Cortical malformations,including focal cortical dysplasia type II(FCDII),are a common cause of drug-resistant epilepsy and developmental delay.Consideration of surgery has become the standard of care for those patient...Cortical malformations,including focal cortical dysplasia type II(FCDII),are a common cause of drug-resistant epilepsy and developmental delay.Consideration of surgery has become the standard of care for those patients.However,10%-50% of patients with FCD experience post-surgical relapses[1],and many do not even qualify as surgical candidates.Effective treatments for FCD-associated epilepsy are lacking.展开更多
Skeletal dysplasia includes numerous genetic disorders marked by abnormal bone and cartilage growth,causing various spinal issues.The 2023 nosology identifies 771 distinct dysplasias involving 552 genes,with achondrop...Skeletal dysplasia includes numerous genetic disorders marked by abnormal bone and cartilage growth,causing various spinal issues.The 2023 nosology identifies 771 distinct dysplasias involving 552 genes,with achondroplasia being the most common and significantly affecting the spine.Other disorders include type II collagenopathies,sulphation defects,Filamin B disorders,and osteogenesis imperfecta,presenting with short stature,limb deformities,joint contractures,and spinal abnormalities.Spinal pathology often impacts physeal growth areas,leading to conditions like foramen magnum stenosis,atlantoaxial instability,spinal stenosis,kyphosis,and scoliosis.Non-orthopaedic symptoms can include hearing and vision loss,neurological issues like hydrocephalus,and cardiac abnormalities.The incidence is around 1 in 4000 to 5000 births,with achondroplasia at about 1 in 30000 live births.Advances in genetics and imaging enable prenatal diagnosis,though milder cases may go undetected.Effective management requires a multidisciplinary approach involving various specialists.This review emphasises early diagnosis,continuous monitoring,and comprehensive management of spinal pathology in skeletal dysplasia.In the current article,the authors present a thorough review on spinal conditions associated with skeletal dysplasia,their pathophysiology and management options.展开更多
BACKGROUND Hip dysplasia is a widespread and debilitating musculoskeletal disorder that affects children.Its prevalence varies across different nations.AIM To evaluate the prevalence of developmental hip dysplasia(DDH...BACKGROUND Hip dysplasia is a widespread and debilitating musculoskeletal disorder that affects children.Its prevalence varies across different nations.AIM To evaluate the prevalence of developmental hip dysplasia(DDH)within the pediatric population of Al Jouf province.METHODS From January 2018 to December 2023,children with DDH from all cities of Al Jouf were included in this retrospective cross-sectional study.The disease prevalence was calculated for the entire province as well as for individual cities within the territory.RESULTS The study included 427 patients with DDH with an overall prevalence of 0.50%,or 5.0 per 1000 live births.At the city level,Sakaka had the highest prevalence at 14.2 per 1000 Live births followed by Qurayyat at 2.2 per 1000 live births.In contrast,cities like Suwayr,Abu Ajram,and Meegowa did not show any incidence of DDH.Significant differences were observed in the sociodemographic characteristics,such as age,sex,and nationality,across the different cities(P<0.05).CONCLUSION The prevalence of DDH in the Al Jouf province is high.The data delivers invaluable insights into the epidemiology of DDH in the Al Jouf locality.The findings highlight the need for targeted screening of DDH across the province.展开更多
BACKGROUND Cleidocranial dysplasia(CCD)is an infrequent clinical condition with an autosomal dominant inheritance pattern.It is characterized by abnormal clavicles,patent sutures and fontanelles,supernumerary teeth,an...BACKGROUND Cleidocranial dysplasia(CCD)is an infrequent clinical condition with an autosomal dominant inheritance pattern.It is characterized by abnormal clavicles,patent sutures and fontanelles,supernumerary teeth,and short stature.Approximately 60%-70%of patients with CCD have mutations in the RUNX family transcription factor 2 gene.However,prenatal diagnosis of CCD is difficult when the family history is unknown.CASE SUMMARY We report a rare case of fetal CCD with an unknown family history,confirmed by prenatal ultrasonography and genetic testing at a gestational age of 16 weeks.The genetic reports indicated that the fetus carried pathogenic mutations in the RUNX family transcription factor 2 gene(c.674G>A).After careful consideration,the pregnant woman and her family decided to continue the pregnancy.CONCLUSION Definitive prenatal diagnosis of CCD should include family history,ultrasound diagnosis,and genetic analysis,especially if family history is unknown.展开更多
AIM:To describe the clinical manifestations,imaging features and surgical treatments in 5 cases of extraocular muscle(EOM)dysplasia presenting as orbital spaceoccupying lesions(SOL).METHODS:Records from the 5 cases wi...AIM:To describe the clinical manifestations,imaging features and surgical treatments in 5 cases of extraocular muscle(EOM)dysplasia presenting as orbital spaceoccupying lesions(SOL).METHODS:Records from the 5 cases with EOM dysplasia between 2004 and 2016 were retrospectively reviewed and clinical data were recorded including family history,age at onset,age at surgery,visual acuity,cycloplegic refraction,ocular alignment and motility,stereoacuity,exophthalmos,anterior segment and fundus,orbital computed tomography(CT)or magnetic resonance imaging(MRI)scan,surgical methods and final outcomes.RESULTS:All 5 cases(1 male,4 females)were unilateral(3 right,2 left eyes).The average age was 5.4y(range 4-6y)with no family history.Patients had unilateral strabismus(horizontal and vertical),restricted eye movement,and eyelid changes(abnormal fissures,lagophthalmos,and/or entropion)in the affected eye.None had proptosis;1 had 2-mm enophthalmos.Orbital CT/MRI showed irregular,ill-defined masses in EOM.Two anterior orbitotomies and 3 strabismus surgeries were performed,and pathology confirmed EOM dysplasia.After surgery,horizontal deviations,which ranged from exotropia(XT)10 prism diopter(PD)to esotropia(ET)10 PD(average 6 PD),decreased by an average of 18 PD,while vertical deviations,which ranged from 4 PD to 20 PD(mean 9.8 PD),decreased by an average of 23.2 PD.CONCLUSION:SOL from EOM dysplasia is non-familial and typically presenting unilaterally characterized by an irregular,diffusely infiltrating mass within the EOM.EOM involvement causes strabismus,restricted eye movement,eyelid changes,and enophthalmos likely due to cicatricial processes.展开更多
Background:Developmental dysplasia of the hip(DDH)is a prevalent pediatric condition with a multifactorial etiology.Its incidence varies geographically,with notably higher rates observed on the Xizang plateau.This stu...Background:Developmental dysplasia of the hip(DDH)is a prevalent pediatric condition with a multifactorial etiology.Its incidence varies geographically,with notably higher rates observed on the Xizang plateau.This study was performed to evaluate the lipidomics signatures associated with DDH by analyzing plasma samples.Methods:Fifty infants were recruited,including 25 diagnosed with DDH and 25 age-matched healthy controls.In addition to plasma samples,comprehensive laboratory test results and medical records were collected for each participant.An untargeted lipidomics profiling approach was employed to identify distinguishing metabolic signatures.Results:Lipidomics profiles differed significantly between patients with DDH and healthy controls.Several differential metabolites were identified,including triacylglycerol(TAG)(17:0/18:1/20:1),TAG(17:0/17:0/17:0),phosphatidylethanolamine(PE)(10:0/26:4),TAG(17:0/18:0/18:0),TAG(16:0/17:0/22:1),TAG(16:0/18:0/22:0),TAG(17:0/19:0/19:0),TAG(13:0/20:0/20:0),TAG(18:0/18:0/22:0),and TAG(16:0/20:0/20:0).The primary lipid species showing differences were TAGs and PE.Conclusions:Distinct shifts in lipidomics profiles were observed in infants with DDH.To the best of our knowledge,this study is the first to explore lipidomics signatures in patients with DDH.The combined assessment of TAG(17:0/18:1/20:1)and TAG(17:0/17:0/17:0)may serve as a potential diagnostic tool for DDH.展开更多
BACKGROUND Traditional serrated adenoma(TSA)is a rare and precancerous lesion of colorectal cancer.The clinical and endoscopic differentiations between TSAs without dysplasia or adenocarcinoma(TSAOs)and TSAs with dysp...BACKGROUND Traditional serrated adenoma(TSA)is a rare and precancerous lesion of colorectal cancer.The clinical and endoscopic differentiations between TSAs without dysplasia or adenocarcinoma(TSAOs)and TSAs with dysplasia or adenocarcinoma(TSADs)remain unclear.AIM To evaluate the characteristics of colorectal TSAs and compare the characteristics of TSAOs with those of TSADs.METHODS This retrospective study included 193 patients who underwent endoscopic resection and received a pathologic diagnosis of TSA.We reviewed the medical,endoscopic,and histopathologic records of patients who underwent endoscopic resection of TSAs between January 2010 and December 2023.RESULTS TSAs were more frequently located in the rectosigmoid colon.Most TSAs had 0-Ip,0-Isp,or 0-Is morphologies.The TSAD lesions were larger than TSAO lesions.TSAD lesions more commonly had a red color and an irregular border than TSAO lesions.TSAOs were usually treated using conventional endoscopic mucosal resection,whereas TSADs were treated using conventional endoscopic mucosal resection,endoscopic submucosal dissection,and surgery.Post-polypectomy bleeding was more common with TSADs than with TSAOs.Univariate analysis showed that gastrointestinal bleeding,red color,0-IIa,irregular border,and lobular mucosal surface were significantly associated with TSADs.Multivariate analysis showed that gastrointestinal bleeding,an irregular border,and a lobular mucosal surface were significantly associated with TSADs.CONCLUSION TSAs with gastrointestinal bleeding,an irregular border,and a lobular mucosal surface are associated with an increased risk of dysplasia or adenocarcinoma.展开更多
The aim of this study is to analyze factors influencing the development of bronchopulmonary dysplasia(BPD)within 28 d after birth in very-low-birth-weight(VLBW)infants with a gestational age of less than 34 weeks who ...The aim of this study is to analyze factors influencing the development of bronchopulmonary dysplasia(BPD)within 28 d after birth in very-low-birth-weight(VLBW)infants with a gestational age of less than 34 weeks who were receiving early parenteral nutrition.Data were retrospectively collected from infants born between January and December 2021,who were admitted to the neonatal intensive care unit within 24 h of birth,had a gestational age of less than 34 weeks,and were classified as VLBW.The study included 14 cases without BPD and 20 cases with BPD,and it compared clinical data during hospitalization between these two groups.On the 1st day of life,the BPD group had a nitrogen-to-calorie ratio of 105.44±26.67,while the non-BPD group had a ratio of 146.81±37.04.This difference was statistically significant,with a P-value of 0.04,indicating a potential association between the nitrogen-to-calorie ratio and the development of BPD.However,no significant differences were observed in other clinical indicators between the two groups.These findings suggested that a larger sample size was needed to further explore and confirm the correlation between the nitrogen-to-calorie ratio and the risk of developing BPD in this population.展开更多
Gain-of-function mutations in fibroblast growth factor receptor(FGFR) genes lead to chondrodysplasia and craniosynostoses. FGFR signaling has a key role in the formation and repair of the craniofacial skeleton. Here, ...Gain-of-function mutations in fibroblast growth factor receptor(FGFR) genes lead to chondrodysplasia and craniosynostoses. FGFR signaling has a key role in the formation and repair of the craniofacial skeleton. Here, we analyzed the impact of Fgfr2- and Fgfr3- activating mutations on mandibular bone formation and endochondral bone repair after non-stabilized mandibular fractures in mouse models of Crouzon syndrome(Crz) and hypochondroplasia(Hch).展开更多
BACKGROUND Endoscopic submucosal dissection(ESD)is increasingly used to treat gastric dysplasia and early neoplasia in the West.Unlike Eastern countries,data for Caucasian patients in the United Kingdom is limited due...BACKGROUND Endoscopic submucosal dissection(ESD)is increasingly used to treat gastric dysplasia and early neoplasia in the West.Unlike Eastern countries,data for Caucasian patients in the United Kingdom is limited due to its limited implementation in a few tertiary centres.AIM To evaluate the outcomes of ESD on gastric dysplasia and neoplasia in Caucasian patients.METHODS Our ten-year retrospective study at a single tertiary centre included data spanning from May 2012 to July 2023.The efficacy of ESD on gastric dysplasia and early neoplasia was measured using parameters set out by the National Institute for Health and Care Excellence,which include en-bloc and curative resection(CR)rates,local recurrence and survival rates.RESULTS ESD was attempted on 111 lesions in 93 patients.95.0%of completed procedures achieved endoscopic clearance.74.3%were en-bloc resections and the rest were hybrid ESD with piecemeal resections.In all,34.7%achieved histological CR.Overall,disease recurrence was 10.9%at latest follow-up(63 months,median follow-up).Importantly 100%of lesions in the CR group showed no disease recurrence at subsequent and latest follow-up.In the Indeterminate and Non-CR group,18.8%of lesions showed disease recurrence at subsequent endoscopic follow-ups.ESD changed the histological staging of 44.5%of lesions.Immediate complications were observed in 9.9%of all ESD procedures.The median survival time was 69 months post-ESD.The mean age at death is 82.2 years old.CONCLUSION The study affirms the long-term efficacy and safety of ESD for gastric dysplasia and early neoplasia in Caucasian patients.展开更多
Craniometaphyseal dysplasia(CMD),a rare craniotubular disorder,occurs in an autosomal dominant(AD)or autosomal recessive(AR)form.CMD is characterized by hyperostosis of craniofacial bones and metaphyseal flaring of lo...Craniometaphyseal dysplasia(CMD),a rare craniotubular disorder,occurs in an autosomal dominant(AD)or autosomal recessive(AR)form.CMD is characterized by hyperostosis of craniofacial bones and metaphyseal flaring of long bones.Many patients with CMD suffer from neurological symptoms.The pathogenesis of CMD is not fully understood.展开更多
Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established treatments.Growing evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RAN...Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established treatments.Growing evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatment strategy.In this study,we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical models.Histological analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL inhibition.RNA sequencing of human and mouse tissue supported these findings.The interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on osteoclasts.The results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within lesions.These findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.展开更多
Cellular communication network factor 2(CCN2)is a secreted extracellular matrix-associated protein,and its aberrantly increased expression has been implicated in a diversity of diseases involving pathological processe...Cellular communication network factor 2(CCN2)is a secreted extracellular matrix-associated protein,and its aberrantly increased expression has been implicated in a diversity of diseases involving pathological processes of fibrosis,chronic inflammation,or tissue injury,which has promoted the evaluation of CCN2 as therapeutic targets for multiple disorders.However,human phenotypes associated with CCN2 deficiency have remained enigmatic;variants in CCN2 have not yet been associated with a human phenotype.Here,we collected families diagnosed with spondyloepimetaphyseal dysplasia(SEMD),and screened candidate pathogenic genes for families without known genetic causes using next-generation sequencing.We identified a monoallelic variant in signal peptide of CCN2(NM_001901.2:c.65 G>C[p.Arg22Pro])as the cause of SEMD in 14 subjects presenting with different degree of short stature,premature osteoarthritis,and osteoporosis.Affected subjects showed decreased serum CCN2 levels.Cell lines harboring the variant displayed decreased amount of CCN2 proteins in culture medium and an increased intracellular retention,indicating impaired protein secretion.And the variant weakened the stimulation effect of CCN2 on osteogenesis of bone marrow mesenchymal stem cells.Zebrafish ccn2a knockout model and osteoblast lineage-specific Ccn2-deficient mice(Ccn2fl/fl;Prx1Cre)partially recapitulated the phenotypes including low bone mass observed in affected subjects.Pathological mechanism implicated in the skeletal abnormality in Ccn2fl/fl;Prx1Cre mice involved decreased bone formation,increased bone resorption,and abnormal growth plate formation.Collectively,our study indicate that monoallelic variants in CCN2 lead to a human inherited skeletal dysplasia,and highlight the critical role of CCN2 in osteogenesis in human.展开更多
For preterm infants, bronchopulmonary dysplasia (BPD) is usually caused by abnormal lung development due to various factors during prenatal and postnatal process. One of the reasons for death and bad prognosis of pret...For preterm infants, bronchopulmonary dysplasia (BPD) is usually caused by abnormal lung development due to various factors during prenatal and postnatal process. One of the reasons for death and bad prognosis of preterm infants is to have BPD. Up to now, there are no unified strategies or drugs to treat BPD. In clinical, many intervention treatments have been applied to achieve BPD therapy, mainly including preterm protection, protective ventilation strategies, and delivery of corticosteroids, pulmonary vasodilators, and antioxidants. This review summarizes the current advances in BPD protection and treatment, and notes that gut microbiota and mesenchymal stem cells (MSCs) can be the promising strategy for protecting and treating BPD in the future.展开更多
BACKGROUND Developmental dysplasia of the hip(DDH)is a common osteoarticular deformity in pediatric orthopedics.A patient with bilateral DDH was diagnosed and treated using our improved technique"(powerful overtu...BACKGROUND Developmental dysplasia of the hip(DDH)is a common osteoarticular deformity in pediatric orthopedics.A patient with bilateral DDH was diagnosed and treated using our improved technique"(powerful overturning acetabuloplasty)"combined with femoral rotational shortening osteotomy.CASE SUMMARY A 4-year-old girl who was diagnosed with bilateral DDH could not stand normally,and sought surgical treatment to solve the problem of double hip extension and standing.As this child had high dislocation of the hip joint and the acetabular index was high,we changed the traditional acetabuloplasty to"powerful turnover acetabuloplasty"combined with femoral rotation shortening osteotomy.During the short-term postoperative follow-up(1,3,6,9,12,and 15 months),the child had no discomfort in her lower limbs.After the braces and internal fixation plates were removed,formal rehabilitation training was actively carried out.CONCLUSION Our"powerful overturning acetabuloplasty"combined with femoral rotational shortening osteotomy is feasible in the treatment of DDH in children.This technology may be widely used in the clinic.展开更多
Combined femoral and acetabular anteversion is the sum of femoral and acetabular anteversion,representing their morphological relationship in the axial plane.Along with the increasing understanding of hip dysplasia in...Combined femoral and acetabular anteversion is the sum of femoral and acetabular anteversion,representing their morphological relationship in the axial plane.Along with the increasing understanding of hip dysplasia in recent years,numerous scholars have confirmed the role of combined femoral and acetabular anteversion in the pathological changes of hip dysplasia.At present,the reconstructive surgery for hip dysplasia includes total hip replacement and redirectional hip preservation surgery.As an important surgery index,combined femoral and acetabular anteversion have a crucial role in these surgeries.Herein,we discuss the role of combined femoral and acetabular anteversion in pathological changes of hip dysplasia,total hip replacement,and redirectional hip preservation surgery.展开更多
Developmental dysplasia of the hip(DDH)poses significant challenges in both childhood and adulthood,affecting up to 10 per 1000 live births in the United Kingdom and United States.While newborn screening aims to detec...Developmental dysplasia of the hip(DDH)poses significant challenges in both childhood and adulthood,affecting up to 10 per 1000 live births in the United Kingdom and United States.While newborn screening aims to detect DDH early,missed diagnoses can lead to severe complications such as hip dysplasia and early onset osteoarthritis in adults.Treatment options range from less invasive procedures like hip-preserving surgery to more extensive interventions such as total hip arthroplasty(THA),depending on the severity of the condition.Preoperative planning plays a critical role in optimizing surgical outcomes for DDH patients undergoing THA.This includes accurate imaging modalities,precise measurement of acetabular bone stock,assessment of femoral head subluxation,and predicting prosthesis size and leg length discrepancy.Recent advancements artificial intelligence and machine learning offer promising tools to enhance preoperative planning accuracy.However,challenges remain in validating these technologies and integrating them into clinical practice.This editorial highlights the importance of ongoing research to refine preoperative strategies and improve outcomes in DDH management through evidence-based approaches and technological innovations.展开更多
BACKGROUND Hip dysplasia(HD)is characterized by insufficient acetabular coverage of the femoral head,leading to a predisposition for osteoarthritis.While radiographic measurements such as the lateral center edge angle...BACKGROUND Hip dysplasia(HD)is characterized by insufficient acetabular coverage of the femoral head,leading to a predisposition for osteoarthritis.While radiographic measurements such as the lateral center edge angle(LCEA)and Tönnis angle are essential in evaluating HD severity,patient-reported outcome measures(PROMs)offer insights into the subjective health impact on patients.AIM To investigate the correlations between machine-learning automated and manual radiographic measurements of HD and PROMs with the hypothesis that artificial intelligence(AI)-generated HD measurements indicating less severe dysplasia correlate with better PROMs.METHODS Retrospective study evaluating 256 hips from 130 HD patients from a hip preservation clinic database.Manual and AI-derived radiographic measurements were collected and PROMs such as the Harris hip score(HHS),international hip outcome tool(iHOT-12),short form(SF)12(SF-12),and Visual Analogue Scale of the European Quality of Life Group survey were correlated using Spearman's rank-order correlation.RESULTS The median patient age was 28.6 years(range 15.7-62.3 years)with 82.3%of patients being women and 17.7%being men.The median interpretation time for manual readers and AI ranged between 4-12 minutes per patient and 31 seconds,respectively.Manual measurements exhibited weak correlations with HHS,including LCEA(r=0.18)and Tönnis angle(r=-0.24).AI-derived metrics showed similar weak correlations,with the most significant being Caput-Collum-Diaphyseal(CCD)with iHOT-12 at r=-0.25(P=0.042)and CCD with SF-12 at r=0.25(P=0.048).Other measured correlations were not significant(P>0.05).CONCLUSION This study suggests AI can aid in HD assessment,but weak PROM correlations highlight their continued importance in predicting subjective health and outcomes,complementing AI-derived measurements in HD management.展开更多
Our case is a 72-year-old female with Fibromuscular Dysplasia (FMD) presented to the Emergency Department (ED) with acute coronary syndrome (ACS), more specifically NSTEMI. In ED, troponin levels were elevated and non...Our case is a 72-year-old female with Fibromuscular Dysplasia (FMD) presented to the Emergency Department (ED) with acute coronary syndrome (ACS), more specifically NSTEMI. In ED, troponin levels were elevated and non-ST segment elevation myocardial infarction (NSTEMI) was detected on electrocardiogram (ECG). Computed tomography (CT) scan showed Internal Carotid artery (ICA) pseudoaneurysm. Cardiac catheterization (CATH) was performed and revealed occlusion of the Left anterior descending (LAD) artery. Spontaneous coronary artery dissection (SCAD) was suspected due to the history of FMD without a history of hypertension, smoking or substance use.展开更多
Bronchopulmonary dysplasia(BPD),also known as neonatal chronic lung disease,is a common respiratory disease in preterm infants.Preterm infants with BPD often exhibit changes in gut and lung microbiota.In recent years,...Bronchopulmonary dysplasia(BPD),also known as neonatal chronic lung disease,is a common respiratory disease in preterm infants.Preterm infants with BPD often exhibit changes in gut and lung microbiota.In recent years,with the development of high-throughput sequencing technology,more and more mechanisms of the gut-lung axis have been confirmed,helping to explore new directions for the treatment of BPD using microecological agents.This paper reviews the roles of gut microbiota,lung microbiota,and the gut-lung axis in the pathogenesis of BPD in preterm infants,providing new research avenues for the prevention and treatment of BPD.展开更多
基金supported by the Natural Science Foundation of Zhejiang Province(LQ23H090002)the National Natural Science Foundation of China(82201607).
文摘Cortical malformations,including focal cortical dysplasia type II(FCDII),are a common cause of drug-resistant epilepsy and developmental delay.Consideration of surgery has become the standard of care for those patients.However,10%-50% of patients with FCD experience post-surgical relapses[1],and many do not even qualify as surgical candidates.Effective treatments for FCD-associated epilepsy are lacking.
文摘Skeletal dysplasia includes numerous genetic disorders marked by abnormal bone and cartilage growth,causing various spinal issues.The 2023 nosology identifies 771 distinct dysplasias involving 552 genes,with achondroplasia being the most common and significantly affecting the spine.Other disorders include type II collagenopathies,sulphation defects,Filamin B disorders,and osteogenesis imperfecta,presenting with short stature,limb deformities,joint contractures,and spinal abnormalities.Spinal pathology often impacts physeal growth areas,leading to conditions like foramen magnum stenosis,atlantoaxial instability,spinal stenosis,kyphosis,and scoliosis.Non-orthopaedic symptoms can include hearing and vision loss,neurological issues like hydrocephalus,and cardiac abnormalities.The incidence is around 1 in 4000 to 5000 births,with achondroplasia at about 1 in 30000 live births.Advances in genetics and imaging enable prenatal diagnosis,though milder cases may go undetected.Effective management requires a multidisciplinary approach involving various specialists.This review emphasises early diagnosis,continuous monitoring,and comprehensive management of spinal pathology in skeletal dysplasia.In the current article,the authors present a thorough review on spinal conditions associated with skeletal dysplasia,their pathophysiology and management options.
文摘BACKGROUND Hip dysplasia is a widespread and debilitating musculoskeletal disorder that affects children.Its prevalence varies across different nations.AIM To evaluate the prevalence of developmental hip dysplasia(DDH)within the pediatric population of Al Jouf province.METHODS From January 2018 to December 2023,children with DDH from all cities of Al Jouf were included in this retrospective cross-sectional study.The disease prevalence was calculated for the entire province as well as for individual cities within the territory.RESULTS The study included 427 patients with DDH with an overall prevalence of 0.50%,or 5.0 per 1000 live births.At the city level,Sakaka had the highest prevalence at 14.2 per 1000 Live births followed by Qurayyat at 2.2 per 1000 live births.In contrast,cities like Suwayr,Abu Ajram,and Meegowa did not show any incidence of DDH.Significant differences were observed in the sociodemographic characteristics,such as age,sex,and nationality,across the different cities(P<0.05).CONCLUSION The prevalence of DDH in the Al Jouf province is high.The data delivers invaluable insights into the epidemiology of DDH in the Al Jouf locality.The findings highlight the need for targeted screening of DDH across the province.
基金Supported by Science and Technology Development Plan Project of Weifang,No.2023YX005。
文摘BACKGROUND Cleidocranial dysplasia(CCD)is an infrequent clinical condition with an autosomal dominant inheritance pattern.It is characterized by abnormal clavicles,patent sutures and fontanelles,supernumerary teeth,and short stature.Approximately 60%-70%of patients with CCD have mutations in the RUNX family transcription factor 2 gene.However,prenatal diagnosis of CCD is difficult when the family history is unknown.CASE SUMMARY We report a rare case of fetal CCD with an unknown family history,confirmed by prenatal ultrasonography and genetic testing at a gestational age of 16 weeks.The genetic reports indicated that the fetus carried pathogenic mutations in the RUNX family transcription factor 2 gene(c.674G>A).After careful consideration,the pregnant woman and her family decided to continue the pregnancy.CONCLUSION Definitive prenatal diagnosis of CCD should include family history,ultrasound diagnosis,and genetic analysis,especially if family history is unknown.
基金Supported by the National Natural Science Foundation of China(No.81670885).
文摘AIM:To describe the clinical manifestations,imaging features and surgical treatments in 5 cases of extraocular muscle(EOM)dysplasia presenting as orbital spaceoccupying lesions(SOL).METHODS:Records from the 5 cases with EOM dysplasia between 2004 and 2016 were retrospectively reviewed and clinical data were recorded including family history,age at onset,age at surgery,visual acuity,cycloplegic refraction,ocular alignment and motility,stereoacuity,exophthalmos,anterior segment and fundus,orbital computed tomography(CT)or magnetic resonance imaging(MRI)scan,surgical methods and final outcomes.RESULTS:All 5 cases(1 male,4 females)were unilateral(3 right,2 left eyes).The average age was 5.4y(range 4-6y)with no family history.Patients had unilateral strabismus(horizontal and vertical),restricted eye movement,and eyelid changes(abnormal fissures,lagophthalmos,and/or entropion)in the affected eye.None had proptosis;1 had 2-mm enophthalmos.Orbital CT/MRI showed irregular,ill-defined masses in EOM.Two anterior orbitotomies and 3 strabismus surgeries were performed,and pathology confirmed EOM dysplasia.After surgery,horizontal deviations,which ranged from exotropia(XT)10 prism diopter(PD)to esotropia(ET)10 PD(average 6 PD),decreased by an average of 18 PD,while vertical deviations,which ranged from 4 PD to 20 PD(mean 9.8 PD),decreased by an average of 23.2 PD.CONCLUSION:SOL from EOM dysplasia is non-familial and typically presenting unilaterally characterized by an irregular,diffusely infiltrating mass within the EOM.EOM involvement causes strabismus,restricted eye movement,eyelid changes,and enophthalmos likely due to cicatricial processes.
基金graciously funded by the Central Government Guidance Fund for Supporting the Local Science and Technology Development(No.XZ202101YD0002C).
文摘Background:Developmental dysplasia of the hip(DDH)is a prevalent pediatric condition with a multifactorial etiology.Its incidence varies geographically,with notably higher rates observed on the Xizang plateau.This study was performed to evaluate the lipidomics signatures associated with DDH by analyzing plasma samples.Methods:Fifty infants were recruited,including 25 diagnosed with DDH and 25 age-matched healthy controls.In addition to plasma samples,comprehensive laboratory test results and medical records were collected for each participant.An untargeted lipidomics profiling approach was employed to identify distinguishing metabolic signatures.Results:Lipidomics profiles differed significantly between patients with DDH and healthy controls.Several differential metabolites were identified,including triacylglycerol(TAG)(17:0/18:1/20:1),TAG(17:0/17:0/17:0),phosphatidylethanolamine(PE)(10:0/26:4),TAG(17:0/18:0/18:0),TAG(16:0/17:0/22:1),TAG(16:0/18:0/22:0),TAG(17:0/19:0/19:0),TAG(13:0/20:0/20:0),TAG(18:0/18:0/22:0),and TAG(16:0/20:0/20:0).The primary lipid species showing differences were TAGs and PE.Conclusions:Distinct shifts in lipidomics profiles were observed in infants with DDH.To the best of our knowledge,this study is the first to explore lipidomics signatures in patients with DDH.The combined assessment of TAG(17:0/18:1/20:1)and TAG(17:0/17:0/17:0)may serve as a potential diagnostic tool for DDH.
基金Supported by The First Research in Lifetime Grant from Chonnam National University Hospital Biomedical Research Institute,No.HCRI23005。
文摘BACKGROUND Traditional serrated adenoma(TSA)is a rare and precancerous lesion of colorectal cancer.The clinical and endoscopic differentiations between TSAs without dysplasia or adenocarcinoma(TSAOs)and TSAs with dysplasia or adenocarcinoma(TSADs)remain unclear.AIM To evaluate the characteristics of colorectal TSAs and compare the characteristics of TSAOs with those of TSADs.METHODS This retrospective study included 193 patients who underwent endoscopic resection and received a pathologic diagnosis of TSA.We reviewed the medical,endoscopic,and histopathologic records of patients who underwent endoscopic resection of TSAs between January 2010 and December 2023.RESULTS TSAs were more frequently located in the rectosigmoid colon.Most TSAs had 0-Ip,0-Isp,or 0-Is morphologies.The TSAD lesions were larger than TSAO lesions.TSAD lesions more commonly had a red color and an irregular border than TSAO lesions.TSAOs were usually treated using conventional endoscopic mucosal resection,whereas TSADs were treated using conventional endoscopic mucosal resection,endoscopic submucosal dissection,and surgery.Post-polypectomy bleeding was more common with TSADs than with TSAOs.Univariate analysis showed that gastrointestinal bleeding,red color,0-IIa,irregular border,and lobular mucosal surface were significantly associated with TSADs.Multivariate analysis showed that gastrointestinal bleeding,an irregular border,and a lobular mucosal surface were significantly associated with TSADs.CONCLUSION TSAs with gastrointestinal bleeding,an irregular border,and a lobular mucosal surface are associated with an increased risk of dysplasia or adenocarcinoma.
基金Science and Technology Program Project of Jiangxi Provincial Health Commission(Grant No.202210200).
文摘The aim of this study is to analyze factors influencing the development of bronchopulmonary dysplasia(BPD)within 28 d after birth in very-low-birth-weight(VLBW)infants with a gestational age of less than 34 weeks who were receiving early parenteral nutrition.Data were retrospectively collected from infants born between January and December 2021,who were admitted to the neonatal intensive care unit within 24 h of birth,had a gestational age of less than 34 weeks,and were classified as VLBW.The study included 14 cases without BPD and 20 cases with BPD,and it compared clinical data during hospitalization between these two groups.On the 1st day of life,the BPD group had a nitrogen-to-calorie ratio of 105.44±26.67,while the non-BPD group had a ratio of 146.81±37.04.This difference was statistically significant,with a P-value of 0.04,indicating a potential association between the nitrogen-to-calorie ratio and the development of BPD.However,no significant differences were observed in other clinical indicators between the two groups.These findings suggested that a larger sample size was needed to further explore and confirm the correlation between the nitrogen-to-calorie ratio and the risk of developing BPD in this population.
基金National Research Agency under the Investments for the Future program (ANR-10-IAHU-01)Filière Nationale TeteCou for financial support。
文摘Gain-of-function mutations in fibroblast growth factor receptor(FGFR) genes lead to chondrodysplasia and craniosynostoses. FGFR signaling has a key role in the formation and repair of the craniofacial skeleton. Here, we analyzed the impact of Fgfr2- and Fgfr3- activating mutations on mandibular bone formation and endochondral bone repair after non-stabilized mandibular fractures in mouse models of Crouzon syndrome(Crz) and hypochondroplasia(Hch).
文摘BACKGROUND Endoscopic submucosal dissection(ESD)is increasingly used to treat gastric dysplasia and early neoplasia in the West.Unlike Eastern countries,data for Caucasian patients in the United Kingdom is limited due to its limited implementation in a few tertiary centres.AIM To evaluate the outcomes of ESD on gastric dysplasia and neoplasia in Caucasian patients.METHODS Our ten-year retrospective study at a single tertiary centre included data spanning from May 2012 to July 2023.The efficacy of ESD on gastric dysplasia and early neoplasia was measured using parameters set out by the National Institute for Health and Care Excellence,which include en-bloc and curative resection(CR)rates,local recurrence and survival rates.RESULTS ESD was attempted on 111 lesions in 93 patients.95.0%of completed procedures achieved endoscopic clearance.74.3%were en-bloc resections and the rest were hybrid ESD with piecemeal resections.In all,34.7%achieved histological CR.Overall,disease recurrence was 10.9%at latest follow-up(63 months,median follow-up).Importantly 100%of lesions in the CR group showed no disease recurrence at subsequent and latest follow-up.In the Indeterminate and Non-CR group,18.8%of lesions showed disease recurrence at subsequent endoscopic follow-ups.ESD changed the histological staging of 44.5%of lesions.Immediate complications were observed in 9.9%of all ESD procedures.The median survival time was 69 months post-ESD.The mean age at death is 82.2 years old.CONCLUSION The study affirms the long-term efficacy and safety of ESD for gastric dysplasia and early neoplasia in Caucasian patients.
基金supported by NIH/NIDCR grant R01DE025664 to IPC.
文摘Craniometaphyseal dysplasia(CMD),a rare craniotubular disorder,occurs in an autosomal dominant(AD)or autosomal recessive(AR)form.CMD is characterized by hyperostosis of craniofacial bones and metaphyseal flaring of long bones.Many patients with CMD suffer from neurological symptoms.The pathogenesis of CMD is not fully understood.
基金supported by the Intramural Research Program of the NIDCR, NICHD,and Clinical Center, National Institutes of Healthsupported by Amgen, Inc.+2 种基金supported in part by the NIDCR Genomics and Computational Biology Core:ZIC DC000086Veterinary Resources Core:ZIC DE000740-05supported by the Research on Women’s Health(ORWH)through the Bench to Bedside Program award#884515.
文摘Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established treatments.Growing evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatment strategy.In this study,we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical models.Histological analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL inhibition.RNA sequencing of human and mouse tissue supported these findings.The interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on osteoclasts.The results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within lesions.These findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.
基金funded by the National Key Research and Development Program of China (2018YFA0800801)the National Basic Research Program of China (2014CB942903)+1 种基金the National Natural Science Foundation of China (81900807)Shanghai Research Center for Endocrine and Metabolic Diseases (2022ZZ01002)。
文摘Cellular communication network factor 2(CCN2)is a secreted extracellular matrix-associated protein,and its aberrantly increased expression has been implicated in a diversity of diseases involving pathological processes of fibrosis,chronic inflammation,or tissue injury,which has promoted the evaluation of CCN2 as therapeutic targets for multiple disorders.However,human phenotypes associated with CCN2 deficiency have remained enigmatic;variants in CCN2 have not yet been associated with a human phenotype.Here,we collected families diagnosed with spondyloepimetaphyseal dysplasia(SEMD),and screened candidate pathogenic genes for families without known genetic causes using next-generation sequencing.We identified a monoallelic variant in signal peptide of CCN2(NM_001901.2:c.65 G>C[p.Arg22Pro])as the cause of SEMD in 14 subjects presenting with different degree of short stature,premature osteoarthritis,and osteoporosis.Affected subjects showed decreased serum CCN2 levels.Cell lines harboring the variant displayed decreased amount of CCN2 proteins in culture medium and an increased intracellular retention,indicating impaired protein secretion.And the variant weakened the stimulation effect of CCN2 on osteogenesis of bone marrow mesenchymal stem cells.Zebrafish ccn2a knockout model and osteoblast lineage-specific Ccn2-deficient mice(Ccn2fl/fl;Prx1Cre)partially recapitulated the phenotypes including low bone mass observed in affected subjects.Pathological mechanism implicated in the skeletal abnormality in Ccn2fl/fl;Prx1Cre mice involved decreased bone formation,increased bone resorption,and abnormal growth plate formation.Collectively,our study indicate that monoallelic variants in CCN2 lead to a human inherited skeletal dysplasia,and highlight the critical role of CCN2 in osteogenesis in human.
文摘For preterm infants, bronchopulmonary dysplasia (BPD) is usually caused by abnormal lung development due to various factors during prenatal and postnatal process. One of the reasons for death and bad prognosis of preterm infants is to have BPD. Up to now, there are no unified strategies or drugs to treat BPD. In clinical, many intervention treatments have been applied to achieve BPD therapy, mainly including preterm protection, protective ventilation strategies, and delivery of corticosteroids, pulmonary vasodilators, and antioxidants. This review summarizes the current advances in BPD protection and treatment, and notes that gut microbiota and mesenchymal stem cells (MSCs) can be the promising strategy for protecting and treating BPD in the future.
文摘BACKGROUND Developmental dysplasia of the hip(DDH)is a common osteoarticular deformity in pediatric orthopedics.A patient with bilateral DDH was diagnosed and treated using our improved technique"(powerful overturning acetabuloplasty)"combined with femoral rotational shortening osteotomy.CASE SUMMARY A 4-year-old girl who was diagnosed with bilateral DDH could not stand normally,and sought surgical treatment to solve the problem of double hip extension and standing.As this child had high dislocation of the hip joint and the acetabular index was high,we changed the traditional acetabuloplasty to"powerful turnover acetabuloplasty"combined with femoral rotation shortening osteotomy.During the short-term postoperative follow-up(1,3,6,9,12,and 15 months),the child had no discomfort in her lower limbs.After the braces and internal fixation plates were removed,formal rehabilitation training was actively carried out.CONCLUSION Our"powerful overturning acetabuloplasty"combined with femoral rotational shortening osteotomy is feasible in the treatment of DDH in children.This technology may be widely used in the clinic.
基金Supported by the Science Project of Hunan Provincial Healthy Commission,No.20230844.
文摘Combined femoral and acetabular anteversion is the sum of femoral and acetabular anteversion,representing their morphological relationship in the axial plane.Along with the increasing understanding of hip dysplasia in recent years,numerous scholars have confirmed the role of combined femoral and acetabular anteversion in the pathological changes of hip dysplasia.At present,the reconstructive surgery for hip dysplasia includes total hip replacement and redirectional hip preservation surgery.As an important surgery index,combined femoral and acetabular anteversion have a crucial role in these surgeries.Herein,we discuss the role of combined femoral and acetabular anteversion in pathological changes of hip dysplasia,total hip replacement,and redirectional hip preservation surgery.
文摘Developmental dysplasia of the hip(DDH)poses significant challenges in both childhood and adulthood,affecting up to 10 per 1000 live births in the United Kingdom and United States.While newborn screening aims to detect DDH early,missed diagnoses can lead to severe complications such as hip dysplasia and early onset osteoarthritis in adults.Treatment options range from less invasive procedures like hip-preserving surgery to more extensive interventions such as total hip arthroplasty(THA),depending on the severity of the condition.Preoperative planning plays a critical role in optimizing surgical outcomes for DDH patients undergoing THA.This includes accurate imaging modalities,precise measurement of acetabular bone stock,assessment of femoral head subluxation,and predicting prosthesis size and leg length discrepancy.Recent advancements artificial intelligence and machine learning offer promising tools to enhance preoperative planning accuracy.However,challenges remain in validating these technologies and integrating them into clinical practice.This editorial highlights the importance of ongoing research to refine preoperative strategies and improve outcomes in DDH management through evidence-based approaches and technological innovations.
基金the University of Texas Southwestern Institutional Review Board(approval No.Stu-2022-1014).
文摘BACKGROUND Hip dysplasia(HD)is characterized by insufficient acetabular coverage of the femoral head,leading to a predisposition for osteoarthritis.While radiographic measurements such as the lateral center edge angle(LCEA)and Tönnis angle are essential in evaluating HD severity,patient-reported outcome measures(PROMs)offer insights into the subjective health impact on patients.AIM To investigate the correlations between machine-learning automated and manual radiographic measurements of HD and PROMs with the hypothesis that artificial intelligence(AI)-generated HD measurements indicating less severe dysplasia correlate with better PROMs.METHODS Retrospective study evaluating 256 hips from 130 HD patients from a hip preservation clinic database.Manual and AI-derived radiographic measurements were collected and PROMs such as the Harris hip score(HHS),international hip outcome tool(iHOT-12),short form(SF)12(SF-12),and Visual Analogue Scale of the European Quality of Life Group survey were correlated using Spearman's rank-order correlation.RESULTS The median patient age was 28.6 years(range 15.7-62.3 years)with 82.3%of patients being women and 17.7%being men.The median interpretation time for manual readers and AI ranged between 4-12 minutes per patient and 31 seconds,respectively.Manual measurements exhibited weak correlations with HHS,including LCEA(r=0.18)and Tönnis angle(r=-0.24).AI-derived metrics showed similar weak correlations,with the most significant being Caput-Collum-Diaphyseal(CCD)with iHOT-12 at r=-0.25(P=0.042)and CCD with SF-12 at r=0.25(P=0.048).Other measured correlations were not significant(P>0.05).CONCLUSION This study suggests AI can aid in HD assessment,but weak PROM correlations highlight their continued importance in predicting subjective health and outcomes,complementing AI-derived measurements in HD management.
文摘Our case is a 72-year-old female with Fibromuscular Dysplasia (FMD) presented to the Emergency Department (ED) with acute coronary syndrome (ACS), more specifically NSTEMI. In ED, troponin levels were elevated and non-ST segment elevation myocardial infarction (NSTEMI) was detected on electrocardiogram (ECG). Computed tomography (CT) scan showed Internal Carotid artery (ICA) pseudoaneurysm. Cardiac catheterization (CATH) was performed and revealed occlusion of the Left anterior descending (LAD) artery. Spontaneous coronary artery dissection (SCAD) was suspected due to the history of FMD without a history of hypertension, smoking or substance use.
文摘Bronchopulmonary dysplasia(BPD),also known as neonatal chronic lung disease,is a common respiratory disease in preterm infants.Preterm infants with BPD often exhibit changes in gut and lung microbiota.In recent years,with the development of high-throughput sequencing technology,more and more mechanisms of the gut-lung axis have been confirmed,helping to explore new directions for the treatment of BPD using microecological agents.This paper reviews the roles of gut microbiota,lung microbiota,and the gut-lung axis in the pathogenesis of BPD in preterm infants,providing new research avenues for the prevention and treatment of BPD.
