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Auckland, New Zealand

Ponzoni M.,San Raffaele Scientific Institute | Issa S.,Middlemore Hospital | Batchelor T.T.,Massachusetts General Hospital | Rubenstein J.L.,University of California at San Francisco
Annals of Oncology

Background: While there has been significant progress in outcomes for patients diagnosed with primary central nervous system (CNS) lymphoma (PCNSL), survival rates will likely plateau with the current armamentarium of agents used to treat these patients. Moreover, given that PCNSL increasingly impacts an older population, a significant proportion of patients are not eligible for intensive therapies such as high-dose chemotherapy or whole-brain radiation. There is a need for the development of novel agents, which target key survival pathways in order to continue to make progress in this disease. Patients and methods: We reviewed the key molecular pathways and genomic aberrations in PCNSL in order to identify candidate targets. We focused on molecules and pathways that have been identified and confirmed by more than one investigator or methodology. Results: While PCNSL tumors usually express a BCL6+, MUM1+ 'activated, germinal center' immunophenotype, they exhibit multiple shared genetic properties with ABC-type diffuse large B-cell lymphomas. Candidate targets and pathways include NFkB, the B-cell receptor, the JAK/STAT pathway, IRF4, BCL-6 as well as PIM kinases. Elements of the tumor microenvironment that may be exploited therapeutically include chemokine pathways, as well as macrophage and T-cell responses. Conclusions: There is a significant need for developing novel therapies in PCNSL, given that an increasing proportion of patients are not eligible for high-dose chemotherapy and brain radiation is associated with detrimental cognitive sideeffects. We provide an overview of potential drug targets and novel agents that may be integrated with existing strategies in order to make further progress in this disease. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. Source

Murgatroyd S.E.,Middlemore Hospital | Frampton C.M.A.,University of Otago | Wright M.S.,Auckland Hospital
Journal of Arthroplasty

This study assessed the early outcomes of total hip arthroplasty compared with body mass index (BMI). 5357 hip arthroplasties were evaluated. Oxford Scores, revision for any reason and other factors including American Society of Anaesthesiology scores, length of surgery and cementation of components were analyzed. Both a high and a low BMI predicted for worse Oxford Hip Scores. Obese and morbidly obese patients had significantly lower six month Oxford Scores than healthy patients, the lowest survival, were younger than all other groups and had greater proportions with fully un-cemented prostheses. At this early stage, the results show that outcome and early revision are statistically and clinically poorer for obese patients. © 2014. Source

Singh P.P.,University of Auckland | Zeng I.S.L.,Center for Health System Innovation and Improvement | Srinivasa S.,University of Auckland | Lemanu D.P.,University of Auckland | And 2 more authors.
British Journal of Surgery

Background Several recent studies have investigated the role of C-reactive protein (CRP) as an early marker of anastomotic leakage following colorectal surgery. The aim of this systematic review and meta-analysis was to evaluate the predictive value of CRP in this setting. Methods A systematic literature search was performed using MEDLINE, Embase and PubMed to identify studies evaluating the diagnostic accuracy of postoperative CRP for anastomotic leakage following colorectal surgery. A meta-analysis was carried out using a random-effects model and pooled predictive parameters were determined along with a CRP cut-off value at each postoperative day (POD). Results Seven studies, with a total of 2483 patients, were included. The pooled prevalence of leakage was 9·6 per cent and the median day on which leakage was diagnosed ranged from POD 6 to 9. The serum CRP level on POD 3, 4 and 5 had comparable diagnostic accuracy for the development of an anastomotic leak with a pooled area under the curve of 0·81 (95 per cent confidence interval 0·75 to 0·86), 0·80 (0·74 to 0·86) and 0·80 (0·73 to 0·87) respectively. The derived CRP cut-off values were 172 mg/l on POD 3, 124 mg/l on POD 4 and 144 mg/l on POD 5; these corresponded to a negative predictive value of 97 per cent and a negative likelihood ratio of 0·26-0·33. All three time points had a low positive predictive value for leakage, ranging between 21 and 23 per cent. Conclusion CRP is a useful negative predictive test for the development of anastomotic leakage following colorectal surgery. © 2013 BJS Society Ltd. Published by John Wiley & Sons Ltd. Source

Mosca V.S.,Seattle Childrens Hospital | Bevan W.P.,Middlemore Hospital
Journal of Bone and Joint Surgery - Series A

Background: Surgical resection of persistently painful talocalcaneal tarsal coalitions may not reliably relieve symptoms in patients with large coalitions associated with excessive hindfoot valgus deformity and subtalar posterior facet narrowing. Since 1991, calcaneal lengthening osteotomy, with or without coalition resection, has been used at our institution to relieve symptoms and to preserve motion at the talonavicular and calcaneocuboid joints. Methods: We retrospectively reviewed the records for eight patients with thirteen painful talocalcaneal tarsal coalitions who had undergone a calcaneal lengthening osteotomy for deformity correction with or without coalition resection between 1991 and 2005. Preoperative and postoperative clinical, radiographic, and computed tomographic records were reviewed. The duration of clinical follow-up ranged from two to fifteen years. Results: Calcaneal lengthening osteotomy fully corrected the valgus deformity and provided short-to-intermediate term pain relief for the five patients (nine feet) in whom the talocalcaneal tarsal coalition was unresectable. The patient with resectable coalitions but excessive valgus deformities underwent calcaneal lengthening osteotomies along with coalition resections and had excellent deformity correction and pain relief in both feet. One of the two patients who underwent calcaneal lengthening osteotomy years after coalition resection had excellent correction and pain relief. The other patient had a coincident calcaneonavicular coalition and severe degenerative arthritis in the talonavicular joint. He underwent concurrent arthrodesis of the talonavicular joint and, although he had excellent deformity correction, had persistent pain. All feet underwent concurrent gastrocnemius or Achilles tendon lengthening. Conclusions: It is generally accepted that resection is the treatment of choice for an intractably painful small talocalcaneal tarsal coalition that is associated with a wide, healthy posterior facet and minimal valgus deformity of the hindfoot. Although triple arthrodesis has been recommended for those who do not meet all three criteria, the present study suggests that an algorithmic treatment approach is justified. Treatment of the valgus deformity appears to be as important as that of the coalition. Calcaneal lengthening osteotomy with gastrocnemius or Achilles tendon lengthening is effective for correcting deformity and relieving pain in rigid flatfeet, just as it is in flexible flatfeet. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2012 by The Journal of Bone and Joint Surgery, Incorporated. Source

Wong T.Y.,Middlemore Hospital
New Zealand Medical Journal

Aim To evaluate the incidence, indications and complications associated with emergency peripartum hysterectomy (EPH) performed at Christchurch Women's Hospital, New Zealand. Methods A retrospective case series analysis of EPH from 2000-2009. Cases were identified using the hospital's computerised database. Those medical records were reviewed. EPH was defined as one performed for major postpartum haemorrhage unresponsive to other treatment within 24 hours of delivery. Results Nineteen EPH cases were identified among 47,520 deliveries, giving an incidence of 0.4 per 1000 deliveries. The indications were invasive placental adhesion-accreta, increta, percreta (63%), uterine atony (16%), placenta praevia (10.5%) and uterine tear with atony (10.5%). All cases of abnormal placentation in this study had previous caesareans or curettages. A significant association between previous uterine surgery and abnormal placentation was shown (p=0.02), especially those with previous caesarean (p=0.003). No maternal or perinatal mortality was recorded. Maternal morbidity was prevalent, including eight disseminated intravascular coagulopathies, seven intensive care, three bladder injuries, two reexplorations, one respiratory failure and one pulmonary embolism. Conclusion Invasive placental adhesion is the major indication for EPH. This study demonstrates an association between the presence of scarred uteri as a result of previous uterine surgery, and abnormal placentation. © NZMA. Source

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