作者: Blaney, Catherine ; Stroud, Catherine ; Lai, Sophie H. Y. ; Pearce, Mark S ; Pearce, Mark S. ; Faust, Saul ; Duque, Jaime S. Rosa ; Flood, Terry ; Ip, Winnie ; Lau, Yu Lung ; Bourne, Helen ; Duque, Jaime S Rosa ; Chan, Jeffery C H ; Gennery, Andrew R. ; Lau, Tsun Ming ; Gennery, Andrew R ; Garcez, Tomaz ; Chan, Jeffery C. H. ; Jolles, Stephen ; Moya, Eduardo ; Shillitoe, Ben ; Herwadkar, Archana ; Worth, Austen ; Lai, Sophie H Y ; Hackett, Scott ; Buckland, Matthew ; Coulter, Tanya

BACKGROUNDX-linked agammaglobulinaemia (XLA), caused by mutations in BTK, is characterised by low or absent peripheral CD19 + B lymphocytes and agammaglobulinaemia. The mainstay of treatment consists of immunoglobulin replacement therapy (IgRT). As this cannot fully compensate for the immune defects in XLA, patients may therefore continue to be at risk of complications.OBJECTIVESTo describe the clinical outcomes of XLA patients in the United Kingdom and Hong Kong and evaluate current treatment strategies.METHODSPatients with a definitive diagnosis of XLA were included in this cross-sectional and retrospective analysis of clinical health outcomes. Data pertaining to diagnosis, infection incidence, IgG trough levels and lung function were collected and analysed.RESULTS99 patients with a median age of 29.02 years (IQR 12.83-37.41) and a total follow up of 1922 patient years, were included this study. The median age at diagnosis was 3.30 years (IQR 1.04-8.38) which decreased over time (p = 0.004). 40% of the cohort had radiological evidence of bronchiectasis. Risk of bronchiectasis was not significantly associated with clinical infection incidence (p = 0.880) or IgG trough levels (p = 0.407). Two patients demonstrated novel complications, namely persistent norovirus infection, leading to haemopoietic stem cell transplantation (HSCT).CONCLUSIONSDespite modern therapy, most XLA patients continue to experience complications, most notably bronchiectasis, likely due to absence of IgA/M in current therapies, but lack of B lymphocytes may also lead to additional sequalae. These data strongly support the need for further research, particularly that of curative modalities including HSCT and gene therapy.

2025-07-01·Bone

In children under two years of age, does the bone health index value differ between those with and without osteogenesis imperfecta?

Article

作者: Offiah, Amaka C ; Shalof, Heba ; Rigby, Alan ; Chong, Rachel Shuyi

BACKGROUNDIn children with unexplained fractures who are below the age of two years, it may be difficult to distinguish those with low bone mineral density (BMD) due to conditions such as osteogenesis imperfecta (OI) from those who have been abused. Currently, no imaging modality can readily or reliably assess BMD or evaluate bone strength in this age group.AIMTo investigate whether bone health index (BHI) and bone health index standard deviation scores (SDS) are sufficiently sensitive to distinguish between children under two years old with and without OI.METHODSIn this retrospective pilot study, we measured BHI and BHI SDS from 122 radiographs (33 OI, 89 suspected abuse) using BoneXpert software. Standard statistical methods (t-test, Pearson's correlation) were applied in addition to clinical diagnostics, sensitivity, specificity, and receiver operating characteristic (ROC) curves. An arbitrary level of p < 0.05 was assumed.RESULTSBHI was significantly greater in the group without OI compared to the group with OI, 3.75 and 3.41, respectively (p = 0.003). The percentage of children in the OI/non-OI groups with BHI ≤ 2.49, 2.5-2.99, 3-3.49, and ≥4 was 0 %/0 %, 27 %/7 %, 58 %/28 %, 18 %/29 %, and 12 %/36 %, respectively. While BHI SDS was significantly greater in the group without OI compared to the group with OI, -0.039 and -0.451, respectively (p = 0.01), BHI SDS was within the normal range (±2) for both groups.CONCLUSIONAlthough BHI SDS is lower in OI children, it remained within the normal range. Infants without OI had better volumetric bone mineral density, associated with stronger bones. This suggests BHI might be used to differentiate between young children with low BMD and those with healthy bones. Clinicians may find the cut-points established in this study useful for assessing the sensitivity and specificity of BHI in detecting OI and identifying individuals without OI. Further research is needed to assess BHI's clinical utility in this age group.

2025-05-01·Journal of Pediatric Orthopaedics B

Rigid intramedullary nailing of lower limb segments in children and adolescents with metabolic bone disease

Article

作者: Al-Naser, Saeed ; Fernandes, James A. ; Giles, Stephen N. ; Chin See, Charlene K. ; Nicolaou, Nicolas

Children and adolescents with metabolic bone disease present to the orthopedic surgeon with pain, fractures (which may be impending), and deformity. Different modalities of orthopedic management are available. Scant literature exists on the use of rigid intramedullary nailing in this population. This study sought to evaluate the utilization of this treatment modality in the pediatric cohort, focusing on indications, techniques, and outcomes of the procedures. A retrospective review was performed over an 11-year period at a single tertiary pediatric institution in the UK. Medical records and radiographs were reviewed. Preoperative surgical and medical management, time to bony union, and complications were specifically ascertained. Twenty-seven patients (63 lower limb segments) had rigid intramedullary nailing over the specified period. The majority of patients had an underlying diagnosis of osteogenesis imperfecta or fibrous dysplasia (including McCune Albright Syndrome). Surgical indications included acute fractures, prophylactic stabilization, previous nonunion and malunions, deformity correction, and limb lengthening. All fractures healed and deformity correction was successful. In one patient, delayed union occurred after deformity correction and was successfully treated with dynamization. Fractures healed faster than corrective osteotomies. Complications included implant prominence, cortical penetrance, and screw loosening. Nonunion occurred with limb lengthening in one patient. Rigid intramedullary nailing is a safe and effective method of treatment for lower limb fractures and deformities in children and adolescents. This technique is, therefore, recommended for patients with metabolic bone disease. However, care must be taken in preoperative surgical planning and a multidisciplinary approach should be utilized.

100 项与 Sheffield Children's NHS Foundation Trust 相关的药物交易

登录后查看更多信息

100 项与 Sheffield Children's NHS Foundation Trust 相关的转化医学

登录后查看更多信息