Lupus de inicio tardío en un grupo de pacientes paraguayos

Introducción: Los pacientes con lupus eritematoso sistémico (LES) diagnosticados después de los 50 años presentan una enfermedad menos severa y un curso clínico más leve. El objetivo de este estudio es describir las características clínicas y de laboratorios del LES en pacientes de edad avanzada. Material y Método: Estudio observacional, descriptivo, de corte trasverso, retrospectivo, de pacientes con el diagnóstico de LES, de inicio posterior a los 50 años de edad, que consultaron en el Hospital Nacional, en el periodo comprendido entre diciembre de 2016 y mayo de 2024. Resultados: Se estudiaron 30 pacientes entre 51 y 87 años (edad media: 62,5 años ± 8,5), 16 mujeres (53,3%) y 14 varones 14 (46,6 %). El tiempo de enfermedad previo al diagnóstico fue de 59,4 ± 8.3 (50-80) días. La duración de la enfermedad fue en promedio 5 años ± 5,1 (1-26). Las principales manifestaciones clínicas fueron las artralgias 26 (86,6%), artritis 22 (72,3%), pérdida de peso 10 (33,3%) y fiebre prolongada (30%). Presentaron comorbilidades 19 pacientes (63,3 %), siendo la hipertensión arterial la principal. El anti-DNA fue positivo en 12 pacientes (42,8%), el anti-Ro en 5/25 pacientes (20%), el anti-Sm en 2/26 (7,9%). La eritrosedimentación en la primera hora fue ≥ 20 mm en 17/23 (73,9%). El 100% recibió tratamiento con hidroxicloroquina, mientras que recibieron corticoides 26 (86.6%) pacientes, micofenolato mofetil 7 (24,4%), ciclofosfamida 4 (13,3%). La mortalidad fue del 6,6 %. Conclusión: Los principales hallazgos fueron artralgias y artritis, siendo menos frecuentes los casos graves. La mayoría presentó comorbilidades, siendo la hipertensión arterial la más frecuente. La mortalidad fue del 6,6% de causa cardiovascular.

Introduction: Patients with systemic lupus erythematosus (SLE) diagnosed after the age of 50 have a less severe disease and a milder clinical course. The objective of this study is to describe the clinical and laboratory characteristics of SLE in elderly patients. Material and Method: Observational, descriptive, cross-sectional, retrospective study of patients with the diagnosis of SLE, with onset after 50 years of age, evaluated at the National Hospital, in the period between December 2016 and May of 2024. Results: 30 patients between 51 and 87 years old (mean age: 62.5 years ± 8.5) were studied, 16 women (53.3%) and 14 men (46.6%). The time to diagnosis was 59.4 ± 8.3 (50-80) days. The duration of the disease was on average 5 years ± 5.1 (1-26). The main clinical manifestations were arthralgia in 26 (86.6%), arthritis in 22 (72.3%), weight loss in 10 (33.3%) and prolonged fever (30%). Nineteen patients (63.3%) had comorbidities, the main one being high blood pressure. Anti-dsDNA was positive in 12 patients (42.8%), anti-Ro in 5/25 patients (20%), anti-Sm in 2/26 (7.9%). The erythrocyte sedimentation rate was ≥ 20 mm in 17/23 (73.9%). All patients were treatment with hydroxychloroquine, 26 (86.6%) patients received corticosteroids, 7 (24.4%) mycophenolate mofetil, 4 (13.3%) cyclophosphamide. Mortality was 6.6%. Conclusion: The main findings were arthralgia and arthritis, with severe cases being less frequent. The majority presented comorbidities, with high blood pressure being the most common. Mortality was 6.6% due to cardiovascular causes.

Effects of Erxian Decoction （二仙汤） on Choroid Plexus Folate Transport-Hippocampal Neurogenesis in Rat Brain Tissue of Late-Onset Depression Model / 中医杂志

ObjectiveThis study aims to investigate the effectiveness and potential mechanism of Erxian Decoction （二仙汤） for late-onset depression （LOD）. MethodsForty Wistar male rats of 7-8 weeks were divided into 20 each of normal group and youth depression group. Sixty Wistar male rats of 20 months were divided into 20 each of elder group， LOD group and Erxian Decoction group. The rats in youth depression group were modelled with chronic unpredictable mild stress （CUMS） for 6 weeks to build a depression model， and the elder rats in LOD group and Erxian Decoction group were modelled with CUMS for 6 weeks to build a LOD model， with no interventions in the normal group and the elder group. Gastric administration was carried out at the same time of modelling， rats in Erxian Decoction group were given 8 g/（kg·d） of Erxian Decoction by gavage， and rats in the normal group， youth depression group， elder group， and LOD group were given 4 ml/（kg·d） of pure water by gavage， for 6 weeks in each group. Sugar water preference experiment and forced swimming experiment were used to evaluate the depression-like behaviour of rats， absent field experiment was used to evaluate the spontaneous activity ability of rats， and T-maze experiment was used to evaluate the cognitive function of rats； Western blot assay was used to detect neuronal nuclei （NeuN）， nestin， doublecortin （DCX） in hippocampal tissue， and zonula occludens-l （ZO-1）， folate receptor α （FRα）， reduced folate carrier （RFC）， and protoncoupledfolate transporter （PCFT） protein expression in choroid plexus； immunofluorescence was used to detect the number of double-positive cells for Ki-67/nestin， the number of double-positive cells for 5-bromodeoxyuracil nucleoside （BrdU）/DCX in hippocampal dentate gyrus， and the protein expression of ZO-1， FRα， RFC， and PCFT in choroid plexus tissues； ELISA technique was used to detect plasma， cerebrospinal fluid， 5-methyltetrahydrofolate （5-MTHF） in hippocampal tissues； Pearson correlation analysis was used to correlate the 5-MTHF content in cerebrospinal fluid and hippocampal tissues and the expression of nestin， DCX， and NeuN proteins in hippocampal tissues of rats in youth depression group and LOD group. ResultsCompared with normal group， rats in youth depression group and LOD group showed reduced sugar water preference， reduced total distance travelled in the absent field， reduced number of times through the grid， prolonged forced swimming immobilisation， reduced hippocampal NeuN， nestin and DCX protein expression， reduced number of Ki-67/nestin double-positive cells in hippocampal dentate gyrus， reduced number of BrdU/DCX double-positive cells in hippocampal dentate gyrus， and reduced expression of ZO-1 and FRα proteins and fluorescence intensity （P＜0.05 or P＜0.01）； the correct rate of T-maze on days 3 and 4 in the rats of youth depression group and on days 2 to 4 in the rats of LOD group significantly decreased， and the content of 5-MTHF in the cerebrospinal fluid and hippocampal tissues of the rats of LOD group significantly decreased as well （P＜0.05 or P＜0.01）. Compared with youth depression group， rats in LOD group showed a decrease in total distance travelled in absenteeism， number of times through the grid， a significant decrease in the correct rate of the T-maze on day 1-4， a decrease in NeuN， nestin， DCX protein expression of hippocampal tissue and the number of Ki-67/nestin double-positive cells， BrdU/DCX double-positive cells of hippocampal dentate gyrus （P＜0.05 or P＜0.01）. Compared with LOD group， rats in Erxian Decoction group had elevated sugar-water preference and total distance travelled in absenteeism and number of times through the grid， shorter forced swimming immobility time， significantly higher correct rate of the T-maze on day 3-4， elevated expression of NeuN， nestin， and DCX proteins in hippocampal tissues， increased number of Ki-67/nestin double-positive cells and BrdU/DCX double-positive cells in hippocampal dentate gyrus， and increased 5-MTHF content in cerebrospinal fluid and hippocampal， and ZO-1， FRα， RFC， PCFT protein expression and fluorescence intensity increased in choroid plexus （P＜0.05 or P＜0.01）. Correlation analysis showed that there was a positive correlation between 5-MTHF content in cerebrospinal fluid （r = 0.466）， hippocampal tissue （r = 0.522） and nestin expression in hippocampal tissue （P＜0.05）. ConclusionErxian Decoction could improve depressive-like behaviour and cognitive impairment in LOD model rats， and its mechanism may promote hippocampal neurogenesis by alleviating structural damage to the choroid plexus of the brain tissue， and improving impaired choroid plexus folate transport.

Risk Factors and Prevention of Late-onset Bacterial Sepsis in Very Preterm Infants / 中山大学学报(医学科学版)

ObjectiveTo investigate the clinical features and high risk of very preterm infants with late-onset bacterial sepsis，so as to propose feasible prevention and treatment suggestions． MethodsTotally 94 very preterm infants with late-onset bacterial sepsis from the Neonatology Department of Women’s Hospital of Jiangnan University were recruited from February， 2012 to January， 2024. Their clinical data， including the perinatal situation， clinical symptoms， pathogens， risk factors and treatment， were collected and analyzed. ResultsThe incidence rate of very preterm infants with late-onset bacterial sepsis were 8.40 for 100 live birth babies. The major pathogens of the infections among these very premature infants included gram-positive bacteria （71.1%）. Logistic regression analysis showed that long term（≥7 d）use of antibiotics， invasive mechanical ventilation， indwelling central venous catheter（≥7 d）， and vaginal delivery were high risk factors of very preterm infants with late-onset bacterial sepsis， the relative risk （OR） values were 2.787， 4.243， 3.033 and 2.174， respectively. ConclusionThe gram-positive bacteria are the main pathogens of late-onset bacterial sepsis in very preterm infants. Long term（≥7 d）use of antibiotics， invasive mechanical ventilation， indwelling central venous catheter（≥7 d）and vaginal delivery are high risk factors of very preterm infants with late-onset bacterial sepsis. The incidence of late-onset bacterial sepsis in very preterm infants can be reduced by strengthening perinatal management， shortening the time of antibiotic application and reducing invasive operations.

Isolated polyhydramnios in the third trimester or polyhydramnios secondary to late-onset gestational diabetes: is it worth distinguishing?

SUMMARY OBJECTIVE: The aim of this study was to compare pregnancy outcomes of patients with polyhydramnios due to late-onset gestational diabetes mellitus and patients with isolated polyhydramnios. METHODS: Of the women who fully participated in prenatal examinations at Etlik Lady Zübeyde Hospital between January 1, 2018, and December 31, 2019, women with polyhydramnios of nonfetal-placental origin manifesting in the third trimester were retrospectively reviewed. Women with normal 75-g oral glucose tolerance test results between 24 and 28 weeks gestation who met the inclusion criteria were enrolled in the study and divided into two groups based on the results of rescreening with the 75-g oral glucose tolerance test for polyhydramnios in the third trimester: women with isolated polyhydramnios (group 1) and women with late-onset polyhydramnios due to gestational diabetes mellitus (group 2). RESULTS: There were a total of 295 participants, of whom 35 (11.8%) were diagnosed with polyhydramnios due to late-onset gestational diabetes mellitus. There were no differences in the main outcomes. Birthweight and gestational age at birth were identified as independent risk factors for predicting composite maternal outcome {[odds ratio (OR)=1.273, 95% confidence interval (CI) 1.063-1.524, p=0.009]} and composite neonatal outcome (OR=0.606, CI 0.494-0.744, p<0.001), respectively. CONCLUSION: Polyhydramnios in late pregnancy without evidence of pregnancy-related causes leading to polyhydramnios may be a sign of late-onset gestational diabetes mellitus in women with a normal prior oral glucose tolerance test. As pregnancy outcomes and management were indifferent, it does not seem necessary or useful to diagnose whether or not late-onset gestational diabetes mellitus is present.

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)

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.

Expression and Clinical Significance of NGF and Syncytin - 1 in Pregnant Women with Severe Preeclampsia / 医学研究杂志

Objective To study the expression levels and clinical significance of nerve growth factor(NGF)and Syncytin-1 in ser-um and placental tissues of pregnant women with severe preeclampsia(SPE).Methods A total of 90 pregnant women who underwent ce-sarean delivery in the Department of Obstetrics,the Affiliated Hospital of Xuzhou Medical University in December 2021 to June 2022 were selected,and they were divided into 30 cases of early-onset SPE(early-onset group),30 cases of late-onset SPE(late-onset group),and 30 cases of normal women in the same period(control group).The maternal blood and placental tissues of the three groups were collected,and the expression levels of NGF and Syncytin-1 in each group were detected by enzyme-linked immunosorbent assay(ELISA)and immunohistochemical(IHC)staining,and their clinical significance was analyzed.Results The results of the ELISA showed that compared with healthy pregnant women in the third trimester,the expression of NGF and Syncytin-1 in the serum of pregnant women with SPE was reduced,and the early-onset group was lower than those in the late-onset group(P<0.05).The results of IHC staining showed that compared with healthy pregnant women in the third trimester,the expression levels of NGF and Syncytin-1 in pla-cental tissues were reduced in pregnant women with SPE,early-onset group was lower than those in the late-onset group(P<0.05).Conclusion The expression of NGF and Syncytin-1 in serum and placental tissues of the three groups of pregnant women was succes-sively reduced,and the expression was successively reduced in normal pregnant women,late-onset SPE and early-onset SPE,which may be involved in the occurrence and development of SPE by affecting the normal development of the placenta.

Clinical characteristics and comprehensive rehabilitation of late onset methylmalonic acidemia / 中国康复医学杂志

Objective:To investigate the clinical characteristics and the effectiveness of comprehensive rehabilitation thera-py in patients with late-onset methylmalonic acidemia(MMA). Method:A retrospective analysis was conducted on clinical data of 8 patients with late-onset MMA,including the main symptoms,physical signs,auxiliary examinations,and comprehensive rehabilitation therapy.Compre-hensive rehabilitation therapy consisted of medication and rehabilitation interventions.Medication included,meth-ylcobalamin,betaine,and L-carnitine,while rehabilitation interventions focused on lower limb muscle strength training,balance training,and gait training.Manual muscle testing,Holden walking function classification,and SF-36 quality of life scores were collected from 6 patients before and after comprehensive rehabilitation therapy,and the Wilcoxon signed-rank test was used for pre-and post-treatment analysis. Result:Among the 8 patients,1 was asymptomatic,while the remaining 7 exhibited initial symptoms such as neuropsychiatric abnormality including dull reaction,memory loss,and mental apathy,as well as motor impair-ments including unstable gait.Multiple systemic impairments such as joint pain,anemia,and thrombosis were also observed.The most prominent finding on cranial MRI in 6 patients was cerebral atrophy,while l patient showed abnormal signal in the cerebellum on cranial MRI.The two most common mutations in the MMACHC gene were c.482G＞A and c.394C＞T.After 12 weeks of treatment,the patients exhibited disappear-ance of psychiatric symptoms,improvement in lower limb muscle strength,Holden walking function classifica-tion,and SF-36 scores,with statistically significant differences(P＜0.05). Conclusion:Late-onset MMA demonstrates high clinical heterogeneity.For patients presenting with motor im-pairments and psychiatric abnormalities,the possibility of this metabolic disorder should be considered.Compre-hensive rehabilitation therapy can significantly ameliorate psychiatric and behavior symptoms,muscle strength,walking function,and health-related quality of life in late-onset MMA patients.

TITE(e)-U-Keyboard:a Two-stage Phase Ⅰ/Ⅱ Design / 中国卫生统计

Objective Aiming at the problem of delayed therapeutic effect of tumor targeting agents and cellular immunotherapy,an innovative TITE(e)-U-Keyboard design is established based on the framework of phaseⅠ/Ⅱclinical trial design.Methods Approximated binomial likelihood method was used to incorporate the unobserved efficacy outcome information and construct approximated distribution to assist decision making.TITE(e)-U-Keyboard was compared with theⅠ/Ⅱ trial design method(U-BOIN、BOIN12)from multiple perspectives.Results Simulation results show that the accuracy of OBD selection and the number of patients allocated at optimal dose of the three methods were similar,but TITE(e)-U-Keyboard requires the shortest trial duration.Sensitivity analysis shows that the effectiveness evaluation window has an effect on the TITE(e)-U-Keyboard duration,which increases with the increase of effectiveness evaluation window.Conclusion TITE(e)-U-Keyboard significantly reduces the trial duration while maintaining good simulation performance and it can address the problem of delayed treatment effects in phase Ⅰ/Ⅱ clinical trials,thus accelerating the clinical trial process.

Late-onset cblC-type methylmalonic aciduria with homocysteinemia：A case report and literature review / 中风与神经疾病杂志

@#Objective To investigate the clinical characteristics and gene mutations of late-onset methylmalonic aciduria with homocysteinemia. Methods We retrospectively analyzed the clinical data and genetic test result of one patient with late-onset cblC-type methylmalonic aciduria with homocysteinemia arising from MMACHC gene mutation. Relevant literature was reviewed. Results This male patient initially presented with numbness in both feet, and gradually developed stiffness and weakness in both lower limbs, with nonspecific mental and behavioral symptoms before onset. Gene testing detected a missense mutation, c.482G>A（p.Arg161Gln） in exon 4 of the MMACHC gene. It was a homozygous mutation, which was different from compound heterozygous mutations of c.482G>A reported in previous literature. Conclusion Methylmalonic aciduria with homocysteinemia is clinically heterogeneous, with a high possibility of a missed diagnosis or misdiagnosis. The diagnosis should be considered in the presence of mental and behavioral abnormities of unknown cause. Gene detection is an important basis for the diagnosis and typing of the disease.

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.

Clinical characteristics and influencing factors of onset age in inpatients with early- and late-onset obsessive-compulsive disorder inpatients / 四川精神卫生

BackgroundThe obsessive-compulsive disorder （OCD） features complexity in etiological factors and high heterogeneity in clinical manifestations. OCD patients with different ages of onset vary in clinical symptoms and etiology. However， current studies on inpatients with early- and late-onset OCD are limited. ObjectiveTo explore the differences in clinical characteristics between early- and late-onset OCD inpatients as well as the factors affecting the onset age of OCD， so as to provide references for early screening and treatment of OCD patients. MethodsThis study was based on collected medical records of 540 patients with OCD who received inpatient treatments at the Affiliated Brain Hospital of Nanjing Medical University between March 2012 and March 2023. Patients with onset age above 18 were placed into early-onset group （n=310） and the others into late-onset group （n=230）. Then differences in demographic data and clinical symptoms between two groups of patients were compared. Binary logistic regression was used to analyze the factors that affect the onset age of OCD. ResultsObserving the demographic data， there were significant differences between the two groups in the results in gender， marital status， family history of mental illness， ratio of comorbidities with other mental illnesses， occupational composition， education level and types of obsessive-compulsive symptoms （χ2=22.302、170.556， 9.224， 13.624， 242.277， 59.791， 7.231， P<0.05 or 0.01）. Also， the results in ages of onset and hospitalization between two groups were significantly different （Z=-19.915， 16.831， P<0.01）. In terms of clinical symptoms， the early onset group had a higher proportion of symptoms including obsessive thinking （χ2=11.998， P<0.05）， ordering （χ2=7.731， P<0.05） and rituals （χ2=7.714， P<0.05）， while the proportion of obsessive checking （χ2=8.204， P<0.05） and washing （χ2=7.506， P<0.05） symptoms were relatively low. In terms of risk factors， there were several independent risk factors that influence the onset age of OCD inpatients， including comorbid neurodevelopmental disorder， comorbid affective disorder， family history of schizophrenia and family history of affective disorder （OR=19.587， 1.830， 3.065， 4.431， P<0.05）. Among them， comorbid neurodevelopmental disorder was the core influencing factor， and female gender was a protective factor for early-onset patients （OR=0.417， P<0.01）. ConclusionThere are differences in demographic data and clinical symptom characteristics between early- and late-onset OCD inpatients， and comorbid neurodevelopmental disorder plays as a core risk factor affecting the onset age of OCD inpatients. ［Funded by Jiangsu Province Key Research and Development Plan for Social Development Special Project（number， BE2021616） ； Jiangsu Province Social Development General Project （number， BE2022678）； Key Project of Nanjing Medical Science and Technology Development Fund （number， ZKX20029）］

Application of probiotics in neonates with late-onset sepsis / 中国小儿急救医学

The intestinal is the main and most important part of human flora settlement.The factors affecting the composition and diversity of intestinal flora in early life mainly include gestational age, delivery mode, feeding mode, antibiotic exposure, etc.The occurrence of neonatal late-onset sepsis(LOS)is associated with intestinal flora imbalance.The use of probiotics to regulate intestinal flora can reduce the incidence and mortality of LOS, which is helpful for treatment and prevention of LOS.

Clinical, imaging, muscle pathological and gene mutational features of patients with late-onset mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes / 中华神经医学杂志

Objective:To summarize the clinical, imaging, muscle pathological and gene mutational features of patients with late-onset mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS).Methods:Three patients with late-onset MELAS, admitted to Department of Neurology, Jiaozuo People's Hospital Affiliated of Xinxiang Medical University from January 1997 to December 2021 were chosen; all patients were screened for mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) mutations by second-generation gene sequencing. The clinical, imaging, muscle pathological and gene mutational features of patients with late-onset MELAS were analyzed retrospectively.Results:The main clinical manifestations of these late-onset MELAS patients included stroke-like attacks, headache, hearing and vision loss, cognitive decline and mental disorder. The muscle tension and muscle strength of both upper extremities in these 3 patients were normal. Increased muscle tension and active tendon reflexes, and positive pathological signs in both lower extremities were noted in 2 patients. Head MRI showed abnormal long T1 and long T2 signals in temporal occipital parietal cortex and subcortex in 3 patients, and CT showed calcification in bilateral globus pallidus in 1 patient. Ragged red fibers (RRF) and ragged blue fibers (RBF) were found in the muscle biopsies of 3 patients, and cytochrome oxidase (COX)-negative muscle fibers were found in 2 patients. MT-TL1 gene m.3243A>G mutation was detected in all 3 patients by genetic testing, among which mutation in the blood of 2 patients was 15% and 17%, respectively, and mutation in the muscle tissues of 1 patient was 73%. Conclusion:Muscle pathology indicates high RRF percentage in patients with late-onset MELAS; and m.3243A>G spot mutation is the most common mutation type in late-onset MELAS, and m.3243A>G mutation ratio in muscle tissues is obviously higher than that in blood.

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.

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.

Device-associated infections in neonatal care units in a middle-income country, 2016-2018

Abstract Objective: Describe the device-associated infections in the NICUs in Cali - Colombia, a middle-income country, between August 2016 to December 2018. Methods: Observational cross-sectional study evaluating reports of device-associated infections in 10 NICUs in Cali, Colombia, between August 2016 and December 2018. Socio-demographic and microbiological data were obtained from the National Public Health surveillance system, through a specialized notification sheet. The relationship of device-associated infections with several outcomes including birth weight, microorganisms, and mortality was evaluated using OR Cl95%, using the logistic regression model. Data processing was performed using the statistical program STATA 16. Results: 226 device-associated infections were reported. The rate of infection with central line-associated bloodstream infections was 2.62 per 1000 days of device use and 2.32 per 1000 days for ventilator-associated pneumonia. This was higher in neonates under 1000 g; 4.59 and 4.10, respectively. 43.4% of the infections were due to gram-negative bacteria and 42.3% were due to gram-positive bacteria. Time from hospitalization to diagnosis of all device-associated infections had a median of 14 days. When compared by weight, infants with a weight lower than 1000 g had a greater chance of death (OR 3.61; 95% CI 1.53-8.49, p = 0.03). Infection by gram-negative bacteria was associated with a greater chance of dying (OR 3.06 CI 95 1.33-7.06, p = 0.008). Conclusions: These results highlight the need to maintain epidemiological surveillance processes in neonatal intensive care units, especially when medical devices are used.

Comparison of clinical features, disease activity, treatment and outcomes between late-onset and early-onset patients with systemic lupus erythematosus. A sex- and year at diagnosis-matched controlled study

Abstract Background Several studies have compared the clinical features and outcomes of late- and early-onset systemic lupus erythematosus (SLE) patients. However, these previous studies were uncontrolled. The current study aimed to compare late- and early-onset SLE patients while controlling for sex and year at diagnosis (± 1 year). Methods The medical records of SLE patients in a lupus cohort from January 1994 to June 2020 were reviewed. Late-onset patients were identified as those with an age at diagnosis ≥ 50 years. The early-onset patients (age at diagnosis < 50 years) were matched by sex and year at diagnosis with the late-onset patients at a ratio of 2:1. Clinical manifestations, disease activity (mSLEDAI-2K), organ damage scores, treatment, and mortality were compared between the two groups. Results The study comprised 62 and 124 late- and early-onset patients, respectively, with a mean follow-up duration of 5 years. At disease onset, when comparing the early-onset patients with the late-onset patients, the latter group had a higher prevalence rate of serositis (37.0% vs. 14.5%, p < 0.001) and hemolytic anemia (50.0% vs. 33.9%, p = 0.034) but lower prevalence rate of malar rash (14.5% vs. 37.1%, p = 0.001), arthritis (41.9% vs. 62.1%, p = 0.009), leukopenia (32.3% vs. 50.0%, p = 0.022) and lymphopenia (50.0% vs. 66.1%, p = 0.034). The groups had similar SLE disease activity (7.41 vs. 7.50), but the late-onset group had higher organ damage scores (0.37 vs. 0.02, p < 0.001). The rates of treatment with corticosteroids, antimalarial drugs, or immunosuppressive drugs were not different. At their last visit, the late-onset patients still had the same pattern of clinically significant differences except for arthritis; additionally, the late-onset group had a lower rate of nephritis (53.2% vs. 74.2%, p = 0.008). They also had a lower level of disease activity (0.41 vs. 0.57, p = 0.006) and received fewer antimalarials (67.7% vs. 85.5%, p = 0.023) and immunosuppressive drugs (61.3% vs. 78.2%, p = 0.044), but they had higher organ damage scores (1.37 vs. 0.47, p < 0.001) and higher mortality rates/100-person year (3.2 vs. 1.1, p = 0.015). After adjusting for disease duration and baseline clinical variables, the late-onset patients only had lower rate of nephritis (p = 0.002), but still received fewer immunosuppressive drugs (p = 0.005) and had a higher mortality rate (p = 0.037). Conclusions In this sex- and year at diagnosis-matched controlled study, after adjusting for disease duration and baseline clinical variables, the late-onset SLE patients had less renal involvement and received less aggressive treatment, but had a higher mortality rate than the early-onset patients.