as early as possible.

Research progress on probiotics and short-term clinical outcomes in extremely premature infants / 中国小儿急救医学

The extremely premature infants have different degrees of immature organ development, abnormal intestinal flora establishment and low immune function, and are prone to necrotizing enterocolitis, late-onset sepsis and other complications.Probiotics can improve intestinal flora, and regulate cell metabolic activity and immune function.Probiotics can be used to prevent necrotizing enterocolitis, and late-onset sepsis and so on.However, the possible harm of probiotics to extremely premature infants should not be ignored.This review summarized the effects of probiotics on extremely premature infants.