Loss of PRDM11 promotes MYC-driven lymphomagenesis.

The PR-domain (PRDM) family of genes encodes transcriptional regulators, several of which are deregulated in cancer. By using a functional screening approach, we sought to identify novel tumor suppressors among the PRDMs. Here we demonstrate oncogenic collaboration between depletion of the previously uncharacterized PR-domain family member Prdm11 and overexpression of MYC. Overexpression of PRDM11 inhibits proliferation and induces apoptosis. Prdm11 knockout mice are viable, and loss of Prdm11 accelerates MYC-driven lymphomagenesis in the Eµ-Myc mouse model. Moreover, we show that patients with PRDM11-deficient diffuse large B-cell lymphomas (DLBCLs) have poorer overall survival and belong to the nongerminal center B-cell-like subtype. Mechanistically, genome-wide mapping of PRDM11 binding sites coupled with transcriptome sequencing in human DLBCL cells evidenced that PRDM11 associates with transcriptional start sites of target genes and regulates important oncogenes such as FOS and JUN. Hence, we characterize PRDM11 as a putative novel tumor suppressor that controls the expression of key oncogenes, and we add new mechanistic insight into B-cell lymphomagenesis.

Long-term results using LigaSure™ 5 mm instrument for treatment of Zenker's diverticulum.

The purpose of the present study was to evaluate the long-term results and patient's satisfaction of a new approach using the LigaSure™ 5 mm instrument for treatment of Zenker's diverticulum (ZD) and to compare with other long-term results using traditional treatment modalities. Between December 2011 and August 2013, a total of 23 patients with ZD underwent endoscopic surgery using the LigaSure™ technique in our department. A retrospective evaluation of the surgery was based on medical records and additionally a long-term follow-up was performed using a standardized questionnaire that was send to all patients. The questions dealt with complaints according to a visual analog scale (VAS) and were sent a minimum of one year after the surgery (mean time 22 months, range 12-32 month). The overall response rate was 91%. The mean age of the patients was 69 years (range 37-89 years). The patients reported nine for overall satisfaction on the VAS (range 0-10: 10 being very content and 0 very uncontent, 25 and 75% quartiles: 7 and 10) regarding the final outcome of their surgery, although several of the patients had continuous symptoms within the first postoperative year. Eight patients (38%) reported no symptoms at all. Our results suggest that endoscopic management of ZD with the LigaSure™ 5 mm instrument is a minimally invasive, fast and safe method with solid long-term outcome with relief of symptoms and patient satisfaction. This new operative instrument was not found inferior to traditional endoscopic techniques and is now the standard treatment method for ZD in our departments.

Validation of data and indicators in the Danish Cholecystectomy Database.

OBJECTIVE: In The Danish Cholecystectomy Database (DCD), quality indicators are derived from clinical data in combination with administrative data from the National Patient Registry. The indicators 'Length of postoperative stay < or =1 day and no readmission', 'Length of stay (LOS) >3 days and/or readmission', 'Additional procedures within 30 days', 'Reconstructive bile duct surgery', 'Other surgery of the bile duct' and 'Death within 30 days' are all derived from administrative data. This study investigates the validity of the administrative data and evaluates the association between these indicators and postoperative complications. RESEARCH DESIGN AND SUBJECTS: Data from 1360 medical records of patients undergoing cholecystectomy were compared with the relevant administrative data from the National Patient Registry. The medical records served as the 'gold standard'. The association between the individual indicators and the occurrence of a postoperative complication was assessed. MEASURES: Validation of administrative data against the gold standard was done by the calculation of per cent agreement (including kappa-values) sensitivity/specificity and predictive values. The association between indicators and complications was analysed with crude event rates and odds ratios. RESULTS: The validity of the administrative data was excellent (97.1-100% agreement, kappa = 0.73-1.00). All of the indicators except 'Other bile duct surgery' were significantly associated with postoperative complications. A subdivision of some indicators strengthened the associations. CONCLUSIONS: The DCD is a valid method for monitoring the quality of cholecystectomy in Denmark.

Acute mastoiditis in children: a 10-year retrospective and validated multicenter study.

BACKGROUND: Conservative treatment of acute otitis media may lead to more complications. This study evaluates changes in incidence, the clinical and microbiological findings, the complications and the outcome of acute mastoiditis in children in a country employing conservative guidelines in treating acute otitis media. METHODS: All admitted children (0-15 years) diagnosed with acute mastoiditis during the period from 1998 to 2007 in eastern Denmark (population 2.2 million) were identified. Patient files were retrieved and reviewed; the data were entered into a database. RESULTS: The average incidence of admitted children with acute mastoiditis was 4.8/100,000 children per year (95% CI were ± 0.03 -0.04), and there was no change in the incidence during the 10-year period. Of the 214 children included (mean age 2.1 years, range 0.3-13.1, median 1.3 years), 100% presented with protrusion of the pinna and 95% with retroauricular swelling and redness, whereas 32% had a retroauricular abscess. Mastoidectomy had been performed in children with a retroauricular abscess. Thirty-one percent had a ventilation tube inserted. The remaining group was treated with antibiotics and analgesics, and 86% also had a myringotomy performed. Streptococcus pneumoniae and group A streptococci were the bacteria most commonly cultured, 94% being susceptible to penicillin. The complication rate was low at 1.9%. All children included were initially admitted; no patients were outpatients. CONCLUSIONS: The incidence of acute mastoiditis is stable in eastern Denmark where conservative management guidelines for treating acute otitis media are used. Bacterial resistance toward penicillin is low (6%), complications are rare and the treatment outcome is good. Furthermore, no severe complications after treatment were observed.

[Treatment of peritonsillar abscess]. / Behandling af peritonsillær absces.

Peritonsillar abscess (PTA) is associated with high morbidity and can cause serious and life-threatening complications. In Denmark, the most commonly isolated bacteria are Fusobacterium necrophorum and Streptococcus pyogenes gr. A. The incidence of PTA in Denmark is 41/100,000/year, the highest incidence ever reported for PTA. There is no definite consensus on the treatment. We recommend most patients treated with puncture and antibiotics as outpatients, and if necessary acute tonsillectomy instead of interval tonsillectomy. Steroids may be of value.

Unexpected findings and surgical complications in 505 consecutive cochlear implantations: a proposal for reporting consensus.

CONCLUSION: Cochlear implantation is a safe procedure in experienced hands, as the rate of severe complications is below 2%. Complications differ between children and adults, and transient disequilibrium/vertigo is the most common complication, followed by wound infection, haematoma/oedema and transient chorda tympani syndrome. An international consensus on the reporting of complications is proposed, as a high degree of variability occurs in the literature, which precludes an overview necessary for adequate patient information and for incentives aimed at prevention. OBJECTIVE: To report unexpected findings and surgical complications in 505 consecutive cochlear implantations, and propose a consensus for reporting complications. METHODS: This was a retrospective file review of 367 consecutive patients (505 implantations), of which 187 children had received 313 implants and 180 adults 192 implants. RESULTS: The overall complication rate was 29.1%, with a major complication rate of 1.8%. When deducting vertigo/disequilibrium, the overall complication rate was 18.3%. Adults had a complication rate of 58.8%, 1.6% being major. Vertigo/disequilibrium was the most common complication (25%), followed by wound infection (8.9%) and transient chorda tympani syndrome (5.7%). In the paediatric group, complications occurred in 14.7%, 1.9% being major. The children suffered most frequently from wound infection (3.8%), vertigo/disequilibrium (2.2%) and haematoma/oedema (2.2%).