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The open abdomen can be a life-saving resuscitative manoeuvre in patients with catastrophic abdominal pathologies, however, can lead to the need for delayed primary closure. The most recent guidelines released from the European Hernia Society and World Society for Emergency Surgery both suggest mesh-mediated fascial traction in conjunction with negative pressure wound therapy as the preferred method in this situation. We present a detailed 'how to do it' on this technique.

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A 79-year-old woman presented with postprandial epigastric pain. She had normal vital signs, inflammatory markers and liver function tests. Ultrasound and CT of the abdomen demonstrated features consistent with acute cholecystitis. Her medical comorbidities and extensive abdominal surgical history prompted the decision to treat non-operatively. Despite optimal medical management, worsening abdominal pain and uptrending inflammatory markers developed. She underwent an emergency laparoscopy which revealed a necrotic gallbladder secondary to an anticlockwise complete gallbladder torsion; a rare condition associated with significant morbidity and mortality if managed non-operatively. Laparoscopic cholecystectomy was achieved without complication and the patient had an uneventful recovery. Preoperative diagnosis of torsion of the gallbladder is difficult. However, there are certain patient demographics and imaging characteristics that can help surgeons differentiate it from acute cholecystitis; a condition which can be safely managed non-operatively in selected patients. The differentiating features are elaborated on in this case report.

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OBJECTIVES: Universal screening of upper tract urothelial carcinoma (UTUC) for Lynch syndrome by mismatch repair (MMR) protein immunohistochemistry (IHC) has been recommended by some investigators. Herein, we assess this recommendation retrospectively by simulating its performance on a retrospective, unselected cohort of UTUCs, with comparison to the established setting of colorectal and endometrial adenocarcinoma. METHODS: We assessed for complete loss of MMR protein (MLH1, MSH2, MSH6, and PMS2) IHC in 74 consecutive cases of UTUC and then tabulated clinical and pathologic factors. MMR findings from same-institution colorectal and endometrial adenocarcinomas were tabulated for comparison. RESULTS: We observed loss of at least one MMR protein in 12% in our UTUC cohort (three MSH2/MSH6, three MSH6 only, one MLH1/PMS2, and two PMS2 only). Of these nine cases (seven males, two females, median age 67 years, five associated with colorectal adenocarcinoma), at least three (4% of the overall cohort) proved to be Lynch syndrome. Overall, MMR loss in UTUC was comparable to colorectal (11%; 50 of 471 cases) and endometrial (12%; 12 of 101 cases) adenocarcinomas. CONCLUSIONS: The rate of MMR loss observed in UTUC was comparable to that in the established setting of colorectal and endometrial adenocarcinomas, supporting universal UTUC screening at our institution and others.

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A 62-year-old patient was admitted with an acute unprovoked portal vein thrombosis with splenic and mesenteric extension. His progress was complicated by progressive small bowel ischaemia and increasing clot burden despite systemic anticoagulation. This case report describes the use of catheter-directed thrombolysis via a transjugular intrahepatic portosystemic shunt, with the disease and its treatment complicated by a ruptured iatrogenic pseudoaneurysm, abdominal compartment syndrome and small bowel infarction necessitating extensive small bowel resection.

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Timely accrual continues to be a challenge in clinical trials. The evolution of Electronic Health Record systems and cohort selection tools like i2b2 have improved identification of potential candidate participants. However, delays in receiving relevant patient information and lack of real time patient identification cause difficulty in meeting recruitment targets. The authors have designed and developed a proof of concept platform that informs authorized study team members about potential participant matches while the patient is at a healthcare setting. This Just-In-Time Alert (JITA) application leverages Health Level 7 (HL7) messages and parses them against study eligibility criteria using Amazon Web Services (AWS) cloud technologies. When required conditions are satisfied, the rules engine triggers an alert to the study team. Our pilot tests using difficult to recruit trials currently underway at the UMass Medical School have shown significant potential by generating more than 90 patient alerts in a 90-day testing timeframe.

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Biological systems are driven by intricate interactions among molecules. Many methods have been developed that draw on large numbers of expression samples to infer connections between genes (or their products). The result is an aggregate network representing a single estimate for the likelihood of each interaction, or "edge," in the network. Although informative, aggregate models fail to capture population heterogeneity. Here we propose a method to reverse engineer sample-specific networks from aggregate networks. We demonstrate our approach in several contexts, including simulated, yeast microarray, and human lymphoblastoid cell line RNA sequencing data. We use these sample-specific networks to study changes in network topology across time and to characterize shifts in gene regulation that were not apparent in the expression data. We believe that generating sample-specific networks will greatly facilitate the application of network methods to large, complex, and heterogeneous multi-omic datasets, supporting the emerging field of precision network medicine.

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STUDY DESIGN: Case report. OBJECTIVE: To present a previously unreported complication of subarachnoid hemorrhage and hydrocephalus after C1 lateral mass screw insertion. To inform spine specialists of this potential postoperative complication. SUMMARY OF BACKGROUND DATA: Damage to the carotid artery, vertebral artery, hypoglossal nerve and dural tears are all recognized complications. Acute hydrocephalus as a result of subarachnoid hemorrhage is not previously reported. METHODS: A 63-year-old female with a traumatic C1 ring and C2 peg fracture underwent C1-C2 fixation. During insertion of the C1 lateral mass screws there was significant hemorrhage from the C1-C2 venous plexus. Three days postoperatively, she developed headache, confusion, and became drowsy. RESULTS: Computed tomographic scan of the brain revealed hydrocephalus and intraventricular blood that was managed with an external ventricular drain. CONCLUSION: The case of acute hydrocephalus due to intraventricular hemorrhage from C1 lateral mass screw placement has not previously been reported. Surgeons performing the procedure should consider the diagnosis if patients display signs of raised intracranial pressure postoperatively. LEVEL OF EVIDENCE: N/A.

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Articular cartilage has a poor intrinsic capacity for self-repair. The advent of autologous chondrocyte implantation has provided a feasible method to treat cartilage defects. However, the associated drawbacks with the isolation and expansion of chondrocytes from autologous tissue has prompted research into alternative cell sources such as mesenchymal stem cells (MSCs) which have been found to exist in the bone marrow as well as other joint tissues such as the infrapatellar fat pad (IFP), synovium and within the synovial fluid itself. In this work we assessed the chondrogenic potential of IFP-derived porcine cells over a 6 week period in agarose hydrogel culture in terms of mechanical properties, biochemical content and histology. It was found that IFP cells underwent robust chondrogenesis as assessed by glycosaminoglycan (1.47+/-0.22% w/w) and collagen (1.44+/-0.22% w/w) accumulation after 42 days of culture. The 1Hz dynamic modulus of the engineered tissue at this time point was 272.8 kPa (+/-46.8). The removal of TGF-beta3 from culture after 21 days was shown to have a significant effect on both the mechanical properties and biochemical content of IFP constructs after 42 days, with minimal increases occurring from day 21 to day 42 without continued supplementation of TGF-beta3. These findings further strengthen the case that the IFP may be a promising cell source for putative cartilage repair strategies.

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The papers in presentation group 2 of Genetic Analysis Workshop 15 (GAW15) conducted association analyses of rheumatoid arthritis data. The analyses were carried out primarily in the data provided by the North American Rheumatoid Arthritis Consortium (NARAC). One group conducted analyses in the data provided by the Canadian Rheumatoid Arthritis Genetics Study (CRAGS). Analysis strategies included genome-wide scans, the examination of candidate genes, and investigations of a region of interest on chromosome 18q21. Most authors employed relatively new methods, proposed extensions of existing methods, or introduced completely novel methods for aspects of association analysis. There were several common observations; a group of papers using a variety of methods found stronger association, on chromosomes 6 and 18 and in candidate gene PTPN22 among women with early onset. Generally, models that considered haplotypes or multiple markers showed stronger evidence for association than did single marker analyses.

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