Intractable & rare diseases research最新文献

Post-transplant lymphoproliferative disease (PTLD) is a rare but life-threatening disease that occurs after organ transplantation. Histopathology is the gold standard for the diagnosis of PTLD. Because of its rarity and atypical symptoms, many patients are misdiagnosed with liver abscess, liver cancer, or missed diagnosis long before pathological diagnosis is obtained, thus delaying treatment. Early and accurate diagnosis, in addition to histopathological examination, is difficult. Contrast-enhanced ultrasound (CEUS) imaging techniques have overwhelming advantages of being safe (noninvasive, radiation-free) and sensitive for evaluating the microcirculation of lesions, thus making them widely used in the diagnosis of hepatic lesions. Unfortunately, there are few reports of CEUS data on hepatic PTLD (HPTLD). This study reported and analyzed four cases of HPTLD in detail, all of which underwent pre-biopsy CEUS examinations and had a complete diagnosis and treatment process. By offering readers comprehensive knowledge of CEUS in the diagnosis of HPTLD, our study aims to help reduce misdiagnoses and missed diagnoses, thereby improving patient treatment and prognosis.

Osteogenesis imperfecta (OI) is a genetic disorder of the connective tissue that is characterized by high bone fragility. It has a worldwide incidence of 1 in 10,000. The diagnosis is mainly clinical-radiological. Treatment is based on the use of bisphosphonates and orthopedic surgeries. The objective of this study was to establish the clinical, radiological, and therapeutic characteristics of OI in pediatric patients of a national reference pediatrics institute. This was conducted through a descriptive and retrospective analysis. All patients under 18 years of age with a diagnosis of OI treated at the Instituto Nacional de Salud del Niño de Breña (INSN-Breña) between 2010 and 2021 were included. In total, 91 patients with OI were studied, more than half of whom were male. A total of 93.4% had a history of fractures, 72.5% had blue sclera, 39.6% had bowed legs and 20.9% had dentinogenesis imperfecta. The minimum-maximum value of fractures was 0-18. A total of 75.8% of patients started treatment with bisphosphonates and 41.8% used adjuvant medications. Less than 50% of patients required surgical treatment. Osteogenesis imperfecta is a genetic and chronic pathology. The use of the Van Dijk severity grade and the Aglan severity scale is simple to apply and therefore should be used to improve the classification of groups with the highest risk of fractures and response to treatment. Due to the low incidence of this disease, it is important to raise awareness and increase the research volume on this subject.

Following the release of China's First List of Rare Diseases in May 2018, the Chinese government officially published China's Second List of Rare Diseases in September 2023. To date, there is no unified standard and international consensus for rare diseases, and epidemiologic data for most rare diseases in China are lacking. We investigated 86 rare diseases on the second list using Orphanet and other databases to clarify the classification, nomenclature, and epidemiologic data for these diseases, and we summarized the genotype and phenotype of hereditary diseases. The results showed that most of 86 rare diseases were coded in the database of Unified Medical Language System (UMLS), Orphanet, Medical Subject Headings (MeSH) and International Classification of Diseases, Eleventh Revision (ICD-11). Some rare diseases are composed by group of different disorders, in which multiple identifiers existed. Meanwhile, some rare diseases have different subtypes, which correspond to different identifiers. This increases the actual number of rare diseases in the second list. Over 50% of rare diseases are genetic rare diseases and they are mainly classified into neoplastic diseases, transplant-related disorders and neurological diseases. Epidemiologic data indicated that these rare diseases had a broad prevalence spectrum and over 20 rare diseases had a prevalence of over 1/10,000, these rare diseases in the China's Second List of Rare Diseases expanded the number and scope of rare diseases according to the China's official definition of rare diseases.

Hypoxic-ischemic encephalopathy (HIE), caused by cardiac arrest (CA) is a refractory condition in clinical settings. The clinician and family members have to make a hard decision: continue expensive life-sustaining therapy or withdraw the expensive intervention. The core problem lies in "whether this patient can still be awakened and achieve neurological recovery". This study briefly summarizes the use of mainstream neuro-prognosticative tools thus far with the latest available evidence. To gain a better understanding of the pathophysiological state of patients with HIE, comprehensive use of these tools and repeated assessments are recommended. The final decision should be made cautiously and comprehensively in light of the patient's medical history, pathophysiological state, results of neuro-prognosticative evaluations, and the clinician's clinical experience per se. Novel computerized technologies such as artificial intelligence, big data, and machine learning should be used to develop neuro-prognosticative tools for refractory CA-induced HIE.

Extrachromosomal DNA (ecDNA) refers to a class of circular, non-chromosomal DNA that has recently gained widespread attention due to its potential role in aging and neurodegenerative diseases. The generation of ecDNA is closely associated with processes such as double-strand breaks, micronuclei formation, and the breakage-fusion-bridge (BFB) cycle, all of which are integral to regulation of gene expression, genetic stability, and clonal evolution. In neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, the aberrant formation of ecDNA is closely linked to defects in DNA repair, alterations in synaptic plasticity, and neuronal dysfunction. The distinct distribution and functional roles of ecDNA in these conditions make it a potential diagnostic biomarker and therapeutic target. This review provides an overview of the mechanisms underlying ecDNA formation and its functions in the nervous system. Additionally, it explores the clinical potential of ecDNA in disease diagnosis, targeted therapy, and personalized medicine, offering new insights for future research and treatment strategies.

Advances in genetic testing over the past decades are driving a continuing increase in the diagnosis and reporting of rare genetic diseases, but no tool has yet been developed to aggregate published molecular and phenotypic data, a task that is nevertheless essential to optimize patient care. In this article, we present PytheasDB, an online database of published clinical data from patients with rare digestive diseases. At the time of writing (August 2024), the database contains data from 833 patients with progressive familial intrahepatic cholestasis or trichohepatoenteric syndrome, collected from 172 articles. Users can compare the phenotypic profiles, sex ratios, survival curves, ages at first symptoms, and consanguinity rates of the included diseases. PytheasDB is the first ever online resource providing access to aggregated clinical data from case reports of rare digestive diseases in the literature. The database is currently being expanded to cover ultra-rare pediatric digestive diseases with regular updates to optimize the study and treatment of these diseases.

Niemann-Pick disease type C (NPC) is a rare, autosomal recessive, neurodegenerative disease associated with a wide variety of progressive neurological manifestations. Miglustat has demonstrated efficacy to delay progressive neurological deterioration in patients with NPC. We conducted a multicenter, open-label, single-arm, phase IV, post-approval commitment study to evaluate the efficacy and safety of miglustat among Chinese patients with NPC. Eligible patients were aged ≥ 4 years with an established diagnosis of NPC with two type C1 or C2 pathogenic markers or one marker with a positive biomarker (oxysterol, lysosphingolipids, or bile acids) and high clinical suspicion of NPC. Patients received oral miglustat ranging from 100 mg twice daily to 200 mg three times daily. The primary outcome was change in horizontal saccadic eye movement parameters from baseline to week 52. Seventeen patients were enrolled (median age: 14.0 years). From baseline to week 52, mean saccadic peak acceleration and velocity increased by 19.2% and 12.5%, respectively, while mean peak duration and linear regression decreased by 6.5% and 15.6%, respectively. By week 52, ambulation, manipulation, language, swallowing, and ocular movements had improved or stabilized versus baseline. All patients experienced treatment-emergent adverse events (TEAEs). Treatment-related TEAEs were reported in 12 patients with the most common being diarrhea (n = 12). Two patients died due to accidental death and asphyxia unrelated to miglustat treatment. This study demonstrated disease stabilization in Chinese patients with NPC receiving miglustat. Safety findings were consistent with miglustat's known safety profile. The study was registered at ClinicalTrials.gov (NCT03910621).

The pathogenesis of diseases in the field of rare diseases is complex. Many rare diseases have yet to be conquered worldwide, and there are still no effective treatments for most rare diseases, resulting in limited accessibility to medications. Over the past few years, China has been committed to ensuring the availability of drugs for rare diseases, both at the national level and in all sectors of society. Through National Healthcare Insurance Negotiations (hereinafter referred to as "national negotiations"), the National Healthcare Security Administration has included several drugs for rare diseases in medical insurance coverage, addressing some of the issues with medications for rare diseases. National Negotiations have reduced the prices of drugs for rare diseases to a certain extent, but they remain expensive for many patients. By the end of 2023, out of the 165 drugs for rare diseases that had been launched, 53 were still not covered by medical insurance, leaving patients with a significant financial burden. Addressing payment issues remains a current challenge, and various regions in China are actively exploring innovative methods of paying for rare disease care to protect the socioeconomic rights and interests of patients with rare diseases.

Inferior vena cava (IVC) leiomyosarcomas are rare smooth muscle neoplasms that account for 0.5% of adult soft tissue sarcomas. They present with nonspecific symptoms and have poor prognosis. We present a case of leiomyosarcoma arising from the retrohepatic IVC that was difficult to diagnose on imaging, showing similar characteristics to intrahepatic cholangiocarcinoma including heterogenous arterial phase enhancement and delayed enhancement on contrast-enhanced magnetic resonance imaging. Important differentiating features of IVC leiomyosarcomas on imaging include dilated IVC, imperceptible IVC lumen, and development of prominent venous collaterals. Despite this, imaging features may be similar to other retrohepatic mass etiologies so IVC leiomyosarcoma should be included in the differential diagnosis of any retrohepatic mass and biopsy should be pursued.

Cervicofacial Emphysema (CFE) is a self-limiting condition, defined by the presence of air in face and neck. The purpose of the manuscript is to systematically review the existing literature on CFE evaluation and management for updated clinical understanding of this condition. A literature search was conducted of publications about CFE on PubMed and Google Scholar by identifying all the articles with key search terms "Cervicofacial Emphysema" and "Sub Cutaneous Emphysema". Inclusion criteria were case series published in English between 1980 and 2024. In total, 241 case series were selected and reviewed to determine presenting symptoms, clinical signs and predisposing factors associated with CFE. Average age at diagnosis was 38.1 years, male and female are almost equally affected. The most common presenting symptoms were face and neck swelling. The most common finding was crepitus. The condition was most commonly reported in patients undergoing dental procedures, otorhinolaryngology procedures, or in patients who experienced transient change in intra nasal/thoracic pressure. The management includes clinical monitoring, reassurance of the patient, antibiotic prophylaxis and monitoring to rule out pneumomediastinum. The odds of concurrent pneumomediastinum is highest in patients with abdominal procedures as an etiology of CFE.