Citations

Clusterin, a widely expressed, tissue-specific glycoprotein, is a diagnostic marker of several tumor types, including anaplastic large cell lymphoma, follicular dendritic cell sarcoma, and tenosynovial giant cell tumor. A recent study has suggested it is highly expressed by well-differentiated neuroendocrine tumors (NET) arising at most anatomic sites, with the exception of jejunoileal tumors, and that it is similarly not expressed by poorly differentiated neuroendocrine carcinomas (NEC). We sought to validate this result in a large cohort of NETs and NECs. Clusterin immunohistochemistry was performed on tissue microarrays of 255 NETs [45 lung, 4 stomach, 8 duodenum, 75 pancreas (62 primary, 13 metastatic), 107 jejunoileum (69 primary, 38 metastatic), 16 appendix] and 88 NECs (43 visceral, 45 Merkel cell). Extent (%) and intensity (0, 1+, 2+, 3+) of staining were assessed and an H-score (extent x intensity) calculated. An average H-score >5 was considered positive. Clusterin expression was noted in 82.4% of 148 nonjejunoileal NETs (average H-score 183) and only 8.4% of 107 jejunoileal NETs (average H-score, 31), as well as 19.3% of NECs (average H-score, 36). Clusterin is frequently, strongly expressed by NETs of diverse anatomic sites, with the exception of jejunoileal tumors, in which it is only rarely, weakly expressed. It is occasionally, weakly expressed by NECs. Most metastatic NETs of occult origin arise in the pancreas or the jejunoileum. For cases in which an initial site of origin immunopanel (eg, islet 1, PAX6, CDX2) is ambiguous, addition of clusterin may be diagnostically useful, with absence of expression suggesting a jejunoileal origin.

Significance Members of the kinesin superfamily serve a wide variety of functions, and a dominant narrative for these molecular motors has been that each member of the superfamily is uniquely specialized to serve a very limited set of functions. However, it is now appreciated that many members of this group serve several distinct physiological roles, and it has been unclear how these kinesins accomplish this functional flexibility. In this report, we describe a posttranslational modification of the kinesin 5 family member Eg5 that dramatically alters its chemomechanical behavior to make it function much more efficiently under load and in ensembles. This work provides the biophysical context required to mechanistically understand the effects of modified Eg5 in dividing cells.

AbstractBackgroundOncologic outcomes of human papillomavirus (HPV)‐related oropharyngeal squamous cell carcinoma (SCC) requiring resection of major muscular or neurovascular tissue during neck dissection for invasive nodal disease remain uncertain.MethodsPatients with HPV‐related oropharyngeal SCC requiring resection of major muscular or neurovascular tissue during their neck dissections were retrospectively identified.ResultsSeventy‐two patients were included. Regional and distant recurrences occurred in 6% and 17% of patients. Advanced T classification, pathological node number of 5 or more, and omission of adjuvant therapy were associated with decreased disease‐free survival (DFS). The addition of adjuvant chemotherapy was not associated with improved survival.ConclusionPatients with invasive nodal disease from HPV‐related oropharyngeal SCC can be managed with up‐front surgery and adjuvant therapy, as indicated with good regional control. Although distant recurrence was the primary site of failure, adjuvant chemotherapy was not associated with improved outcomes. The T classification, node number, and adjuvant radiotherapy are independent prognostic factors in this patient population.

Objectives: The current standard of care for an amputee is a socket-based prostheses. An osseointegrated implant (OI) is an alternative for prosthetic attachment. Osseointegration addresses reported problems related to wearing a socket interface, such as skin issues, discomfort, diminished function, quality of life, prosthetic use, and abandonment. The purpose of this report is to systematically review current literature regarding OI to identify and categorize the reported clinically relevant outcome measures, rate the quality of available evidence, and synthesize the findings. Data sources: A multidisciplinary team used PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methods. Search methodology was based on identifying clinically relevant articles. Three databases were searched: PubMed, CINAHL, and Web of Science. Study Selection: Clinical studies with aggregated data reporting at least 1 clinically relevant outcome measure were included. Data Extraction: The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criterion was used for critical appraisal and recommendations. Conclusions: This review identified 21 clinically relevant observational studies. Outcome measures were categorized into the following 9 categories: vibratory stimulation, complications, biomechanics, economics, patient-reported outcome measures, electromyography, x-ray, physical functional performance, and energy consumption. This systematic review consisted of Level III and IV observational studies. Homogeneous outcome measures with strong psychometric properties across prospective studies do not exist to date. Higher-level, prospective, randomized, long-term, clinically relevant trials are needed to prove efficacy of OI compared with socket prosthetic attachment. Osseointegration was at least equivalent to sockets in most studies. In some cases, it was superior. Osseointegration represents a promising alternative to socket prosthetic attachments for extremity amputees. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Goals: To determine patient preference for the Barrett esophagus (BE) screening techniques. Background: Sedated esophagogastroduodenoscopy (sEGD) and unsedated transnasal endoscopy (uTNE) are both potential techniques for BE screening. However, systematic assessment of patient preference for these 2 techniques is lacking. As part of a comparative effectiveness randomized trial of BE screening modalities, we measured short-term patient preferences for the following approaches: in-clinic uTNE (huTNE), mobile-based uTNE (muTNE), and sEGD using a novel assessment instrument. Study: Consenting community patients without known BE were randomly assigned to receive huTNE, muTNE, or sEGD, followed by a telephone administered preference and tolerability assessment instrument 24 hours after study procedures. Patient preference was measured by the waiting trade-off method. Results: In total, 201 patients completed screening with huTNE (n=71), muTNE (n=71), or sEGD (n=59), and a telephone interview. Patients’ preferences for sEGD and uTNE using the waiting trade-off method were comparable (P=0.51). Although tolerability scores were superior for sEGD (P<0.001) compared with uTNE, scores for uTNE examinations were acceptable. Conclusions: Patient preference is comparable between sEGD and uTNE for diagnostic examinations conducted in an endoscopy suite or in a mobile setting. Given acceptable tolerability, uTNE may be a viable alternative to sEGD for BE screening.

A healthy 20‐year‐old male presented with aborted sudden death. Both thoracic echocardiography and cardiac computed tomographic angiography demonstrated the characteristic findings of ALCAPA noting a dilated and tortuous right coronary artery, dilated coronary collateral arteries within the interventricular septum or along the surface of the heart, and visualization of the left coronary artery origin from the posterior aspect of the main pulmonary artery. Both imaging modalities demonstrated all three characteristic findings of this rare coronary anomaly and served as complementary imaging studies for surgical correction.

Objective To analyze the topography of the opposite condyle to treat focal femoral condyle articular defects with an osteochondral allograft (OCA). Design Three groups were created: Group 1, same condyle with same width; Group 2, opposite condyle with same width; Group 3, opposite condyle with different width. Computed tomography (CT) of 22 cadaveric femoral hemi-condyles was used to create 3-dimensional CT models that were exported into point-cloud models. Three zones of the donor condyle (anterior, middle, and posterior) were quantified. Four defect sizes were created (15, 18, 23, 25 mm) at the weight-bearing region. The defect was moved throughout each donor condyle zone and the least distance was calculated, defined as the shortest distance between the defect and the donor condyle. Results The mean least distance increased with larger defect size in all groups, yet there was a less than 0.2 mm difference in the least distance among defect sizes. The 15, 18, and 23 mm defect models in Group 1 exhibited greater least distances at the anterior than middle and posterior zones. The 15 mm defect model exhibited greater least distance at the anterior zone than posterior zone in Group 3. However, there was a less than 0.05 mm difference in the mean least distance between zones. There was no significant difference in the least distance between groups. Conclusion OCAs from opposite condyles yield similar topographic matching to OCAs from the same condyles, suggesting that opposite condyles can be utilized. Clinical correlation and outcomes are necessary.