Focal reactive periostitis ossificans in a long bone: radiologic and pathologic findings.

Florid reactive periostitis ossificans (FRPO) is a benign juxta-cortical lesion of unknown etiology which most commonly occurs in the hands and feet. We report the radiographic, CT, and MR features of a pathologically confirmed FRPO in the distal femur, a location in which only a handful of cases has been reported. A 26-year-old male who presented with distal thigh pain initially underwent radiograph and CT, which illustrated a well-circumscribed, ossified lesion associated with the cortex of the femur without contiguity with the medullary canal. A subsequent MRI demonstrated heterogeneous signal intensity corresponding to the ossified portion of the lesion with a T2 hyperintense cartilaginous cap and surrounding edema. The lesion was surgically excised and pathologic diagnosis of FRPO, a mixture of osteoid, mature bone, cartilage and fibrous tissue, with associated inflammatory cells, was confirmed. Follow up four months after surgery revealed significant improvement in the patient's pain.

Evaluating the Impact of a Call Triage Assistant on Resident Efficiency, Errors, and Stress.

OBJECTIVE: The aim of this study was to evaluate whether a call triage assistant, who answered telephone calls to the main reading room during the busiest hours of weekend call, would impact resident workflow efficiency, diagnostic errors, and stress level. METHODS: The call triage assistant answered all telephone calls to the main reading room from 12 pm to 7 pm on 6 weekend days over a 3-month period. We compared report turnaround times and resident discrepancy rates on these days with control days, when the same residents were on call without the assistant. We also surveyed residents to determine whether the assistants relieved anxiety associated with the call shift. RESULTS: We recorded 168 telephone calls over the study period. We found the majority of telephone calls could be handled by the assistant without disturbing the on-call resident, resulting in a 71% reduction in interruptions. The mean turnaround time for studies read on the days the assistant was on duty was 44.3 min, compared with 75.2 min on the control days (P < .01). Resident major discrepancy rates (0.4% on the intervention days compared to 0.2% on the control days) were similar (P = .58), as were minor discrepancy rates (7.5% on the intervention days compared with 6.7% on the control days; P = .61). Residents reported fewer distractions, improved workflow efficiency, and decreased call-related stress when the assistant was on duty. CONCLUSIONS: A call triage assistant effectively improved workflow efficiency and reduced resident stress on call. Resident error rates were unaffected by the presence of the assistant.

Correction to: ADAR2 mislocalization and widespread RNA editing aberrations in C9orf72-mediated ALS/FTD.

The original article was published erroneously without mentioning the support of the U.S.

ADAR2 mislocalization and widespread RNA editing aberrations in C9orf72-mediated ALS/FTD.

The hexanucleotide repeat expansion GGGGCC (G4C2)n in the C9orf72 gene is the most common genetic abnormality associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recent findings suggest that dysfunction of nuclear-cytoplasmic trafficking could affect the transport of RNA binding proteins in C9orf72 ALS/FTD. Here, we provide evidence that the RNA editing enzyme adenosine deaminase acting on RNA 2 (ADAR2) is mislocalized in C9orf72 repeat expansion mediated ALS/FTD. ADAR2 is responsible for adenosine (A) to inosine (I) editing of double-stranded RNA, and its function has been shown to be essential for survival. Here we show the mislocalization of ADAR2 in human induced pluripotent stem cell-derived motor neurons (hiPSC-MNs) from C9orf72 patients, in mice expressing (G4C2)149, and in C9orf72 ALS/FTD patient postmortem tissue. As a consequence of this mislocalization we observe alterations in RNA editing in our model systems and across multiple brain regions. Analysis of editing at 408,580 known RNA editing sites indicates that there are vast RNA A to I editing aberrations in C9orf72-mediated ALS/FTD. These RNA editing aberrations are found in many cellular pathways, such as the ALS pathway and the crucial EIF2 signaling pathway. Our findings suggest that the mislocalization of ADAR2 in C9orf72 mediated ALS/FTD is responsible for the alteration of RNA processing events that may impact vast cellular functions, including the integrated stress response (ISR) and protein translation.

Stenosis of gastric sleeve after laparoscopic sleeve gastrectomy: clinical, radiographic and endoscopic findings.

OBJECTIVE: To determine the clinical, radiographic, and endoscopic findings of sleeve stenosis after sleeve gastrectomy and to correlate treatment with outcomes. METHODS: We identified 43 patients who underwent barium studies to evaluate upper GI symptoms after laparoscopic sleeve gastrectomy. The clinical, radiographic, and endoscopic findings were reviewed and correlated with treatment and outcomes. RESULTS: 26 patients (60%) had sleeve stenoses. All stenoses appeared as short segments of smooth, tapered narrowing, with a mean length of 8.0 mm and mean width of 7.5 mm, and 24 (92%) were located in the proximal or distal third of the sleeve. 23 patients (88%) had upstream dilation, and 1 (4%) had retained food proximal to the stenosis. 23 (70%) of 33 patients with obstructive symptoms and 3 (30%) of 10 without obstructive symptoms had sleeve stenoses. Endoscopy revealed sleeve stenosis in 8 (67%) of 12 patients with radiographic stenosis. Endoscopic dilation resulted in improvement/resolution of symptoms in seven (88%) of 8 patients. CONCLUSION: Sleeve stenosis after sleeve gastrectomy was characterized radiographically by a short segment of smooth, tapered narrowing, typically in the proximal or distal third of the sleeve. Approximately, 70% of patients with obstructive symptoms and 30% with non-obstructive symptoms had sleeve stenosis. One-third of radiographically diagnosed stenoses were not seen at endoscopy. The barium study, therefore, is a useful test for sleeve stenosis in patients with obstructive or nonobstructive symptoms after sleeve gastrectomy. Advances in knowledge: This article describes the appearance and location of sleeve stenoses after laparoscopic sleeve gastrectomy and the clinical presentation and treatment options for these patients.

Findings of Esophagography for 25 Patients After Peroral Endoscopic Myotomy for Achalasia.

OBJECTIVE: The purpose of this study is to better characterize the findings of esophagography after peroral endoscopic myotomy for achalasia. MATERIALS AND METHODS: We evaluated 25 patients who underwent peroral endoscopic myotomy for achalasia. The findings noted on pre- and postprocedural esophagrams were reviewed retrospectively and were correlated with clinical outcomes. RESULTS: None of the patients had esophageal perforation noted on esophagrams obtained after myotomy, and all but two patients had a hospital stay that lasted 1 day only. Esophagrams obtained on postoperative day 1 revealed endoscopic clips in 25 patients (100%), pneumoperitoneum in 18 (72%), retroperitoneal gas in 10 (40%), gastric pneumatosis in nine (36%), intramural dissections in seven (28%), and pneumomediastinum in four (16%). Repeat esophagrams obtained 3 weeks later for 22 of the patients revealed endoscopic clips in 16 patients (73%) and intramural dissections in five patients (23%), but the remaining findings had resolved. Eighteen patients (72%) had a successful myotomy and seven (28%) had suboptimal results on the basis of clinical outcomes. Observation of a distal esophageal width of 5 mm or less on postprocedural esophagrams was often associated with suboptimal results. CONCLUSION: Peroral endoscopic myotomy is a novel procedure that is less invasive than is laparoscopic Heller myotomy for the treatment of achalasia, with fewer complications and shorter recovery times. Radiologists should be aware of the findings expected on esophagography (including pneumoperitoneum, retroperitoneal gas, gastric pneumatosis, intramural dissections, and pneumomediastinum) and should also know that fluoroscopic studies may be helpful for predicting patient outcomes on the basis of the width of the distal esophagus after myotomy.

Percutaneous biliary drainage effectively lowers serum bilirubin to permit chemotherapy treatment.

PURPOSE: For digestive tract cancers, the bilirubin threshold for administration of systemic chemotherapy can be 5 or 2 mg/dL (85.5 or 34.2 µmol/L) depending upon the regimen. We examined the ability of percutaneous biliary drainage (PBD) in patients with malignant biliary obstruction to achieve these clinically relevant endpoints. METHODS: 106 consecutive patients with malignant biliary obstruction and a baseline serum bilirubin >2 mg/dL underwent PBD. Time to achieve a bilirubin of 5 mg/dL (85.5 µmol/L), 2 mg/dL (34.2 µmol/L), and survival was estimated by Kaplan-Meier analysis. Potential technical and clinical prognostic factors were subjected to univariate and multivariate analysis. Categorical variables were analyzed by the log rank test. Hazard ratios were calculated for continuous variables. RESULTS: Median survival was 100 days (range 1-3771 days). Among 88 patients with a pre-drainage bilirubin >5 mg/dL, 62% achieved a serum bilirubin ≤5 mg/dL within 30 days and 84% within 60 days, median 21 days. Among 106 patients with a pre-drainage bilirubin >2 mg/dL, 37% achieved a serum bilirubin ≤2 mg/dL by 30 days and 70% within 60 days, median 43 days. None of the technical or clinical factors evaluated, including pre-drainage bilirubin, were significant predictors of time to achieve a bilirubin ≤2 mg/dL (p = 0.51). Size and type of biliary device were the only technical variables found to affect time to bilirubin of 5 mg/dL (p = 0.016). CONCLUSION: PBD of malignant obstruction achieves clinically relevant reduction in serum bilirubin in the majority of patients within 1-2 months, irrespective of the pre-drainage serum bilirubin, sufficient to allow administration of systemic chemotherapy. However, the decision to undergo this procedure for this indication alone must be considered in the context of patients' prognosis and treatment goals.

Insulin metabolism in human adipocytes from subcutaneous and visceral depots.

Subjects with the metabolic syndrome (insulin resistance, glucose intolerance, dyslipidemia, hypertension, etc.) have a relative increase in abdominal fat tissue compared to normal individuals and obesity has also been shown to be associated with a decrease in insulin clearance. The majority of the clearance of insulin is due to the action of insulin-degrading enzyme (IDE) and IDE is present throughout all tissues. Since abdominal fat is increased in obesity we hypothesized that IDE may be altered in the different fat depots. Adipocytes were isolated from fat samples obtained from subjects during elective abdominal surgery. Fat samples were taken from subcutaneous (SQ) and visceral (VIS) sites. Insulin metabolism was compared in adipocytes isolated from SQ and VIS fat tissue. Adipocytes from the VIS site degraded more insulin that those from SQ fat tissue. Inhibitors of cathepsins B and D has no effect on the degradation of insulin, while bacitracin, an inhibitor of IDE, inhibited degradation by approx. 33% in both SQ and VIS adipocytes. These data show that insulin metabolism is relatively greater in VIS than in SQ fat tissue and potentially due to IDE.

Retinoblastoma protein co-purifies with proteasomal insulin-degrading enzyme: implications for cell proliferation control.

Previous investigations on proteasomal preparations containing insulin-degrading enzyme (IDE; EC 3.4.24.56) have invariably yielded a co-purifying protein with a molecular weight of about 110kDa. We have now found both in MCF-7 breast cancer and HepG2 hepatoma cells that this associated molecule is the retinoblastoma tumor suppressor protein (RB). Interestingly, the amount of RB in this protein complex seemed to be lower in HepG2 vs. MCF-7 cells, indicating a higher (cytoplasmic) protein turnover in the former vs. the latter cells. Moreover, immunofluorescence showed increased nuclear localization of RB in HepG2 vs. MCF-7 cells. Beyond these subtle differences between these distinct tumor cell types, our present study more generally suggests an interplay between RB and IDE within the proteasome that may have important growth-regulatory consequences.

Regulation of protein degradation by insulin-degrading enzyme: analysis by small interfering RNA-mediated gene silencing.

Proteins are vital to the overall structure of cells and to the function of cells in the form of enzymes. Thus the control of protein metabolism is among the most important aspects of cellular metabolism. Insulin's major effect on protein metabolism in the adult animal is inhibition of protein degradation. This is via inhibition of proteasome activity via an interaction with insulin-degrading enzyme (IDE). IDE is responsible for the majority of cellular insulin degradation. We hypothesized that a reduction in IDE would reduce insulin degradation and insulin's ability to inhibit protein degradation. HepG2 cells were transfected with siRNA against human IDE and insulin degradation and protein degradation measured. Both IDE mRNA and protein were reduced by >50% in the IDE siRNA transfected cells. Insulin degradation was reduced by approximately 50%. Cells were labeled with [3H]-leucine to investigate protein degradation. Short-lived protein degradation was unchanged in the cells with reduced IDE expression. Long-lived and very-long-lived protein degradation was reduced in the cells with reduced IDE expression (14.0+/-0.16 vs. 12.5+/-0.07%/4h (long-lived), 9.6+/-2.2% vs. 7.3+/-0.2%/3h (very-long-lived), control vs. IDE transfected, respectively, P<0.005). The inhibition of protein degradation by insulin was reduced 37-76% by a decreased expression of IDE in HepG2 cells. This shows that IDE is involved in cellular insulin metabolism and provides further evidence that insulin inhibits protein degradation via an interaction with IDE.