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Journal of Clinical Medicine Jan 2024Paediatric and adolescent shoulder instability is caused by a unique combination of traumatic factors, ligamentous laxity, and pattern of muscle contractility. The... (Review)
Review
Paediatric and adolescent shoulder instability is caused by a unique combination of traumatic factors, ligamentous laxity, and pattern of muscle contractility. The multifactorial nature of its aetiology makes interpretation of the literature difficult as nomenclature is also highly variable. The purpose of this review is to summarize the existing literature and shed light on the nuances of paediatric and adolescent shoulder instability. The epidemiology, clinical features, imaging, and management of all forms of paediatric shoulder instability are presented. The main findings of this review are that structural abnormalities following a dislocation are uncommon in pre-pubertal paediatric patients. Young post-pubertal adolescents are at the highest risk of failure of non-operative management in the setting of traumatic instability with structural abnormality, and early stabilisation should be considered for these patients. Remplissage and the Latarjet procedure are safe treatment options for adolescents at high risk of recurrence, but the side-effect profile should be carefully considered. Patients who suffer from instability due to generalized ligamentous laxity benefit from a structured, long-term physiotherapy regimen, with surgery in the form of arthroscopic plication as a viable last resort. Those who suffer from a predominantly muscle patterning pathology do not benefit from surgery and require focus on regaining neuromuscular control.
PubMed: 38337418
DOI: 10.3390/jcm13030724 -
Cureus Jul 2023Crohn's disease (CD) is a chronic inflammatory bowel disease involving entire gastrointestinal tract, most commonly affecting terminal ileum and colon. It usually...
Crohn's disease (CD) is a chronic inflammatory bowel disease involving entire gastrointestinal tract, most commonly affecting terminal ileum and colon. It usually presents with gastrointestinal symptoms like bloody diarrhea, fever and loss of weight. The clinical course of CD includes gastrointestinal complications like fistulas, abscesses and perianal disease. Inflammatory bowel diseases (IBD) are usually diagnosed during childhood and adolescence, majority during puberty and pubertal growth spurt. Various extraintestinal manifestations may be a presentation of CD that poses a diagnostic challenge. Growth failure is an important complication of IBD rather than a manifestation. Herein we present a case of a 16-year-old Sri Lankan girl presenting with growth failure and primary amenorrhea. She had minimal gastrointestinal symptoms. She also had microcytic anemia with marginally elevated inflammatory markers and hormonal profile. She underwent colonoscopy and was diagnosed to have Crohn's disease confirmed by ileal biopsy. On initiation of treatment with immunosuppressants, she attained menarche, although no improvement in height was observed.
PubMed: 37593289
DOI: 10.7759/cureus.42020 -
JCEM Case Reports Jun 2024OMIM 273750 (3-M) syndrome is a rare cause of severe short stature with variable dysmorphic features caused by pathogenic variants in several genes including cullin7...
OMIM 273750 (3-M) syndrome is a rare cause of severe short stature with variable dysmorphic features caused by pathogenic variants in several genes including cullin7 gene (). Hypogonadism and hypospadias have been described in only a few males. We report a patient with 7 pathogenic variant who had bifid scrotum and perineal hypospadias at birth. He entered puberty spontaneously at age 12 years and appropriately completed pubertal development by 15 years. Subsequently, a regression of testicular volumes, increased gonadotropin levels, and reduced (although normal) testosterone levels were observed. This case highlights the importance of careful pubertal monitoring as pubertal dysfunction may be associated with 3-M syndrome.
PubMed: 38847008
DOI: 10.1210/jcemcr/luae084 -
Wellcome Open Research 2022Endstage kidney failure rates are higher in South Asians than in White Europeans. Low birth weight is associated with adult chronic kidney disease and is more common in...
Endstage kidney failure rates are higher in South Asians than in White Europeans. Low birth weight is associated with adult chronic kidney disease and is more common in South Asians. Foetal kidney size was smaller in South Asians in the Born in Bradford (BiB) birth cohort. As part of BiB follow up, we aimed to investigate if there were ethnic differences in kidney function and blood pressure in early childhood and whether this was different by foetal kidney size. Serum creatinine, cystatin C, urea, and urinary albumin to creatinine ratio (ACR), protein to creatinine ratio (PCR) and retinol binding protein (RBP) were analysed in blood and urine samples from those who participated in the BiB follow-up at 7-11 years. Ethnicity was categorised by parental self-report as White European and South Asian. Estimated glomerular filtration rate (eGFR) was calculated using Schwartz, and cystatin C Zappitelli and Filler equations. Linear regression was used to examine the association between ethnicity and eGFR, PCR and blood pressure. 1591 children provided blood (n=1403) or urine (n=625) samples. Mean eGFR was 92 ml/min/1.73m (standard deviation (SD) 9) using Schwartz (n=1156) and 94 (SD 11) using Zappitelli (n=1257). CKD prevalence was rare (1 with eGFR <60 ml/min/1.73m , 14 (2.4%) had raised ACR (>2.5 mg/mmol in boys/3.5 mg/mmol in girls). Diastolic blood pressure was higher in South Asian children (difference 2.04 mmHg, 95% CI 0.99 to 3.10) but was not significant in adjusted analysis. There was no evidence of association in adjusted models between ethnicity and any eGFR or urinary measure at this age. There was no evidence of significant ethnic differences in kidney function at pre-pubertal age despite differences in kidney volume at birth. Longitudinal follow-up is required to track ethnic patterns in kidney function and blood pressure as children develop through puberty.
PubMed: 37274450
DOI: 10.12688/wellcomeopenres.17796.1 -
Osteoporosis International : a Journal... Feb 2024Glucocorticoid use in Duchenne and Becker muscular dystrophy prolongs ambulation but cause significant skeletal toxicity. Our analysis has immediate clinical...
UNLABELLED
Glucocorticoid use in Duchenne and Becker muscular dystrophy prolongs ambulation but cause significant skeletal toxicity. Our analysis has immediate clinical implications, suggesting that growth hormone and testosterone have a stronger effect prior to first and subsequent vertebral fracture, respectively, relative to bisphosphonates alone in children with dystrophinopathies on chronic glucocorticoids.
PURPOSE
Glucocorticoids prolong ambulation in boys with Duchenne muscular dystrophy; however, they have significant endocrine side effects. We assessed the impact of growth hormone (GH), testosterone, and/or zoledronic acid (ZA) on vertebral fracture (VF) incidence in patients with dystrophinopathies on chronic glucocorticoids.
METHODS
We conducted a longitudinal retrospective review of 27 males with muscular dystrophy. Accelerated failure time (AFT) models were used to estimate the relative time to VF while on GH, testosterone, and/or ZA compared to ZA alone. Results are reported as failure time ratio, where >1 indicates prolonged time versus <1 indicates shorter time to next VF.
RESULTS
The prevalence of growth impairment was 96% (52% utilized GH), pubertal delay was 86% (72% utilized testosterone), and low trauma fractures were 87% (72% utilized ZA). Multivariable analysis of the AFT models showed that participants on either GH or testosterone treatment relative to ZA alone experienced prolonged time to next VF (1.253, P<0.001), with GH being the significant contributor when analyzed independently from testosterone (1.229, P<0.001). Use of ZA with GH or testosterone relative to ZA alone resulted in prolonged time to next VF (1.171, P<0.001), with testosterone being a significant contributor (1.130, P=0.033).
CONCLUSION
GH and testosterone each decreased VF risk in patients independent of or in combination with ZA, respectively.
Topics: Male; Child; Humans; Spinal Fractures; Glucocorticoids; Testosterone; Growth Hormone; Muscular Dystrophy, Duchenne; Zoledronic Acid
PubMed: 37872346
DOI: 10.1007/s00198-023-06951-z -
Human Reproduction (Oxford, England) Feb 2024Fertility restoration using autologous testicular tissue transplantation is relevant for infertile men surviving from childhood cancer and, possibly, in men with absent...
Fertility restoration using autologous testicular tissue transplantation is relevant for infertile men surviving from childhood cancer and, possibly, in men with absent or incomplete spermatogenesis resulting in the lack of spermatozoa in the ejaculate (non-obstructive azoospermia, NOA). Currently, testicular tissue from pre-pubertal boys extracted before treatment with gonadotoxic cancer therapy can be cryopreserved with good survival of spermatogonial stem cells. However, strategies for fertility restoration, after successful cancer treatment, are still experimental and no clinical methods have yet been developed. Similarly, no clinically available treatments can help men with NOA to become biological fathers after failed attempts of testicular surgical sperm retrieval. We present a case of a 31-year-old man with NOA who had three pieces of testis tissue (each ∼2 × 4 × 2 mm3) extracted and cryopreserved in relation to performing microdissection testicular sperm extraction (mTESE). Approximately 2 years after mTESE, the thawed tissue pieces were engrafted in surgically created pockets bilaterally under the scrotal skin. Follow-up was performed after 2, 4, and 6 months with assessment of reproductive hormones and ultrasound of the scrotum. After 6 months, all engrafted tissue was extracted and microscopically analyzed for the presence of spermatozoa. Furthermore, parts of the extracted tissue were analyzed histologically and by immunohistochemical analysis. Active blood flow in the engrafted tissue was demonstrated by doppler ultrasound after 6 months. No spermatozoa were found in the extracted tissue. Histological and immunohistochemical analysis demonstrated graft survival with intact clear tubules and normal cell organization. Sertoli cells and spermatocytes with normal morphology were located near the basement membrane. MAGE-A and VASA positive spermatogonia/spermatocytes were detected together with SOX9 positive Sertoli cells. Spermatocytes and/or Sertoli cells positive for γH2AX was also detected. In summary, following autologous grafting of frozen-thawed testis tissue under the scrotal skin in a man with NOA, we demonstrated graft survival after 6 months. No mature spermatozoa were detected; however, this is likely due to the pre-existing spermatogenic failure.
Topics: Adult; Humans; Male; Child; Testis; Semen; Spermatozoa; Spermatogonia; Sertoli Cells; Azoospermia; Sperm Retrieval
PubMed: 38140699
DOI: 10.1093/humrep/dead243 -
Kidney International Reports Jun 2024Growth failure is considered the most important clinical outcome parameter in childhood chronic kidney disease (CKD). Central to the pathophysiology of growth failure is...
INTRODUCTION
Growth failure is considered the most important clinical outcome parameter in childhood chronic kidney disease (CKD). Central to the pathophysiology of growth failure is the presence of a chronic proinflammatory state, presumed to be partly driven by the accumulation of uremic toxins. In this study, we assessed the association between uremic toxin concentrations and height velocity in a longitudinal multicentric prospective pediatric CKD cohort of (pre)school-aged children and children during pubertal stages.
METHODS
In a prospective, multicentric observational study, a selection of uremic toxin levels of children (aged 0-18 years) with CKD stage 1 to 5D was assessed every 3 months (maximum 2 years) along with clinical growth parameters. Linear mixed models with a random slope for age and a random intercept for child were fitted for height (in cm and SD scores [SDS]). A piecewise linear association between age and height was assumed.
RESULTS
Data analysis included data from 560 visits of 81 children (median age 9.4 years; 2/3 male). In (pre)school aged children (aged 2-12 years), a 10% increase in concurrent indoxyl sulfate (IxS, total) concentration resulted in an estimated mean height velocity decrease of 0.002 SDS/yr ( < 0.05), given that CKD stage, growth hormone (GH), bicarbonate concentration, and dietary protein intake were held constant. No significant association with height velocity was found in children during pubertal stages (aged >12 years).
CONCLUSION
The present study demonstrated that, especially IxS contributes to a lower height velocity in (pre)school children, whereas we could not find a role for uremic toxins with height velocity during pubertal stages.
PubMed: 38899199
DOI: 10.1016/j.ekir.2024.03.021 -
Current Issues in Molecular Biology May 2024Disorders/differences of sex development (DSDs) are defined as broad, heterogenous groups of congenital conditions characterized by atypical development of genetic,... (Review)
Review
Disorders/differences of sex development (DSDs) are defined as broad, heterogenous groups of congenital conditions characterized by atypical development of genetic, gonadal, or phenotypic sex accompanied by abnormal development of internal and/or external genitalia. gene mutation is one of the principal genetic alterations implicated in causing DSD. This review outlines the role of gene during the process of gonadal development in humans, provides an overview of the molecular and functional characteristics of gene, and discusses potential clinical phenotypes and additional organ diseases due to mutations. mutations were analyzed in patients with 46,XY DSD and 46,XX DSD both during the neonatal and pubertal periods. Loss of function of the gene causes several different phenotypes, including some associated with disease in additional organs. Clinical phenotypes may vary, even among patients carrying the same variant, indicating that there is no specific genotype-phenotype correlation. Genetic tests are crucial diagnostic tools that should be used early in the diagnostic pathway, as early as the neonatal period, when gonadal dysgenesis is the main manifestation of mutation. gene mutations could be mainly associated with amenorrhea, ovarian failure, hypogonadism, and infertility during puberty. Fertility preservation techniques should be considered as early as possible.
PubMed: 38785542
DOI: 10.3390/cimb46050274 -
BioRxiv : the Preprint Server For... Nov 2023Uterine glands are branched, tubular structures whose secretions are essential for pregnancy success. It is known that pre-implantation glandular expression of leukemia...
Uterine glands are branched, tubular structures whose secretions are essential for pregnancy success. It is known that pre-implantation glandular expression of leukemia inhibitory factor (LIF) is crucial for embryo implantation, however contribution of uterine gland structure to gland secretions such as LIF is not known. Here we use mice deficient in estrogen receptor 1 (ESR1) signaling to uncover the role of ESR1 signaling in gland branching and the role of a branched structure in LIF secretion and embryo implantation. We observed that deletion of ESR1 in neonatal uterine epithelium, stroma and muscle using the progesterone receptor causes a block in uterine gland development at the gland bud stage. Embryonic epithelial deletion of ESR1 using a mullerian duct Cre line - , displays gland bud elongation but a failure in gland branching. Surprisingly, adult uterine epithelial deletion of ESR1 using the lactoferrin-Cre () displays normally branched uterine glands. Intriguingly, unbranched glands from uteri fail to express glandular pre-implantation , preventing implantation chamber formation and embryo alignment along the uterine mesometrial-antimesometrial axis. In contrast, branched glands from uteri display reduced expression of glandular resulting in delayed implantation chamber formation and embryo-uterine axes alignment but deliver a normal number of pups. Finally, pre-pubertal unbranched glands in control mice express in the luminal epithelium but fail to express in the glandular epithelium even in the presence of estrogen. These data strongly suggest that branched glands are necessary for pre-implantation glandular expression for implantation success. Our study is the first to identify a relationship between the branched structure and secretory function of uterine glands and provides a framework for understanding how uterine gland structure-function contributes to pregnancy success.
PubMed: 37961508
DOI: 10.1101/2023.11.01.565233 -
Medicine Dec 202317α-Hydroxylase/17, 20-lyase deficiency (17OHD) is a recessively inherited autosomal disease caused by CYP17A1 gene mutations. It is characterized by failure to...
RATIONALE
17α-Hydroxylase/17, 20-lyase deficiency (17OHD) is a recessively inherited autosomal disease caused by CYP17A1 gene mutations. It is characterized by failure to synthesize cortisol, adrenal androgens and gonadal steroids. However, it is rare in clinic combining with type 2 diabetes mellitus (T2DM).
PATIENT CONCERNS
A 21-year-old woman was transferred to an endocrinology clinic because of paroxysmal paralysis. In addition, she presented with hypertension, primary amenorrhea and lack of pubertal development. Blood evaluation revealed hypokalemia, and a low cortisol level with an increased adrenocorticotropic hormone concentration. The renin activity and testosterone and estrogen levels were suppressed, and the gonadotropin levels were high. CT scan showed bilateral adrenal hyperplasia. Besides, this patient had hyperglycemia, hyperinsulinism and negative diabetes type 1 related antibodies. A homozygous mutation c. 985 to 987delinsAA in exon 6 was found in the patient which caused the missense mutation (p.Y329fs).
DIAGNOSES
17α-hydroxylase/17, 20-lyase deficiency combined with T2DM was considered.
INTERVENTIONS
The patient received dexamethasone, estradiol valerate, metformin, amlodipine besylate and D3 calcium carbonate tablets. The doses of dexamethasone was changed according to her blood potassium levels.
OUTCOMES
After treatment, the blood pressure, blood potassium and blood glucose returned to normal range. Besides, she had restored her menstrual cycle.
LESSONS
For patients with hypertension, hypokalemia and lack of pubertal development, the possibility of 17OHD should be considered. The subsequent treatment would be challenging in patients with combined 17OHD and T2DM, considering the potential contribution of glucocorticoids to diabetic balance and osteoporosis.
Topics: Female; Humans; Young Adult; Adrenal Hyperplasia, Congenital; Dexamethasone; Diabetes Mellitus, Type 2; Hydrocortisone; Hypertension; Hypokalemia; Lyases; Mixed Function Oxygenases; Mutation; Potassium; Steroid 17-alpha-Hydroxylase
PubMed: 38206738
DOI: 10.1097/MD.0000000000036727