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International Journal of Surgery Case... Oct 2023Baclofen is a γ -aminobutyric acid (GABA) agonist used to treat spasticity; however, it may be toxic at dosages above 200 mg. The psychological, nervous,...
INTRODUCTION
Baclofen is a γ -aminobutyric acid (GABA) agonist used to treat spasticity; however, it may be toxic at dosages above 200 mg. The psychological, nervous, cardiovascular, gastrointestinal, musculoskeletal, and respiratory systems are all affected. This report represents a case with the rare respiratory complications brought on by baclofen toxicity: atelectasis and pneumomediastinum.
PRESENTATION OF CASE
A 19-year-old female was admitted to the emergency department after attempting suicide by taking 20 baclofen tablets (500 mg). Imaging revealed pneumomediastinum, atelectasis, and a leftward displacement of mediastinal structures. Her therapy included a chest tube to relieve the pneumomediastinum and sodium valproate, promethazine, biperiden, and quetiapine for neurological symptoms. Four days after being admitted, she was successfully extubated without any complications.
DISCUSSION
Baclofen activates GABA-A and GABA-B receptors. High doses of baclofen may induce central nervous system and respiratory depression, requiring intensive care. GABA receptors may cause hallucinations, delusions, and agitation in baclofen overdose. High dosages of baclofen may cause bronchial and bronchiolar muscular spasms, leading to breathing problems and atelectasis. Recent animal studies on baclofen toxicity showed that increased alveolar pressure, circulatory abnormalities, edema, alveolar hemorrhages, and infiltration cause rupture and pneumomediastinum. Pneumomediastinum may need bed rest, oxygen, antitussives, and analgesics, but severe cases may necessitate a chest tube.
CONCLUSION
A high index of suspicion is required for early diagnosis of acute baclofen poisoning, which could manifest as respiratory complications, including pneumomediastinum and atelectasis. Since most cases are benign, it is still crucial for clinicians to detect complications early for further management.
PubMed: 37801962
DOI: 10.1016/j.ijscr.2023.108901 -
Biomolecules Apr 2024Ehlers-Danlos syndromes (EDSs) constitute a heterogeneous group of connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue... (Review)
Review
Ehlers-Danlos syndromes (EDSs) constitute a heterogeneous group of connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Asymptomatic EDSs, joint hypermobility without associated syndromes, EDSs, and hypermobility spectrum disorders are the commonest phenotypes associated with joint hypermobility. Joint hypermobility syndrome (JHS) is a connective tissue disorder characterized by extreme flexibility of the joints, along with pain and other symptoms. JHS can be a sign of a more serious underlying genetic condition, such as EDS, which affects the cartilage, bone, fat, and blood. The exact cause of JHS could be related to genetic changes in the proteins that add flexibility and strength to the joints, ligaments, and tendons, such as collagen. Membrane proteins are a class of proteins embedded in the cell membrane and play a crucial role in cell signaling, transport, and adhesion. Dysregulated membrane proteins have been implicated in a variety of diseases, including cancer, cardiovascular disease, and neurological disorders; recent studies have suggested that membrane proteins may also play a role in the pathogenesis of JHS. This article presents an exploration of the causative factors contributing to musculoskeletal pain in individuals with hypermobility, based on research findings. It aims to provide an understanding of JHS and its association with membrane proteins, addressing the clinical manifestations, pathogenesis, diagnosis, and management of JHS.
Topics: Humans; Ehlers-Danlos Syndrome; Joint Instability; Membrane Proteins
PubMed: 38672488
DOI: 10.3390/biom14040472 -
BMC Pediatrics Jul 2023Adolescent idiopathic scoliosis (AIS) is a common spinal deformity with physical and psychosocial implications for adolescents. The aim of this qualitative evidence...
BACKGROUND
Adolescent idiopathic scoliosis (AIS) is a common spinal deformity with physical and psychosocial implications for adolescents. The aim of this qualitative evidence synthesis (QES) was to systematically search for, identify, and synthesise qualitative research in order to improve our understanding of what it is like to live with AIS and to facilitate empathetic and effective healthcare.
METHODS
We systematically searched 4 databases (Medline, EMBASE, PsycINFO and CINAHL) and used the 7 phases of meta-ethnography to synthesise qualitative evidence including studies with children and adolescents, and additional viewpoints from parents about the experience of AIS.
RESULTS
We distilled 7 themes. (1) Diagnosis turned time on its head revolves around the AIS diagnosis and the uncertainty of the future that accompanied it. (2) Usual activities no longer the same explores how activities and participation in everyday life are impacted by AIS. (3) Hiding my body describes the pervasive struggle with self-image and appearance. (4) I want to feel normal again explores adolescents' desire to return to 'normality' and challenges of feeling different. (5) Balancing isolation and support considers the relationships in the adolescents' lives alongside their feelings of isolation. (6) Trying to keep control of treatment decisions explores how adolescents and their parents strive to feel in control. (7) Fearing surgery yet feeling hopeful focused on the apprehension and fear around spinal surgery and the beacon of hope it represented.
CONCLUSIONS
Our QES contributes to the understanding of the adolescent experience of living with AIS. From our findings, clinicians can better understand the physical and psychosocial obstacles and the challenges faced throughout the journey of AIS to inform their clinical interactions with these patients.
Topics: Child; Humans; Adolescent; Scoliosis; Anthropology, Cultural; Emotions; Qualitative Research; Databases, Factual; Kyphosis
PubMed: 37481537
DOI: 10.1186/s12887-023-04183-y -
Sensors (Basel, Switzerland) May 2024Incorrect sitting posture, characterized by asymmetrical or uneven positioning of the body, often leads to spinal misalignment and muscle tone imbalance. The prolonged... (Review)
Review
Incorrect sitting posture, characterized by asymmetrical or uneven positioning of the body, often leads to spinal misalignment and muscle tone imbalance. The prolonged maintenance of such postures can adversely impact well-being and contribute to the development of spinal deformities and musculoskeletal disorders. In response, smart sensing chairs equipped with cutting-edge sensor technologies have been introduced as a viable solution for the real-time detection, classification, and monitoring of sitting postures, aiming to mitigate the risk of musculoskeletal disorders and promote overall health. This comprehensive literature review evaluates the current body of research on smart sensing chairs, with a specific focus on the strategies used for posture detection and classification and the effectiveness of different sensor technologies. A meticulous search across MDPI, IEEE, Google Scholar, Scopus, and PubMed databases yielded 39 pertinent studies that utilized non-invasive methods for posture monitoring. The analysis revealed that Force Sensing Resistors (FSRs) are the predominant sensors utilized for posture detection, whereas Convolutional Neural Networks (CNNs) and Artificial Neural Networks (ANNs) are the leading machine learning models for posture classification. However, it was observed that CNNs and ANNs do not outperform traditional statistical models in terms of classification accuracy due to the constrained size and lack of diversity within training datasets. These datasets often fail to comprehensively represent the array of human body shapes and musculoskeletal configurations. Moreover, this review identifies a significant gap in the evaluation of user feedback mechanisms, essential for alerting users to their sitting posture and facilitating corrective adjustments.
Topics: Humans; Sitting Position; Neural Networks, Computer; Monitoring, Physiologic; Posture
PubMed: 38733046
DOI: 10.3390/s24092940 -
European Journal of Obstetrics &... Dec 2023The objective was to compare the ultrasound scan frequency and rate of congenital malformations between urban and rural areas. (Review)
Review
OBJECTIVE
The objective was to compare the ultrasound scan frequency and rate of congenital malformations between urban and rural areas.
STUDY DESIGN
We conducted a population-based retrospective study using linked data from administrative data sources and register data. All singleton live births in 2018 that could be linked (n = 18,759) were included in the data analysis. Place of residence was categorized into three groups: Riga (capital city), other big cities and rural areas (including regional cities). Adjusted ORs were calculated. The multiple regression model was adjusted for maternal age, living area and prenatal screenings.
RESULTS
Overall, 3% (n = 536) of the live-born infants were reported to have congenital malformations at birth. The proportion of congenital anomalies was, on average, 2% higher (p < 0.001) in Riga (4%, n = 334) than in the rural regions (2%, n = 93) and other cities (1%, n = 109). Women whose infants had congenital anomalies at birth had higher and statistically significant odds of having abnormal findings on ultrasound (US) screening (OR=2.3; 95% CI 1.5-3.4; p < 0.001) and undergoing invasive diagnostic tests during pregnancy (OR=2.2; 95% CI 1.4-3.5; p < 0.001). The median number of ultrasound scans during pregnancy was 3 (IQR 2) in Riga and 4 (IQR 2) in the other cities and rural regions. The top 3 types of congenital anomalies at birth were deformations of the musculoskeletal system and congenital malformations of the circulatory system and genital organs.
CONCLUSIONS
The findings of this study showed a statistically significant association between the rate of foetal anomalies and the frequency of prenatal examinations. A higher average number of US examinations per pregnancy was observed in the rural regions. Regional variations exist in the rates of specific congenital anomalies. Further studies are recommended in this field for better understanding. Surveillance systems that are able to analyse the efficiency of US examinations need to be developed for the early prenatal detection of congenital anomalies.
PubMed: 37771958
DOI: 10.1016/j.eurox.2023.100242 -
Clinical and Experimental Rheumatology Feb 2024To assess nailfold video capillaroscopic (NVC) abnormalities and their association with clinical features, myositis-specific autoantibodies (MSA), and...
OBJECTIVES
To assess nailfold video capillaroscopic (NVC) abnormalities and their association with clinical features, myositis-specific autoantibodies (MSA), and myositis-associated antibodies (MAA) in a large multi-ethnic cohort of patients with idiopathic inflammatory myopathies (IIM).
METHODS
We recruited 155 IIM patients from three centres in Mexico, Spain, and the USA. We evaluated the clinical and laboratory features of the patients and performed semiquantitative and quantitative analyses of the NVC. Each NVC study was defined as having a normal, non-specific, early systemic sclerosis (SSc), active SSc, or late SSc pattern. Twenty-three patients had at least one follow-up NVC when disease control was achieved. Quantitative variables were expressed as medians and interquartile range (IQR) and were compared with the Kruskal-Wallis, the Mann-Whitney U-test, and the Wilcoxon test for paired medians. Associations between qualitative variables were assessed with the χ2 test.
RESULTS
Most patients were women (68.3%), Hispanic (73.5%), and had dermatomyositis (DM) (61.2%). Fourteen patients (9%) had a normal NVC. A non-specific abnormality pattern was the most frequent (53.9%), and was associated with joint involvement, interstitial lung disease, Jo1 autoantibodies, anti-synthetase syndrome, and immune-mediated necrotising myopathy. The SSc pattern was observed mostly in DM and overlap myositis and was associated with cutaneous features and anti-TIF-1g autoantibodies. After treatment, there was a decrease in the capillaroscopic score, the capillary diameter, and the number of avascular areas, and an increase in capillary density and bushy capillary number.
CONCLUSIONS
NVC abnormalities are related to the diagnosis, clinical features, disease activity, and autoantibodies of patients with IIM.
Topics: Humans; Female; Male; Microscopic Angioscopy; Nails; Myositis; Capillaries; Autoantibodies; Scleroderma, Systemic
PubMed: 38488092
DOI: 10.55563/clinexprheumatol/l9gudh -
Clinical Cancer Research : An Official... Oct 2023On September 30, 2022, the FDA granted accelerated approval to futibatinib for the treatment of adult patients with previously treated, unresectable, locally advanced or...
FDA Approval Summary: Futibatinib for Unresectable Advanced or Metastatic, Chemotherapy Refractory Intrahepatic Cholangiocarcinoma with FGFR2 Fusions or Other Rearrangements.
On September 30, 2022, the FDA granted accelerated approval to futibatinib for the treatment of adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma (iCCA) with FGFR2 fusions or other rearrangements. Approval was based on Study TAS-120-101, a multicenter open-label, single-arm trial. Patients received futibatinib 20-mg orally once daily. The major efficacy outcome measures were overall response rate (ORR) and duration of response (DoR) as determined by an independent review committee (IRC) according to RECIST v1.1. ORR was 42% (95% confidence interval, 32%-52%). Median DoR was 9.7 months. Adverse reactions occurring in ≥30% patients were nail toxicity, musculoskeletal pain, constipation, diarrhea, fatigue, dry mouth, alopecia, stomatitis, and abdominal pain. The most common laboratory abnormalities (≥50%) were increased phosphate, increased creatinine, decreased hemoglobin, and increased glucose. Ocular toxicity (including dry eye, keratitis, and retinal epithelial detachment) and hyperphosphatemia are important risks of futibatinib, which are listed under Warnings and Precautions. This article summarizes the FDA's thought process and data supporting the approval of futibatinib.
Topics: Adult; Humans; Pyrimidines; Cholangiocarcinoma; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Drug Approval; Receptor, Fibroblast Growth Factor, Type 2; Pyrazoles; Pyrroles
PubMed: 37289037
DOI: 10.1158/1078-0432.CCR-23-1042 -
Scientific Reports Jan 2024Femoroacetabular impingement has increasingly been recognized as a cause of primary hip osteoarthritis; however, its epidemiological indications remain unclear. We aimed...
Femoroacetabular impingement has increasingly been recognized as a cause of primary hip osteoarthritis; however, its epidemiological indications remain unclear. We aimed to clarify the epidemiological indications and factors associated with cam deformity in a large-scale population-based cohort in Japan. Overall, 1480 participants (2960 hips) (491 men, 989 women; mean age, 65.3 years) analyzed in the third survey of the Research on Osteoarthritis/Osteoporosis Against Disability study were included. The α angle and spinopelvic parameters (lumbar lordosis, sacral slope, pelvic tilt, and pelvic incidence) were radiographically measured. Cam deformity was defined as α angle ≥ 60°. Overall, the cam deformity prevalence was 147/2960 (5.0%). Cam deformity prevalence tended to increase with age; in the univariate analysis, a higher percentage of men was observed in the group with cam deformity than in the group without it. No relationship was observed between cam deformity and hip pain. Factors associated with α angle were examined via multiple regression analysis for each gender; α angle was significantly associated with age and BMI in each gender. The α angle and PT were correlated in women. Thus, α angle and cam deformity prevalence increase with age in Japanese individuals. Accordingly, cam deformity can be considered a developmental disease.
Topics: Male; Humans; Female; Aged; Hip Joint; Japan; Femoracetabular Impingement; Hip; Pelvis
PubMed: 38238438
DOI: 10.1038/s41598-024-51876-0 -
PloS One 2023A novel machine learning framework that is able to consistently detect, localize, and measure the severity of human congenital cleft lip anomalies is introduced. The...
A novel machine learning framework that is able to consistently detect, localize, and measure the severity of human congenital cleft lip anomalies is introduced. The ultimate goal is to fill an important clinical void: to provide an objective and clinically feasible method of gauging baseline facial deformity and the change obtained through reconstructive surgical intervention. The proposed method first employs the StyleGAN2 generative adversarial network with model adaptation to produce a normalized transformation of 125 faces, and then uses a pixel-wise subtraction approach to assess the difference between all baseline images and their normalized counterparts (a proxy for severity of deformity). The pipeline of the proposed framework consists of the following steps: image preprocessing, face normalization, color transformation, heat-map generation, morphological erosion, and abnormality scoring. Heatmaps that finely discern anatomic anomalies visually corroborate the generated scores. The proposed framework is validated through computer simulations as well as by comparison of machine-generated versus human ratings of facial images. The anomaly scores yielded by the proposed computer model correlate closely with human ratings, with a calculated Pearson's r score of 0.89. The proposed pixel-wise measurement technique is shown to more closely mirror human ratings of cleft faces than two other existing, state-of-the-art image quality metrics (Learned Perceptual Image Patch Similarity and Structural Similarity Index). The proposed model may represent a new standard for objective, automated, and real-time clinical measurement of faces affected by congenital cleft deformity.
Topics: Humans; Cleft Lip; Cleft Palate; Computer Simulation; Musculoskeletal Diseases; Machine Learning; Image Processing, Computer-Assisted
PubMed: 37535557
DOI: 10.1371/journal.pone.0288228 -
Human Molecular Genetics Jul 2023ATRX is a chromatin remodelling ATPase that is involved in transcriptional regulation, DNA damage repair and heterochromatin maintenance. It has been widely studied for...
ATRX is a chromatin remodelling ATPase that is involved in transcriptional regulation, DNA damage repair and heterochromatin maintenance. It has been widely studied for its role in ALT-positive cancers, but its role in neurological function remains elusive. Hypomorphic mutations in the X-linked ATRX gene cause a rare form of intellectual disability combined with alpha-thalassemia called ATR-X syndrome in hemizygous males. Clinical features also include facial dysmorphism, microcephaly, short stature, musculoskeletal defects and genital abnormalities. As complete deletion of ATRX in mice results in early embryonic lethality, the field has largely relied on conditional knockout models to assess the role of ATRX in multiple tissues. Given that null alleles are not found in patients, a more patient-relevant model was needed. Here, we have produced and characterized the first patient mutation knock-in model of ATR-X syndrome, carrying the most common causative mutation, R246C. This is one of a cluster of missense mutations located in the chromatin-binding domain and disrupts its function. The knock-in mice recapitulate several aspects of the patient disorder, including craniofacial defects, microcephaly, reduced body size and impaired neurological function. They provide a powerful model for understanding the molecular mechanisms underlying ATR-X syndrome and testing potential therapeutic strategies.
Topics: Animals; Male; Mice; alpha-Thalassemia; Mental Retardation, X-Linked; Microcephaly; Mutation; Nuclear Proteins; X-linked Nuclear Protein; Humans
PubMed: 37171606
DOI: 10.1093/hmg/ddad075