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Vaccine nonresponse during the coronavirus disease 2019 (COVID-19) pandemic has considerable individual and societal risks.To investigate the clinical characteristics of patients with lack of seroconversion after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Demographic and clinical data were collected from 805 patients who had validated antibody assays against the SARS-CoV-2 spike protein at least 14 days after completion of their COVID-19 vaccination. Clinical characteristics from patients with a negative (0.4 U/mL) antibody response were assessed and summarized.A total of 622 (77.3%) patients attained seroconversion as defined by a titer of greater than or equal to 0.4 U/mL, whereas 183 out of 805 (22.7%) patients exhibited no seroconversion after vaccination against SARS-CoV-2. Univariately, older age (P = .02) and male sex were associated with a lower likelihood of seroconversion (P = .003). Therapy with immunosuppressive drugs was noted in 93 (50.8%) of seronegative patients with most (n = 83/93, 89.2%) receiving ongoing immunosuppressive therapy at the time of vaccination. Among the 134 (73.2%) seronegative patients with immunodeficiency, 110 (82.1%) had primary immunodeficiency. Cancer (n = 128, 69.9%), B cell depletion therapy (n = 90/115, 78.3%), and immunosuppressant steroid use (n = 71/93 on immunosuppressants, 76.3%) were the other common characteristics among the vaccine nonresponders. More importantly, our study did not evaluate the actual efficacy of COVID-19 vaccination.Vaccine responses vary by age and sex, with men showing lower rates of seroconversion as compared with women. Primary immunodeficiency along with active malignancy and ongoing immunosuppression with steroids or B cell depletion therapy appeared to be the most common characteristics for those with a lack of vaccine seroconversion after COVID-19 vaccination.

PURPOSE OF REVIEW: Anterior cruciate ligament reconstruction (ACLR) is a common surgical procedure with an estimated 120,000 cases performed in the USA each year. Physical therapy plays a critical role in the successful recovery of both surgically and non-surgically managed patients. Interestingly, ACL rehabilitation protocols vary greatly with little consensus among practitioners. Nonetheless, there has been agreement over the last decade to shift from conservative, standardized length protocols to more accelerated, individualized protocols that vary in length and modalities based on patient-specific findings and preferences. This review summarizes the most recent trends, opinions, and modalities in ACL rehabilitation research, with a specific focus on novel methods to treat the specific psychosocial needs of ACL deficient patients. RECENT FINDINGS: We found that new protocols emphasize early weight bearing, open kinetic chain (OKC) exercises, and other alternative modalities such as neuromuscular electrical stimulation and blood flow restriction. We also found a recent trend toward the use of clinical milestones to determine when a patient is ready for the next phase of a “step-up” rehabilitation program. One particularly nascent topic of research is the inclusion of methods to treat the psychosocial impacts of ACL injury, recovery, and the anxiety around return to sport. SUMMARY: Rehabilitation strategy has become increasingly patient-dependent, and the new modalities being utilized are accelerating patient recovery. Return to sport is a particularly important factor for many ACLR patients, and recovery has an important psychological component that has only recently been addressed in the literature, with positive preliminary findings.

Long head biceps tendon pathology is a substantial contributor to anterior shoulder pain and often requires surgical intervention to offer a return to normal functionality. Surgical treatment options consist of both open and arthroscopic tenodesis or tenotomy of the long head biceps brachii. Several techniques exist for tenodesis and tenotomy of the biceps, although current debate continues regarding which surgical approach is the optimal intervention for symptomatic bicep pathology. In this technical note, we describe a subpectoral biceps tenodesis of the long head bicep tendon using an all-suture anchor. Our technique offers the advantages of using an all-suture anchor that incorporates a self-tensioning mechanism with direct visualization of the tendon during biceps tenodesis and anchor insertion.

Context.— Studies of lungs in patients with COVID-19 have focused on early findings. Objective.— To systematically study histopathologic and imaging features and presence of SARS-CoV-2 RNA in lung tissue from patients in later stages of COVID-19. Design.— Autopsies, explants, surgical lung biopsies, transbronchial biopsies, cryobiopsies, and needle biopsies from patients with COVID-19 whose onset of symptoms/confirmed diagnosis was more than 28 days before the procedure were studied. Available images were reviewed. Reverse transcription droplet digital polymerase chain reaction for SARS-CoV-2 RNA was performed on lung tissue. Results.— Of 44 specimens (43 patients; median age, 59.3 years; 26 [60.5%] male) features of acute lung injury (ALI) were seen in 39 (88.6%), predominantly organizing pneumonia and diffuse alveolar damage, up to 298 days after onset of COVID-19. Fibrotic changes were found in 33 specimens (75%), most commonly fibrotic diffuse alveolar damage (n = 22) and cicatricial organizing pneumonia (n = 12). Time between acquiring COVID-19 and specimen was shorter in patients with diffuse ALI (median, 61.5 days) compared with patients with focal (140 days) or no ALI (130 days) (P = .009). Sixteen (of 20; 80%) SARS-CoV-2 reverse transcription droplet digital polymerase chain reaction tests were positive, up to 174 days after COVID-19 onset. Time between COVID-19 onset and most recent computed tomography in patients with consolidation on imaging was shorter (median, 43.0 days) versus in patients without consolidation (87.5 days; P = .02). Reticulations were associated with longer time to computed tomography after COVID-19 onset (median, 82 versus 23.5 days; P = .006). Conclusions.— ALI and SARS-CoV-2 RNA can be detected in patients with COVID-19 for many months. ALI may evolve into fibrotic interstitial lung disease.

Anterior talofibular ligament (ATFL) tear is the most common ankle ligament injury. This can lead to recurrent ankle instability, which is detrimental to ankle function and the patient's quality of life. Currently, several techniques have shown successful outcomes for ATFL repair. In this technical note, we describe an open ATFL repair using a single knotless suture anchor at the distal fibula location. This approach is rapid, equipment-efficient, and reproducible, while promising excellent results and high patient satisfaction by restoring ATFL anatomy.

Objectives To compare the rate of lost reduction between two groups of non-age segregated type III supracondylar humeral fracture patients: a unicolumnar versus bicolumnar fixation group. Design Retrospective cohort study. Setting Pediatric Academic Trauma Center. Patients We identified 257 patients with Type III supracondylar humerus fractures from surgical billing records over a 5-year period. There were 183 patients identified with bicolumnar fixation (71.2%) and 74 patients identified with unicolumnar fixation (28.8%). Intervention Closed reduction percutaneous pinning of the distal humerus. Main outcome measures The primary outcome measure was difference in rate of lost reduction between patients with bicolumnar (lateral and medial column) and unicolumnar (lateral column only) fixation (Figure1). The reduction and fixation at time of fluoroscopy was assessed using the Baumann angle, Gordon index, and anterior humeral line. Loss of reduction was assessed at time of healing, defined by a Baumann angle change ≥ 10 degrees and Gordon index of ≥ 50 percent (Figure2). Results There were 183 patients with bicolumnar fixation and 74 patients with unicolumnar fixation included in the study (average age 5.8 years, range 2-14 years). The rate of lost reduction in patients with bicolumnar fixation was 6.01% (11/183) whereas 17.57% (13/74) of patients with unicolumnar fixation experienced lost reduction. These rates were significantly different (p=0.008) with a 3.3 times higher odds [95% CI = 1.3, 8.6] of lost reduction with unicolumnar fixation. Conclusions There is a statistically significant increase in the rate of supracondylar fracture loss of reduction for patients with unicolumnar fixation when compared to bicolumnar fixation. Level of evidence Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

PDF file - 118KB, Supplementary Table 1. number of patients for each observed clusters with 4 autoantibodies. Supplementary Table 2. Number of patients for each observed clusters with 5 autoantibodies.

Steatosis is the most important prognostic histologic feature in the setting of liver procurement. The currently utilized diagnostic methods, including gross evaluation and frozen section examination, have important shortcomings. Novel techniques that offer advantages over the current tools could be of significant practical utility. The aim of this study is to evaluate the accuracy of surface color spectrophotometry in the quantitative assessment of steatosis in a murine model of fatty liver. C57BL/6 mice were divided into a control group receiving normal chow (n = 19), and two steatosis groups receiving high-fat diets for up to 20 weeks—mild steatosis (n = 10) and moderate-to-severe steatosis (n = 19). Mouse liver surfaces were scanned with a hand-held spectrophotometer (CM-600D; Konica-Minolta, Osaka, Japan). Spectral reflectance data and color space values (L*a*b*, XYZ, L*c*h*, RBG, and CMYK) were correlated with histopathologic steatosis evaluation by visual estimate, digital image analysis (DIA), as well as biochemical tissue triglyceride measurement. Spectral reflectance and most color space values were very strongly correlated with histologic assessment of total steatosis, with the best predictor being % reflectance at 700 nm (r = 0.91 [0.88–0.94] for visual assessment, r = 0.92 [0.88–0.95] for DIA of H&E slides, r = 0.92 [0.87–0.95] for DIA of oil-red-O stains, and r = 0.78 [0.63–0.87] for biochemical tissue triglyceride measurement, p

The current standard technique for cardiopulmonary resuscitation (CPR), initially described in the early 1960s, has quickly become the expected response for all persons found without a pulse or respiration. Despite the potentially lifesaving properties of external cardiac massage, the mainstay of resuscitation, it consists of repeated blunt force trauma to the chest, which can lead to extensive traumatic skeletal and nonskeletal injuries. Numerous autopsy-based studies have documented the incidence and patterns of rib and sternal fractures associated with attempted CPR, but there is relatively little data on the incidence and severity of nonskeletal CPR-related injuries. We reviewed reports from 1878 autopsies performed between September 2017 and December 2019 (inclusive), for documentation of CPR-related injuries. Among these cases, there were 93 cases with resuscitation-related nonskeletal injuries. The most common type of injury identified were visceral contusions, documented in 57.0% of cases. These contusions predominantly involved the heart, lungs, neck soft tissue, and surrounding structures. Resuscitation-related lacerations were seen in 17.2% of the cases, most predominantly involving the pericardium, heart, and liver. Statistical analysis of the data demonstrated that lacerations were more likely to be seen in females and with associated sternal fractures. Additionally, hemothoraces were present in 34.4% of cases and hemopericardium was seen in 8.6% of cases. This study provides additional documentation of the range, severity, and incidence of various types of resuscitation-related visceral injuries to better assist autopsy pathologists in distinguishing these injuries from other antecedent traumatic injuries.

Introduction Optimal screening for detection of anal precancer has not been established, and most studies involve very high-risk populations. We evaluated high-risk human papillomavirus (HPV) testing and anal cytology to detect high-grade anal intraepithelial neoplasia ( > AIN2) in a cohort with mostly moderate risk factors for AIN. Materials and Methods Patients > 35-years-old undergoing anal biopsy for various lesions received HPV testing by Roche cobas and a subset by Hologic APTIMA HPV assays with concurrent anal ThinPrep cytology. Biopsies were blindly reviewed by 3 authors, and consensus diagnosis was compared with HPV and cytology results. Sensitivity and specificity for > AIN2 detection by HPV testing and cytology ( > ASC-US) were calculated. Results Among 64 patients, 19 (29.7%) showed > AIN2 on biopsy. All patients were tested by cobas, and 35 (54.7%) were positive. A subset of 39 patients were also tested by APTIMA, and 18 (46.2%) were positive. Positive cytology ( > ASC-US) was present in 37 (57.8%) patients, with 27 (73.0%) of these positive by cobas. HPV testing alone yielded 75.0% and 84.2% sensitivity for APTIMA and cobas, respectively; specificity was 66.7% and 57.8%. Sensitivity and specificity of cytology alone was 78.9% and 51.1%. Combined HPV testing and cytology had a sensitivity and specificity of 91.7% and 37.0% for APTIMA and 94.7% and 40.0% for cobas. Conclusions Combined HPV testing and cytology had the highest sensitivity for > AIN2 detection, with a performance comparable to cervical cancer screening tests, suggesting this strategy may represent a viable screening option in a population with moderate risk factors for AIN.

Background African Americans (AAs) and other racial/ethnic minority groups continue to be underrepresented in medical research and clinical trials. Failure to create more racially diverse research cohorts can exacerbate existing health disparities among these groups. Objective To investigate best practices and strategies for enhancing participation of AAs in medical research among attendees of a preconference Institute at a faith-based public health conference. Design Qualitative study using semi-structured interviews. Participants A total of 21 out of 29 attendees (90% AA) of the Institute (72% response rate). Approach A culturally tailored preconference Institute was held at the 2017 Healthy Churches 2020 National Conference. The Institute was led by AA researchers focused on underrepresentation of AAs in medical research. Semi-structured interviews were conducted 1-year post-Institute (n=21) and were audio-recorded, transcribed verbatim, and reviewed using thematic analysis. Key Results The majority of attendees reported that they were more likely to participate in medical research after attending the Institute (75%). Salient learning points reported by attendees demonstrated attainment of the Institute objectives. Key themes emerged describing barriers preventing AAs from participating in medical research including fear/lack of trust, lack of information on research projects, and not being approached to participate. Key themes regarding facilitators for participation in medical research by AAs were clear communication of study objectives and research benefits along with trust in researchers. Conclusions Attendees’ perceptions of participation in medical research were largely positive following their attendance at a conference-based Institute aimed to address the underrepresentation of AAs in medical research. Our culturally tailored approach to disseminating knowledge of the research process could extend to other national conferences prioritizing AAs and other racial/ethnic minority populations to improve research participation.

Antibody responses to pneumococcal polysaccharide vaccination are frequently used as a diagnostic tool for humoral immunodeficiencies, part of the larger collection of inborn errors of immunity. Currently, arbitrary criteria, such as a serotype specific titer of >/= 1.3 µg/mL is most often used as a cut-off for interpretation of pneumococcal antibody responses. The magnitude of the antibody response to each of the 23 serotypes in Pneumovax®, and serotype-specific cut-offs in healthy pneumococcal vaccine-naive adults has not been previously characterized. IgG antibody concentrations were measured prospectively for 23 pneumococcal serotypes pre and 4–6 weeks post-Pneumovax® vaccination in 100 healthy adults, using a multiplex bead-based assay. Antibodies to 19 of 23 serotypes were informative for distinguishing subjects who responded to vaccination, and the serotype threshold was determined to be 9 of 19 serotypes, which characterized an antibody response to pneumococcal vaccination. While this study may facilitate classification of IgG serotype-specific antibody responses post-pneumococcal vaccination in adult patients undergoing diagnostic immunological evaluation for antibody immunodeficiencies or other relevant contexts, additional studies in healthy children and S. pneumoniae protein-conjugate-vaccinated healthy adults will need to be undertaken in the future.

Posterior fossa (PF) diffuse gliomas in pediatric patients frequently harbor the H3 K27M mutation. Among adults, PF diffuse gliomas are rare, with limited data regarding molecular features and clinical outcomes. We identified 28 adult PF diffuse glioma patients (17 males; median: 50 y, range: 19 to 78 y), with surgery performed at our institution (13 brainstem; 15 cerebellum). Histologic subtypes included anaplastic astrocytoma (n=21), glioblastoma (n=6), and diffuse astrocytoma (n=1). Immunohistochemistry was performed for H3 K27M (n=26), IDH1-R132H (n=28), and ATRX (n=28). A 150-gene neuro-oncology-targeted next-generation sequencing panel was attempted in 24/28, with sufficient informative material in 15 (51.7%). Tumors comprised 4 distinct groups: driver mutations in H3F3A (brainstem=4; cerebellum=2), IDH1 (brainstem=4; cerebellum=4), TERT promotor mutation (brainstem=0; cerebellum=3), and none of these (n=5), with the latter harboring mutations of TP53, PDGFRA, ATRX, NF1, and RB1. All TERT promoter-mutant cases were IDH-wild-type and arose within the cerebellum. To date, 20 patients have died of disease, with a median survival of 16.3 months, 1-year survival of 67.5%. Median survival within the subgroups included: H3F3A=16.4 months, IDH mutant=113.4 months, and TERT promoter mutant=12.9 months. These findings suggest that PF diffuse gliomas affecting adults show molecular heterogeneity, which may be associated with patient outcomes and possible response to therapy, and supports the utility of molecular testing in these tumors.

Supplemental Digital Content is available in the text., Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant clinical presentation, coronavirus disease 2019 (COVID-19), is an emergent cause of mortality worldwide. Cardiac complications secondary to this infection are common; however, the underlying mechanisms of such remain unclear. A detailed cardiac evaluation of a series of individuals with COVID-19 undergoing postmortem evaluation is provided, with 4 aims: (1) describe the pathological spectrum of the myocardium; (2) compare with an alternate viral illness; (3) investigate angiotensin-converting enzyme 2 expression; and (4) provide the first description of the cardiac findings in patients with cleared infection. Methods: Study cases were identified from institutional files and included COVID-19 (n=15: 12 active, 3 cleared), influenza A/B (n=6), and nonvirally mediated deaths (n=6). Salient information was abstracted from the medical record. Light microscopic findings were recorded. An angiotensin-converting enzyme 2 immunohistochemical H-score was compared across cases. Viral detection encompassed SARS-CoV-2 immunohistochemistry, ultrastructural examination, and droplet digital polymerase chain reaction. Results: Male sex was more common in the COVID-19 group (P=0.05). Nonocclusive fibrin microthrombi (without ischemic injury) were identified in 16 cases (12 COVID-19, 2 influenza, and 2 controls) and were more common in the active COVID-19 cohort (P=0.006). Four active COVID-19 cases showed focal myocarditis, whereas 1 case of cleared COVID-19 showed extensive disease. Arteriolar angiotensin-converting enzyme 2 endothelial expression was lower in COVID-19 cases than in controls (P=0.004). Angiotensin-converting enzyme 2 myocardial expression did not differ by disease category, sex, age, or number of patient comorbidities (P=0.69, P=1.00, P=0.46, P=0.65, respectively). SARS-CoV-2 immunohistochemistry showed nonspecific staining, whereas ultrastructural examination and droplet digital polymerase chain reaction were negative for viral presence. Four patients (26.7%) with COVID-19 had underlying cardiac amyloidosis. Cases with cleared infection had variable presentations. Conclusions: This detailed histopathologic, immunohistochemical, ultrastructural, and molecular cardiac series showed no definitive evidence of direct myocardial infection. COVID-19 cases frequently have cardiac fibrin microthrombi, without universal acute ischemic injury. Moreover, myocarditis is present in 33.3% of patients with active and cleared COVID-19 but is usually limited in extent. Histological features of resolved infection are variable. Cardiac amyloidosis may be an additional risk factor for severe disease.

The diagnosis of inflammatory bowel disease (IBD)-associated dysplasia is challenging, and past studies have demonstrated considerable interobserver variability in such diagnoses. This study aimed to assess interobserver agreement in IBD dysplasia diagnoses among subspecialty GI pathologists and to explore the impact of mentorship on diagnostic variability. Twelve GI pathologist mentees and 7 GI pathologist mentors reviewed 163 digitized slides. Participants rendered a diagnosis of negative for dysplasia, indefinite for dysplasia, low-grade dysplasia, or high-grade dysplasia and provided a confidence level for each case. Interobserver agreement and reliability were assessed using Cohen's and Fleiss' kappa (κ) statistics and intraclass correlation coefficient (ICC) analysis. The overall κ coefficient was 0.42 (95% CI: 0.38-0.46). The overall ICC was 0.67 (95% CI: 0.62-0.72). Κ coefficients ranged from 0.31 to 0.49 for mentor/mentee pairs and from 0.34 to 0.55 for pairs of mentees of the same mentor. The combined κ coefficient was 0.44 (95% CI: 0.39-0.48) for all mentees and 0.39 (95% CI: 0.34-0.43) for all mentors. Common features in low agreement cases included mucosal atrophy, areas of stark contrast, serrations, decreased goblet cells, absent surface epithelium, and poor orientation. Participants were confident in most diagnoses, and increased confidence levels generally correlated with higher interobserver agreement. Interobserver agreement among subspecialist GI pathologists in this curated cohort of IBD dysplasia cases was fair to moderate. Mentorship during GI pathology fellowship does not appear to be a significant factor contributing to interobserver variability, but increased experience also does not seem to improve interobserver agreement.

The objective of this study is to determine the association of proliferation indices and pathologic biomarkers on overall and recurrence/metastasis-free survival (OS and RMFS) in patients with sinonasal mucosal melanoma (SNMM) and to assess the genetic mutational landscape of SNMM.This is a retrospective cohort study of 45 SNMM patients without neoadjuvant therapy who underwent surgical therapy with curative intent and had tumor tissue available for histopathologic review, molecular analysis, and genetic mutational assessment. The OS and RMFS were assessed for associations with numerous tumor and patient-related factors.Among proliferative indices, higher Ki67 and mitotic rates were associated with worsened OS and RMFS (Ki67: p = 0.0007 and p 0.0001; mitotic rate: p = 0.005 and p = 0.0009, respectively). The presence of brisk tumor-infiltrating lymphocytes (TILs) was associated with improved RMFS (p = 0.007) and the presence of lymphovascular invasion was associated with worsened OS and RMFS (p = 0.02 and p = 0.04, respectively). Patients with amelanotic tumors were more likely to have higher T-stage (p = 0.046), less likely to have brisk TILs (p = 0.02) and had worsened RMFS (p = 0.03). Patients on immunotherapy with tumor Ki67 40% had better 3-year OS compared to those with higher Ki67 index (p = 0.004). Actionable genetic mutations such as BRAF V600E are rare and present in only 1 of 20 patients tested.In SNMM patients, pathologic and proliferation markers such as Ki67, mitotic rate and brisk TILs are associated with survival and may be considered in future staging systems. Clinical response to immunotherapy appears to correlate with the Ki67 index. Given the distinct genetic profile of SNMM, targeted therapies against the MAPK kinase pathway have limited utility.3 Laryngoscope, 132:2350-2358, 2022.

Background: The morphologic distinction between thymic carcinomas and thymomas, specifically types B3, A, and occasionally micronodular thymomas with lymphoid stroma (MNTLS) can be challenging, as has also been shown in interobserver reproducibility studies. Since thymic carcinomas have a worse prognosis than thymomas, the diagnosis is important for patient management and treatment. This study aimed to identify a panel of immunohistochemical (IHC) markers that aid in the distinction between thymomas and thymic carcinomas in routine practice. Materials and Method: Thymic carcinomas, type A and B3 thymomas, and MNTLS were identified in an institutional database of thymic epithelial tumors (TET) (1963–2021). IHC was performed using antibodies against TdT, Glut-1, CD5, CD117, BAP1, and mTAP. Percent tumor cell staining was recorded (Glut-1, CD5, CD117); loss of expression (BAP1, mTAP) was considered if essentially all tumor cells were negative; TdT was recorded as thymocytes present or absent (including rare thymocytes). Results: 81 specimens included 44 thymomas (25 type A, 11 type B3, 8 MNTLS) and 37 thymic carcinomas (including 24 squamous cell carcinomas). Using BAP1, mTAP, CD117 (cut-off, 10%), and TdT, 88.9% of thymic carcinomas (95.7% of squamous cell carcinomas) and 77.8% of thymomas could be predicted. Glut-1 expression was not found to be useful in that distinction. All tumors that expressed CD5 in ≥50% of tumor cells also expressed CD117 in ≥10% of tumor cells. In four carcinomas with homozygous deletion of CDKN2A, mTAP expression was lost in two squamous cell carcinomas and in a subset of tumor cells of an adenocarcinoma and was preserved in a lymphoepithelial carcinoma. Conclusion: A panel of immunostains including BAP1, mTAP, CD117 (using a cut-off of 10% tumor cell expression), and TdT can be useful in the distinction between thymomas and thymic carcinomas, with only a minority of cases being inconclusive.

Growth hormone-producing pituitary adenomas are divided into two clinically relevant histologic subtypes, densely (DG-A) and sparsely (SG-A) granulated. Histologic subtype was evaluated in a large cohort of patients with acromegaly, separating DG-A and SG-A, and correlated with clinicopathological characteristics. Patients with acromegaly undergoing surgery as initial therapy between 1995 and 2015 were identified. Histologic subtype was determined by keratin expression pattern with CAM5.2 and correlated with clinical and imaging parameters, somatostatin receptor subtype 2 (SST2) expression, post-surgical remission rate, and application of a prognostic scoring system incorporating proliferation and invasiveness. One hundred thirty-one patients were included. Tumors were classified as DG-A (75, 57.3%), SG-A (29, 22.1%), intermediate (I-A) (9, 6.9%), and unclassified (18, 13.7%) when CAM5.2 was negative. DG-A and I-A were combined for analysis (DG/I-A) and compared to SG-A. Age, gender, proliferation, and post-surgical remission did not differ. SG-A were larger [2 vs. 1.5 cm (median), p = 0.03], more frequently invasive [65.5% vs. 32.9%, p = 0.004], associated with higher MRI T2-weighted signal ratio [1.01 vs. 0.82 (median), p = 0.01], showed lower SST2 expression (p

Aims: Recently, a novel isoform of anaplastic lymphoma kinase, with alternative transcription initiation (ALKATI ), has been described in melanoma and is susceptible to targeted ALK-inhibitor therapy. Clinical outcomes of patients with ALKATI mutated melanoma as well as correlation with immunohistochemical (IHC) methods has not yet been described. Methods and results: Clinicopathologic characteristics were abstracted for 324 patients with metastatic melanoma (MM). IHC, fluorescence in situ hybridization, and RNA based digital molecular analysis (NanoString Technologies) assays were performed on archival tissue from 173 stage III and 192 stage IV tumors. ALKATI was identified in 12.7% and 4.8% stage III and IV tumors, respectively. Discrete presentations of the ALKATI are seen: isolated ALKATI (N=20) and mixed ALKATI (combined ALKATI and ALKWT ; N=7). Isolated ALKWT expression (N=4) was seen with no ALK fusions. Stage III patients showed improved survival with ALKATI expression as compared to those with ALKWT or no expression [5-year survival 80% (95% CI: 57%-100%) versus 43% (95% CI: 34%-55%), p=0.013]. Clinicopathologic characteristics were not statistically significant. Strong diffuse cytoplasmic staining of ALK IHC (N=12), has a sensitivity of 52.2%, specificity 100%, PPV of 100% and NPV of 92.5% of detecting isolated ALKATI . Conclusion: Presence of ALKATI is a good prognostic indicator in MM. ALK IHC and digital molecular analysis can be incorporated into MM evaluation to identify patients with ALKATI for targeted therapy.

Problem: Conferences are the most common form of continuing medical education (CME), but their effect on clinician practice is inconsistent. Reflection is a critical step in the process of practice...

BACKGROUND: Physicians play a key role in mitigating and managing costs in healthcare which are rising. OBJECTIVE: Conduct a cross-sectional survey in 2017, comparing results to a 2012 survey to understand US physicians’ evolving attitudes and strategies concerning healthcare costs. PARTICIPANTS: Random sample of 1200 US physicians from the AMA Masterfile. MEASURES: Physician views on responsibility for costs of care, enthusiasm for cost-saving strategies, cost-consciousness scale, and practice strategies on addressing cost. KEY RESULTS: Among 1200 physicians surveyed in 2017, 489 responded (41%). In 2017, slightly more physicians reported that physicians have a major responsibility for addressing healthcare costs (32% vs. 27%, p = 0.03). In 2017, more physicians attributed “major responsibility” for addressing healthcare costs to pharmaceutical companies (68% vs. 56%, p 70%). After adjusting for specialty, political affiliation, practice setting, age, and gender, only democratic/independent affiliation remained a significant predictor of cost-consciousness. CONCLUSIONS AND RELEVANCE: US physicians increasingly attribute responsibility for rising healthcare costs to organizations and express less enthusiasm for strategies that increase patient out-of-pocket cost. Interventions that focus on physician knowledge and communication strategies regarding cost of care may be helpful. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-020-05807-0) contains supplementary material, which is available to authorized users.

Purpose The purpose of this study was to describe participant characteristics and effective teaching methods at a national continuing medical education (CME) conference on hospital medicine for physician assistants (PAs) and nurse practitioners (NPs). Methods In this cross-sectional study, participants provided demographic information and teaching effectiveness scores for each presentation. Associations between teaching effectiveness score and presentation characteristics were determined. Results In total, 163 of 253 participants (64.4%) completed evaluations of 28 presentations. Many of the participants were younger than 50 years (69.0%), had practiced for fewer than 5 years (41.5%), and worked in nonacademic settings (76.7%). Teaching effectiveness scores were significantly associated with the use of clinical cases (perfect scores for 68.8% of presentations with clinical cases vs. 59.8% without; P = .04). Conclusion Many PAs and NPs at an HM CME conference were early-career clinicians working in nonacademic settings. Presenters at CME conferences in hospital medicine should consider using clinical cases to improve their teaching effectiveness among PA and NP learners.

Context.— Pulmonary carcinoids are classified as typical or atypical by assessing necrosis and mitoses, which usually cannot be adequately assessed on small biopsies. Ki-67 is not currently used to grade pulmonary carcinoids, but it may be helpful to determine preliminary grade in biopsies. However, the rate at which Ki-67 could underestimate or overestimate grade on small biopsies has not been well studied. Objective.— To compare Ki-67 labeling obtained on small biopsies to subsequent resection. Design.— Ki-67 was performed on paired biopsy and resection specimens from 55 patients. Slides were scanned using Aperio ScanScope. Labeling index was determined using automated hot spot and tumor tracing methods. Results.— The study included 41 typical and 14 atypical carcinoids. Atypical carcinoids were larger and had more distant metastases. Death from disease occurred in 3 patients (all had atypical carcinoids). Median hot spot Ki-67 labeling index was greater in resection compared with biopsy by 0.7% (P = .02). Median tumor tracing Ki-67 was lower in resection compared with biopsy by 0.5% (P < .001). Receiver-operating characteristic analysis showed similar hot spot Ki-67 cutoffs to predict atypical histology (3.5% for biopsy, 3.6% for resection; area under the curve [AUC], 0.75 and 0.74, respectively). Different optimal cutoffs were needed for tracing method based on biopsy (2.1%; AUC, 0.75) compared with resection (1.0%; AUC, 0.67). Conclusions.— Hot spot Ki-67 tends to underestimate grade on small biopsies, whereas grade is overestimated by tumor tracing. Hot spot Ki-67 cutoff of 3.5% predicted atypical histology for both biopsy and resection. Different biopsy and resection cutoffs were necessary for tumor tracing, which would make clinical implementation more difficult.

Combined anterior cruciate ligament and posterior cruciate ligament tibial avulsion fractures are rare knee injuries that are primarily seen in adults. Prompt surgical intervention is indicated for displaced fractures to restore knee stability. Arthroscopic techniques are now the preferred method for treating anterior tibial spine avulsion fractures with posterior cruciate ligament tibial avulsion fractures being treated arthroscopically or with open reduction and internal fixation methods. This Technical Note and accompanying video demonstrate an arthroscopically assisted repair of bicruciate tibial avulsion fractures using an arthroscopic lever push technique. Two sutures are passed through the anterior cruciate ligament and pulled down through two bone tunnels placed within the tibial fracture bed, and one suture is passed around the posterior cruciate ligament and pulled down through one bone tunnel passing from the anterior tibia to the tibial fracture bed. Our technique is simple and effective in reducing bicruciate tibial avulsion fractures to anatomic position.

Background Measurement of cholesterol within lipoprotein subfractions may aid in cardiovascular disease prediction. Simple, homogenous enzymatic assays for the direct measurement of lipoprotein subfractions have been developed to measure small dense low-density lipoprotein cholesterol (sdLDL-C), high-density lipoprotein-3 cholesterol (HDL3-C), and triglyceride-rich lipoprotein (TRL-C) cholesterol. The objective of this study was to determine biological variability for sdLDL-C, HDL3-C, and TRL-C in a healthy reference population to facilitate interpretation of these analytes. Methods Serum samples were collected from 24 healthy subjects (n = 14 female/10 male) daily for 3 days while non-fasting, and daily for 5 days, weekly for 4 weeks, and monthly for 6 months after overnight fasting. sdLDL-C, HDL3-C, and TRL-C cholesterol were measured by homogenous enzymatic assays. Sources of variability (between-subject, within-subject, and analytical) were calculated using random-effects regression models. Reference change value (RCV) and index of individuality (II) for each time period were determined from the variance components. Results Analytic variability (daily, weekly, and monthly CVA) was Conclusions sdLDL-C, HDL3-C, and TRL-C showed moderate within-subject variability, but high between-subject variability, in a healthy reference population. Given the high individuality of each analyte, population-based reference intervals may be inadequate to detect clinically significant changes.

In heart failure (HF), pulmonary venous hypertension (PVH) produces pulmonary hypertension (PH) with remodeling of pulmonary veins (PV) and arteries (PA). In a porcine PVH model, we performed proteomic-based bioinformatics to investigate unique pathophysiologic mechanisms mediating PA and PV remodeling.Large PV were banded (PVH, n = 10) or not (Sham, n = 9) in piglets. At sacrifice, PV and PA were perfusion labeled for vessel specific histology and proteomics. The PA and PV were separately sampled with laser-capture micro-dissection for mass spectrometry.Pulmonary vascular resistance (Wood Units; 8.6 [95% Confidence Interval, 6.3,12.3] versus 2.0 [1.7,2.3]) and PA (19.9 [standard error of mean, 1.1] versus 10.3 [1.1]) and PV (14.2 [1.2] versus 7.6 [1.1]) wall thickness/external diameter (%) were increased in PVH (p 0.05 for all). Similar numbers of proteins were identified in PA (2093) and PV (2085) with 94% overlap, but biological processes differed. There were more differentially expressed proteins (287 versus 161), altered canonical pathways (17 versus 3) and predicted up-stream regulators (PUSR; 22 versus 6) in PV than PA. In PA and PV, bioinformatics indicated activation of the integrated stress response and mTOR signaling with dysregulated growth. In PV, there was also activation of Rho/Rho kinase signaling with decreased actin cytoskeletal signaling and altered tight and adherens junctions, ephrin B, and caveolae-mediated endocytosis signaling; all indicating disrupted endothelial barrier function. Indeed, protein biomarkers and the top PUSR in PV (TGF-β) suggested endothelial mesenchymal transition (EndoMT) in PV. Findings were similar in human autopsy specimens.These findings provide new therapeutic targets to oppose pulmonary vascular remodeling in HF-related PH.In heart failure (HF) related (Group 2) PH, despite remodeling of pulmonary veins (PV) and arteries (PA), therapies targeting PA biology altered in Group 1 PH have not shown consistent benefit. In a porcine Group 2 PH model, microdissection allowed vessel specific (PV and PA) proteomics/bioinformatics. In PA and PV, the integrated stress response and mTOR signaling were activated with evidence of dysregulated growth. In PV, more pathways were altered with broad evidence of disrupted endothelial barrier function and endothelial mesenchymal transition. Findings were confirmed in human specimens and provide new targets for potential therapeutic translation in Group 2 PH.

BackgroundCeramides are bioactive lipid species that mediate numerous cell-signaling events. Elevated plasma ceramides concentration constitutes a risk factor for several pathologies. Multiple studies have affirmed the plasma concentrations of 4 specific ceramides (Cer16:0, Cer18:0, Cer24:0, and Cer24:1) can predict cardiovascular disease risk. Furthermore, these ceramides can be altered by many lipid-lowering therapies. Understanding the biological variability within an individual, and within a population, will further inform the clinical use of plasma ceramides as a biomarker. In this study, we aimed to define the intra- and interbiological variability of ceramides in a healthy reference population in a weekly and monthly manner.MethodsFasting plasma from 24 healthy adults was collected daily (5 days), weekly (4 weeks), and monthly (7 months). Ceramide concentrations were measured with liquid chromatography–mass spectrometry (LC–MS). For analysis, we used random-effects regression models to estimate variance components.ResultsThe analytical variability was smaller compared to the biological variability overall. The greatest variation reported was between-subject variation for all ceramide species. The critical difference-reference change value (RCV) for within-subject variations monthly were 0.07 mcmol/L (Cer16:0), 0.04 mcmol/L (Cer18:0), 1.09 mcmol/L (Cer24:0), and 0.27 mcmol/L (Cer24:1). The index of individuality (IOI) of ceramides were 0.82 (Cer16:0), 0.96 (Cer18:0), 1.06 (Cer24:0), and 0.89 (Cer24:1). The most consistent ceramide species was Cer18:0 with the lowest within- and between-subject critical differences in weekly and monthly measurements.ConclusionsOverall, this study demonstrates that the variability of ceramide concentrations at different time points is minimal within individuals, allowing a single draw to be sufficient at least in a yearly time frame.

Peroneal tendon subluxation often occurs because of sudden dorsiflexion of the ankle, leading to a traumatic rupture of the superior peroneal retinaculum. Currently, there are several surgical techniques to deepen the fibular groove, but there is no universally accepted gold standard. This technique article describes a fibular groove deepening with preservation of the fibrocartilage in conjunction with repair of the superior peroneal retinaculum. Addressing the main pathologies that may be leading to subluxation of the peroneal tendons, we offer an approach that avoids many of the common pitfalls from previously proposed techniques while preserving the natural fibrocartilage within the malleolar groove and repairing the retinaculum.

Objective To reevaluate the frequency and pattern of complementary and integrative medicine (CIM) use in patients with fibromyalgia (FM). Patients and Methods Consecutive patients with FM who were referred to the Mayo Clinic fibromyalgia treatment program from January 5 through July 27, 2017, were invited to complete a survey about their use of CIM therapies in the preceding 6 months. The survey asked about 3 primary CIM domains: treatments and techniques, vitamins and minerals, and herbs and other dietary supplements. For direct comparative purposes, we reused the survey instrument from our prior analogous study of CIM use, performed in 2003. Results Of the 310 patients who completed the survey, 304 (98.1%) reported using some form of CIM, similar to the percentage reported in our 2003 study (98%). The most frequently used CIM therapies in the current cohort were spiritual healing (54.0% [163 of 302]), massage therapy (50.0% [152 of 304]), chiropractic treatments (39.3% [118 of 300]), aromatherapy (39.0% [117 of 300]), exercise for a specific medical problem (38.6% [117 of 303]), melatonin (37.9% [77 of 203]), magnesium (36.3% [107 of 295]), green tea (36.1% [73 of 202]), and fish oil (34.5% [68 of 197]). We noted numerous substantial differences from the 2003 data in terms of the pattern of CIM use. Conclusion The use of CIM therapies among patients with FM continues to be extremely common for adult patients of all ages. Given the continued high prevalence of CIM use, health care professionals must have awareness and knowledge of these various modalities and their potential incorporation into a multifaceted FM treatment regimen.

Background Every case of breast cancer is unique, and treatment must be personalized to incorporate a woman’s values and preferences. We developed an individually-tailored mobile patient education application for women with breast cancer. Methods Pre-post surveys were completed by 255 women who used the tool. Results Patients thought the application included helpful information (N = 184, 72%) and was easy to navigate (N = 156, 61%). Most patients thought the amount of information in the tool was “about right” (N = 193, 87%). Decision making confidence increased by an average of 0.8 points (10-point scale) following a consultation and use of the tool (p Conclusions Tailored mobile applications may optimize care by facilitating shared decision making and knowledge transfer, and they may also enhance the experience of patients as they navigate through their breast cancer journey.

Melanomas of female genital tract are rare tumors with poor prognosis. While BRAF-V600E is the most common pathogenic mutation seen in cutaneous sun-exposed melanomas, mucosal and anogenital melanomas usually lack BRAF mutations and instead they harbor KIT alterations. The American Joint Committee on Cancer staging guideline (AJCC eighth edition) recommends using cutaneous melanoma guidelines for vulvar melanoma staging and does not provide any recommendations for vaginal melanoma staging. The aim of this study is to investigate the mutational status of invasive melanomas arising from different anatomic sites in lower female genital tract (vulvar hair-bearing skin, glabrous skin, vagina and urethra) in a group of 37 patients. Tumors were analyzed using a DNA targeted next-generation sequencing panel covering the 21 most common genes and mutation hotspots in melanomas. The most common genetic alterations in invasive melanomas of lower female genital tract are KIT (32%), TP53 (22%), and NF1 (19%). Overall 66% (21/32) of cases showed a pathogenic alteration in at least one of the MAPK pathway genes. No statistical significance seen between different primary tumor sites and the frequency of the oncogenic mutations, nor were any significant differences found by mutation status. Only one case of urethral melanoma showed a BRAF non-V600E mutation (D594G). Our results suggest a similar molecular pathogenesis and overall survival in melanomas arising from lower female genital tract, irrespective of their exact location in the urogenital area. Future classifications of melanoma should consider grouping vulvar melanomas with mucosal rather than cutaneous melanomas.

Hepatocellular adenomas (HCAs) often pursue an innocuous clinical course. Recent work has elucidated important subtypes of HCA and biomarkers to identify them, including HCA at an increased risk for malignant transformation. Another key complication of HCAs is the risk of spontaneous tumoral hemorrhage, which may be life-threatening. Identification of a predictive biomarker for this clinical complication would therefore be of clinical value. It has been suggested that Argininosuccinate Synthase 1 (ASS1) immunohistochemistry (IHC) identifies HCA with a high propensity for hemorrhage. The aim of our study was to validate ASS1 IHC as a predictive marker of hemorrhage. Eighty-nine HCAs were collected for ASS1 IHC and subtyped according to published criteria. Clinical records were examined for evidence of tumoral hemorrhage. Twenty-one (23.6%) HCAs were complicated by clinically detected hemorrhage and were more likely to be resected (P=0.0002). Hemorrhage complicated all WHO subtypes of HCA. There was no association between hemorrhage and HCA subtype (P=0.92). Neither the distribution of ASS1 expression nor the intensity of ASS1 expression compared to normal liver showed a significant association with hemorrhage (P=0.051 and 0.34). Interlaboratory comparison of 8 cases showed good agreement regarding the intensity (6/8 and 7/8) and distribution of staining (7/8 and 7/8) across 3 laboratories performing ASS1 IHC. In conclusion, all subtypes of HCA may be complicated by hemorrhage. ASS1 IHC expression did not correlate with hemorrhagic complications. Caution is prudent before routine implementation of ASS1 IHC in clinical practice.

Objective: To evaluate the potential impact of a workplace well-being champion on employee and organizational measures of well-being. Patients and Methods: Baseline well-being measures were collected in October 2-20, 2017 and analyzed from January 1, 2018 through June 30, 2018 by incorporating a focused question set (addressing meaning in work, work-life integration, and physical, social, financial, emotional, and general well-being) into the biennial Mayo Clinic All-Staff Survey. Results: The survey was distributed to 64,059 employees, with a response rate of 73%. Employees with a work unit well-being champion had more favorable responses overall than did employees reporting no well-being champion. The percentage responding “favorably” to each well-being measure differed from 2 to 12 percentage points and were all highly statistically significant (P

OBJECTIVES Paragangliomas have unique features in the mediastinum, in part due to their location. Because of their paucity, they have not been thoroughly investigated. We studied the clinical, pathological, immunohistochemical and molecular features of mediastinal paragangliomas. METHODS Immunohistochemistry, next-generation sequencing mutation panel and the Oncoscan assay were performed. RESULTS Twenty-four patients with mediastinal paraganglioma (7 men, 29.2%) had a median age of 45.5 years (19.8–72.2). Twenty-one (87.5%) paragangliomas were completely resected. Six (of 24, 25.0%) tumours were considered metastatic. Mitotic activity occurred in 11 (of 24, 45.8%) paragangliomas. Programmed death-ligand 1 (PD-L1) (n = 23) was expressed in 6 (26%) patients in 10% (n = 2) and 1% (n = 4) of tumour cells, respectively. SDHB expression was lost in 19 (of 22, 86.4%) cases. ATRX expression was lost in 11 (of 23, 47.8%) cases. Next-generation sequencing revealed a single pathogenic mutation in 10 (of 19) specimens including SDHB (n = 4), SDHD (n = 6), SDHC (n = 1), ATRX (n = 1), and ≥2 mutations in 2 cases [SDHC and TERT (n = 1); SDHB, ATRX and TP53 (n = 1)]. Germline mutation analysis revealed the same succinate dehydrogenase mutation (or lack thereof) as identified in the paraganglioma in 11 (of 12) cases. During a median follow-up (n = 21) of 4.8 years (0.8–14.9), 3 patients developed metastases; 4 patients died, at least 1 of disease. CONCLUSIONS Mediastinal paragangliomas can be associated with morbidity and mortality. Many mediastinal paragangliomas have been reported to be associated with syndromes such as multiple endocrine neoplasia, von Hippel-Lindau or succinate dehydrogenase syndrome with mutation profiles dominated by alterations in genes associated with these syndromes.

OBJECTIVES The aim of this study is to evaluate the efficacy of chest computed tomography (CT) to predict the pathological stage of thymic epithelial tumours (TET) using the recently introduced tumour, node and metastasis (TNM) staging with comparison to the modified Masaoka staging. METHODS Preoperative chest CT examinations in cases of resected TET with sampled lymph nodes (2006–2016) were retrospectively reviewed by 2 thoracic radiologists and radiologically (r) staged using both staging systems. A thoracic pathologist reviewed all cases for the pathological (p) stage. Concordance between r-staging and p-staging was assessed by % agreement and unweighted kappa statistics. Associations between r-stage and p-stage with outcomes were assessed using the Cox proportional hazards regression. RESULTS Sixty patients with TET were included (47 thymomas, 12 thymic carcinomas and 1 atypical carcinoid tumour). Sixteen patients (26.7%) had received neoadjuvant therapy. Fifty-four patients (90.0%) had complete resection. The overall agreement between the r-stage and p-stage was 66.7% (κ = 0.46) for TNM staging and 46.7% (κ = 0.30) for modified Masaoka staging. Agreement between r-assessment and p-assessment of the T, N and M components of the TNM stage was 61.7% (κ = 0.28), 86.7% (κ = 0.48) and 98.3% (κ = 0.88), respectively. CT overstaged 12 patients (20.0%) for TNM staging and 12 patients (20.0%) for modified Masaoka staging and understaged 8 (13.3%) and 20 (33.3%) patients for TNM staging modified Masaoka staging, respectively. The r-TNM staging accuracy was lower for patients with neoadjuvant therapy (50.0% with vs 72.7% without). During a median follow-up of 2.6 years (range 0.1–10.5 years), 12 patients had metastases and/or recurrence; 11 patients died (4 of disease). The r-TNM stage and modified Masaoka stage were associated with overall survival and progression-free survival (P CONCLUSIONS Preoperative chest CT is able to accurately predict p-TNM stage in two-thirds of surgically resected TET, with an agreement between radiological staging and pathological staging superior to the modified Masaoka staging.

Introduction: Type 1 diabetes specific autoantibodies are glutamic acid decarboxylase (GAD65), protein tyrosine phosphatase-like islet antigen 2 (IA2), insulin (IAA), and Zinc transporter 8 protein (ZnT8). The aim of our study was to determine if the presence of ZnT8 antibodies(Ab) was predictive of clinical presentation at diagnosis or subsequent disease course. Methods: Between January 2003 and May 2019, 105 patients aged ≤ 21 years with a clinical diagnosis of T1DM had at least 1 diabetes autoantibody measured. For subjects who had less than 4 autoantibodies analyzed initially, residual serum sample was retrieved, and remaining autoantibodies were analyzed. Retrospective chart review was completed. At diagnosis, we evaluated BMI z-score, HbA1c, and the presence and severity of DKA. Complications recorded post diagnosis included episodes of DKA, diagnosis of autoimmune (AI) disease, and the presence of vascular complications. Results: Of the 105 patients, 71 were ZnT8(+) (68%). When comparing ZnT8Ab(+) to (-) patients at diagnosis, there was no difference in age (p=0.94), BMI z-score (p=0.83) or presence of DKA (p=0.26). There was no difference in duration of follow up between ZnT8 Ab (+) and (-) groups (p=0.54). Over follow-up, (0.05-15.7 years), there was no difference in rates of DKA episodes (p=0.71). There were no macrovascular complications recorded and no difference in microvascular complications between the 2 groups (p=0.14). There were more AI conditions in the ZnT8Ab(+) group, 77% compared to 23% in ZnT8Ab(-), but this did not reach statistical significance (p=0.12). Conclusions: Our study, unlike others, suggests that the presence of ZnT8 Ab does not result in a difference in disease course at presentation. This study adds to the literature as it has follow up on patients. Over up to 15 years of follow-up, there is no difference in complications between those with and without ZnT8 Ab’s. This study should be validated with larger numbers and longer follow up. Disclosure A. R. Dahl: None. S. Jenkins: None. J. Zbacnik: None. J. Foster: None. S. Pittock: None.

Objectives To evaluate SATB2 expression and prognostic implications in a large cohort of thoracic neuroendocrine tumors. Methods Surgical pathology files (1995-2017) and an institutional thymic epithelial tumor database (2010-2020) were searched for resected neuroendocrine tumors. Cases were stained with SATB2 (clone EP281). Percent SATB2-positive tumor cells and expression intensity were scored. Results In the lung, SATB2 was expressed in 5% or more of tumor cells in 29 (74.4%) of 39 small cell carcinomas and 9 (22.5%) of 40 atypical and 26 (40.6%) of 64 typical carcinoid tumors. SATB2 percent tumor cell expression and intensity were higher in small cell carcinomas than in carcinoid tumors (both P Conclusions SATB2 (clone EP281) is expressed in a large subset of pulmonary and thymic neuroendocrine tumors and therefore does not appear to be a useful marker to identify the origin of neuroendocrine tumors. Validation studies are needed, specifically including thymic neuroendocrine tumors, as the expression pattern might be different in those tumors.