RESUMEN
OBJECTIVE: There is increasing interest in applying artificial intelligence chatbots like generative pretrained transformer 4 (GPT-4) in the medical field. This study aimed to explore the universality of GPT-4 responses to simulated clinical scenarios of developmental dysplasia of the hip (DDH) across diverse global settings. METHODS: Seventeen international experts with more than 15 years of experience in pediatric orthopaedics were selected for the evaluation panel. Eight simulated DDH clinical scenarios were created, covering 4 key areas: (1) initial evaluation and diagnosis, (2) initial examination and treatment, (3) nursing care and follow-up, and (4) prognosis and rehabilitation planning. Each scenario was completed independently in a new GPT-4 session. Interrater reliability was assessed using Fleiss kappa, and the quality, relevance, and applicability of GPT-4 responses were analyzed using median scores and interquartile ranges. Following scoring, experts met in ZOOM sessions to generate Regional Consensus Assessment Scores, which were intended to represent a consistent regional assessment of the use of the GPT-4 in pediatric orthopaedic care. RESULTS: GPT-4's responses to the 8 clinical DDH scenarios received performance scores ranging from 44.3% to 98.9% of the 88-point maximum. The Fleiss kappa statistic of 0.113 ( P = 0.001) indicated low agreement among experts in their ratings. When assessing the responses' quality, relevance, and applicability, the median scores were 3, with interquartile ranges of 3 to 4, 3 to 4, and 2 to 3, respectively. Significant differences were noted in the prognosis and rehabilitation domain scores ( P < 0.05 for all). Regional consensus scores were 75 for Africa, 74 for Asia, 73 for India, 80 for Europe, and 65 for North America, with the Kruskal-Wallis test highlighting significant disparities between these regions ( P = 0.034). CONCLUSIONS: This study demonstrates the promise of GPT-4 in pediatric orthopaedic care, particularly in supporting preliminary DDH assessments and guiding treatment strategies for specialist care. However, effective integration of GPT-4 into clinical practice will require adaptation to specific regional health care contexts, highlighting the importance of a nuanced approach to health technology adaptation. LEVEL OF EVIDENCE: Level IV.
Asunto(s)
Displasia del Desarrollo de la Cadera , Humanos , Inteligencia Artificial , Reproducibilidad de los Resultados , OrtopediaRESUMEN
PURPOSE: The incidence of developmental dysplasia of the hip (DDH) is higher in Eastern Europeans and Middle Easterners. This study aimed to establish consensus among experts in this geographical area on the management of DDH before walking age. METHODS: Fourteen experienced orthopedic surgeons agreed to participate in a four-round online consensus panel by the Delphi method. The questionnaire included 31 statements concerning the prevention, diagnosis, and treatment of DDH before walking age. RESULTS: Consensus was established for 26 (84%) of 31 statements. Hip ultrasonography is the proper diagnostic tool under six months in DDH; universal newborn hip screening between three and six weeks is necessary; positive family history, breech presentation, female gender, and postnatal swaddling are the most important risk factors; Ortolani, Barlow tests, and limitation of abduction are the most important clinical findings; Pavlik harness is the first bracing preference; some Graf type IIa hips and all Graf type IIb and worse hips need abduction bracing treatment; the uppermost age limit for closed and open reductions is 12 months and 12-24 months, respectively; anatomic reduction is essential in closed and open reductions, postoperative MRI or CT is not always indicated; anterior approach open reduction is better than medial approach open reduction; forceful reduction and extreme positioning of the hips (> 60° hip abduction) are the two significant risk factors for osteonecrosis of the femoral head. CONCLUSION: The findings of the present study may be useful for clinicians because a practical reference, based on the opinions of the multinational expert panel, but may not be applicable to all settings is provided.
Asunto(s)
Consenso , Técnica Delphi , Displasia del Desarrollo de la Cadera , Humanos , Medio Oriente/epidemiología , Femenino , Masculino , Lactante , Recién Nacido , Displasia del Desarrollo de la Cadera/diagnóstico , Displasia del Desarrollo de la Cadera/terapia , Displasia del Desarrollo de la Cadera/cirugía , Europa Oriental/epidemiología , Factores de Riesgo , Tamizaje Neonatal/métodos , Encuestas y CuestionariosRESUMEN
BACKGROUND: The mainstay of deformity correction and fracture prevention for patients with osteogenesis imperfecta (OI) includes osteotomies and intramedullary rodding. Guided growth, described in the setting of skeletal dysplasias, offers a less invasive means of deformity correction. We report a multicenter case series of guided growth procedures in the setting of OI. METHODS: We retrospectively reviewed patients with OI at three institutions from April 2012 to April 2019: 18 patients underwent guided growth for angular deformity correction with minimum 1-year follow-up or full deformity correction and removal of guided growth hardware. Clinical characteristics, deformity measurements, and complications were collected. Distal femoral and proximal tibial hemiepiphysiodesis was performed using figure-of-eight plates and screws, and distal tibial medial hemiepiphysiodesis with cannulated screws. Preoperative and postoperative lateral distal femoral angle, medial proximal tibial angle, and lateral distal tibial angle were measured. Frequency and descriptive statistics were completed. RESULTS: Eighteen patients with OI (five-I, four-III, six-IV, three-V) underwent 33 guided growth procedures with mean follow-up of 3.09 years; all received routine bisphosphonate treatment. Preoperative and postoperative mean joint angles were measured. The location for hemiepiphysiodesis included 8 distal femoral medial, 2 distal femoral lateral, 8 proximal tibial medial, 3 proximal tibial lateral, and 12 distal tibial medial. Twelve of the 33 procedures were in patients who had an intramedullary rod; 1 demonstrated backout of the epiphyseal and metaphyseal screws of a distal femoral medial figure-of-eight plate. It was revised to a larger plate with longer screws and removed upon completion of deformity correction. CONCLUSION: Guided growth may be used as an effective means of angular deformity correction with dysplastic OI bone. Having an intramedullary rod did not preclude the use of a guided growth technique. One procedure demonstrated screw backout. Given the short stature associated with OI, performing a guided growth procedure at an early enough age to allow time for correction should be considered. LEVEL OF EVIDENCE: Level IV-case series.
Asunto(s)
Enfermedades del Desarrollo Óseo , Osteogénesis Imperfecta , Placas Óseas , Tornillos Óseos , Humanos , Osteogénesis Imperfecta/complicaciones , Osteogénesis Imperfecta/cirugía , Estudios Retrospectivos , Tibia/cirugíaRESUMEN
Camptodactyly and clinodactyly are most commonly considered just cosmetic defects, but they can pose a major diagnostic and therapeutic challenge, mainly because of their apparently similar clinical presentation. For years, experts have been arguing over definitions, descriptions, and therapeutic approaches to these deformities, with some favoring surgical approach, some advocating conservative treatment, while others are prone to use a combination of the aforementioned approaches. This article provides an overview of the current literature on two different entities, with emphasis on differences in clinical presentation and treatment modalities. This may improve the understanding and recognition of these deformities in children, and help the attending physician select the most appropriate therapy for the individual patient.
Asunto(s)
Tratamiento Conservador , Niño , HumanosRESUMEN
Osteoarthritis is a common cause of disability worldwide. Although commonly referred to as a disease of the joint cartilage, osteoarthritis affects all joint tissues equally. The pathogenesis of this degenerative process is not completely understood; however, a low-grade inflammation leading to an imbalance between anabolic and katabolic processes is a well-established factor. The complex network of cytokines regulating these processes and cell communication has a central role in the development and progression of osteoarthritis. Concentrations of both proinflammatory and anti-inflammatory cytokines were found to be altered depending on the osteoarthritis stage and activity. In this review, we analyzed individual cytokines involved in the immune processes with an emphasis on their function in osteoarthritis.
Asunto(s)
Quimiocinas/metabolismo , Citocinas/metabolismo , Susceptibilidad a Enfermedades , Osteoartritis/etiología , Osteoartritis/metabolismo , Animales , Biomarcadores , Humanos , Mediadores de Inflamación/metabolismo , Osteoartritis/patologíaRESUMEN
PURPOSE OF REVIEW: We present the reader with insight on the most common disorders of the knee in newborns and infants. Knee issues in this population may confuse the first contact physicians due to certain peculiarities of the immature immune system, small size and underdevelopment of joint anatomy. Data presented here are recent and significant, and something to bear in mind when caring for children of this age. RECENT FINDINGS: With the advent of new diagnostic methods, a shift in the causative agent of pediatric knee infections has been noted. Minimally invasive methods such as arthrocentesis and arthroscopy are successfully employed in treatment of knee problems in newborns and infants. A trial of conservative therapy in congenital patellar instability can give good results, and obviate the need for surgery in some cases. Various syndromes that affect the knee have specific characteristics that need to be recognized early to avoid problems in the future. SUMMARY: Although rare, knee problems in infants can and do occur. Their cause varies significantly and good outcomes require a multidisciplinary approach. Early diagnosis, referral and initiation of treatment protocols can significantly influence the fate of the joint and with it the patients' functional status for life.
Asunto(s)
Enfermedades Óseas/diagnóstico , Enfermedades Óseas/terapia , Artropatías/diagnóstico , Artropatías/terapia , Articulación de la Rodilla , Enfermedades Óseas/congénito , Niño , Humanos , Lactante , Recién Nacido , Artropatías/congénito , Rodilla/anomalías , Articulación de la Rodilla/anomalías , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Menisco/anomalías , Anomalías Musculoesqueléticas/diagnóstico , Anomalías Musculoesqueléticas/terapiaRESUMEN
Longitudinal epiphyseal bracket (LEB) is a rare bone dysplasia of the tubular bones. Owing to an abnormal secondary ossification center, the affected bones can develop progressive shortening and angular deformity. The aim of our study was to provide an overview of the reported data regarding epidemiology and surgical procedures available for LEB of the first metatarsal bone in a pediatric population combined with a small case series. We report a retrospective case series of 3 nonsyndromic pediatric patients with different ages and with confirmed dysplasia of the first metatarsal bone. All patients presented with unilateral congenital hallux varus deformity and underwent surgical treatment. The radiographs and medical records were reviewed to evaluate the deformity characteristics, treatment, and clinical results. The mean patient age at initial surgery was 34 (range 12 to 63) months, and the median follow-up period was 46 (range 31 to 75) months. Almost all specific radiographic measurements showed correction of the deformity, and each foot demonstrated functional and cosmetic improvement. A standardized literature search was performed to obtain studies of LEB of the first metatarsal bone in the pediatric population. From on our results and the current data available, surgical treatment should be tailored to the patient's age and radiographic stage of LEB. However, monitoring until skeletal maturity of the feet is necessary to assess the final results.
Asunto(s)
Enfermedades del Desarrollo Óseo/cirugía , Deformidades Congénitas del Pie/cirugía , Hallux Varus/cirugía , Huesos Metatarsianos/anomalías , Huesos Metatarsianos/cirugía , Enfermedades del Desarrollo Óseo/etiología , Preescolar , Epífisis/cirugía , Femenino , Deformidades Congénitas del Pie/etiología , Hallux Varus/etiología , Humanos , Lactante , Recién Nacido , MasculinoRESUMEN
BACKGROUND: There is an evident lack of research on timing of polydactyly surgery and its effects on treatment results. METHODS: Retrospective comparative study on foot polydactyly patients treated at our department from 1995 to 2009. Patients were divided into 2 groups, group A - under the age of 5 at surgery, and group B - 5 years and older. RESULTS: There were 24 patients (8 male, 16 female), 30 feet. Median age at surgery was 1 year (range, 9 months-4.5 years) for group A, and 8.5 years (range, 6-37 years) for group B. Median follow-up was 16.2 years (range, 7-21 years). There were 16 postaxial and 8 preaxial cases. At the last follow-up 12 patients' feet were "excellent" and 12 "good". No significant differences were identified between the two groups at final follow-up. CONCLUSIONS: Timing of surgery for foot polydactyly is not crucial for final results.
Asunto(s)
Deformidades Congénitas del Pie/cirugía , Polidactilia/cirugía , Dedos del Pie/anomalías , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Femenino , Deformidades Congénitas del Pie/diagnóstico por imagen , Deformidades Congénitas del Pie/rehabilitación , Humanos , Lactante , Masculino , Polidactilia/diagnóstico por imagen , Polidactilia/rehabilitación , Recuperación de la Función , Estudios Retrospectivos , Factores de Tiempo , Dedos del Pie/diagnóstico por imagen , Dedos del Pie/cirugía , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Lower extremity angular deformities are common in children with skeletal dysplasia and can be treated with various surgical options. Both acute correction by osteotomy with internal fixation and gradual correction by external fixation have been used with acceptable results. Recently, the Guided Growth concept using temporary hemiepiphysiodesis for correction of angular deformities in the growing child has been proposed. This study presents the results of temporary hemiepiphysiodesis using eight-Plates and medial malleolus transphyseal screws in children with skeletal dysplasia with lower extremity angular deformities. METHODS: Twenty-nine patients (50 lower extremities) with skeletal dysplasia of different types were treated for varus or valgus deformities at 2 centers. The mean age at the time of hemiepiphysiodesis was 10±2.9 years. A total of 66 eight-Plates and 12 medial malleolus screws were used. The average follow-up time between the index surgery and the latest follow-up with the eight-Plate in was 25±13.4 months. Erect long-standing anteroposterior and lateral view radiographs were obtained for deformity planning before the procedure. Angular deformities on radiograph were evaluated by mechanical axis deviation, mechanical lateral distal femoral angle, medial proximal tibial angle, and lateral distal tibial angle. Mechanical axis deviation was also expressed as a percentage to one half of the width of the tibial plateau, and the magnitude of the deformity was classified by determining the zones through which the mechanical axis of the lower extremity passed. Four zones were determined on both the medial and lateral side of the knee and the zones were labeled 1, 2, 3, and 4, corresponding to the severity of the deformity. A positive value was assigned for valgus alignment and a negative for varus alignment. RESULTS: Patients were analyzed in valgus and varus groups. There was correction in 34 of 38 valgus legs and 7 of 12 varus legs. In the valgus group, the mean preoperative and postoperative mechanical lateral distal femoral angles were 82.1±3.7 and 91.1±4.9 degrees, respectively (P<0.001). The mean preoperative and postoperative medial proximal tibial angles were 98.5±8 and 87.8±7.1 degrees, respectively (P<0.001). Six patients with bilateral ankle valgus deformities (12 ankles) underwent single-screw medial malleolus hemiepiphysiodesis. The mean preoperative and postoperative lateral distal tibial angles were 73.9±8.7 and 86.1±6.8 degrees, respectively (P<0.001). The numbers of plates in each anatomic location were not enough to make statistical conclusions in varus legs. Four patients in the valgus group and 3 patients in the varus group did not benefit from the procedure. Mechanical axes were in zone 2 or over in 94% of the legs preoperatively, whereas postoperatively, only 23% of the legs had mechanical axes in zone 2 or over in varus and valgus groups. CONCLUSIONS: Growth modulation with an eight-Plate is a relatively simple surgery and has low risk of mechanical failure or physeal damage. It can be performed in very young patients, which is an important advantage in skeletal dysplasia. Screw purchase is reliable even in the abnormal epiphysis and metaphysis. Our results show that Guided Growth using eight-Plates in skeletal dysplasia is safe and effective. LEVEL OF EVIDENCE: Level IV.
Asunto(s)
Enfermedades del Desarrollo Óseo/diagnóstico por imagen , Enfermedades del Desarrollo Óseo/cirugía , Epífisis/diagnóstico por imagen , Epífisis/cirugía , Extremidad Inferior/diagnóstico por imagen , Extremidad Inferior/cirugía , Adolescente , Articulación del Tobillo/diagnóstico por imagen , Articulación del Tobillo/cirugía , Tornillos Óseos , Niño , Preescolar , Femenino , Fémur/diagnóstico por imagen , Fémur/cirugía , Estudios de Seguimiento , Placa de Crecimiento/diagnóstico por imagen , Placa de Crecimiento/cirugía , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Masculino , Osteotomía/instrumentación , Osteotomía/métodos , Radiografía , Informe de Investigación , Tibia/diagnóstico por imagen , Tibia/cirugía , Resultado del TratamientoRESUMEN
Osteogenesis imperfecta or brittle bone disease, a heritable disorder of connective tissue, is the most common of the inherited disorders primarily affecting bone. There are approximately 400 individuals with OI in Croatia alone. It is estimated that twice that number is present, represented by individuals with mild OI in whom the diagnosis has not been made. Due to the relatively low number of patients in the general population, treating physicians have limited experience with this disease, either with children or adults. The basis of this disease in European populations is mostly the result of defects in the structure or processing of collagen type I, an important protein of the extracellular matrix of many tissues. Presently, molecular defects in 16 different genes have been discovered to result in at least one type of OI of which 14 are not COL1 mutation loci. Although fractures occurring with no injury or minor injury are the hallmark of OI, other non-mineralized tissues can be affected as well and the pathological changes can be present in skin, tendons, eyes, teeth and blood vessels. Clinical manifestations are very heterogeneous and numerous signs and symptoms such as blue sclera, deafness, abnormal teeth development, joint hypermobility, increased risk of hernias, capillary fragility, aneurysms etc. Although there is no cure for this disease, there are specific therapies that can reduce the pain and complications associated with OI. The purpose of this review is to provide a brief overview of the molecular basis of this disease, describe clinical presentations, as well as to present orthopaedic therapeutic modalities for the patients with OI.
Asunto(s)
Familia , Osteogénesis Imperfecta/fisiopatología , Humanos , Osteogénesis Imperfecta/enfermeríaRESUMEN
The aim is to show our experience in anesthesia of patients with osteogenesis imperfecta (OI) who have undergone orthopedic surgical procedures. This is a retrospective analysis of OI patients treated at our Department from 1980 to 2012. We analyzed demographics, comorbidities, preoperative characteristics, anesthesia types, anesthetics and intraoperative and postoperative complications. In the given period, 26 OI patients were treated, using 103 surgeries, and 103 anesthesia procedures. Most procedures, a total of 68, were used in children aged 0-10 years. According to the diagnosis, OI type III was mostly encountered. The rating of the American Society of Anesthesiologist (ASA) physical status was II in most cases, a total of 99. General anesthesia was used in 89 cases, and regional anesthesia in 14. Fourteen intraoperative complications were seen, mostly difficult intubation, and six postoperative cardiovascular instability cases. With careful preparation, and knowledge of pitfalls, anesthesia in these patients should be a safe procedure.
Asunto(s)
Anestesia , Procedimientos Ortopédicos , Osteogénesis Imperfecta , Complicaciones Posoperatorias , Anestesia/efectos adversos , Anestesia/métodos , Anestésicos/uso terapéutico , Niño , Preescolar , Croacia/epidemiología , Femenino , Humanos , Lactante , Masculino , Procedimientos Ortopédicos/efectos adversos , Procedimientos Ortopédicos/métodos , Osteogénesis Imperfecta/epidemiología , Osteogénesis Imperfecta/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVES: Using proteomic approach in this study, we sought to identify proteins with heparin affinity associated with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and non-inflammatory arthritis (NIA). METHODS: Plasma samples from adult RA, PsA and NIA patients, 20 of each, were collected. After enrichment of proteins with heparin affinity, SDS-PAGE and in-gel digestion with trypsin were performed. Peptides were concentrated, micro-purified, separated and measured by nano-scale HPLC system coupled to a mass spectrometer. Peak lists were generated from raw spectra and searched against human complete proteome set by MaxQuant software. Statistical analysis of protein relative expression levels was done in IPython interactive Python shell using NumPy and Matplotlib libraries. Individual protein impact on the whole dataset correlation was done by excluding one protein at a time and calculating the correlation coefficient of remaining data points. RESULTS: Three hundred and eighty-four different proteins were identified keeping false discovery rate to 1%, from which 163 were identified in all three conditions. The plasma proteome showed a good correlation between rheumatoid (RA) and psoriatic arthritis (PsA). Out of 10 proteins whose impact on the correlation coefficient fell outside of two standard deviations from the mean, four were up-regulated (complement factor I, complement component C8 beta, glyceraldehyde-3-phosphate dehydrogenase and inter-alpha-trypsin inhibitor heavy chain H1), and two were down-regulated (immunoglobulin heavy chain V-III region BRO, and immunoglobulin J chain), both in PsA and RA by a similar ratio when compared to NIA. The remaining four proteins (Serpin A11, complement factor H-related protein 5, cartilage acidic protein 1 and coagulation factor IX) were down-regulated in PsA and up-regulated in RA when compared to NIA. CONCLUSIONS: We found differently expressed proteins in patients with inflammatory and non-inflammatory rheumatic conditions. Out of 384 proteins with heparin affinity four proteins should be further validated as potential diagnostic biomarkers in patients with RA and PsA.
Asunto(s)
Artritis Psoriásica/sangre , Artritis Reumatoide/sangre , Proteínas Sanguíneas/metabolismo , Heparina/metabolismo , Adulto , Anciano , Artritis Psoriásica/diagnóstico , Artritis Reumatoide/diagnóstico , Biomarcadores/sangre , Cromatografía de Afinidad , Bases de Datos de Proteínas , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Unión Proteica , Proteómica/métodos , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
The problem of low back pain (LBP) in children is very common and many specialists are dealing with it in everyday practice. The cause for low back pain often is not found and classified under the diagnosis of non specific low back pain. The objective of this prospective study is to determine wether children with non specific low back pain and existence of anomalies in LS spine (transitional vertebra- TV and/or Spina bifida occulta SBO) also have the degeneration of the intervertebral disc (DD) L4-L5 and/or L5-S1. This prospective study included 69 patients from 8 to 16 years of age (X 12.81) of whom 40 were male (57.97%), and 29 female (42.03%). They all were examinated in University of Zagreb, "Sestre milosrdnice" University Hospital Center, Zagreb Children's Hospital, Department of Orthopaedic, Zagreb, Croatia. The reason of their visit was non specific low back pain. Pain was measured by visual analog scale (VAS) and mean score was three, duration of pain was between two and four weeks. Also, pain was sporadic, during daytime and not connected with level of physical activity. They all have undergone an algorithm of radiological examinations. Standard AP and LL radiographs (RTG) were made, as well as magnetic resonance (MR) of LS spine and sacrum in sagittal and transversal plane in T1 and T2 weighted sequence. The anomalies of L5 and S1 were found in 65 patients: transitional vertebra classified according to Castellvi et al. and SBO. In MRI in T2 weighted sequence DD was found in 61 patients which was classified modified from Pearce. Data analysis and comparison showed that 56patients with TV and/or SBO have changes on vertebral dynamic segment L5-S1 (VDS) and that means DD. In 13 patients only DD or spinal anomaly (TV and/or SBO) were found. Correlation between anomalies and DD in those patients was established by McNemar analysis and has shown significant difference (p=0.581) in favour of the patients with anomaly and DD. This has established that all of 56 patients with spinal anomaly could have DD as known cause of LBP.
Asunto(s)
Degeneración del Disco Intervertebral/complicaciones , Dolor de la Región Lumbar/etiología , Vértebras Lumbares/patología , Sacro/patología , Espina Bífida Oculta/complicaciones , Adolescente , Niño , Femenino , Humanos , Degeneración del Disco Intervertebral/patología , Dolor de la Región Lumbar/patología , Imagen por Resonancia Magnética , Masculino , Estudios Prospectivos , Espina Bífida Oculta/patologíaRESUMEN
Langerhans' cell histiocytosis (LCH) is a disease characterised by pathologic accumulation and proliferation of histiocytes, cells from the monocyte-macrophage system, in various tissues and organs. In this retrospective study we analyzed patients charts treated in the Department of pediatric hematology and oncology at the University Hospital Zagreb with the diagnosis of LCH. Twenty-two children were diagnosed between January 1st 1996 and December 31st 2010, and all were treated with chemotherapy. 19 patients survived (86%) and the remaining 3 (14%), all under the age of 2 with multisystem disease, died. At the time of diagnosis 12 children (55%) presented with single-system disease, the most common were bone lesions in 8 children (36%). All children were treated according to protocols LCH-I and LCH -III. Eight children had mild complications of treatment and the disease itself. Diabetes insipidus remains in 4 children.
Asunto(s)
Histiocitosis de Células de Langerhans/tratamiento farmacológico , Niño , Preescolar , Femenino , Histiocitosis de Células de Langerhans/diagnóstico , Histiocitosis de Células de Langerhans/patología , Humanos , Lactante , MasculinoRESUMEN
Osteogenesis imperfecta (OI) represents a complex spectrum of genetic bone diseases that occur primarily due to mutations and deletions of the COL1A1 and COL1A2 genes. Recent molecular studies of the network of signaling pathways have contributed to a better understanding of bone remodeling and the pathogenesis of OI caused by mutations in many other genes associated with normal bone mineralization. In this paper, a case of a rare X-linked variant of OI with a change in the gene encoding plastin 3-a protein important for the regulation of the actin cytoskeleton, is presented. A 16-year-old patient developed ten bone fractures caused by minor trauma or injury, including a compression fracture of the second lumbar vertebra during his lifetime. Next-generation sequencing analysis did not show pathologically relevant deviations in the COL1A1 and COL1A2 genes. Targeted gene analyses (Skeletal disorder panel) of the patient, his father, mother and sister were then performed, detecting variants of uncertain significance (VUS) for genes PLS3, FN1 and COL11A2. A variant in the PLS3 gene were identified in the patient, his mother and sister. Since the PLS3 gene is located on the X chromosome, the mother and sister showed no signs of the disease. Although the variant in the PLS3 gene (c.685G>A (p.Gly229Arg)) has not yet been described in the literature, nor is its pathogenicity known, clinical findings combined with genetic testing showed that this variant may explain the cause of X-linked OI in our patient. This rare case of the PLS3 variant of X-linked OI might point to a novel target for personalized therapy in patients with this severe disease.
Asunto(s)
Genes Ligados a X/genética , Glicoproteínas de Membrana/genética , Proteínas de Microfilamentos/genética , Osteogénesis Imperfecta/genética , Adolescente , Adulto , Densidad Ósea/genética , Remodelación Ósea/genética , Femenino , Fracturas Óseas/genética , Pruebas Genéticas/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Vértebras Lumbares/patología , Masculino , Mutación/genética , Osteoporosis/genéticaRESUMEN
Osteoarthritis is the most common musculoskeletal progressive disease, with the knee as the most commonly affected joint in the human body. While several new medications are still under research, many symptomatic therapy options, such as analgesics (opioid and non-opioid), nonsteroid anti-inflammatory drugs, symptomatic slow-acting drugs in osteoarthritis, and preparations for topical administration, are being used, with a diverse clinical response and inconsistent conclusions across various professional societies guidelines. The concept of pharmacogenomic-guided therapy, which lies on principles of the right medication for the right patient in the right dose at the right time, can significantly increase the patient's response to symptom relief therapy in knee osteoarthritis. Corticosteroid intra-articular injections and hyaluronic acid injections provoke numerous discussions and disagreements among different guidelines, even though they are currently used in daily clinical practice. Biological options, such as platelet-rich plasma and mesenchymal stem cell injections, have shown good results in the treatment of osteoarthritis symptoms, greatly increasing the patient's quality of life, especially when combined with other therapeutic options. Non-inclusion of the latter therapies in the guidelines, and their inconsistent stance on numerous therapy options, requires larger and well-designed studies to examine the true effects of these therapies and update the existing guidelines.
RESUMEN
The oculocerebrorenal syndrome of Lowe (LS) is a rare, progressive, multisystemic X-linked disorder caused by mutations in OCRL gene. Patients classically present with ocular abnormalities including bilateral congenital cataracts and glaucoma, intellectual delay, severe generalized hypotonia with absent tendon reflexes, and proximal renal tubular dysfunction. Congenital bilateral cataracts and hypotonia are present at birth in almost all patients, while other classical symptoms develop gradually with variable severity. Consequently, differential diagnosis in infant period in these patients can be broad including other rare metabolic and neurologic disorders. Herein we present a 4.5 year old boy with Lowe syndrome caused by mutation of OCRL gene, NM_000276.4:c.643C > T; p.(Gln215*), initially diagnosed as having mitochondriopathy due to alteration of mitochondria on electron microscopic examination in different tissues and decreased values of mitochondrial energy metabolism measurements in muscle. No pathogenic mutations in mitochondrial DNA were found on whole exome sequencing. This patient recall historical hypothesis of secondary mitochondrial dysfunction in Lowe syndrome, that may be caused/intensified by some of disease symptoms.
Asunto(s)
Mitocondrias/metabolismo , Síndrome Oculocerebrorrenal/diagnóstico , Síndrome Oculocerebrorrenal/genética , Monoéster Fosfórico Hidrolasas/metabolismo , Preescolar , Humanos , Masculino , Microscopía Electrónica , Mitocondrias/genética , Mitocondrias/patología , Mitocondrias/ultraestructura , Músculos/metabolismo , Músculos/ultraestructura , Mutación , Síndrome Oculocerebrorrenal/complicaciones , Síndrome Oculocerebrorrenal/metabolismo , Monoéster Fosfórico Hidrolasas/genética , Secuenciación del ExomaRESUMEN
Osteogenesis imperfecta (OI) is a genetic disorder characterized by fragile bones. It is our aim to illustrate variability in clinical presentation of severe form of OI. As an example of personalized surgery approach we present an 11-year-old girl with OI type III. Prior to referral to our hospital, she was treated with 18 cycles of bisphosphonates as well as with several different surgical procedures. Due to no improvement in her mobility status she underwent two additional surgeries at our hospital with a 5-month interval between them. Prior to the surgery, molecular genetic analysis was performed and the clinical diagnosis of OI was confirmed. Using the Fassier-Duval intramedullary telescoping nail, we performed correction osteotomies of both femurs and lower legs in two separate settings, with a very good final result. According to our experience, the Fassier-Duval nailing system is good option, but one should pay attention to many details while performing surgery. Thus, making treatment of OI patients very personalized. In this paper we present a unique personalized approach in OI: firstly, diagnosing COL1A1 gene mutations and secondly, performing a complex two-part surgery.