The role of genetic factors in pediatric myelodysplastic syndromes with different outcomes.

BACKGROUND: Pediatric myelodysplastic syndromes (MDS) are rare disorders with an unrevealed pathogenesis. Our aim is to explore the role of genetic factors in the pathogenesis of MDS in children with different outcomes and to discover the correlation between genetic features and clinical outcomes as well as disease characteristics. METHODS: We conducted an analysis of archived genetic data from 26 patients diagnosed with pediatric MDS at our institution between 2015 and 2021, examining the association between different genetic characteristics and clinical manifestations as well as prognosis. Additionally, We presented three cases with distinct genetic background and outcomes as examples to elaborate the role of genetic factors in pediatric MDS with different prognoses. RESULTS: Genetic variations were detected in 13 out of the 26 patients, including 8 patients with co-occurrence of somatic and germline mutations (CSGMs) and 5 patients with somatic mutations alone. Our analysis revealed that advanced MDS (4/8, 50% vs. 1/5, 20% and 4/11, 36.4%), PD (3/8, 37.5% vs. 1/5, 20% and 1/11 9.1%), and TD (6/8, 75% vs. 2/5, 40% and 2/11, 18.2%) were more common in patients with CSGMs than those with somatic mutations alone or without any mutations. We also found out in our study that 8 patients with CSGMs had evidently different clinical outcomes, and we presented 3 of them as examples for elaboration. Case 1 with germline and somatic mutations of unknown significance had a relatively slow disease course and a good prognosis. Case 2 with compound heterozygous germline SBDS variants and somatic mutations like del20q had a stable disease course and a reversed outcome. Case 3 with a germline GATA2 variant and somatic mutations including - 7 had a rapidly progressive disease course and a worst prognosis. CONCLUSION: Our findings indicate that genetic background of pediatric MDS is closely linked with disease characteristics as well as outcomes and that CSGMs may lead to disease progression. It should be emphasized that the interaction between certain germline variants and somatic mutations, such as SBDS and del20q, may result in hematopoietic stem cell adaptation (improved hematopoiesis) and reversed clinical outcomes, which can facilitate the development of targeted therapy.

Prevalence of eosinophilic, atopic, and overlap phenotypes among patients with severe asthma in Saudi Arabia: a cross-sectional study.

BACKGROUND: Eosinophilia is a significant factor in asthma severity; however, the prevalence of severe eosinophilic asthma in Saudi Arabia is largely unknown. We aimed to determine the prevalence of the eosinophilic (defined in this study as ≥ 300 cells/mm3 in blood), atopic (atopic phenotype 1, defined in this study as > 100 IU/mL total serum IgE; atopic phenotype 2, defined in this study as > 150 IU/mL), and overlap phenotypes among patients with severe asthma in Saudi Arabia. METHODS: A cross-sectional study was conducted in centers specialized in severe asthma management. Patients aged ≥ 12 years with severe asthma were enrolled. Study patients responded to the Global Initiative for Asthma 2018 assessment of asthma control questionnaire and provided study investigators with current information related to the study objectives. Additional medical record data and a blood sample for total serum IgE and complete blood count were collected. RESULTS: A total of 101 patients were enrolled; 83% were female and the mean (standard deviation) age was 48.7 (13.2) years. Forty-five (45%) patients had the eosinophilic phenotype, 50 (50%) had atopic phenotype 1, and 25 (25%) had phenotypic overlap (eosinophilic and atopic 1). Forty-one (41%) patients had atopic phenotype 2 and 23 (23%) had phenotypic overlap (eosinophilic and atopic 2). Asthma control and oral corticosteroid use patterns were similar and there were no significant differences in number of asthma exacerbations across phenotypes. CONCLUSIONS: In Saudi Arabia, 45% of patients with severe asthma had the eosinophilic phenotype, which is most likely an underestimation as no clinical features of eosinophilia were taken into account in the definition of eosinophilia. Approximately half of them had phenotypic overlap with the atopic phenotype. Trial registration NCT03931954; ClinicalTrials.gov, April 30, 2019.

The relation of blood cell division control protein 42 level with disease risk, comorbidity, tumor features/markers, and prognosis in colorectal cancer patients.

BACKGROUND: Cell division control protein 42 (CDC42) is involved in colorectal cancer (CRC) progression by modulating CD8+ T cell activation, immune escape, and direct oncogenetic biological processes. This study aimed to explore the correlation of blood CDC42 with disease risk, comorbidities, disease features, tumor markers, and prognosis among CRC patients. METHODS: CDC42 in peripheral blood mononuclear cells was detected by reverse transcription-quantitative polymerase chain reaction from 250 resectable CRC patients and 50 healthy controls (HCs). CDC42 was divided by quartiles, as well as high and low expressions in CRC patients for correlation and survival analysis. RESULTS: CDC42 was elevated in CRC patients vs. HCs (p < 0.001), which had a good ability to distinguish CRC patients from HCs with the area under the curve (95% confidence interval) of 0.889 (0.841-0.937). In CRC patients, CDC42 was not associated with demographics or comorbidities (all p > 0.05), while its higher quartile was linked to increased T stage (p < 0.001), N stage (p = 0.009), TNM stage (p < 0.001), abnormal carcinoembryonic antigen (p = 0.043), and adjuvant chemotherapy administration (p = 0.002). Higher CDC42 quartile (p = 0.002) and CDC42 high (vs. low) (p < 0.001) were related to worse disease-free survival (DFS); meanwhile, elevated CDC42 quartile (p = 0.002) and CDC42 high (vs. low) (p = 0.001) were also linked to poor overall survival (OS). Multivariate Cox's regression analysis presented that CDC42 quartile 3 and 4 (vs. quartile 1) independently predicted declined DFS and OS (all p < 0.05). CONCLUSION: Circulating CDC42 relates to higher disease risk, T, N, and TNM stage, abnormal tumor marker, and poor prognosis among CRC patients.

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 in rheumatoid arthritis: Longitudinal change after treatment and correlation with treatment efficacy of tumor necrosis factor inhibitors.

BACKGROUND: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) correlates with treatment outcomes in inflammatory bowel disease and rheumatoid arthritis (RA). This study aimed to further evaluate the MALT1 longitudinal change and its relationship with tumor necrosis factor inhibitors (TNFi) response in RA patients. METHODS: Seventy-one RA patients receiving TNFi [etanercept (n = 42) or adalimumab (n = 29)] were enrolled. MALT1 was detected by RT-qPCR in peripheral blood samples of RA patients before treatment (W0), at week (W)4, W12, and W24 after treatment. RA patients were divided into response/non-response, remission/non-remission patients according to their treatment outcome at W24. Meanwhile, MALT1 was also detected by RT-qPCR in 30 osteoarthritis patients and 30 healthy controls (HCs). RESULTS: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 was elevated in RA patients compared with HCs (Z=-6.392, p < 0.001) and osteoarthritis patients (Z = -5.020, p < 0.001). In RA patients, MALT1 was positively correlated with C-reactive protein (rs  = 0.347, p = 0.003), but not other clinical characteristics, treatment history, or current TNFi category. Meanwhile, MALT1 decreased from W0 to W12 in total RA patients (x2  = 86.455, p < 0.001), etanercept subgroup (x2  = 46.636, p < 0.001), and adalimumab subgroup (x2  = 41.291, p < 0.001). Moreover, MALT1 at W24 (p = 0.012) was decreased in response patients compared with non-response patients; MALT1 at W12 (p = 0.027) and W24 (p = 0.010) were reduced in remission patients than non-remission patients. In etanercept subgroup, MALT1 at W24 (p = 0.013) was decreased in response patients compared with non-response patients. In adalimumab subgroup, MALT1 at W24 (p = 0.015) was lower in remission patients than non-remission patients. CONCLUSION: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 reduction after treatment is associated with response and remission to TNFi in RA patients.

[Analysis of animal models of heart failure based on characteristics of clinical symptoms of traditional Chinese and Western medicine].

The incidence of heart failure has increased year by year, with a negative impact on quality of life and life expectancy of patients. Reproduction of animal models that meet the characteristics of clinical symptoms is a prerequisite for conducting experimental studies relating to heart failure. Based on the characteristics of clinical symptoms of heart failure in traditional Chinese medicine(TCM) and Western medicine, the existing common animal models of heart failure were explored, and the clinical anastomosis of the existing animal models was analyzed based on the clinical diagnostic criteria of heart failure in TCM and Western medicine. After analysis and comparison, it can be seen that the existing modeling methods are mostly single-factor animal models, with certain gaps between the characteristics of clinical multi-factors and interactions that jointly lead to heart failure, and the modeling methods were mostly guided by Western medicine, with a lack of TCM pathogenic factors in the model process, which is different from the clinical diagnostic criteria of Chinese and Western medicine for heart failure. In terms of syndrome differentiation, heart failure is classified into heart and lung Qi deficiency syndrome, Qi and Yin deficiency syndrome, heart and kidney Yang deficiency syndrome, Qi deficiency and blood stasis syndrome, Yang deficiency and water flooding syndrome, phlegm-drinking obstructive lung syndrome, Yin and yang exhausted syndrome. The existing animal models mostly confused them, with no effective and recognized method for modeling at present. There are major limitations in studies of Chinese medicine. Therefore, based on clinical characteristics of heart failure in Chinese and Western medicine, this article analyzed the existing animal models, defined their advantages and disadvantages and application prospects, and then suggested further improving the corresponding animal models of heart failure and standardizing the model evaluation, so as to improve the clinical coincidence between animal models and Chinese and Western medicine, make heart failure animal models better serve scientific studies, and promote relevant mechanism studies, pathological change studies and drug screening.

Clinical characteristics of patients with 2019 coronavirus disease in a non-Wuhan area of Hubei Province, China: a retrospective study.

BACKGROUND: Since December 2019, the 2019 coronavirus disease (COVID-19) has expanded to cause a worldwide outbreak that more than 600,000 people infected and tens of thousands died. To date, the clinical characteristics of COVID-19 patients in the non-Wuhan areas of Hubei Province in China have not been described. METHODS: We retrospectively analyzed the clinical characteristics and treatment progress of 91 patients diagnosed with COVID-19 in Jingzhou Central Hospital. RESULTS: Of the 91 patients diagnosed with COVID-19, 30 cases (33.0%) were severe and two patients (2.2%) died. The severe disease group tended to be older (50.5 vs. 42.0 years; p = 0.049) and have more chronic disease (40% vs. 14.8%; p = 0.009) relative to mild disease group. Only 73.6% of the patients were quantitative polymerase chain reaction (qPCR)-positive on their first tests, while typical chest computed tomography images were obtained for each patient. The most common complaints were cough (n = 75; 82.4%), fever (n = 59; 64.8%), fatigue (n = 35; 38.5%), and diarrhea (n = 14; 15.4%). Non-respiratory injury was identified by elevated levels of aspartate aminotransferase (n = 18; 19.8%), creatinine (n = 5; 5.5%), and creatine kinase (n = 14; 15.4%) in laboratory tests. Twenty-eight cases (30.8%) suffered non-respiratory injury, including 50% of the critically ill patients and 21.3% of the mild patients. CONCLUSIONS: Overall, the mortality rate of patients in Jingzhou was lower than that of Wuhan. Importantly, we found liver, kidney, digestive tract, and heart injuries in COVID-19 cases besides respiratory problems. Combining chest computed tomography images with the qPCR analysis of throat swab samples can improve the accuracy of COVID-19 diagnosis.

[Analysis of clinical application characteristics of Xingnaojing Injection in treating cerebral hemorrhage in real world].

To explore the population characteristics and clinical application characteristics of patients with cerebral hemorrhage treated with Xingnaojing Injection in real world. The model was established by Apriori algorithm, and the general information and medication information of 8 369 patients with cerebral hemorrhage treated with Xingnaojing Injection were analyzed by using Clementine 12.0 in the databases of information systems of 33 class Ⅲ grade A hospitals in China. The results showed that among the 8 369 patients with cerebral hemorrhage treated with Xingnaojing Injection, the median age was 59 years old. And the male to female ratio was about 1.74∶1. Most of them did manual labor(31.26%), and were hospitalized in winter(27.46%), especially during the Cold Dew(5.1%). The majority of the patients were in a stable condition(50.94%), and preferred neurosurgery department(48.82%). 29.03% of patients were hospitalized for 15-28 days, and 42.47% of patients spent 10 000-50 000 Yuan of hospitalization expenses. The single dose of Xingnaojing Injection was 10-20 mL at most(46.03%). And the course of medication was mostly 3 days or less(68.60%). Lidocain was the most frequently used Western medicine in drug combination(5.05%), and Huayu Tongmai Ji was the most frequently used traditional Chinese medicine in drug combination(10.73%). The most frequently used one type of traditional Chinese medicine combined with one type of Western medicine was Huayu Tongmai Ji + Dexamethasone(8.08%). The most frequently used two Western medicines in drug combination were Omeprazole + Dexamethasone(5.07%). Prilosec + Dexamethasone + Lidocaine(3.35%) were three Western drugs with the most frequent combination. When the dosage was 10-20 mL and the number of days of treatment was > 15 days, the largest number of the patients was cured and improved(44.78%, 45.85%). The results showed that cerebral hemorrhage patients treated with Xingnaojing Injection were mostly middle-aged and elderly people, with more males than females. Brain hemorrhage often occurred in winter and spring. Xingnaojing Injectiont was often combined with glucocorticoids, proton pump inhibitors and cardiovascular drugs to prevent cerebral hemorrhage complications. The clinical medication met the guidelines for the treatment of cerebral hemorrhage. Some patients had over-treatment use, which can provide a reference for clinicians in treating cerebral hemorrhage.

Patient and disease characteristics of type-2 diabetes patients with or without chronic kidney disease: an analysis of the German DPV and DIVE databases.

BACKGROUND: To evaluate the characteristics of type 2 diabetes (T2DM) patients with or without chronic kidney disease (CKD) in Germany. METHODS: Using combined DPV/DIVE registry data, the analysis included patients with T2DM at least ≥ 18 years old who had an estimated glomerular filtration rate (eGFR) value available. CKD was defined as an eGFR < 60 mL/min/1.73 m2 or eGFR ≥ 60 mL/min/1.73 m2 and albuminuria (≥ 30 mg/g). Median values of the most recent treatment year per patient are reported. RESULTS: Among 343,675 patients with T2DM 171,930 had CKD. Patients with CKD had a median eGFR of 48.9 mL/min/1.73 m2 and 51.2% had a urinary albumin level ≥ 30 mg/g. They were older, had a longer diabetes duration and a higher proportion was females compared to patients without CKD (all p < 0.001). More than half of CKD patients (53.5%) were receiving long-acting insulin-based therapy versus around 39.1% of those without (p < 0.001). CKD patients also had a higher rate of hypertension (79.4% vs 72.0%; p < 0.001). The most common antihypertensive drugs among CKD patients were renin-angiotensin-aldosteron system inhibitors (angiotensin converting enzyme inhibitors 33.8%, angiotensin receptor blockers 14.2%) and diuretics (40.2%). CKD patients had a higher rate of dyslipidemia (88.4% vs 86.3%) with higher triglyceride levels (157.9 vs 151.0 mg/dL) and lower HDL-C levels (men: 40.0 vs 42.0 mg/dL; women: 46.4 vs 50.0 mg/dL) (all p < 0.001) and a higher rate of hyperkalemia (> 5.5 mmol/L: 3.7% vs. 1.0%). Comorbidities were more common among CKD patients (p < 0.001). CONCLUSION: The results illustrate the prevalence and morbidity burden associated with diabetic kidney disease in patients with T2DM in Germany. The data call for more attention to the presence of chronic kidney disease in patients with diabetes, should trigger intensified risk factor control up and beyond the control of blood glucose and HbA1c in these patients. They may also serve as a trigger for future investigations into this patient population asking for new treatment options to be developed.

Demographic and Clinical Characteristics of COPD Patients at Different Blood Eosinophil Levels in the UK Clinical Practice Research Datalink.

Blood eosinophil count may be a useful biomarker for predicting response to inhaled corticosteroids and exacerbation risk in chronic obstructive pulmonary disease (COPD) patients. The optimal cut point for categorizing blood eosinophil counts in these contexts remains unclear. We aimed to determine the distribution of blood eosinophil count in COPD patients and matched non-COPD controls, and to describe demographic and clinical characteristics at different cut points. We identified COPD patients within the UK Clinical Practice Research Database aged ≥40 years with a FEV1/FVC <0.7, and ≥1 blood eosinophil count recorded during stable disease between January 1, 2010 and December 31, 2012. COPD patients were matched on age, sex, and smoking status to non-COPD controls. Using all blood eosinophil counts recorded during a 12-month period, COPD patients were categorized as "always above," "fluctuating above and below," and "never above" cut points of 100, 150, and 300 cells/µL. The geometric mean blood eosinophil count was statistically significantly higher in COPD patients versus matched controls (196.6 cells/µL vs. 182.1 cells/µL; mean difference 8%, 95% CI: 6.8, 9.2), and in COPD patients with versus without a history of asthma (205.0 cells/µL vs. 192.2 cells/µL; mean difference 6.7%, 95%, CI: 4.9, 8.5). About half of COPD patients had all blood eosinophil counts above 150 cells/µL; this persistent higher eosinophil phenotype was associated with being male, higher body mass index, and history of asthma. In conclusion, COPD patients demonstrated higher blood eosinophil count than non-COPD controls, although there was substantial overlap in the distributions. COPD patients with a history of asthma had significantly higher blood eosinophil count versus those without.

Familial aggregation of Parkinson's disease may affect progression of motor symptoms and dementia.

BACKGROUND: Familial aggregation has been described in PD of both early and late onset, but has not been studied in a true population-based sample. Moreover, little is known about its association with disease progression and endophenotypes. OBJECTIVES: The objectives of this work were to determine familial aggregation of idiopathic PD in a population-based cohort and study the association with clinical endophenotypes and disease progression. METHODS: We examined family history data from the Norwegian ParkWest study, a well-characterized, population-based cohort of incident PD patients and age-matched healthy controls. Family data were collected at baseline with a simplified questionnaire (192 cases and 193 controls) and after 3 years of longitudinal follow-up using an extended questionnaire (172 cases and 171 controls). RESULTS: Compared to the controls, the PD patients had an increased relative risk of having a first-degree relative with PD when using the extended questionnaire (relative risk = 1.988; P = 0.036), but not when using the simplified questionnaire (relative risk = 1.453; P = 0.224). There was no significant difference in age of onset or motor subtype (P = 0.801). However, cases with a family history of PD had reduced progression over 7 years as measured by UPDRS II (P = 0.008) and smaller rate of decrease of MMSE (P = 0.046). CONCLUSIONS: Our findings confirm familial aggregation in a population-based cohort of idiopathic PD. Moreover, we show that positive family history of PD in patients is associated with a slower progression of PD symptoms and cognitive decline. © 2016 International Parkinson and Movement Disorder Society.

Correlates of objectively measured sedentary behavior in breast cancer survivors.

BACKGROUND: Emerging evidence indicates increased sedentary behavior is associated with poorer health outcomes and quality of life among cancer survivors. However, very little is known about which factors are associated with increased sedentary behavior. The purpose of the present study was to examine potential correlates of sedentary behavior among breast cancer survivors. METHODS: We used hierarchical general linear modeling to examine the associations between demographic, disease-specific, and psychosocial factors at baseline and accelerometer-estimated daily proportion of time spent sedentary at 6 months in breast cancer survivors [n = 342; M age = 56.7 (SD = 9.4)]. All models adjusted for objectively measured moderate and vigorous intensity physical activity and sedentary behavior at baseline. RESULTS: The final model including all baseline potential predictor variables and physical activity and sedentary behavior explained 49.8 % of the variance in the proportion of daily time spent sedentary at 6 months. The following factors were significantly (p < 0.05) associated with increased sedentary behavior among breast cancer survivors: higher number of comorbidities, more advanced disease stage, and increased fatigue severity. Additionally, being treated with surgery and chemotherapy was significantly related to a lower proportion of time spent sedentary compared to women who had received surgery alone. CONCLUSIONS: This study provides preliminary insight into factors associated with sedentary behavior in breast cancer survivors. Future research is warranted to understand the potential demographic, disease-specific, psychosocial correlates of sedentary behavior to determine which correlates are potential mechanisms of behavior change and intervention targets.

Eighty-six cases of clinical characteristics and outcomes of systemic lupus erythematosus-associated macrophage activation syndrome: A meta-analysis study.

OBJECTIVE: To improve our understanding of systemic lupus erythematosus (SLE)-macrophage activation syndrome (MAS). METHODS: A systematic review was performed, to retrieve all those papers on patients with SLE-MAS, in individual or aggregated form. The data in each of these medical records were extracted and analyzed to identify the characteristics of SLE-MAS. RESULTS: A total of 86 SLE-MAS patients were included (25 males and 61 females. The mean (±standard error of the mean) age was 31.21 ± 1.694 years. MAS occurred as the initial presentation of SLE in 47 people (54.65%) and during the course of SLE in 39 (45.35%). A coinfection was reported in 23 (26.74%) patients. The mean Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score was 16.54 ± 0.9462. Overall, 10 patients (11.63%) died. The SLEDAI-2K score was higher in patients with MAS as an initial manifestation of SLE than in those where MAS occurred during the course of SLE. The proportion of patients receiving steroid pulse therapy was lower in patients with coinfections. The deceased group demonstrated lower platelet and ferritin levels. Multiple regression analysis revealed that age and thrombocytopenia were independent factors associated with poor prognosis. In receiver operating characteristic analysis, a platelet count cutoff value of ≤47 × 109/L was a predictor of poor outcome. CONCLUSIONS: SLE-MAS patients demonstrated high lupus activity, and lupus activity was especially higher in patients with MAS as an initial manifestation. Lupus activity was the predominant trigger of lupus MAS. Thrombocytopenia was an independent factor for poor prognosis.

Perception and recognition of primary and secondary emotions by children with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is a genetic disease that can lead to impaired social adaptation and functioning, thus affecting quality of life. To date, studies of these children's social cognition abilities have been scant and far from exhaustive. Therefore, the purpose of the present study was to assess the ability of children with NF1, compared with controls, to process facial expressions of emotions - not only including the usual primary emotions (happiness, anger, surprise, fear, sadness and disgust), but secondary emotions, too. To do so, the links between this ability and the characteristics of the disease (mode of transmission, visibility, and severity) were examined. A total of 38 children with NF1 aged 8-16 years 11 months (mean = 11.4, SD = 2.3) and 43 sociodemographically comparable control children performed the emotion perception and recognition tests of a social cognition battery. Results confirmed that the processing of primary and secondary emotions is impaired in children with NF1, but there were no significant links with either mode of transmission, severity, or visibility. These results encourage further comprehensive assessments of emotions in NF1, and suggest that investigations should be extended to higher level social cognition skills, such as theory of mind and moral judgments.

Exploring paediatric rheumatology care: a ten-year retrospective analysis of the patient population in Ghana.

BACKGROUND: Rheumatic diseases can seriously impact children's general health, development, and growth. However, due to a lack of resources, paediatric rheumatology is a largely underdeveloped speciality in many African nations. Children with rheumatic disorders face obstacles in accessing specialized medical care, including lack of specialists, care centres, medication access, and limited research and education to increase understanding of paediatric rheumatic disease among healthcare practitioners. This study described the disease characteristics, prevalence, and challenges faced by paediatric rheumatic disease patients receiving care at a teaching hospital in Accra, Ghana. METHODS: A retrospective record-based study was conducted among all paediatric cases presenting to the rheumatology clinic of the Korle Bu Teaching Hospital (KBTH) from January 2011 to December 2021. Data collected include clinical features, laboratory findings at disease presentation, andtherapeutic regimens prescribed per standard guidelines and experiences. RESULTS: A total of 121 cases were identified as of 2021, indicating a point prevalence of 0.0011%. The majority (73%) were females with a mean age of 13.4 ± 3.2 years. The mean duration of symptoms in months experienced by patients before being successfully referred to a rheumatologist was 18 months. There were significant differences between referred and confirmed diagnoses, especially in cases involving mixed connective tissue diseases (MCTD), systemic lupus erythematosus (SLE), and juvenile dermatomyositis (JDM), suggesting that these conditions may be under-recognised. Arthralgia and arthritis were the most common presenting symptoms. More than three-quarters (86.8%) of the cases studied were treated with steroids (oral or intravenous). In cases requiring immunosuppressive therapy, methotrexate was the most commonly prescribed in 33.9% of instances. Mortality was recorded at 8.3%, with the majority involving SLE cases. Most (95.7%) of the primary caregivers expressed positive experiences regarding care received at the adult rheumatology clinic. CONCLUSION: There were significant delays in diagnosis and diagnostic accuracy for patients with paediatric rheumatic disease (PRD). This highlights the pressing need for strengthening paediatric rheumatology services in Africa, including increasing awareness about these conditions among the public and healthcare providers to improve early diagnosis and quality of life for children with these conditions.

A 1-year analysis from a natural history study in Chinese individuals with Duchenne muscular dystrophy.

Background: Duchenne muscular dystrophy (DMD) is a disabling and life-threatening, X-linked recessive disorder caused by mutations in dystrophin. Natural history studies can inform the disease characteristics of DMD, and data from these studies can be used to plan and design clinical trials and as external controls for long-term studies. We report 12-month results from the largest natural history study of individuals with DMD in China receiving standard of care treatment. Methods: This ongoing, multicentre, prospective, single-cohort study (ClinicalTrials.gov: NCT03760029) was conducted in Chinese male participants with DMD (ambulatory aged <6 years [Group 1; n = 99]; ambulatory aged ≥6 years [Group 2; n = 177], and non-ambulatory of any age [Group 3; n = 36]. The follow-up period is ≥24 months, with some participants followed for 30 months. The primary endpoint was time to clinical milestones due to DMD disease progression, and motor, pulmonary, and cardiac function. Secondary endpoints were quality of life (QoL) assessments. Findings: Mean (standard deviation [SD]) age at screening was 3.4 (1.2), 8.6 (2.0), 12.3 (2.7) and 7.4 (3.5) years in Groups 1, 2, 3 and total respectively. Mean (SD) North Star Ambulatory Assessment (NSAA) total score at baseline was 21.2 (5.8) in Group 1, 19.5 (8.3) in Group 2 and 20.0 (7.7) in ambulatory total. Overall, the time to clinical milestones due to DMD disease progression was consistent with previous findings, in which loss of ambulation occurred at 13 years. There was a trend towards a decline over 12 months in NSAA and timed motor function from age 6 years, with the greatest reductions observed thereafter. There were no consistent trends in measures of QoL, although participants of any age generally had poorer outcomes at Month 12 versus their domain scores at baseline. Interpretation: This study improves the understanding of DMD progression according to the current standards of care in the Chinese DMD population and may inform selected endpoints and patient populations in clinical trials. Funding: Pfizer Inc.

Dupilumab improves pediatric type 2 asthma outcomes independent of patient baseline characteristics.

CLINICAL IMPLICATIONS: Dupilumab, a biological therapy that blocks the shared receptor component for interleukins-4/13, reduced exacerbations and improved lung function in children with uncontrolled moderate-to-severe type 2 asthma independent of most baseline patient and asthma characteristics.

Clinical analysis of 2790 children with retinoblastoma: a single-center experience in China.

BACKGROUND: In this study, we aimed to analyze the clinical characteristics and prognosis of children with retinoblastoma (RB) in a single center in China with a large sample collection spanning 17 years. METHODS: The clinical data of 2790 children with RB treated in Beijing Tongren Hospital from 2005 to 2021 were collected, and a retrospective analysis was conducted. RESULTS: The median age of the participants was 28.3 months. There were 3624 affected eyes, 12.4% of which were in groups A-C, 67.1% in groups D-E and 16.2% were not specified. The primary symptom observed in most cases was a white pupil, accounting for 66.5%, followed by strabismus (12.8%). The median follow-up time was 59.7 months. The enucleation rate was 71.3% (703/986) in a single left eye and 72.5% (702/968) in a single right eye. The overall survival (OS) rate was 95.8% (2444/2552) because 237 patients dropped out, and 109 died. Kaplan‒Meier survival analysis showed that the median survival time (MST) was 125.92 months [95% confidence interval (CI) = 124.83-127.01]. Cox multivariate survival analysis showed that trilateral RB (P = 0.017), metastasis site (P = 0.001), and combined distant tissue metastasis (P = 0.001) were independent prognostic factors for RB. The OS of 44 cases of familial RB was 93.2% (41/44), with an MST of 80.62 months (95% CI = 67.70-93.54). CONCLUSIONS: The timing of eye protection treatment and enucleation should be comprehensively judged to avoid worsening prognosis due to operation time delay. More importantly, the promotion and popularization of diagnosis and treatment technologies are necessary to further improve RB prognosis.

Baseline demographics and disease characteristics of patients with episodic or chronic cluster headache: data from two phase 3 randomized clinical trials in Europe and North America.

Objective: Two phase 3 galcanezumab trials were conducted in Europe and North America to analyze the reduction of weekly cluster headache (CH) attack frequency in populations with episodic and chronic CH. The current study aims to illustrate prospectively recorded baseline clinical data from these trials and to identify possible predictors of response. Methods: Patients (aged 18-65 years) met The International Classification of Headache Disorders 3rd edition-beta criteria for CH. Attacks were evaluated using an electronic headache diary for 7-day (episodic) or 14-day (chronic) eligibility assessments before patients were randomized 1:1 to monthly subcutaneous galcanezumab 300 mg or placebo. Results: Data were collected from 106 patients with episodic and 237 with chronic CH. Overall, the mean age [standard deviation] was 45.4 [11.0] years; patients were predominantly White (84.5%), male (75.8%), and European (77.6%). Patients with episodic CH reported 17.5 [10.0] attacks/week; patients with chronic CH reported 18.8 [10.2] attacks/week. The average pain severity score (range 0-4) was 2.5 [0.7] for episodic CH and 2.7 [0.7] for chronic CH. Higher attack frequency was a possible predictor of response to galcanezumab; potential negative predictors of response were greater attack severity and duration. Conclusion: This large dataset of patients with CH provides reliable systematically and prospectively collected information on disease characteristics. The analysis in episodic CH underscores potential predictors of response worth considering for future CH trial design. Clinical Trial Registration: ClinicalTrials.gov, identifiers: NCT02397473 and NCT02438826.

Clinical and radiologic differences between early onset, late onset, and very late onset adult multiple sclerosis.

BACKGROUND: Previous studies suggested possible differences in clinical and radiologic characteristics between early-onset multiple sclerosis (EOMS) and late-onset MS (LOMS). However, differences between LOMS and very late onset MS (VLOMS) are largely unknown. METHODS: We performed a retrospective review of medical records of patients diagnosed with MS between 8/1/2017 and 3/1/2022 at the comprehensive MS center of the Froedtert and Medical College of Wisconsin. We included adult patients with MS diagnosis who were 60 years or older - VLOMS, 50-59 years old at diagnosis - LOMS, or were 18-30 years old at diagnosis - EOMS and had complete imaging and clinical records. Clinical presentation and location of demyelinating lesions at the onset of diagnosis were extracted and compared using the chi-square test, p<0.05. RESULTS: A total of 246 newly diagnosed patients were identified. Of which 54 were EOMS, 29 were LOMS, and 35 were VLOMS. The sex ratio was not different between groups. EOMS had a higher percentage of patients who self-identified as black, while LOMS had a higher percentage of patients who self-identified as white. LOMS and VLOMS showed significant differences in the presence of tremors and lesion distribution at the onset. Older onset patients were more likely to present with motor symptoms, sphincter dysfunction, fatigue, and tremor. EOMS was more likely to present with cerebellum and occipital lobe lesions, and lesions were more likely to show contrast enhancement on MRI at diagnosis. CONCLUSION: Our findings revealed novel clinical and imaging characteristics differences between VLOMS and LOMS. The current classification of LOMS may benefit from revision to better align with chronological age classification for old age >60 instead of the current standard in the literature of >50 years.

Characterization of Disease Severity and Stability in NMOSD: A Global Clinical Record Review with Patient Interviews.

INTRODUCTION: We sought insights into the classification of and factors associated with relapse severity and disease stability in neuromyelitis optica spectrum disorder (NMOSD) clinical practice worldwide. METHODS: Neurologists recruited from six countries (the USA, Germany, Italy, Brazil, South Korea, and China) participated in a 30-60 minute online survey and submitted two to four clinical records for aquaporin-4-immunoglobulin G (AQP4-IgG)-seropositive adults with NMOSD, which included patient demographics, diagnosis, maintenance treatment history, relapse occurrence, and severity. Separately, patients with NMOSD receiving maintenance therapy were interviewed over the telephone about their treatment journey, as well as perceptions of relapse severity and disease stability, and their potential influence on treatment decisions. RESULTS: Clinical records for 1185 patients with AQP4-IgG-seropositive NMOSD were provided by 389 neurologists (July-August 2020); 33 patients were interviewed (October-November 2020). There was no clear consensus on how relapse severity was defined in clinical practice, with geographical variations in relapse classification also found. Neurologists tended to rely on clinical assessments when determining severity, viewing each relapse in isolation, whereas patients had a more subjective view based on the changes in their daily lives and comparisons with prior relapses. Similarly, there was a disconnect in the definition of disease stability: the complete absence of relapses was more important for patients than for neurologists. CONCLUSION: A clear consensus on how to assess relapse severity and disease stability is needed to ensure that patients receive appropriate and timely treatment. In the future, clinical measures should be combined with patient-focused assessments.