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We report the first case series of 14 children with intracranial germ cell tumour (iGCT) and concomitant central diabetes insipidus (DI), who developed hyponatremia secondary to renal salt wasting syndrome (RSWS) following the administration of carboplatin. Clinicians prescribing platinum-based chemotherapy for this group of patients should be alert to the risk of RSWS. Regular monitoring should be performed as hyponatraemia can be asymptomatic until it is severe.

Background: Ibrutinib is a Bruton’s tyrosine-kinase (BTK) inhibitor that is approved as a second-line treatment in chronic lymphocytic leukemia (CLL). While recent trials have demonstrated impressive results for ibrutinib, there remains a paucity of real-world data on its use in the clinical setting. Methods: In this single-center study carried out at Brighton and Sussex University Hospitals, we retrospectively compared outcomes in 38 patients with relapsed CLL who received ibrutinib versus those who received conventional first- and second-line therapies. Results: Our results demonstrate improved progression-free survival (PFS, p=0.022) with ibrutinib versus conventional second-line therapies and survival comparable to conventional first-line therapies. However, there was a high frequency (81.6%) of adverse events associated with ibrutinib therapy, including 2 cases of death secondary to sepsis and a further 7 cases of discontinuation of treatment due to adverse events. We also identify del13q14.3 as an adverse predictor of response to ibrutinib with respect to both overall survival (p=0.014) and PFS (p=0.008), suggesting that these patients may be better suited to receiving the BCL2 inhibitor venetoclax. Conclusion: Whilst there is robust evidence for improved outcomes with ibrutinib, we find that survival in patients with del13q14.3 is reduced and that the rate of adverse events and discontinuation in clinical practice is higher than anticipated from clinical trials.

Introduction: Body mass index (BMI) categories and physical fitness are associated but the reciprocal relationship between BMI categories and physical fitness has not been investigated. This study aims to investigate the longitudinal reciprocal relationship between BMI categories and physical fitness. Methods: This is a population-based 4-year cohort study in 48 elementary schools. Children aged 6 to 9 years at recruitment were included. BMI categories and physical fitness including handgrip strength, core muscle endurance, flexibility, and cardiorespiratory fitness were measured using standard equipment and protocol. Results: Among 26 392 eligible participants, 19 504 (73.9%) were successfully followed for 3 years. Baseline obesity prevalence was 5.9%. After 3 years, those who were unfit at baseline had an increased risk of obesity (risk ratio [RR] 1.41, 95% CI 1.16-1.71, P

Osteogenesis imperfecta (OI) type I is usually caused by COL1A1 stop or frameshift mutations, leading to COL1A1 haploinsufficiency. Here we report on 12 individuals from 5 families who had OI type I due to an unusual cause—heterozygous deletions of the entire COL1A1 gene. The deletions were initially detected by semiconductor-based sequencing of genomic DNA and confirmed by quantitative PCR. Array comparative genomic hybridization in DNA of the index patient in each family showed that deletion size varied from 18.5 kb to 2.23 Mb between families, encompassing between 1 and 47 genes (COL1A1 included). The skeletal phenotype of the affected individuals was similar to that of patients with haploinsufficiency caused by COL1A1 stop or frameshift mutations. However, one individual with a deletion that included also DLX3 and DLX4 had tooth discoloration and bone fragility. Three individuals from 2 families had deletions that included also CACNA1G, and these individuals had learning disabilities. These features are not usually observed in COL1A1 haploinsufficiency, but are in accordance with previously described individuals in whom deletions included the same genes. In summary, we found deletions of COL1A1 in 5 out of 161 families (3 %) with OI type I that were evaluated. Deletions encompassing not only COL1A1 but also neighboring genes can lead to contiguous gene syndromes that may include dental involvement and learning disability.

As a result of low-dose ionizing radiation exposure during clinical practice, female orthopaedic surgeons may be at increased risk for breast cancer.The 2009 American Academy of Orthopaedic Surgeons (AAOS) membership directory was used to mail a survey to all female AAOS fellows. Survey responses were collected between June 2009 and June 2010 among 505 (69.7%) of the eligible women. We calculated standardized prevalence ratios (SPRs) and 95% confidence intervals (CIs) by dividing the observed number of cancers among female orthopaedic surgeons by the expected number, based on the gender-specific, age-specific, and race-specific cancer prevalence statistics in the general U.S. population. We compared the distribution of breast cancer risk factors in our study population to that of the women in the 2007 California Health Interview Survey (CHIS, n=30,541).Twenty-four women reported a prior diagnosis of invasive cancer. Female orthopaedic surgeons had a prevalence of cancer that was 85% higher than that of the general U.S. female population (SPR 1.85, 95% CI 1.19-2.76). Orthopaedic surgeons in our study also had a statistically significant 2.9-fold higher prevalence of breast cancer compared to the general U.S. female population (SPR 2.9, 95% CI 1.66-4.71). Survey respondents had a higher prevalence of both protective and predisposing breast cancer factors compared to California women.Our findings confirm that breast cancer prevalence is elevated among female orthopaedic surgeons. Although further research is needed to determine the factors behind this population's hypothesized increased risk, taken together, our results and others suggest that the orthopaedic community consider educating current practitioners of the use of protective shielding and other modifiable breast cancer risk factors.

Medulloblastoma is the most common malignancy of the central nervous system in childhood. With the current combined treatment with surgery, chemotherapy and radiotherapy, the survival rates had improved dramatically in recent years. However, these survivors are prone to develop various late sequelae secondary to treatment.