全身性強皮症

Progressive hemifacial atrophy (PHA) or Parry-Romberg syndrome is a rare, insidiously progressive disorder that typically presents in childhood and is considered part of the morphea spectrum. This longitudinal, ambispective, observational study included 8 pediatric patients (4 female) diagnosed with PHA, with a mean age at symptom onset of 4.5 ± 2 years and at diagnosis of 8.2 ± 2.9 years. All 8 patients presented superficial and deep cutaneous findings (dyspigmentation, dermal and subcutaneous atrophy, and facial asymmetry); 7 had associated extracutaneous abnormalities (maxillofacial, ophthalmological, and neurological), all received systemic immunosuppressive therapy (average of 2.2 ± 1 regimens for a mean duration of 35.2 ± 29.3 months), and 4 had subsequent fat grafting procedures. In conclusion, pediatric patients with PHA suffer an important diagnostic delay, require long-term treatment with multiple immunosuppressive drugs and surgical interventions, as well as multidisciplinary management of frequent associated extracutaneous abnormalities.

Objective: To explore the clinical characteristics and prognosis of patients with thyroid cancer complicated by connective tissue disease. Methods: A retrospective analysis was conducted on the clinical data of 70 patients with thyroid cancer complicated by connective tissue disease who were admitted to the Cancer Hospital, Chinese Academy of Medical Sciences from May 30, 2006, to April 30, 2024 and telephone follow-up was performed. Results: Among the 70 patients with thyroid cancer complicated by connective tissue disease, 68 cases (97.1%, 68/70) had papillary thyroid carcinoma, and 2 (2.9%, 2/70) had medullary thyroid carcinoma; 67 cases (95.7%, 67/70) were female. The age at diagnosis of thyroid cancer was (48.73±11.74) years, and the median interval from connective tissue disease diagnosis to thyroid cancer diagnosis was 7 years (range, 3 to 12 years). Among them, there were 29 cases (41.4%, 29/70) of rheumatoid arthritis, 24 cases (34.3%, 24/70) of Sjögren's syndrome, 12 cases (17.1%, 12/70) of systemic lupus erythematosus, 3 cases (4.3%, 3/70) of systemic sclerosis, and 2 cases (2.9%, 2/70) of dermatomyositis. The stages of thyroid cancer were stage Ⅰ in 55 cases (78.6%, 55/70), stage Ⅱ in 11 cases (15.7%, 11/70), stage Ⅲ in 1 case (1.4%, 1/70), and unknown in 3 cases (4.3%, 3/70). Multifocality was observed in 37 cases (52.9%,37/70), capsular invasion in 46 (65.7%,46/70) cases, perineural invasion in 1 (1.4%,1/70) case, and lymphovascular invasion in 3 (4.3%,3/70) cases. The median follow-up time was 73.50 months (range, 20.9 to 235.0 months). Six patients were lost to follow-up, one patient died of COVID-19 and the remaining 63 patients (98.4%, 63/64) did not experience recurrence or metastasis. Conclusions: Patients with thyroid cancer complicated by connective tissue disease are mostly female, and the predominant pathological type is papillary thyroid carcinoma. Most patients are diagnosed at an early stage. No recurrence or metastasis was observed during follow-up,and further confirmation by large-sample studies is needed.

Immune checkpoint inhibitors have transformed cancer treatment; however, resistance, on-target toxicity, and limited efficacy in autoimmune disorders have motivated next-generation immunotherapies. T cell engagers (TCEs) redirect cytotoxic T cells to kill pathogenic cells independently of MHC restriction, whereas antibody-drug conjugates (ADCs) deliver potent payloads directly into target cells via receptor-mediated internalization. This review synthesizes preclinical and clinical data on TCEs and ADCs in oncology and immune-mediated inflammatory disorders (IMIDs). The CD47/SIRPα innate immune checkpoint is briefly examined as a case study in next-generation immunopharmacology, with agents like evorpacept and BYON4228 showing encouraging objective response rates (50% ORR) in non-hodgkin lymphoma when combined with rituximab, with next-generation designs reducing hematologic toxicity. Recent compassionate use findings in autoimmunity demonstrate that CD19 × CD3 TCE (blinatumomab) and (B-cell maturation antigen) BCMA × CD3 TCE (teclistamab) elicit rapid clinical improvement in refractory antisynthetase syndrome and systemic sclerosis, accompanied by cytokine release syndrome (CRS) (grade 3 in 40% and 100% of patients, respectively) and no neurotoxicity. In engineered TCEs with attenuated CD3 affinity, grade 1-2 CRS occurs in < 20% of patients. Beyond cell-depleting strategies, bispecific antibodies targeting OX40L/TNFα and anti-TL1A antibodies are advancing in hidradenitis suppurativa and rheumatic diseases. Conversely, ADC strategies have yielded mixed results; an anti-TNF-glucocorticoid receptor modulator ADC failed to outperform adalimumab in a phase 2b trial. Safety profiles differ: TCEs predominantly cause cytokine release syndrome, whereas ADCs pose off-target payload toxicity risks. Emerging dual-targeting TCEs, half-life-extended formats, and rational combinations illustrate key immunopharmacological principles that may broaden the therapeutic landscape for cancer and autoimmune diseases.

BACKGROUND: Road injuries are a leading cause of mortality and morbidity worldwide. Years of international efforts have aimed to strengthen policy engagement, including the 2020 UN General Assembly's proclamation of the Second Decade of Action for Road Safety (2021-30), targeting a 50% reduction in road traffic deaths and serious injuries by 2030. The aim of this study is to provide estimates to monitor progress and identify intervention gaps. METHODS: As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2023, we estimated incidence, mortality, and morbidity of road injuries for 204 countries and territories from 1990 to 2023. Four road injury types and 47 nature-of-injury categories were examined. Morbidity and mortality data from clinical records, vital registration, and police reports were harmonised using meta-analytic techniques to ensure consistency and correct for systematic bias. Incidence was modelled with the meta-regression tool Disease Modelling-Meta-Regression version 2.1 and cause-specific mortality with the Cause of Death Ensemble model, both incorporating location-specific covariates to support interpolation. Years of life lived with disability (YLDs) were estimated from the prevalence and severity of the nature of road injury, and years of life lost (YLLs) from the number of cause-specific deaths multiplied by the standard life expectancy at the age of death. Disability-adjusted life-years (DALYs) were the sum of YLLs and YLDs. All metrics were calculated with 95% uncertainty intervals (UIs). FINDINGS: In 2023, there were 50·9 million (95% UI 46·1-56·1) road injury incident cases, 1·34 million (1·04-1·58) deaths, and 75·3 million (59·8-89·2) DALYs globally. Road injuries were the leading global cause of death among males aged 10-39 years. Between 1990 and 2023, age-standardised incidence decreased by 38·3% (95% UI 36·9-39·7) and mortality decreased by 32·3% (6·1-49·0), but progress varied widely by World Bank income group. Mortality in low-income countries (43·8 [95% UI 31·7-56·0] deaths per 100 000 population) was approximately six times higher than in high-income countries (7·5 [7·1-7·9] deaths per 100 000), despite the high-income countries showing the highest age-standardised incidence rates (858·1 [95% UI 781·9-947·1] cases per 100 000). In the past decade, many countries achieved notable reductions in road injuries, but others, including Ghana and the USA, saw increases. More severe injuries tended to occur in low-income and middle-income countries. INTERPRETATION: Although global incidence, mortality, and DALY rates from road injuries have declined, progress remains uneven, with pronounced disparities across income groups reflecting systemic inadequacies in infrastructure, vehicle standards, enforcement, and post-crash care. Strengthening emergency response, improving road design, enforcing safety measures, and adapting policies to the evolving demographics remain essential. FUNDING: Gates Foundation.