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Arquivos de Neuro-psiquiatria May 2024Wilson disease (WD) is an autosomal recessive disorder that leads to organ toxicity due to copper overload. Early diagnosis is complicated by the rarity and diversity...
BACKGROUND
Wilson disease (WD) is an autosomal recessive disorder that leads to organ toxicity due to copper overload. Early diagnosis is complicated by the rarity and diversity of manifestations.
OBJECTIVE
To describe the diagnostic features and response to treatment in our cohort of WD patients.
METHODS
This was a retrospective analysis of 262 WD patients stratified by clinical presentation, complementary exams, genotyping, and response to treatment.
RESULTS
Symptoms occurred at an average age of 17.4 (7-49) years, and patients were followed up for an average of 9.6 (0-45) years. Patients presented mainly with hepatic (36.3%), neurologic (34.7%), and neuropsychiatric (8.3%) forms. Other presentations were hematologic, renal, or musculoskeletal, and 16.8% of the patients were asymptomatic. Kayser-Fleischer rings occurred in 78.3% of the patients, hypoceruloplasminemia in 98.3%, and elevated cupruria/24h in 73.0%, with an increase after D-penicillamine in 54.0%. Mutations of the gene were detected in 84.4% of alleles. Brain magnetic resonance imaging showed abnormalities in the basal ganglia in 77.7% of patients. D-penicillamine was the first choice in 93.6% of the 245 patients, and 21.1% of these patients were switched due to adverse effects. The second-line therapies were zinc and trientine. The therapeutic response did not differ significantly between the drugs ( = 0.2). Nine patients underwent liver transplantation and 82 died.
CONCLUSION
Wilson disease is diagnosed at a late stage, and therapeutic options are limited. In people under 40 years of age with compatible manifestations, WD could be considered earlier in the differential diagnosis. There is a need to include genotyping and therapeutic alternatives in clinical practice.
Topics: Humans; Hepatolenticular Degeneration; Retrospective Studies; Female; Male; Adolescent; Child; Adult; Copper-Transporting ATPases; Young Adult; Penicillamine; Treatment Outcome; Middle Aged; Adenosine Triphosphatases; Mutation; Genotype; Magnetic Resonance Imaging; Chelating Agents; Cation Transport Proteins; Copper
PubMed: 38811021
DOI: 10.1055/s-0044-1786855 -
JAMA Dermatology May 2024Masculinizing gender-affirming hormonal therapy is associated with the development of acne. While isotretinoin is a highly effective acne treatment, little is known...
IMPORTANCE
Masculinizing gender-affirming hormonal therapy is associated with the development of acne. While isotretinoin is a highly effective acne treatment, little is known about its effectiveness and safety among transgender and gender-diverse individuals receiving gender-affirming hormonal therapy.
OBJECTIVE
To evaluate clinical outcomes of isotretinoin among transgender and gender-diverse individuals receiving gender-affirming hormonal therapy.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter retrospective case series study was conducted at 4 medical centers: Mass General Brigham, University of Pennsylvania, Emory University, and Fenway Health. It included patients aged between 12 and 49 years who were receiving masculinizing gender-affirming hormonal therapy and prescribed isotretinoin for the management of acne between August 14, 2015, and September 20, 2023.
EXPOSURE
Isotretinoin therapy for the management of acne.
MAIN OUTCOMES AND MEASURES
The percentage of patients experiencing improvement or clearance of acne, as well as rates of acne recurrence. Adverse effects and reasons for treatment discontinuation were also evaluated.
RESULTS
Among 55 included patients, the mean (SD) age was 25.4 years; 4 (7.3%) were Asian, 2 (3.6%) were Black, 4 (7.2%) were Hispanic, 1 was (1.8%) multiracial, and 36 (65.5%) were White. The median isotretinoin course duration was 6 months (IQR, 4.0-8.0), with a median cumulative dose of 132.7 mg/kg (IQR, 66.4-168.5); the cumulative dose was less than 90 mg/kg for 16 patients (29.1%) and less than 120 mg/kg for 22 patients (40.0%). Isotretinoin was associated with improvement in 48 patients (87.3%) and clearance in 26 patients (47.3%). For the 33 patients treated with a cumulative dose of 120 mg/kg or more, these rates increased to 32 patients (97.0%) and 21 patients (63.6%), respectively. Among the 20 patients who achieved acne clearance and had any subsequent health care encounters, the risk of recurrence was 20.0% (n = 4). The most frequently reported adverse effects were dryness (n = 44; 80.0%), joint pain (n = 8; 14.5%), and eczema (n = 5; 9.1%). Laboratory abnormalities were uncommon. Reasons for premature treatment discontinuation included cost, pharmacy issues, adverse effects, logistical reasons (scheduling), and wound healing concerns for gender-affirming surgery.
CONCLUSION AND RELEVANCE
In this case series study of individuals with acne who were receiving masculinizing gender-affirming hormonal therapy and underwent isotretinoin treatment, isotretinoin was often effective and well tolerated. However, premature treatment discontinuation was common and associated with poorer outcomes. Further efforts are needed to understand optimal dosing and treatment barriers to improve outcomes in transgender and gender-diverse individuals receiving masculinizing gender-affirming hormonal therapy.
PubMed: 38809569
DOI: 10.1001/jamadermatol.2024.1420 -
Journal of Orthopaedic Surgery and... May 2024Humeral shaft fractures, constituting 3-5% of musculoskeletal injuries, are commonly managed conservatively using functional braces. However, this approach may not be...
BACKGROUND
Humeral shaft fractures, constituting 3-5% of musculoskeletal injuries, are commonly managed conservatively using functional braces. However, this approach may not be feasible in resource-limited settings. This study aimed to evaluate the functional outcomes of nonoperative treatment for humeral shaft fractures in adults utilizing a U-shaped slab.
METHODS
This prospective study was conducted from August 2021 to August 2022 involving 16-year-old and older individuals who received nonsurgical treatment for humeral shaft fractures at public tertiary hospitals in Rwanda. The assessment focused on various functional outcomes, including alignment, union rate, range of motion, return to activities of daily living, and DASH score.
RESULTS
The study included 73 participants, predominantly males (73.9%), with a median age of 33 years. The union rate was high at 89.04%, and 10.96% experienced delayed union. Radial nerve palsy occurred in 4.11% of patients, but all the patients fully recovered within three months. Despite angular deformities during healing in the majority of participants, these deformities did not significantly impact functional outcomes. According to the international classification of disabilities, 77% of participants achieved a good functional grade.
CONCLUSION
The conservative U-shaped slab method was effective at managing humeral shaft fractures. However, optimal results necessitate careful participant selection and comprehensive rehabilitation education. Implementing these measures can improve the overall success of nonoperative management.
Topics: Humans; Humeral Fractures; Female; Male; Prospective Studies; Adult; Treatment Outcome; Middle Aged; Young Adult; Adolescent; Conservative Treatment; Rwanda; Cohort Studies; Range of Motion, Articular; Activities of Daily Living; Recovery of Function; Fracture Healing; Health Resources; Resource-Limited Settings
PubMed: 38807217
DOI: 10.1186/s13018-024-04794-w -
Relative Energy Deficiency in Sport (RED-S) and Knee Injuries: Current Concepts for Female Athletes.Journal of ISAKOS : Joint Disorders &... May 2024In athletes, a mismatch between caloric intake and energy expended in exercise can result in Low Energy Availability (LEA). LEA can lead to Relative Energy Deficiency in...
In athletes, a mismatch between caloric intake and energy expended in exercise can result in Low Energy Availability (LEA). LEA can lead to Relative Energy Deficiency in Sport (RED-S), where the athlete suffers from physiological derangements and decreased sport performance. The prevalence of RED-S is higher in females than males. RED-S more comprehensively describes the syndrome originally known as "Female Athlete Triad" (FAT). FAT encompasses the triad of LEA (with or without disordered eating), menstrual dysfunction and low bone mineral density. RED-S includes other physiological derangements such as poor cardiovascular health, abnormalities of metabolic rate, immunity, and protein synthesis. Females are already at a higher risk of knee injuries, which has been attributed to a multitude of factors such as hormonal influences, differences in musculoskeletal anatomy and neuromuscular control compared to males. The literature demonstrates an even higher risk of knee injuries in female athletes with symptoms of RED-S. We propose the various factors that influence this risk. A reduction in anabolic hormones can affect muscle development and tendon repair. A relationship between poor neuromuscular control and knee injury has been established, and this can be further worsened in patients with menstrual dysfunction. Chronic deficiency in nutrients such as collagen and vitamin D can result in poorer recovery from microtrauma in tendon and ligaments. All these factors may contribute to increasing the risk of knee injuries, which may include anterior cruciate ligament tears, patella tendinopathy and patellofemoral pain syndrome. This review aims to educate sports clinicians to have a high index of suspicion when treating knee injuries in females; to screen and then manage for RED-S if present, for holistic patient care.
PubMed: 38795863
DOI: 10.1016/j.jisako.2024.05.012 -
Medicina (Kaunas, Lithuania) Apr 2024: The pancreas, ensconced within the abdominal cavity, requires a plethora of sophisticated imaging modalities for its comprehensive evaluation, with ultrasonography... (Review)
Review
: The pancreas, ensconced within the abdominal cavity, requires a plethora of sophisticated imaging modalities for its comprehensive evaluation, with ultrasonography serving as a primary investigative technique. A myriad of pancreatic pathologies, encompassing pancreatic neoplasia and a spectrum of inflammatory diseases, are detectable through these imaging strategies. Nevertheless, the intricate anatomical confluence and the pancreas's deep-seated topography render the visualization and accurate diagnosis of its pathologies a formidable endeavor. The objective of our paper is to review the best diagnostic imagistic tools for the pancreas. : we have gathered several articles using Prisma guidelines to determine the best imagistic methods. The imperative of pancreatic scanning transcends its diagnostic utility, proving to be a pivotal element in a multitude of clinical specialties, notably surgical oncology. Within this domain, multidetector computed tomography (MDCT) of the pancreas holds the distinction of being the paramount imaging modality, endorsed for its unrivaled capacity to delineate the staging and progression of pancreatic carcinoma. In synergy with MDCT, there has been a notable advent of avant-garde imaging techniques in recent years. These advanced methodologies, including ultrasonography, endoscopic ultrasonography, contrast-enhanced ultrasonography, and magnetic resonance imaging (MRI) conjoined with magnetic resonance cholangiopancreatography (MRCP), have broadened the horizon of tumor characterization, offering unparalleled depth and precision in oncological assessment. Other emerging diagnostic techniques, such as elastography, also hold a lot of potential and promise for the future of pancreatic imaging. Fine needle aspiration (FNA) is a quick, minimally invasive procedure to evaluate lumps using a thin needle to extract tissue for analysis. It is less invasive than surgical biopsies and usually performed as an outpatient with quick recovery. Its accuracy depends on sample quality, and the risks include minimal bleeding or discomfort. Results, guiding further treatment, are typically available within a week. Elastography is a non-invasive medical imaging technique that maps the elastic properties and stiffness of soft tissue. This method, often used in conjunction with ultrasound or MRI, helps differentiate between hard and soft areas in tissue, providing valuable diagnostic information. It is particularly useful for assessing liver fibrosis, thyroid nodules, breast lumps, and musculoskeletal conditions. The technique is painless and involves applying gentle pressure to the area being examined. The resulting images show tissue stiffness, indicating potential abnormalities. Elastography is advantageous for its ability to detect diseases in early stages and monitor treatment effectiveness. The procedure is quick, safe, and requires no special preparation, with results typically available immediately. : The assembled and gathered data shows the efficacy of various techniques in discerning the nature and extent of neoplastic lesions within the pancreas. : The most common imaging modalities currently used in diagnosing pancreatic neoplasms are multidetector computed tomography (MDCT), endoscopic ultrasound (EUS), and magnetic resonance imaging (MRI), alongside new technologies, such as elastography.
Topics: Humans; Pancreatic Neoplasms; Ultrasonography; Magnetic Resonance Imaging; Multidetector Computed Tomography; Pancreas
PubMed: 38792878
DOI: 10.3390/medicina60050695 -
International Journal of Molecular... May 2024Macrocephaly, characterized by an abnormally large head circumference, often co-occurs with distinctive finger changes, presenting a diagnostic challenge for clinicians.... (Review)
Review
Macrocephaly, characterized by an abnormally large head circumference, often co-occurs with distinctive finger changes, presenting a diagnostic challenge for clinicians. This review aims to provide a current synthetic overview of the main acquired and genetic etiologies associated with macrocephaly and finger changes. The genetic cause encompasses several categories of diseases, including bone marrow expansion disorders, skeletal dysplasias, ciliopathies, inherited metabolic diseases, RASopathies, and overgrowth syndromes. Furthermore, autoimmune and autoinflammatory diseases are also explored for their potential involvement in macrocephaly and finger changes. The intricate genetic mechanisms involved in the formation of cranial bones and extremities are multifaceted. An excess in growth may stem from disruptions in the intricate interplays among the genetic, epigenetic, and hormonal factors that regulate human growth. Understanding the underlying cellular and molecular mechanisms is important for elucidating the developmental pathways and biological processes that contribute to the observed clinical phenotypes. The review provides a practical approach to delineate causes of macrocephaly and finger changes, facilitate differential diagnosis and guide for the appropriate etiological framework. Early recognition contributes to timely intervention and improved outcomes for affected individuals.
Topics: Humans; Megalencephaly; Fingers
PubMed: 38791606
DOI: 10.3390/ijms25105567 -
Biomedicines Apr 2024In the biomedical field, the differentiation between sex and gender is crucial for enhancing the understanding of human health and personalizing medical treatments,... (Review)
Review
Investigating and Practicing Orthopedics at the Intersection of Sex and Gender: Understanding the Physiological Basis, Pathology, and Treatment Response of Orthopedic Conditions by Adopting a Gender Lens: A Narrative Overview.
In the biomedical field, the differentiation between sex and gender is crucial for enhancing the understanding of human health and personalizing medical treatments, particularly within the domain of orthopedics. This distinction, often overlooked or misunderstood, is vital for dissecting and treating musculoskeletal conditions effectively. This review delves into the sex- and gender-specific physiology of bones, cartilage, ligaments, and tendons, highlighting how hormonal differences impact the musculoskeletal system's structure and function, and exploring the physiopathology of orthopedic conditions from an epidemiological, molecular, and clinical perspective, shedding light on the discrepancies in disease manifestation across sexes. Examples such as the higher rates of deformities (adolescent idiopathic and adult degenerative scoliosis and hallux valgus) in females and osteoporosis in postmenopausal women illustrate the critical role of sex and gender in orthopedic health. Additionally, the review addresses the morbidity-mortality paradox, where women, despite appearing less healthy on frailty indexes, show lower mortality rates, highlighting the complex interplay between biological and social determinants of health. Injuries and chronic orthopedic conditions such osteoarthritis exhibit gender- and sex-specific prevalence and progression patterns, necessitating a nuanced approach to treatment that considers these differences to optimize outcomes. Moreover, the review underscores the importance of recognizing the unique needs of sexual minority and gender-diverse individuals in orthopedic care, emphasizing the impact of gender-affirming hormone therapy on aspects like bone health and perioperative risks. To foster advancements in sex- and gender-specific orthopedics, we advocate for the strategic disaggregation of data by sex and gender and the inclusion of "Sexual Orientation and Gender Identity" (SOGI) data in research and clinical practice. Such measures can enrich clinical insights, ensure tailored patient care, and promote inclusivity within orthopedic treatments, ultimately enhancing the precision and effectiveness of care for diverse patient populations. Integrating sex and gender considerations into orthopedic research and practice is paramount for addressing the complex and varied needs of patients. By embracing this comprehensive approach, orthopedic medicine can move towards more personalized, effective, and inclusive treatment strategies, thereby improving patient outcomes and advancing the field.
PubMed: 38790936
DOI: 10.3390/biomedicines12050974 -
Children (Basel, Switzerland) May 2024Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. The standard and most effective treatment is wide resection of the tumor...
Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. The standard and most effective treatment is wide resection of the tumor combined with neoadjuvant chemotherapy. Adolescent idiopathic scoliosis (AIS) is a genetically determined three-dimensional spinal deformity, which occurs in teenage patients and is mostly progressive. The basic management strategy is surgical treatment when the curve exceeds 50 degrees. However, the indications are different in oncologic patients. The aim of this study was to describe a case of adolescent scoliosis with osteosarcoma of the pelvis. The authors conducted a scoping review using PubMed and Embase to analyze the state of knowledge. The presented paper is the first report of pelvis osteosarcoma coexisting with adolescent idiopathic scoliosis. Treatment for this complex case finished with very good results, with no recurrence observed during the nine-year follow-up.
PubMed: 38790602
DOI: 10.3390/children11050607 -
Children (Basel, Switzerland) Apr 2024CACNA1C gene encodes the alpha 1 subunit of the CaV1.2 L-type Ca2+ channel. Pathogenic variants in this gene have been associated with cardiac rhythm disorders such as... (Review)
Review
CACNA1C gene encodes the alpha 1 subunit of the CaV1.2 L-type Ca2+ channel. Pathogenic variants in this gene have been associated with cardiac rhythm disorders such as long QT syndrome, Brugada syndrome and Timothy syndrome. Recent evidence has suggested the possible association between CACNA1C mutations and neurologically-isolated (in absence of cardiac involvement) phenotypes in children, giving birth to a wider spectrum of CACNA1C-related clinical presentations. However, to date, little is known about the variety of both neurological and non-neurological signs/symptoms in the neurologically-predominant phenotypes. We conducted a systematic review of neurologically-predominant presentations without cardiac conduction defects, associated with CACNA1C mutations. We also reported a novel de novo missense pathogenic variant in the CACNA1C gene of a children patient presenting with constructional, dressing and oro-buccal apraxia associated with behavioral abnormalities, mild intellectual disability, dental anomalies, gingival hyperplasia and mild musculoskeletal defects, without cardiac conduction defects. The present study highlights the importance of considering the investigation of the CACNA1C gene in children's neurological isolated syndromes, and expands the phenotype of the CACNA1C related conditions. In addition, the present study highlights that, even in absence of cardiac conduction defects, nuanced clinical manifestations of the Timothy syndrome (e.g., dental and gingival defects) could be found. These findings suggest the high variable expressivity of the CACNA1C gene and remark that the absence of cardiac involvement should not mislead the diagnosis of a CACNA1C related disorder.
PubMed: 38790536
DOI: 10.3390/children11050541 -
Spine Deformity May 2024Postoperative physical therapy (PT) is a cornerstone of orthopedic and musculoskeletal rehabilitation, proven to provide various positive clinical benefits. However,... (Review)
Review
PURPOSE
Postoperative physical therapy (PT) is a cornerstone of orthopedic and musculoskeletal rehabilitation, proven to provide various positive clinical benefits. However, there is a paucity of literature evaluating the utility of preoperative rehabilitation specific to spine surgery. Thus, this review article aims to provide an overview of previously published studies discussing the efficacy of preoperative rehabilitation programs and its role in spinal surgery. Special emphasis was given to preoperative frailty assessments, physical performance tests, interventional strategies, feasibility, and future directions.
METHODS
We performed a literature review using PubMed, Google Scholar, EMBASE, and PubMed Central (PMC) using directed search terms. Articles that examined preoperative rehabilitation in adult spine surgery were compiled for this review. Prehabilitation programs focused on exercise, flexibility, and behavioral modifications have been shown to significantly improve pain levels and functional strength assessments in patients undergoing elective spine surgery. In addition, studies suggest that these programs may also decrease hospital stays, return to work time, and overall direct health care expenditure costs. Screening tools such as the FRAIL scale can be used to assess frailty while physical function tests like the timed-up-and go (TUGT), 5 repetition sit-to-stand test (5R-STST), and hand grip strength (HGS) can help identify patients who would most benefit from prehabilitation.
CONCLUSIONS
This review illustrates that prehabilitation programs have the potential to increase quality of life, improve physical function and activity levels, and decrease pain, hospital stays, return to work time, and overall direct costs. However, there is a paucity of literature in this field that requires further study and investigation.
PubMed: 38789728
DOI: 10.1007/s43390-024-00893-0