Bone Density and Trabecular Bone Score Decline Rapidly in the First Year After Bone Marrow Transplantation with a Marked Increase in 10-Year Fracture Risk.

As outcomes from allogeneic bone marrow transplantation (BMT) have improved, prevention of long-term complications, such as fragility fractures, has gained importance. We aimed to assess areal bone mineral density (aBMD) and trabecular bone score (TBS) changes post BMT, and determine their relationship with fracture prevalence. Patients who attended the Royal Melbourne Hospital (RMH) BMT clinic between 2005-2021 were included. Patient characteristics and dual-energy X-ray absorptiometry (DXA) values were collected from the electronic medical record and a survey. TBS iNsight™ was used to calculate TBS for DXA scans performed from 2019 onwards. 337 patients with sequential DXAs were eligible for inclusion. Patients were primarily male (60%) and mean age ± SD was 45.7 ± 13.4 years. The annualised decline in aBMD was greater at the femoral neck (0.066g/cm2 (0.0038-0.17)) and total hip (0.094g/cm2 (0.013-0.19)), compared to the lumbar spine (0.049g/cm2 (- 0.0032-0.16)), p < 0.0001. TBS declined independently of aBMD T-scores at all sites. Eighteen patients (5.3%) sustained 19 fractures over 3884 person-years of follow-up post-transplant (median follow-up 11 years (8.2-15)). This 5.3% fracture prevalence over the median 11-year follow-up period is higher than what would be predicted with FRAX® estimates. Twenty-two patients (6.5%) received antiresorptive therapy, and 9 of 18 (50%) who fractured received or were on antiresorptive therapy. In BMT patients, aBMD and TBS decline rapidly and independently in the first year post BMT. However, FRAX® fracture probability estimates incorporating these values significantly underestimate fracture rates, and antiresorptive treatment rates remain relatively low.

Prevalence of irritable bowel syndrome and functional abdominal pain disorders in children with inflammatory bowel disease in remission.

Despite evidence of an increased prevalence of irritable bowel syndrome (IBS) in adults with inflammatory bowel disease (IBD) compared with the general population, the prevalence of IBS in children with IBD is unclear. In this review, we aimed to identify the reported prevalence of IBS or functional abdominal pain disorders (FAPDs) in children with IBD in remission. A search of three databases (MEDLINE, Embase, and PubMed) was performed to identify studies reporting the prevalence of IBS or FAPDs in pediatric patients with IBD in remission. A total of 60 studies were identified, with four eligible studies remaining following abstract screening. In children with IBD in remission, the overall prevalence of IBS ranged between 3.9 and 16.1%, and the overall prevalence of FAPDs ranged between 9.6 and 29.5%. The prevalence of FAPDs in patients in biomarker-based remission was generally higher than those in clinical remission (range 16-22.5% vs 9.6-16.7%, respectively). There is a paucity of literature reporting on the prevalence of IBS or FAPDs in children with IBD in remission. Despite the differences in criteria used to define IBD remission in the included articles, there seems to be an increased overall prevalence of IBS or FAPDs in children with IBD.

ßIII-tubulin: a novel mediator of chemoresistance and metastases in pancreatic cancer.

Pancreatic cancer is a leading cause of cancer-related deaths in Western societies. This poor prognosis is due to chemotherapeutic drug resistance and metastatic spread. Evidence suggests that microtubule proteins namely, ß-tubulins are dysregulated in tumor cells and are involved in regulating chemosensitivity. However, the role of ß-tubulins in pancreatic cancer are unknown. We measured the expression of different ß-tubulin isotypes in pancreatic adenocarcinoma tissue and pancreatic cancer cells. Next, we used RNAi to silence ßIII-tubulin expression in pancreatic cancer cells, and measured cell growth in the absence and presence of chemotherapeutic drugs. Finally, we assessed the role of ßIII-tubulin in regulating tumor growth and metastases using an orthotopic pancreatic cancer mouse model. We found that ßIII-tubulin is highly expressed in pancreatic adenocarcinoma tissue and pancreatic cancer cells. Further, we demonstrated that silencing ßIII-tubulin expression reduced pancreatic cancer cell growth and tumorigenic potential in the absence and presence of chemotherapeutic drugs. Finally, we demonstrated that suppression of ßIII-tubulin reduced tumor growth and metastases in vivo. Our novel data demonstrate that ßIII-tubulin is a key player in promoting pancreatic cancer growth and survival, and silencing its expression may be a potential therapeutic strategy to increase the long-term survival of pancreatic cancer patients.