Individuals with thalidomide embryopathy are now approximately 60 years old. For years, they have been compensating for their hypoplastic limbs in various aspects of daily living, and they face secondary problems such as limb and back pain. Imaging analysis is beneficial for understanding the pathogenesis of these problems. However, previous studies on skeletal imaging were mainly radiographic studies conducted at young ages, and there are few studies on skeletal imaging after aging, with most of them being case reports. In this study, detailed analyses of the skeletons of the upper extremities were performed using three-dimensional computed tomography and multiplanar reconstruction images in five individuals with thalidomide embryopathy aged approximately 60 years. Each individual frequently complained of neck, shoulder, and/or back pain. Dislocation, subluxation, and osteoarthritis were observed in the shoulder joints in some individuals. Hypoplasia of the trochlea and/or capitulum of the humerus, coronoid fossa, olecranon, and coronoid processes was observed in the elbow joints. Fusion and hypoplasia of the carpal bones were frequently observed in wrist joints. Radiocarpal and ulnocarpal synostoses were also observed. The joint instability and osteoarthritis found in this study may have contribute to upper limb pain in individuals with thalidomide embryopathy.

Extrahepatic portal vein obstruction (EHPVO) is a rare disease with myeloproliferative neoplasm (MPN) as the most common cause. We report that hypersplenic hematologic changes in EHPVO might be eliminated by MPN. Through experience with splenectomy for variceal control with EHPVO, we suspected that spleen might mask MPN-induced thrombocytosis, and that MPN might have a significant influence on excessive thrombocytosis after splenectomy. To clarify the influence of MPN and spleen on platelet trends, we conducted a retrospective hospital database analysis, evaluating 8 EHPVO patients with splenectomy (2 males, 6 females; from 17 years to 64 years, mean 38.3 years). Three (37.5%) of 8 were diagnosed as MPN by JAK2V617F mutation. The perioperative serum platelet counts in EHPVO without MPN were 10.5, 35.4, and 36.6 (x10⁴/μL) preoperatively, after 1 week and 3 weeks, respectively. The platelet counts in EHPVO with MPN were 34.2, 86.4, and 137.0 (x10⁴/μL), respectively. Splenectomy and MPN showed positive interaction on platelet increasing with statistical significance. We also examined the spleen volume index (SpVI: splenic volume (cm³) / body surface area (m²) and postoperative platelet elevations ratio (PER: 3-week postoperative platelet counts / preoperative platelet counts). However, both SpVI and PER showed no significant difference with or without MPN. Histological examination revealed splenic congestion in all 8 EHPVO cases, and splenic extramedullary hematopoiesis in 2 of 3 MPN. In EHPVO with MPN, hypersplenism causes feigned normalization of platelet count by masking MPN-induced thrombocytosis; however, splenectomy unveils postoperative thrombocytosis. Spleen in EHPVO with MPN also participates in extramedullary hematopoiesis.

Pneumomediastinum is a rare condition defined by the presence of air in the mediastinum. In the absence of traumatic injury, iatrogenic injury, or clear etiology, it is called spontaneous pneumomediastinum (SPM). Spontaneous pneumomediastinum most commonly occurs in younger individuals and has a self-limiting course with a good outcome. The purpose of the present manuscript is to systematically review the existing literature on SPM evaluation and management for updated clinical understanding of this condition. A literature search was conducted of publications about SPM on MEDLINE/PubMed and Google Scholar by identifying all the articles with key search terms "pneumomediastinum" and "spontaneous pneumomediastinum". Inclusion criteria were case series published in English between 1980 and 2023. In total, 24 case series were selected and reviewed to determine presenting symptoms, clinical signs and predisposing factors associated with spontaneous pneumomediastinum. Most patients were male; the average age at diagnosis was 26.3 years. The most common presenting symptoms were chest pain and dyspnea. The most common exam finding was subcutaneous emphysema, in 35.4% of patients. Only 5.9% had the classic Hamman's sign. Risk factors include history of asthma, history of smoking, and recent physical activity. This manuscript presents an extensive review of relevant literature highlighting the diagnosis and essential management of spontaneous pneumomediastinum.

This study aimed to assess the cost-utility of romiplostim (ROMI) compared to eltrombopag (EPAG) as a second-line treatment for chronic primary immune thrombocytopenia (cITP) in Chinese adults. A decision tree-embedded Markov model with a lifetime horizon was used to estimate the qualityadjusted life years (QALYs) and costs for ROMI versus EPAG from the perspective of the Chinese health care system. The model was driven by platelet response with a 4-week cycle. Both QALYs and costs were discounted 5% per year. Clinical data comparing ROMI and EPAG were obtained by matching-adjusted indirect comparison (MAIC), utilizing individual patient data on ROMI and published Chinese Phase III trial data on EPAG. Costs were reported in 2022 US dollars and included drug acquisition costs, monitoring costs, bleeding-related costs, and costs associated with adverse events. Deterministic and probabilistic sensitivity analyses were performed. The CEA model indicated that treatment with ROMI resulted in an average of $4,344.4 higher costs for 0.004 QALYs. One-way sensitivity analysis (OSA) indicated that the model was most sensitive to the high bleeding rate in response (Markov stage) for EPAG and ROMI. Probabilistic sensitivity analysis (PSA) indicated that ROMI was likely to be cost effective in 0.16% cases at a willingness-to-pay threshold of $12039.1 (China per capita GDP in 2022) per QALY. If the price of ROMI is either lower than or equal to that of EPAG, ROMI could likely be considered cost-effective as a second-line treatment for Chinese adults with cITP.

Myasthenia gravis (MG) is an autoimmune disease mediated by B cells and is associated with acetylcholine receptor (AChR) and muscle-specific receptor tyrosine kinase (MuSK) antibodies in the postsynaptic membrane at the neuromuscular junction. Anti-CD20 monoclonal antibodies, such as ofatumumab demonstrated promising disease control in MG patients. We presented the rare case of a 34-year-old female with acetylcholine receptor-positive myasthenia gravis (AChR-MG), concomitant with systemic lupus erythematosus (SLE) and metastatic thyroid carcinoma, who was treated with ofatumumab and exhibited improvements during follow-up.

Neurodegeneration with brain iron accumulation (NBIA) is a heterogeneous group (genetically and phenotypically) of genetically determined disorders. Up to date there is no cure for this disease, so the applied treatments focus on symptoms control and palliative care. The main problems are delayed motor development, gait deterioration, postural instability, cognitive dysfunctions, abnormal muscle tone and many others. As gait and balance deficits are predominant features of NBIA patients this study aimed at the use of the objective, instrumented functional tests as well as functional assessment scales to assess their functional impairments. Twenty three NBIA patients recruited for the study underwent objective, instrumented gait analysis, balance assessment, pedobarography and functional evaluation with Gross Motor Function Measure (GMFM-88). The results showed high variability and heterogeneity of NBIA functional status (GMFM from 27.5 to 100.0), but also showed some differences in gait pattern between their types (p < 0.05 at the pelvis, hip and knee). We think that these results could help design objective assessment protocols in future clinical studies.

The aim of this study was to investigate a novel FBN1 gene mutation in a pediatric patient with Marfan syndrome (MFS) to provide a theoretical basis for genetic counseling. The subject was a 5-month-old male infant. With informed consent from the proband and his family, 2 mL of peripheral venous blood was collected from the patient, his father, mother, and sister. DNA was extracted using a DNA extraction kit with EDTA-K as an anticoagulant. The extracted DNA was subjected to minigene transcription and bioinformatics analysis. For minigene construction, wild-type and mutant minigenes were inserted into pcMINI and pcMINI-C vectors, respectively. Four recombinant vectors were transfected into the HeLa and 293T cell lines. After transfection for 48 hours, RNA was extracted from eight samples. DNA was also extracted from the family members' samples to construct a library. Target regions were captured using the SureSelect Human All Exon V6 (Agilent) kit and were sequenced with Illumina NovaSeq (sequencing read length 2×150 bp). Bioinformatic analysis identified the c.8226+5del mutation as a variant of uncertain clinical significance (VOUS). Literature and database reviews confirmed that this mutation had not been previously reported, identifying it as a novel mutation. The study identified a novel FBN1 mutation, c.8226+5del, that may be associated with clinical features such as low-set ears and distinctive facial characteristics in the proband. This mutation likely affects normal mRNA splicing, altering the structure and function of Exon 64 and potentially contributing to the development of autosomal dominant MFS.

Chiari Malformation type I (CM-I) is a neurological disorder characterized by cerebellar tonsillar herniation. Chronic pain, particularly headaches, is a prevalent symptom in CM-I patients, significantly impacting their quality of life. The objective of this study was to evaluate the perceived quality of life in adults with CM-I and examine the influence of chronic pain and comorbid symptoms on their well-being. 26 CM-I patients (8 with decompressive surgery) and 26 matched healthy controls were recruited. Participants completed the following questionnaires: WHOQOL-BREF, HDI, NDI, OLBPDQ and HADS. CM-I patients exhibited significantly lower scores across all domains of quality of life when compared to healthy controls. Chronic pain, including headache, neck pain, and low back pain, was more pronounced among CM-I patients and demonstrated a significant correlation with depressive symptoms. Notably, after controlling for chronic pain, the differences in quality of life between CM-I patients and controls diminished. The results suggest that chronic pain, especially headaches, and comorbid depressive symptoms exert a substantial impact on the quality of life of CM-I patients. Surgical intervention alone may not fully address these issues, highlighting the importance of considering psychological interventions as part of the comprehensive treatment. Further research with larger samples and pre-post-surgery assessments is needed to validate these findings and explore the potential benefits of psychological therapies in enhancing the quality of life for CM-I patients.

Paroxysmal nocturnal hemoglobinuria is a rare clonal hematopoietic stem cell disorder with debilitating health consequences if untreated. Although cases have been described globally, precise epidemiological distribution is difficult to assess due to geographical underrepresentation in disease reporting. Evaluation of the burden of paroxysmal nocturnal hemoglobinuria in Bulgaria is currently missing. To provide epidemiological estimates, a systematic literature search for publications in the Bulgarian language or by Bulgarian authors was performed for a ten-year period (2013-2022), and clinically relevant information on case presentation was collected. Additionally, data was retrieved from the National Health Insurance Fund and National Statistical Institute on the count of registered cases with ICD-10 code "D59.5" and census for the same period. The estimated prevalence of paroxysmal nocturnal hemoglobinuria is relatively lower in the Bulgarian population than in other countries, and it is estimated to be 2.77 cases per 1,000,000 patient years. The treatment pattern mainly shows conventional blood product support use and is consistent with the pre-complement inhibition era. Underdiagnosis, lack of a reliable disease reporting system, and, until recently, restricted access to complement inhibitor therapy are significant impediments to the management of paroxysmal nocturnal hemoglobinuria in Bulgaria.

The global aging population has led to a significant rise in the prevalence of age-related non-communicable diseases such as dementia and other cognitive disorders. In 2019, there were 57.4 million people with dementia worldwide, and this number is projected to triple by 2050. Intervening in and managing 12 potentially modifiable dementia risk factors can prevent or delay the onset and progression of about 40% of dementia cases. Neuroimaging, biomarkers, and advanced neuropsychological testing offer promising pathways for the early detection of dementia. Emphasis should be placed on educating the public about the importance of brain health and the early signs of cognitive impairment, as well as promoting dementia prevention measures. Adopting a healthy lifestyle - including a balanced diet, regular physical exercise, active social engagement, cognitive activities, and avoiding smoking and excessive alcohol consumption - can help reduce the risk of cognitive decline and prevent cognitive disorders. Government policies on dementia prevention and health care, along with early and regular dementia screening programs, can enhance the early identification and management of individuals at risk. In addition, integrating cognitive health assessments into routine medical check-ups is essential for the early screening and management of dementia.