Citations

Abstract Objectives: Hemostatic clip migration into the lower urinary tract is a potential complication of radical prostatectomy that may cause symptoms, anxiety, and functional concern. Our objective was to evaluate initial presentation, endoscopic management, and outcomes of patients with hemostatic clip migration following radical prostatectomy. Patients and Methods: We retrospectively identified all patients with hemostatic clip migration at our institution from 1977 to 2012. Patient records were then reviewed to identify causative factors, presentation, and long-term functional outcomes. Results: Seventeen patients were identified with clip migration following radical prostatectomy. Eight (47%) patients had undergone open retropubic radical prostatectomy, and 9 (53%) had received robot-assisted radical prostatectomy. Hemostatic clip migration was diagnosed at a median of 8 (range, 1–252) months after prostatectomy. The majority of patients ( n = 16, 94%) were symptomatic upon the diagnosis of clip migration. Symptoms included irritative urinary symptoms ( n = 14, 82%), perineal pain ( n = 3, 18%), hematuria ( n = 2, 12%), and infection ( n = 2, 12%). Five (29%) had concomitant bladder neck contracture. Fifteen (88%) underwent successful endoscopic clip removal, whereas 2 (13%) patients required a repeat operation for recurrent clip erosion. With a median follow-up of 1.6 years, the majority ( n = 13, 87%) had complete symptom resolution after clip removal, although 2 patients had recurrent bladder neck contracture. Conclusions: Hemostatic clip migration after prostatectomy is often symptomatic with irritative voiding complaints, perineal pain, hematuria, infection, or bladder neck contracture. Fortunately, clips can be removed endoscopically with expected symptom resolution in the vast majority of patients.

Abstract Anterior shoulder instability is often accompanied by a Hill‐Sachs defect on the humeral head that can contribute to recurrent instability if not addressed at the time of surgery. We describe a method of performing arthroscopic remplissage to treat engaging Hill‐Sachs lesions in patients with glenohumeral instability. It has the benefits of being an efficient procedure that can be performed with minimal technical difficulty and can be used to augment other stabilization procedures such as labral repair. The indications for this technique include the presence of an engaging Hill‐Sachs defect in patients will little or no glenoid bone loss. In appropriately selected patients, arthroscopic remplissage has shown reduced rates of recurrent instability. Technique Video video See video under supplementary data.

ABSTRACTThere is a clear discrepancy between the growth of cell therapy and tissue engineering research in orthopaedics over the last two decades and the number of approved clinical therapies and products available to patients. At the 2015 annual meeting of the Orthopaedic Research Society, a workshop was held to highlight important considerations from the perspectives of an academic scientist, clinical researcher, and industry representative with the aim of helping researchers to successfully translate their ideas into clinical and commercial reality. Survey data acquired from workshop participants indicated an overall positive opinion on the future potential of cell‐based therapies to make a significant contribution to orthopaedic medicine. The survey also indicated an agreement on areas requiring improvement in the development of new therapies, specifically; increased support for fundamental research and education and improved transparency of regulatory processes. This perspectives article summarises the content and conclusions of the workshop and puts forward suggestions on how translational success of cell‐based therapies in orthopaedics may be achieved. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:17–21, 2016.

Background: Patients with patellar instability and a tibial tubercle–trochlear groove (TT-TG) distance ≥20 mm may be candidates for distal tubercle realignment surgery. Although this variable has proven valuable in predicting recurrent dislocations, it is not individualized to patient size, bony structure, or patellofemoral mechanics. Purpose: To develop a patellar instability ratio (PIR) that predicts the risk of recurrent instability based on the TT-TG distance to patient-specific anatomy. Study Design: Cohort study; Level of evidence, 3. Methods: On magnetic resonance imaging scans of 59 knees with patellar instability, the TT-TG distance, tibial tubercle–posterior cruciate ligament (TT-PCL) distance, sagittal patellar length (PL), sagittal trochlear length (TL), axial patellar width (PW), and axial trochlear width (TW) were calculated by 2 observers in a blinded and randomized fashion. Patients were divided into 2 groups: those with a single dislocation and those with multiple (≥2) dislocations. The ability of the TT-TG and TT-PCL distances as well as the 8 different ratios to predict recurrent instability was assessed by calculating odds ratios (ORs), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for each measure. Results: Twelve knees (20%) experienced a single dislocation, while 47 (80%) sustained multiple dislocations. A TT-TG distance ≥20 mm was predictive of recurrent instability, with a sensitivity, specificity, and PPV of 21%, 100%, and 100%, respectively. The OR for TT-TG ≥20 mm was 5.38 ( P = .29), while the highest ORs for recurrent instability were noted for a TT-TG/PW ≥0.4 (OR, 7.37; P = .02) and a TT-TG/TW ≥0.5 (OR, 8.88; P = .04). The sensitivity, specificity, and PPV of a TT-TG/PW ≥0.4 were 62%, 83%, and 94%, respectively, while those of a TT-TG/TW ≥0.5 were 45%, 92%, and 95%, respectively. Conclusion: Two novel PIRs (TT-TG/TW and TT-TG/PW) were identified and found to more effectively predict recurrent instability than the TT-TG distance alone. Each ratio takes into account patient-specific anatomy and can be measured in an accurate and reliable fashion by clinicians. These PIRs are a step toward overcoming some of the limitations of using the TT-TG distance in isolation. Further investigation into the clinical applications and utility of the TT-TG/TW is warranted.

Abstract Background Acetylcholinesterase inhibitors ( ACI s), e.g., neostigmine, are known to increase upper and lower gastrointestinal ( GI ) motility and are used to treat acute colonic pseudoobstruction. However, their effects on gastroduodenal motility in humans are poorly understood. Our hypotheses were that, in patients with suspected GI motility disorders, neostigmine increases gastric and small intestinal motor activity, and these effects are greater in patients with cardiovagal neuropathy, reflecting denervation sensitivity. Methods In this open label study, the effects of neostigmine (1 mg intravenously) on gastroduodenal motor activity recorded with manometry were assessed in 28 patients with a suspected GI motility disorder. Cardiovagal function was assessed with the heart rate response to deep breathing and GI transit by scintigraphy. Key Results The final diagnoses were gastroparesis (6 patients), gastroparesis with intestinal neuropathy (3 patients), intestinal neuropathy or pseudoobstruction (5 patients), functional dyspepsia (6 patients), chronic abdominal pain (3 patients), mechanical small intestinal obstruction (3 patients), and pelvic floor dysfunction (2 patients). Neostigmine increased both antral and intestinal phasic pressure activity ( p < 0.001). Neostigmine increased antral and intestinal pressure activity in 81% and 50% of patients with reduced postprandial antral and intestinal contractile responses to meal, respectively. The antroduodenal pressure response to neostigmine was not higher in patients with cardiovagal dysfunction. Conclusions & Inferences Neostigmine increased antral and intestinal motor activity in patients with hypomotility, including intestinal dysmotility. These responses to neostigmine were not greater in patients with cardiovagal dysfunction. The use of longer‐acting ACI s for treating antroduodenal dysmotility warrant further study.

Aberrant intracellular calcium levels and increased cAMP signaling contribute to the development of polycystic kidney disease (PKD). cAMP can be hydrolyzed by various phosphodiesterases (PDEs). To examine the role of cAMP hydrolysis and the most relevant PDEs in the pathogenesis of PKD, we examined cyst development in Pde1 - or Pde3 -knockout mice on the Pkd2 −/WS25 background (WS25 is an unstable Pkd2 allele). These PDEs were selected because of their importance in cross-talk between calcium and cyclic nucleotide signaling ( PDE1 ), control of cell proliferation and cystic fibrosis transmembrane conductance regulator (CFTR) –driven fluid secretion (PDE3), and response to vasopressin V2 receptor activation (both). In Pkd2 −/WS25 mice, knockout of Pde1a , Pde1c , or Pde3a but not of Pde1b or Pde3b aggravated the development of PKD and was associated with higher levels of protein kinase A–phosphorylated (Ser133) cAMP–responsive binding protein (P-CREB), activating transcription factor-1, and CREB–induced CRE modulator proteins in kidney nuclear preparations. Immunostaining also revealed higher expression of P-CREB in Pkd2−/ WS25 ; Pde1a −/− , Pkd2− /WS25 ; Pde1c −/− , and Pkd2−/ WS25 ; Pde3a −/− kidneys. The cystogenic effect of desmopressin administration was markedly enhanced in Pkd2 −/WS25 ; Pde3a −/− mice, despite PDE3 accounting for only a small fraction of renal cAMP PDE activity. These observations show that calcium- and calmodulin-dependent PDEs ( PDE1A and PDE1C ) and PDE3A modulate the development of PKD, possibly through the regulation of compartmentalized cAMP pools that control cell proliferation and CFTR–driven fluid secretion. Treatments capable of increasing the expression or activity of these PDEs may, therefore, retard the development of PKD.

Abstract Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk. Cancer Epidemiol Biomarkers Prev; 24(11); 1680–91. ©2015 AACR.