Isolated injury of the caudate lobe of the liver due to cardiopulmonary resuscitation.

Chest compressions are the mainstay of cardiopulmonary resuscitation. Secondary injuries are frequently reported, most frequently to the thorax and less frequently to the abdomen. Review of existing literature highlights liver lacerations as the most common abdominal injury following cardiopulmonary resuscitation; however, an isolated hepatic caudate lobe injury due to CPR has not yet been reported. We discuss existing literature regarding resuscitation-related injuries, report a case of an isolated hepatic caudate lobe injury due to cardiopulmonary resuscitation, and discuss possible mechanisms of injury.

Characterisation of retinoblastomas without RB1 mutations: genomic, gene expression, and clinical studies.

BACKGROUND: Retinoblastoma is the childhood retinal cancer that defined tumour-suppressor genes. Previous work shows that mutation of both alleles of the RB1 retinoblastoma suppressor gene initiates disease. We aimed to characterise non-familial retinoblastoma tumours with no detectable RB1 mutations. METHODS: Of 1068 unilateral non-familial retinoblastoma tumours, we compared those with no evidence of RB1 mutations (RB1(+/+)) with tumours carrying a mutation in both alleles (RB1(-/-)). We analysed genomic copy number, RB1 gene expression and protein function, retinal gene expression, histological features, and clinical data. FINDINGS: No RB1 mutations (RB1(+/+)) were reported in 29 (2·7%) of 1068 unilateral retinoblastoma tumours. 15 of the 29 RB1(+/+) tumours had high-level MYCN oncogene amplification (28-121 copies; RB1(+/+)MYCN(A)), whereas none of 93 RB1(-/-) primary tumours tested showed MYCN amplification (p<0·0001). RB1(+/+)MYCN(A) tumours expressed functional RB1 protein, had fewer overall genomic copy-number changes in genes characteristic of retinoblastoma than did RB1(-/-) tumours, and showed distinct aggressive histological features. MYCN amplification was the sole copy-number change in one RB1(+/+)MYCN(A) retinoblastoma. One additional MYCN(A) tumour was discovered after the initial frequencies were determined, and this is included in further analyses. Median age at diagnosis of the 17 children with RB1(+/+)MYCN(A) tumours was 4·5 months (IQR 3·5-10), compared with 24 months (15-37) for 79 children with non-familial unilateral RB1(-/-) retinoblastoma. INTERPRETATION: Amplification of the MYCN oncogene might initiate retinoblastoma in the presence of non-mutated RB1 genes. These unilateral RB1(+/+)MYCN(A) retinoblastomas are characterised by distinct histological features, only a few of the genomic copy-number changes that are characteristic of retinoblastoma, and very early age of diagnosis. FUNDING: National Cancer Institute-National Institutes of Health, Canadian Institutes of Health Research, German Research Foundation, Canadian Retinoblastoma Society, Hyland Foundation, Toronto Netralaya and Doctors Lions Clubs, Ontario Ministry of Health and Long Term Care, UK-Essen, and Foundations Avanti-STR and KiKa.

Hospital discharge information after elective total hip or knee joint replacement surgery: A clinical audit of preferences among general practitioners.

The demand for elective joint replacement (EJR) surgery for degenerative joint disease continues to rise in Australia, and relative to earlier practices, patients are discharged back to the care of their general practitioner (GP) and other community-based providers after a shorter hospital stay and potentially greater post-operative acuity. In order to coordinate safe and effective post-operative care, GPs rely on accurate, timely and clinically-informative information from hospitals when their patients are discharged. The aim of this project was to undertake an audit with GPs regarding their preferences about the components of information provided in discharge summaries for patients undergoing EJR surgery for the hip or knee.GPs in a defined catchment area were invited to respond to an online audit instrument, developed by an interdisciplinary group of clinicians with knowledge of orthopaedic surgery practices. The 15-item instrument required respondents to rank the importance of components of discharge information developed by the clinician working group, using a three-point rating scale.Fifty-three GPs and nine GP registrars responded to the audit invitation (11.0% response rate). All discharge information options were ranked as 'essential' by a proportion of respondents, ranging from 14.8-88.5%. Essential information requested by the respondents included early post-operative actions required by the GP, medications prescribed, post-operative complications encountered and noting of any allergies. Non-essential information related to the prosthesis used. The provision of clinical guidelines was largely rated as 'useful' information (47.5-56.7%).GPs require a range of clinical information to safely and effectively care for their patients after discharge from hospital for EJR surgery. Implementation of changes to processes used to create discharge summaries will require engagement and collaboration between clinical staff, hospital administrators and information technology staff, supported in parallel by education provided to junior medical staff.

Identification of clinically relevant mosaicism in type I hereditary haemorrhagic telangiectasia.

BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder affecting the vascular system, characterised by epistaxis, arteriovenous malformations and mucocutaneous and gastrointestinal telangiectases. Mutations in two genes, ENG and ACVRL1, account for the majority of cases. Almost all cases of HHT show a family history of HHT-associated symptoms; few cases are de novo. Mutational mosaicism is the presence of two populations of cells, with both mutant and normal genotypes in one individual and generally occurs through de novo mutation events in embryogenesis. Some isolated cases of HHT with no detectable ENG or ACVRL1 mutation may be caused by a mosaic ENG or ACVRL1 mutation that is present at levels below the limit of detection of current molecular screening methods. OBJECTIVE: To identify clinically relevant mosaicism in type I HHT. METHODS: Sequencing, quantitative multiplex-PCR and marker analysis were used to identify three HHT families with founders who showed mosaicism for endoglin mutations. Where available, mosaicism was verified by testing different sampling sites, including blood, hair and buccal swabs. RESULTS: All three mosaic samples exhibited the mutation in an estimated ≤ 25% of the DNA. Two of the mosaic patients had clinically confirmed HHT by the Curaçao criteria and the other showed symptoms of HHT. In each case the heterozygous mutation had already been identified in another family member before detection in the mosaic founder. CONCLUSIONS: The results show the importance of investigating patients without prior family history for the presence of mutational mosaicism, as detecting this would enable appropriate genetic screening and targeted medical care for at-risk children of mosaic patients.

Overlapping spectra of SMAD4 mutations in juvenile polyposis (JP) and JP-HHT syndrome.

Juvenile polyposis (JP) and hereditary hemorrhagic telangiectasia (HHT) are clinically distinct diseases caused by mutations in SMAD4 and BMPR1A (for JP) and endoglin and ALK1 (for HHT). Recently, a combined syndrome of JP-HHT was described that is also caused by mutations in SMAD4. Although both JP and JP-HHT are caused by SMAD4 mutations, a possible genotype:phenotype correlation was noted as all of the SMAD4 mutations in the JP-HHT patients were clustered in the COOH-terminal MH2 domain of the protein. If valid, this correlation would provide a molecular explanation for the phenotypic differences, as well as a pre-symptomatic diagnostic test to distinguish patients at risk for the overlapping but different clinical features of the disorders. In this study, we collected 19 new JP-HHT patients from which we identified 15 additional SMAD4 mutations. We also reviewed the literature for other reports of JP patients with HHT symptoms with confirmed SMAD4 mutations. Our combined results show that although the SMAD4 mutations in JP-HHT patients do show a tendency to cluster in the MH2 domain, mutations in other parts of the gene also cause the combined syndrome. Thus, any mutation in SMAD4 can cause JP-HHT. Any JP patient with a SMAD4 mutation is, therefore, at risk for the visceral manifestations of HHT and any HHT patient with SMAD4 mutation is at risk for early onset gastrointestinal cancer. In conclusion, a patient who tests positive for any SMAD4 mutation must be considered at risk for the combined syndrome of JP-HHT and monitored accordingly.

Detection of mosaic RB1 mutations in families with retinoblastoma.

The RB1 gene mutation detection rate in 1,020 retinoblastoma families was increased by the use of highly sensitive allele specific-PCR (AS-PCR) to detect low-level mosaicism for 11 recurrent RB1 CGA>TGA nonsense mutations. For bilaterally affected probands, AS-PCR increased the RB1 mutation detection sensitivity from 92.6% to 94.8%. Both RB1 oncogenic changes were detected in 92.7% of sporadic unilateral tumors (357/385); 14.6% (52/357) of unilateral probands with both tumor mutations identified carried one of the tumor mutations in blood. Mosaicism was evident in 5.5% of bilateral probands (23 of 421), in 3.8% of unilateral probands (22 of 572), and in one unaffected mother of a unilateral proband. Half of the mosaic mutations were only detectable by AS-PCR for the 11 recurrent CGA>TGA mutations, and not by standard sequencing. This suggests that significant numbers of low-level mosaics with other classes of RB1 mutations remain unidentified by current technology. We show that the use of linkage analysis in a two-generation retinoblastoma family resulted in the erroneous conclusion that a child carried the parental mutation, because the founder parent was mosaic for the RB1 mutation. Of 142 unaffected parental pairs tested, only one unaffected parent of a proband (0.7%) showed somatic mosaicism for the proband's mutation, in contrast to an overall 4.5% somatic mosaicism rate for retinoblastoma probands, suggesting that mosaicism for an RB1 mutation is highly likely to manifest as retinoblastoma.