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Background: The shift toward outpatient total knee arthroplasties (TKAs) has led to a demand for effective perioperative pain control methods. A surgeon-performed "low" adductor canal block ("low-ACB") technique, involving an intraoperative ACB, is gaining popularity due to its efficiency and early pain control potential. This study examined the transition from traditional preoperative anesthesiologist-performed ultrasound-guided adductor canal blocks ("high-ACB") to low-ACB, evaluating pain control, morphine consumption, first physical therapy visit gait distance, hospital length-of-stay, and complications., Methods: There were 2,620 patients at a single institution who underwent a primary total knee arthroplasty between January 1, 2019, and December 31, 2022, and received either a low-ACB or high-ACB. Cohorts included 1,248 patients and 1,372 patients in the low-ACB and high-ACB groups, respectively. Demographics and operative times were similar. Patient characteristics and outcomes such as morphine milligram equivalents (MMEs), Visual Analog Scale pain scores, gait distance (feet), length of stay (days), and postoperative complications (30-day readmission and 30-day emergency department visit) were collected., Results: The low-ACB cohort had higher pain scores over the first 24 hours (5.05 versus 4.86, P < .001) and higher MME at 6 hours (11.49 versus 8.99, P < .001), although this was not clinically significant. There was no difference in pain scores or MME at 12 or 24 hours (20.81 versus 22.07 and 44.67 versus 48.78, respectively). The low-ACB cohort showed longer gait distance at the first physical therapy visit (188.5 versus 165.1 feet, P < .001) and a shorter length of stay (0.88 versus 1.46 days, P < .01), but these were not clinically significant. There were no differences in 30-day complications., Conclusions: The low-ACB offers effective pain relief and comparable early recovery without increasing operative time or the complication rate. Low-ACB is an effective, safe, and economical alternative to high-ACB., Level of Evidence: Therapeutic study, Level III (retrospective cohort study)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Myofibroblastic tumors are extremely rare in the larynx, with just over 40 published cases. Despite being a benign tumor, it presents with a marked inflammatory character, local destruction, and the possibility of degeneration to malignant histological types with metastatic capacity. Anatomopathological differential diagnosis is fundamental in these cases., Competing Interests: There are no conflicts of interest., (© 2023 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Undifferentiated anaplastic thyroid tumours are uncommon and constitute a diagnostic challenge on fine needle aspiration. A case showing large, single neoplastic cells in a background of Hashimoto's disease is presented., (© 2023 John Wiley & Sons Ltd.)

Background: Periprosthetic infection is a devastating complication following total knee arthroplasty. A 2-stage protocol often includes an interim antibiotic spacer with intramedullary (IM) dowels. However, the necessity of IM dowels has recently been challenged. Specifically, the data supporting bacterial colonization of the IM canal are limited and controversial. The purpose of this study was to identify the rate of positive IM cultures during resection arthroplasty in periprosthetic knee infection., Methods: A total of 66 IM diaphyseal cultures were taken during resection arthroplasty from 34 patients diagnosed with periprosthetic knee infection. These IM cultures were taken from the femoral and tibial canals using separate sterile instruments. All patients had infected primary total knee arthroplasty implants at the time of resection., Results: Thirty one percent (n = 21) of IM canal cultures in this study were positive from either the tibial or the femoral diaphysis at the time of resection arthroplasty. There were 18 of 21 (86%) of the positive IM canal cultures with concordant intraoperative joint cultures where the IM cultures matched the intraarticular cultures., Conclusion: With a 31% positive IM canal culture rate, this study confirms the logic of using IM dowels with an antibiotic spacer to treat periprosthetic knee infection. Since the failure of a 2-stage reimplantation is catastrophic, any attempt to provide additional local antibiotic delivery seems warranted. Since nearly one-third of our patients had positive IM cultures, this simple addition to an antibiotic spacer has the potential to improve 2-stage results. Claims supporting the elimination of IM dowels during resection arthroplasty seem ill-advised., (Copyright © 2023. Published by Elsevier Inc.)

Background: The American Association of Hip and Knee Surgeons tasked a 2013 workgroup to provide obesity-related recommendations in total joint arthroplasty. Morbidly obese patients (body mass index (BMI) ≥ 40) seeking hip arthroplasty were determined to be at increased perioperative risk, and surgeons were recommended to encourage these patients to reduce their BMI <40 presurgery. We report the effect of instituting a 2014 BMI <40 threshold on our primary total hip arthroplasties (THAs)., Methods: We queried our institutional database to select all primary THAs from January 2010 to May 2020. There were 1,383 THAs that were pre-2014 and 3,273 THAs that were post-2014. The 90-day emergency department (ED) visits, readmissions, and returns to operating room (OR) were identified. Patients were propensity score weight-matched according to comorbidities, age, initial surgical consultation (consult) BMI, and sex. We conducted 3 comparisons: A) pre-2014 patients who had a consult and surgical BMI ≥40 against post-2014 patients who had a consult BMI ≥40 and surgical BMI <40; B) pre-2014 patients against post-2014 patients who had a consult and surgical BMI <40; and C) post-2014 patients who had a consult BMI ≥40 and surgical BMI <40 against post-2014 patients who had a consult BMI ≥40 and surgical BMI ≥40., Results: Post-2014 patients who had a consult BMI ≥ 40 and surgical BMI <40 had less ED visits (7.6 versus 14.1%, P = .0007), but similar readmissions (11.9 versus 6.3%, P = .22) and returns to OR (5.4 versus 1.6%, P = .09) compared to pre-2014 patients who had a consult BMI and surgical BMI ≥ 40. Post-2014 BMI <40 had less readmissions (5.9 versus 9.3%, P < .0001), and similar all-cause returns to OR and ED visits than patients pre-2014. Post-2014 patients who had a consult and surgical BMI ≥ 40 had lower readmissions (12.5 versus 12.8%, P = .05), and similar ED visits and returns to OR than consult BMI ≥ 40 and surgical BMI <40., Conclusion: Patient optimization prior to total joint arthroplasty is critical. However, the BMI optimization that mitigates risk in primary total knee arthroplasty may not apply to primary THA. We observed a paradoxical increased readmission rate for patients who reduced their BMI before THA., Level of Evidence: III., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: In 2013, the American Association of Hip and Knee Surgeons tasked a workgroup to provide obesity-related recommendations in total joint arthroplasty and determined that patients who had body mass index (BMI) ≥ 40 seeking hip/knee arthroplasty were at increased perioperative risk and recommended preoperative weight reduction. Few studies have shown the actual results of instituting this; therefore, we reported the effect of instituting a BMI < 40 threshold in 2014 on our elective, primary total knee arthroplasties (TKAs)., Methods: We queried an institutional database to select all TKAs conducted from January 2010 to May 2020. There were 2,514 TKA pre-2014 and 5,545 TKA post-2014 that were identified. The 90-day emergency department (ED) visits, readmissions, and returns-to-operating room (OR) outcomes were identified. Patients were propensity score weight-matched as per comorbidities, age, initial surgical consultation (consult) BMI, and sex. We conducted 3 outcome comparisons: (1) pre-2014 patients who had a consult and surgical BMI ≥ 40 against post-2014 patients who had a consult BMI ≥ 40 and surgical BMI < 40; (2) pre-2014 patients against post-2014 patients who had a consult and surgical BMI < 40; (3) post-2014 patients who had a consult BMI ≥ 40 and surgical BMI < 40 against post-2014 patients who had a consult BMI ≥ 40 and surgical BMI ≥ 40., Results: Pre-2014 patients who had a consult and surgical BMI ≥ 40 had more ED visits (12.5% versus 6%, P = .002) but similar readmissions and returns-to-OR than post-2014 patients who had a consult BMI ≥ 40 and surgical BMI < 40. Pre-2014 patients who had a consult and surgical BMI < 40 had more readmissions (8.8% versus 6%, P < .0001) but similar ED visits and returns-to-OR when compared to their post-2014 counterparts. Post-2014 patients who had a consult BMI ≥ 40 and surgical BMI < 40 had fewer ED visits (5.8% versus 10.6%) but similar readmissions and returns-to-OR than patients who had a consult BMI ≥ 40 and surgical BMI ≥ 40., Discussion: Patient optimization prior to total joint arthroplasty is essential. Enacting BMI reduction pathways prior to total knee arthroplasty seems to afford morbidly obese patients major risk mitigation. We must continue to ethically balance the pathology, expected improvement after surgery, and the overall risks of complications for each patient., Level of Evidence: III., (Copyright © 2023 Elsevier Inc. All rights reserved.)

➤: Dual mobility (DM) refers to a now widely available option for total hip articulation. DM implants feature a small inner head, a hard bearing, that connects via a taper fit onto the femoral trunnion. This head freely rotates but is encased inside a larger, outer polyethylene head that articulates with a smooth acetabular component., ➤: DM acetabular components are available in the form of a monoblock shell or as a liner that is impacted into a modular shell, providing a metal articulation for the polyethylene outer head., ➤: DM is designed to increase hip stability by providing the arthroplasty construct with a higher jump distance, head-to-neck ratio, and range of motion prior to impingement., ➤: The use of DM in total hip arthroplasty continues to increase in the United States for both primary and revision arthroplasty. Surgeons should be aware of the potential benefits and pitfalls., ➤: Long-term data are lacking, especially for modular DM implants. Points of concern include a potential for accelerated polyethylene wear, intraprosthetic dislocation, and modular backside fretting corrosion., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H349 )., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

Several fields of orthopedics have concluded benefits from volume thresholds. We postulate that we could similarly optimize periprosthetic joint infection (PJI) treatment by creating a regional referral center, concentrating expertise and resources. Here, we review our reasoning and our first-year experience of a PJI referral center in the United States., Competing Interests: At least one of the (co-)authors is a member of the editorial board of . The peer-review process was guided by an independent editor, and the authors have no other competing interests to declare., (Copyright: © 2022 Murillo Adrados et al.)

Follicular dendritic cells (FDCs) are antigen-presenting cells located in the germinal centers of the lymph nodes. Among the few tumors showing FDC differentiation are follicular dendritic cell sarcoma (FDCS) and Castleman disease (CD), more precisely the unicentric hyaline vascular (HV) variant. Both are relatively rare tumors, and the diagnostic cytological experience is limited to descriptions of isolated cases or small series. The purpose of this review is to bring together all the available cytological published information, and our personal experience, in order to obtain a global idea of the cytological features of these peculiar FDC-derived tumors. The different descriptions of FDCS are very similar, reflecting a tumor that shows repetitive and characteristic cytological features. It shows a dimorphic population of mature lymphocytes and large tumoral cells with partial spindle morphology. Most cases of HV variant of CD can be recognized as benign upon cytology, however a precise diagnosis seems more difficult. It is characterized by reactive lymphocytes mixed with vessels and FDCs, either single or forming syncytial aggregates. Both, FDCS and CD are challenging for cytological diagnosis in which a high index of suspicion is necessary for a correct preoperative assessment. Cytology is very useful for follow-up of recurrences and metastases.

High Grade B Cell Lymphoma, NOS, and High Grade B Cell Lymphoma with Dual Hit or Triple Hit have been recently recategorized in the 2016 revision of the WHO classification of lymphoid neoplasms. In this study we have characterized the genetic, histopathological, and clinical features of a series of this type of lymphoid neoplasia (17 HGBCL NOS and 53 HGBCL DH/TH).HGBCL NOS showed better response to first line treatment than HGBCL with DH/TH but no significant differences in PFS or OS were found between the two categories. Survival analysis in the whole cohort of cases found that only the presence of BCL2 translocation was significantly associated with PFS. Other clinical features such as IPI, LDH or stage were equivalent in both categories. Furthermore, both high grade and DLBCL morphological patterns showed equivalent PFS and OS in this set of High grade BCL NOS/DH/TH.Key points BCL2 translocation in High Grade B Cell Lymphoma NOS and High Grade B Cell Lymphoma with DH/TH is associated with reduced progression free survival.Both high grade and DLBCL morphological patterns showed equivalent outcome regarding PFS and OS in HGBCL.

An 86-year-old female presented with anemia and dyspepsia. She underwent esophagogastroduodenoscopy, which revealed a giant pedunculated polyp located in the gastric corpus, protruding into the duodenal bulb, causing gastric outlet obstruction (GOO). Thus, an endoscopic resection was scheduled.

Two-stage exchange remains the standard of care for treatment of chronic periprosthetic infections in the United States. The strategy involves three steps; a resection arthroplasty with a thorough debridement and placement of a temporary spacer, an extended period of targeted antibiotics, and finally, a second definitive reconstruction procedure. The lengthy period of time between surgeries, where patients have diminished mobility, a long period of IV antibiotics and its considerable side effects, and the need for two large operations and hospitalizations places physiologic and emotional demands on patients and their families. A two-stage exchange has considerable morbidity and mortality, with significant attrition between stages. Nonetheless, it remains the gold standard for treatment of chronic periprosthetic infections, with good historic success rates. In this review, we outline its historical origins, surgical technique, outcomes and current research shaping two-stage exchanges. (Journal of Surgical Orthopaedic Advances 30(4):220-225, 2021).

Introduction: The Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey is a federally mandated survey that assesses patient satisfaction after hospitalization. It has been noted that a minority of patients actually return the survey. Potential bias in who does and does not respond to the survey (nonresponse bias) after total hip arthroplasty (THA) may affect the survey results., Methods: All adult patients undergoing inpatient elective primary THA between February 2013 and May 2020 at a single institution were selected for retrospective analysis. After discharge, all had been mailed the HCAHPS survey, and the primary outcome for the current study was survey return. Patient characteristics and 30-day perioperative outcomes were assessed. Univariate and multivariate analyses were performed to determine correlations between the above variables and HCAHPS survey return status., Results: Of 3,310 THA patients analyzed, 1,049 (31.69%) returned the HCAHPS surveys. On multivariate regression analyses, patients who did not return the survey were more likely to have a higher American Society of Anesthesia score (score of three or higher, odds ratio [OR] = 2.27; P < 0.001), be more functionally dependent (OR = 2.69; P = 0.005), or be Black/African American (OR = 3.40; P < 0.001). Similarly, patients who did not return the survey were more likely to have had any adverse event (OR = 1.80; P = 0.012), major adverse event (OR = 2.88; P = 0.007), readmission (OR = 2.13; P < 0.001), be discharged to a place other than home (OR = 1.71; P < 0.001), or stay in the hospital for longer than 3 days (OR = 1.89; P < 0.001)., Discussion: After THA, the HCAHPS survey response rate was only 31.69% and completion of the survey correlated with demographic and perioperative variables. These findings suggest that the HCAHPS survey results should be interpreted as a skewed sample of the true surgical patient population. Nonresponse bias is an important factor to consider when evaluating healthcare quality, patient satisfaction survey results, and their effects on federal hospital reimbursement rates., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Introduction: Shorter length of stays (LOS) at a Skilled Nursing Facility (SNF) after hip fracture surgery would be expected to lead to costs savings for the healthcare system. Evidence also suggests that shorter SNF stays also leads to improved 30-day outcomes, thus compounding this value proposition. Our Integrated Fragility Hip Fracture Program created a simple algorithm at discharge to provide each post-operative hip fracture patient with an expected SNF LOS. We studied whether this intervention produced a shorter SNF LOS and other observable short-term outcomes., Methods: We retrospectively reviewed all original Medicare hip fracture patients treated with operative fixation who were admitted to our hospital in 2015, 2017 and 2018. We selected patients who were discharged to a single SNF following hospitalization, and excluded patients with incomplete records. The algorithm for the expected LOS recommendation was based on the degree of assistance the patient needed for ambulation: 7 days ("0-person assist"), 14 days ("1-person assist"), or 21 days ("2-person assist"). We compare the SNF LOS of our hip fracture patient population between those discharged to a program participant, those SNF that agreed to this algorithm, and those discharged to a non-program participant SNF., Results: We identified 246 patients meeting our selection criteria. 69 were discharged to a program participant SNF. Patients discharged to a participant SNF had similar baseline demographics and ASA distributions to those discharged to a non-participant provider. There was a statistically significant difference in length of stay between the groups, with program participant patients spending an average of 23 days at the SNF while the control group spent an average of 31 days. (p < 0.001). Program participant discharges were also associated with additional cost savings. There was no significant difference in ED visits within 90 days of discharge., Discussion: SNF LOS for geriatric hip fractures can be decreased with implementation of a simple physical therapy driven algorithm based on the patient's ambulatory independence at hospital discharge. Conclusion : This is a simple, yet completely unique program that seems to have increased the value of healthcare provided., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Objective: The objective of the current study was to perform a retrospective review of a national database to assess the safety of cement augmentation for vertebral compression fractures in geriatric populations in varying age categories., Methods: The 2005-2016 National Surgical Quality Improvement Program databases were queried to identify patients undergoing kyphoplasty or vertebroplasty in the following age categories: 60-69, 70-79, 80-89, and 90+ years old. Demographic variables, comorbidity status, procedure type, provider specialty, inpatient/outpatient status, number of procedure levels, and periprocedure complications were compared between age categories using chi-square analysis. Multivariate logistic regressions controlling for patient and procedural variables were then performed to assess the relative periprocedure risks of adverse outcomes of patients in the different age categories relative to those who were 60-69 years old., Results: For the 60-69, 70-79, 80-89, and 90+ years old cohorts, 486, 822, 937, and 215 patients were identified, respectively. After controlling for patient and procedural variables, 30-day any adverse events, serious adverse events, reoperation, readmission, and mortality were not different for the respective age categories. Cases in the 80- to 89-year-old cohort were at increased risk of minor adverse events compared to cases in the 60- to 69-year-old cohort., Conclusion: As the population ages, cement augmentation is being considered as a treatment for vertebral compression fractures in increasingly older patients. These results suggest that even the very elderly may be appropriately considered for these procedures (level of evidence: 3).

Aim: Lymphoplasmacytic lymphoma (LPL) is an indolent mature B-cell-neoplasm with involvement of the bone marrow. At least 90% of LPLs carry MYD88-L265P mutation and some of them (~10%) transform into diffuse large B-cell-lymphoma (DLBCL)., Material and Methods: Over the past 15 years we have collected 7 cases where the both LPL and DLBCL were diagnosed in the same patient. Clinical records, analytical data and histopathological specimens were reviewed. FISH studies on paraffin-embedded tissue for MYC, BCL2 and BCL6 genes were performed, as well as MYD88-L265P mutation and IGH rearrangement analysis by PCR. A mutational study was done by massive next generation sequencing (NGS)., Results: There were 4 women and 3 men between 36-91 years of age. Diagnoses were made simultaneously in 4 patients. In two cases the LPL appeared before the DLBCL and in the remaining case the high-grade component was discovered 5 years before the LPL. In 6 cases both samples shared the MYD88-L265P mutation. IGH rearrangement analysis showed overlapping features in two of 6 cases tested. Mutational study was evaluable in three cases for both samples showing shared and divergent mutations., Conclusions: These data suggest different mechanisms of DLBCL development in LPL patients., Competing Interests: The authors of this manuscript read the journal’s policy and have the following competing interests: MP is being sponsored by TAKEDA. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Cancer cells develop mechanisms that increase nutrient uptake, including key nutrient carriers, such as amino acid transporter 1 (LAT-1) and glucose transporter 1 (GLUT-1), regulated by the oxygen-sensing Von Hippel Lindau-hypoxia-inducible factor (VHL-HIF) transcriptional pathway. We aimed to analyze these metabolic players in gastroenteropancreatic neuroendocrine tumors (GEP-NET) and correlate them with tumor malignancy and progression. LAT-1, GLUT-1, and pVHL expression was analyzed in 116 GEP-NETs and 48 peritumoral tissue samples by immunohistochemistry. LAT-1 was stably silenced using specific shRNA in the human NET BON cell line. LAT-1 expression was significantly increased in tumor tissue compared to non-tumor tissue in both gastrointestinal (67% vs. 44%) and pancreatic NETs (54% vs. 31%). Similarly, GLUT-1 was substantially elevated in gastrointestinal (74% vs. 19%) and pancreatic (58% vs. 4%) NETs. In contrast, pVHL expression was decreased (85% vs. 58%) in pancreatic NETs. Tumors with metastases at diagnosis displayed increased LAT-1 and GLUT-1 and decreased pVHL expression ( p < 0.001). In accordance with these data, silencing LAT-1 curtailed cell proliferation in BON cells. These findings suggest that specific mechanisms that increase nutrient uptake, such as LAT-1 and GLUT-1, are increased in GEP-NETs, whereas pVHL is decreased. These markers might be related to the proliferation and metastatic capacity of these tumors., Competing Interests: M.M. and M.S.N. have received speaker’s fees from Novartis and Ipsen. The remaining authors have nothing to disclose.

Background: Various parameters have been considered for predicting survival in pancreatic ductal adenocarcinoma. Information about western population is missing. The aim of this study is to assess the association between Glucose transporter type 1 (GLUT-1) expression and prognosis for patients with PDAC submitted for surgical resection in a European cohort., Methods: Retrospective analysis of PDAC specimens after pancreatoduodenectomy assessing GLUT-1 expression according to intensity (weak vs strong) and extension (low if < 80% cells were stained, high if > 80%) was performed. Statistical analysis was performed using the exact Fisher test, Student t test or the Mann-Whitney U test. Survival was analysed using the Kaplan-Meier method and compared with the Log-rank test. The differences were considered significant at a two-sided p value of < 0.05. All statistical analyses were performed using SPSS® 23.0 for Windows (SPSS Inc., Chicago, IL, USA)., Results: Our study consisted of 39 patients of which 58.9% presented with weak and 41.1% with strong intensity. The median extension was 90%: 28.2% cases presented with a low extension and 71.8% with a high extension. No significant differences related to intensity were found. The high-extension group showed a higher percentage of T3 PDAC (92.9% vs 63.6%, p = 0.042) and LNR20 (35.7% vs 0%, p = 0.037) as well as shorter disease-free survival (17.58 vs 54.46 months; p = 0.048)., Conclusions: Our findings suggest that GLUT-1 could be related to higher aggressivity in PDAC and could be used as a prognostic marker, identifying patients with a worse response to current therapies who could benefit from more aggressive treatments.

Immunotherapy is an effective treatment in advanced cancer, although predictors of response are limited. We studied whether excess weight influences the efficacy outcomes of immunotherapy. We have also evaluated the combined prognostic effect of excess weight and immune-related adverse events (irAEs). Efficacy of anti-PD-1 treatment was evaluated with both objective radiological response (ORR) rate and progression-free survival (PFS), and toxicity with irAEs. We studied the association between excess weight and ORR, PFS or irAEs. 132 patients diagnosed with advanced cancer were included. Median body mass index (BMI) was 24.9 kg/m2. 64 patients had normal weight (BMI<25 kg/m2), and 64 patients had excess weight (BMI≥25 kg/m2). Four patients had underweight and were excluded from further analysis. ORR was achieved in 50 patients (38.0%), median PFS was 6 months. 44 patients developed irAEs (33.3%). ORR was higher in excess weight patients than in patients with normal weight (51.6% vs 25.0%; OR 3.45, p = .0009). PFS was improved in patients with excess weight (7.25 months vs 4 months, HR 1.72, p = .01). The incidence of IrAEs was not different in patients with excess weight (54.5% vs 43.2%, p = .21). When high BMI and irAEs were combined, we observed a marked prognostic trend in ORR rate (87.5% vs 6.2%; OR 161.0, p < .00001), and in PFS (14 months vs 3 months; HR 5.89, p < .0001). Excess weight patients with advanced cancer that receive single-agent anti-PD-1 antibody therapy exhibit a significantly improved clinical outcome compared with normal BMI patients. This association was especially marked when BMI and irAEs were considered combined., (© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Study Design: Retrospective cohort study., Objective: To assess nonresponder biases for the HCAHPS survey following spine surgery., Summary of Background Data: The Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey is a publicly reported patient satisfaction survey. In addition to having the potential of impacting a hospital's reputation, it is directly linked to government reimbursement. However, it is known that a minority of patients return this survey, and it is expected that there are nonresponder biases., Methods: All adult inpatient spine surgery patients at a single institution between January 2013 and August 2017 at a single institution were selected for retrospective analysis. Patient demographics and perioperative outcomes were assessed as potential predictors of not returning HCAHPS surveys. Univariate and multivariate analyses were performed., Results: Of 5517 spine surgeries analyzed, 1505 (27.3%) patients returned the HCAHPS survey. Response rate was variable based on patient characteristics (with statistically significant differences based on age, functional status, race, and American Society of Anesthesiologists score) but not variable based on anatomic region of the spine surgery. Multivariate analysis revealed that patients who did not return the HCAHPS survey were more likely to be black/African American (OR = 2.8, P < 0.001), have a higher American Society of Anesthesiologists score (OR 1.76, P < 0.001), and have had a major adverse event (OR = 1.66; P = 0.001), minor adverse event (OR = 2.50; P < 0.001), discharged to a destination other than home (OR = 2.16, P < 0.001), hospital readmission (OR = 2.58; P < 0.001), and a long hospital length of stay (OR = 1.28, P = 0.001)., Conclusion: For spine surgery patients, patient characteristics and perioperative outcomes were found to be significantly associated with the nonresponder bias for HCAHPS surveys. Although the potential resultant bias in HCAHPS scores cannot be directly determined, this must be considered in interpreting the results of such satisfaction surveys given that less than one-third of patients actually completed this survey in the study population., Level of Evidence: 3.

Introduction: The current study sought to determine the factors predictive of postoperative pressure ulcer development by analyzing extensive multicenter outcomes data from the 2016 American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database., Methods: The 2016 NSQIP Participant Use File and Hip Fracture Procedure Targeted file were used to identify the risk factors for the development of postoperative pressure ulcers after hip fracture surgery in a geriatric cohort. Multivariate regressions were performed to identify preoperative comorbidities and postoperative complications that are risk factors for developing postoperative pressure ulcers., Results: Of 8,871 geriatric hip fracture patients included in the study cohort, 457 (5.15%) developed pressure ulcers. Multivariate regressions identified the following preoperative risk factors for developing a postoperative pressure ulcer (in order of decreasing relative risk): preoperative sepsis, elevated platelet count, insulin-dependent diabetes, and preexisting pressure ulcer. Multivariate regressions also identified the following postoperative complications as risk factors for developing a postoperative pressure ulcer: postoperative sepsis, postoperative pneumonia, urinary tract infection, and postoperative delirium., Discussion: The identified preoperative factors and postoperative complications should help guide quality improvement programs.

Background: In the search for novel antibody-drug conjugates (ADCs) with therapeutic potential, it is imperative to identify novel targets to direct the antibody moiety. CD13 seems an attractive ADC target as it shows a differential pattern of expression in a variety of tumors and cell lines and it is internalized upon engagement with a suitable monoclonal antibody. PM050489 is a marine cytotoxic compound tightly binding tubulin and impairing microtubule dynamics which is currently undergoing clinical trials for solid tumors., Methods: Anti-CD13 monoclonal antibody (mAb) TEA1/8 has been used to prepare a novel ADC, MI130110, by conjugation to the marine compound PM050489. In vitro and in vivo experiments have been carried out to demonstrate the activity and specificity of MI130110., Results: CD13 is readily internalized upon TEA1/8 mAb binding, and the conjugation with PM050489 did not have any effect on the binding or the internalization of the antibody. MI130110 showed remarkable activity and selectivity in vitro on CD13-expressing tumor cells causing the same effects than those described for PM050489, including cell cycle arrest at G2, mitosis with disarrayed and often multipolar spindles consistent with an arrest at metaphase, and induction of cell death. In contrast, none of these toxic effects were observed in CD13-null cell lines incubated with MI130110. Furthermore, in vivo studies showed that MI130110 exhibited excellent antitumor activity in a CD13-positive fibrosarcoma xenograft murine model, with total remissions in a significant number of the treated animals. Mitotic catastrophes, typical of the payload mechanism of action, were also observed in the tumor cells isolated from mice treated with MI130110. In contrast, MI130110 failed to show any activity in a xenograft mouse model of myeloma cells not expressing CD13, thereby corroborating the selectivity of the ADC to its target and its stability in circulation., Conclusion: Our results show that MI130110 ADC combines the antitumor potential of the PM050489 payload with the selectivity of the TEA1/8 monoclonal anti-CD13 antibody and confirm the correct intracellular processing of the ADC. These results demonstrate the suitability of CD13 as a novel ADC target and the effectiveness of MI130110 as a promising antitumor therapeutic agent.

Study Design: Retrospective cohort study of prospectively collected data., Objective: Assess correlation between preoperative platelet counts and postoperative adverse events after elective posterior lumbar surgery procedures., Summary of Background Data: Preoperative low platelet counts have been correlated with adverse outcomes after posterior lumbar surgery. Nonetheless, the effect of varying platelet counts has not been studied in detail for a large patient population, especially on the high end of the platelet spectrum., Methods: Patients who underwent elective posterior lumbar surgery were identified in the 2011 to 2016 National Surgical Quality Improvement Program database. Preoperative platelet counts were considered relative to 30-day perioperative adverse outcomes. Patients were classified into platelet categories based on determining upper and lower bounds on when the adverse outcomes crossed a relative risk of 1.5. Univariate and multivariate analyses compared 30-day postoperative complications, readmissions, operative time, and hospital length of stay between those with low, normal, and high platelet counts., Results: In total, 137,709 posterior lumbar surgery patients were identified. Using the relative risk threshold of 1.5 for the occurrence of any adverse event, patients were divided into abnormally low (≤140,000/mL) and abnormally high (≥447,000/mL) platelet cohorts. The abnormally low and high platelet groups were associated with higher rates of any, major, minor adverse events, transfusion, and longer hospital length of stay. Furthermore, the abnormally low platelet counts were associated with a higher risk of readmissions., Conclusion: The data-based cut-offs for abnormally high and low platelet counts closely mirrored those found in literature. Based on these definitions, abnormally high and low preoperative platelet counts were associated with adverse outcomes after elective posterior lumbar surgery. These findings facilitate risk stratification and suggest targeted consideration for patients with high, as well as low, preoperative platelet counts., Level of Evidence: 3.

Study Design: Retrospective cohort study OBJECTIVE.: The aim of this study was to investigate how elective spine surgery patient preoperative opioid use (as determined by admission NarxCare narcotics use scores) correlated with 30-day perioperative outcomes and postoperative patient satisfaction., Summary of Background Data: The effect of preoperative narcotics usage on postoperative outcomes and patient satisfaction following spine surgery has been of question. The NarxCare platform analyzes the patients' state Physician Drug Monitoring Program (PDMP) records to assign numerical scores that approximate a patient's overall opioid drug usage., Methods: Elective spine surgery cases performed at a single institution between October 2017 and March 2018 were evaluated. NarxCare narcotics use scores at the time of admission were assessed. Patient characteristics, as well as 30-day adverse events, readmissions, reoperations, and mortality, were abstracted from the medical record. Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey data were also abstracted when available.Cases were binned based on the following ranges of admission NarxCare scores: 0, 1 to 99, 100 to 299, 300 to 499, and 500+. Multivariate logistic regressions were performed to compare the odds of having an adverse events, readmission, reoperation, and mortality between the different narcotics groups. One-way analysis of variance analyses were performed to compare HCAHPS survey response rates and HCAHPS survey results between the different narcotics score groups., Results: In total, 346 patients met criteria for inclusion in the study (NarxScore 0: n = 74, 1-99: n = 58, 300-499: n = 117, and 500+: n = 21). Multivariate logistic regressions did not detect statistically significant differential odds of experiencing adverse events, readmission, reoperation, or mortality between the different groups of admissions narcotics scores. Analyses of variance did not detect statistically significant differences in HCAHPS survey response rates, total HCAHPS scores, or HCAHP subgroup scores between the different narcotics score groups., Conclusion: Although there are many reasons to address preoperative patient narcotic utilization, the present study did not detect perioperative outcome differences or patient satisfaction based on the narcotic use scores as stratified here., Level of Evidence: 3.

Lymphoblastic lymphomas (LBLs) are uncommon malignant neoplasms derived from immature T- or B-lymphoid progenitor cells. Although cutaneous involvement may reach 33% in B-LBL, only 12 cutaneous cases of T-LBL have been published. We report the case of a 49-year-old woman with 2-month history of erythematous-violaceous plaques in the sternal region and breasts. Histopathologic examination showed a dense monomorphus infiltrate in dermis and positive immunostainings for CD3, CD99 and terminal deoxynucleotidyl transferase, thus indicating T-LBL. Staging work-up only revealed a mediastinal mass at diagnosis. After a 51-month follow-up and different treatment regimens, the patient remains alive although she has presented four relapses, all of them extramedullary., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The incidence of periprosthetic hip fractures is increasing due to higher numbers of total hip arthroplasties being performed. Unlike native hip fractures, the effect of time to surgery of periprosthetic hip fractures is not well established. This study evaluates the effect of time to surgery on perioperative complications for patients with periprosthetic hip fractures., Methods: Patients who underwent surgery for periprosthetic hip fracture were identified in the 2005-2016 National Surgical Quality Improvement Program database and stratified into 2 groups: <2 and ≥2 days from hospital admission to surgery. Multivariate regressions were used to compare risk for perioperative complications between the 2 groups. Independent risk factors for postoperative serious adverse events were characterized., Results: In total, 409 (<2 days from admission to surgery) and 272 (≥2 days from admission to surgery) patients were identified. Multivariate analysis revealed only higher risk of extended postoperative stay for patients who had delays of ≥2 days to surgery compared to those who had <2 days from admission to surgery. Independent risk factors for serious adverse events included increasing age, dependent preoperative functional status, and preoperative congestive heart failure, but not time to surgery., Conclusion: Unlike for native hip fractures, time to surgery for periprosthetic hip fractures does not appear to affect most 30-day perioperative complications. However, it is worth noting that this study was unable to control for all potential confounders and therefore the results may not be generalizable to all types of periprosthetic hip fractures., (Copyright © 2018 Elsevier Inc. All rights reserved.)

TNF-Receptor Associated Factor (TRAF)-3 is a master regulator of B cell homeostasis and function. TRAF3 has been shown to bind and regulate various proteins involved in the control of innate and adaptive immune responses. Previous studies showed that TRAF3 overexpression renders B cells hyper-reactive to antigens and Toll-like receptor (TLR) agonists, while TRAF3 deficiency has been implicated in the development of a variety of B cell neoplasms. In this report, we show that transgenic mice overexpressing TRAF3 and BCL2 in B cells develop with high incidence severe lymphadenopathy, splenomegaly and lymphoid infiltrations into tissues and organs, which is the result of the growth of monoclonal and oligoclonal B cell neoplasms, as demonstrated by analysis of V H DJ H gene rearrangement. FACS and immunohistochemical analyses show that different types of mature B cell neoplasms arise in TRAF3/BCL2 double-transgenic (tg) mice, all of which are characterized by the loss of surface IgM and IgD expression. However, two types of lymphomas are predominant: (1) mature B cell neoplasms consistent with diffuse large B cell lymphoma and (2) plasma cell neoplasms. The Ig isotypes expressed by the expanded B-cell clones included IgA, IgG, and IgM, with most having undergone somatic hypermutation. In contrast, mouse littermates representing all the other genotypes ( TRAF3 -/ BCL2 -; TRAF3 +/ BCL2 -, and TRAF3 -/ BCL2 +) did not develop significant lymphadenopathy or clonal B cell expansions within the observation period of 20 months. Interestingly, a large representation of the HCDR3 sequences expressed in the TRAF3 -tg and TRAF3/BCL2 -double-tg B cells are highly similar to those recognizing pathogen-associated molecular patterns and damage-associated molecular patterns, strongly suggesting a role for TRAF3 in promoting B cell differentiation in response to these antigens. Finally, allotransplantation of either splenocytes or cell-containing ascites from lymphoma-bearing TRAF3/BCL2 mice into SCID/NOD immunodeficient mice showed efficient transfer of the parental expanded B-cell clones. Altogether, these results indicate that TRAF3, perhaps by promoting exacerbated B cell responses to certain antigens, and BCL2, presumably by supporting survival of these clones, cooperate to induce mature B cell neoplasms in transgenic mice.

The immune checkpoint based therapy targeting the programmed death-1 (PD-1) receptor and its PD-L1 ligand has recently been approved for the therapy of different malignant conditions, but not yet for gastroenteropancreatic neuroendocrine tumors (GEP-NETs). In this context, we evaluated the expression of PD-1 and PD-L1 in GEP-NETs and its potential correlations with clinical outcomes. Expression of PD-1/PD-L1 was analyzed by immunohistochemistry in 116 GEP-NETs and 48 samples of peritumoral tissue. In addition, the expression of these molecules was assessed by flow cytometry in peripheral blood mononuclear cells (PBMC) from patients with GEP-NETs (n = 32) and healthy controls (n = 32) and in intratumoral mononuclear cells (TMCs) (n = 3). Expression of PD-L1 and PD-1 was detected by immunohistochemistry in 6% and 1% of tumor tissue samples, respectively, and in 8% of peritumoral tissue samples, for both markers. We also observed that PD-1 expression by TMCs was associated with metastatic disease at diagnosis, and the levels of circulating PD-1+ PBMCs were associated with progressive disease upon follow-ups. In addition, circulating PD-1+ PBMCs were significantly correlated with PD-L1 expression by tumor cells. Our data suggest that PD-1/PD-L1 is expressed in 1 to 8% of GEP-NETs, and that this feature is significantly associated with disease evolution (p < 0.01).

Introduction: colon lymphoma (CL) is an uncommon variety of non-Hodgkin lymphoma (NHL) that represents less than 0.6% of all primary colonic neoplasms. Early diagnosis is challenging as clinical manifestations are non-specific. The goal of this review was to discuss our experience over the last few years regarding the clinical, endoscopic, histological, diagnostic, therapeutic and evolutionary characteristics of CL., Patients and Methods: a retrospective, descriptive analysis of patients with CL diagnosed from 1994 to 2016 at the Hospital Universitario de La Princesa (Madrid, Spain) was performed., Results: a total of 29 patients with CL were identified, with a median age of 67 years; 18 were male (62%). The most common clinical manifestations included abdominal pain, constitutional syndrome, diarrhea and a palpable abdominal mass. Eight (27.6%) patients were asymptomatic and six (20.6%) initially presented with surgical complications. A colonoscopy was performed in 24 patients and the most common findings included diffuse infiltration and solid growth. The most common location was the descending and sigmoid colon. The most common histological subtypes included mantle B-cell NHL and diffuse large B-cell lymphoma. Chemotherapy was administered to 28 patients (96.5%), surgery was performed in six (20.7%) and combined chemo-radiotherapy was administered to one patient. Median survival was 156 months. Survival was 100.0% at one year and 55.0% at ten years., Conclusions: due to the variable aspects of CL on endoscopy, a histological study of all colonic segments is required. Chemotherapy is the treatment of choice and emergency surgery followed by chemotherapy is required for complications. Primary factors associated with poorer survival include age above 65 years, relapsing disease and partial or nil responses.

Reductions in concentrations of persistent organic pollutants were observed for polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in a comparison of two consecutive decades ending in December 31, 2015 (n = 413) and compiled from a 48-station long-term air-monitoring network in Catalonia, Spain. Reductions were observed in geometric mean concentration of total PCDD/Fs, decreasing at a rate of 11% yr -1 . Results reflect the relative success of improved pollution control measures at industry and traffic locations. At traffic and industrial locations, PCDD/Fs were reduced by around 68% (from 70 to 22 fg I-TEQ/m 3 ) and 66% (from 57 to 19 fg I-TEQ/m 3 ), respectively. The highest concentration of 1196 fg I-TEQ/m 3 was observed during the first decade at an industrial location. The highest concentration over the second decade was at a background location during winter (674 fg I-TEQ/m 3 ). Winter observations are generally higher than those recorded in summer, as evident in an 8-year period of moderate PCDD/F levels (<250 fg I-TEQ/m 3 , n = 143). PCDD/F congener profiles were identified has having less chlorinated PCDD/F, indicating the presence of nearby combustion sources at selected locations. More long-term sampling campaigns, combined with network optimization and integration into a meteorological model, can offer a tool for future PCDD/Fs control measures in not only Catalonia - but also applicable to other areas., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Yoga has become a popular form of exercise, recreation, and meditation for adults in the United States. As the popularity of both yoga and the incidence of hip replacements have both coincidentally increased over the last 2 decades, we imagine that the number of total hip replacement patients partaking in the practice of yoga has also increased. There are no clear guidelines available for yoga practice following hip replacement. To date, there have been no published reports of prosthetic hip dislocations during yoga. We present 2 cases of late total hip dislocations during yoga and provide a review of the available orthopaedic literature and our recommendations on patient restrictions and education with respect to practicing yoga after a hip replacement.

Lyme arthritis, caused by the spirochete Borrelia burgdorferi sensu stricto, is a common tick-borne illness in New England and the upper Midwest. Most often, the disease affects the knee and has typically been reported as a cause of native joint infection. There has been only 1 case of Lyme periprosthetic joint infection (associated with a total knee arthroplasty) reported in the literature, and to our knowledge, no other reported cases of Lyme periprosthetic joint infections exist. In this article, we report on 2 patients diagnosed with prosthetic joint infections who were subsequently found to have Lyme prosthetic joint infections, with B burgdorferi as the infectious organism. We discuss the medical and surgical management of these patients.

Background: Malignant melanoma showing numerous osteoclast-like giant cells (OGCs) is an uncommon morphologic phenomenon, rarely mentioned in the cytologic literature. The few reported cases seem to have an aggressive clinical behavior. Although most findings support monocyte/macrophage differentiation, the exact nature of OGCs is not clear., Case: A 57-year-old woman presented with an inguinal lymphadenopathy. Sixteen years before, cutaneous malignant melanoma of the lower limb had been excised. Needle aspiration revealed abundant neoplastic single cells as well as numerous multinucleated OGCs. Occasional neoplastic giant cells were also present. Nuclei of OGCs were monomorphic with oval morphology and were smaller than those of melanoma cells. The immunophenotype of OGCs (S100-, HMB45-, Melan-A-, SOX10-, Ki67-, CD163-, BRAF-, CD68+, MiTF+, p16+) was the expected for reactive OGCs of monocyte/macrophage origin. The tumor has shown an aggressive behavior with further metastases to the axillary lymph nodes and oral cavity., Conclusion: Numerous OGCs are a rare and relevant finding in malignant melanoma. Their presence should not induce confusion with other tumors rich in osteoclastic cells. Since a relevant number of OGCs in melanoma may mean a more aggressive behavior, and patients may benefit from specific treatments, their presence should be mentioned in the pathologic report., (© 2018 S. Karger AG, Basel.)

Background: Venous thromboembolism is a common complication of traumatic brain injury with an estimated incidence of 25% when chemoprophylaxis is delayed. The timing of initiating prophylaxis is controversial given the concern for hemorrhage expansion., Objective: To determine the safety of initiating venous thromboembolic event (VTE) chemoprophylaxis within 24 h of presentation., Methods: We performed a retrospective analysis of patients with traumatic intracranial hemorrhage presenting to a level I trauma center. Patients receiving early chemoprophylaxis (<24 h) were compared to the matched cohort of patients who received heparin in a delayed fashion (>48 h). The primary outcome of the study was radiographic expansion of the intracranial hemorrhage. Secondary outcomes included VTE, use of intracranial pressure (ICP) monitoring, delayed decompressive surgery, and all-cause mortality., Results: Of 282 patients, 94 (33%) received chemoprophylaxis within 24 h of admission. The cohorts were evenly matched across all variables. The primary outcome occurred in 18% of patients in the early cohort compared to 17% in the delayed cohort (P = .83). Fifteen patients (16%) in the early cohort underwent an invasive procedure in a delayed fashion; this compares to 35 patients (19%) in the delayed cohort (P = .38). Five patients (1.7%) in our study had a VTE during their hospitalization; 2 of these patients received early chemoprophylaxis (P = .75). The rate of mortality from all causes was similar in both groups., Conclusion: Early (<24 h) initiation of VTE chemoprophylaxis in patients with traumatic intracranial hemorrhage appears to be safe. Further prospective studies are needed to validate this finding., (Copyright © 2017 by the Congress of Neurological Surgeons)

Study Design: Observational database review., Objective: To determine the effect of patient severity of illness (SOI) on the cost of spine surgery among New York state hospitals., Summary of Background Data: National health care spending has risen at an unsustainable rate with musculoskeletal care, and spine surgery in particular, accounting for a significant portion of this expenditure. In an effort towards cost-containment, health care payers are exploring novel payment models some of which reward cost savings but penalize excessive spending. To mitigate risk to health care institutions, accurate cost forecasting is essential. No studies have evaluated the effect of SOI on costs within spine surgery., Materials and Methods: The New York State Hospital Inpatient Cost Transparency Database was reviewed to determine the costs of 69,831 hospital discharges between 2009 and 2011 comprising the 3 most commonly performed spine surgeries in the state. These costs were then analyzed in the context of the specific all patient refined diagnosis-related group (DRG) SOI modifier to determine this index's effect on overall costs., Results: Overall, hospital-reported cost increases with the patient's SOI class and patients with worse baseline health incur greater hospital costs (P<0.001). Moreover, these costs are increasingly variable for each worsening SOI class (P<0.001). This trend of increasing costs is persistent for all 3 DRGs across all 3 years studied (2009-2011), within each of the 7 New York state regions, and occurs irrespective of the hospital's teaching status or size., Conclusions: Using the 3M all patient refined-DRG SOI index as a measure of patient's health status, a significant increase in cost for spine surgery for patients with higher SOI index was found. This study confirms the greater cost and variability of spine surgery for sicker patients and illustrates the inherent unpredictability in cost forecasting and budgeting for these same patients.

We identified 168,247 total hip and total knee arthroplasties performed in New York State between 2010 and 2012 to examine the evidence for increased geographical and institutional centralization of these procedures. We measured the increased growth of high volume institutions as compared to lower volume hospitals in New York State. We found a high proportion of total arthroplasties already performed in the dozen biggest hospitals in New York back in 2010 and a significant higher growth of these high volume, "centers of excellence," hospitals when compared to low volume hospitals.

Purpose: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and heterogeneous tumors, and their biological behavior is not well known. We studied the presence and potential functional roles of somatostatin receptors (sst1-5), focusing particularly on the truncated variants (sst5TMD4, sst5TMD5) and on their relationships with the angiogenic system (Ang/Tie-2 and VEGF) in human GEP-NETs., Experimental Design: We evaluated 42 tumor tissue samples (26 primary/16 metastatic) from 26 patients with GEP-NETs, and 30 non-tumoral tissues (26 from adjacent non-tumor regions and 4 from normal controls) from a single center. Expression of sst1-5, sst5TMD4, sst5TMD5, Ang1-2, Tie-2 and VEGF was analyzed using real-time qPCR, immunofluorescence and immunohistochemistry. Expression levels were associated with tumor characteristics and clinical outcomes. Functional role of sst5TMD4 was analyzed in GEP-NET cell lines., Results: sst1 exhibited the highest expression in GEP-NET, whilst sst2 was the most frequently observed sst-subtype (90.2%). Expression levels of sst1, sst2, sst3, sst5TMD4, and sst5TMD5 were significantly higher in tumor tissues compared to their adjacent non-tumoral tissue. Lymph-node metastases expressed higher levels of sst5TMD4 than in its corresponding primary tumor tissue. sst5TMD4 was also significantly higher in intestinal tumor tissues from patients with residual disease of intestinal origin compared to those with non-residual disease. Functional assays demonstrated that the presence of sst5TMD4 was associated to enhanced malignant features in GEP-NET cells. Angiogenic markers correlated positively with sst5TMD4, which was confirmed by immunohistochemical/fluorescence studies., Conclusions: sst5TMD4 is overexpressed in GEP-NETs and is associated to enhanced aggressiveness, suggesting its potential value as biomarker and target in GEP-NETs.

Study Design: A retrospective review of an administrative database., Objective: The purpose of this study is to determine the current extent of regionalization by mapping lumbar spine procedures according to hospital and patient zip code, as well as examine the rate of growth of lumbar spine procedures performed at high-, medium-, and low-volume institutions in New York State., Summary of Background Data: The association between hospital and spine surgeon volume and improved patient outcomes is well established. There is no study investigating the actual process of patient migration to high-volume hospitals., Methods: New York Statewide Planning and Research Cooperative System (SPARCS) administrative data were used to identify 228,695 lumbar spine surgery patients from 2005 to 2014. The data included the patients' zip code, hospital of operation, and year of discharge. The volume of lumbar spine surgery in New York State was mapped according to patient and hospital 3-digit zip code. New York State hospitals were categorized as low, medium, and high volume and descriptive statistics were used to determine trends in changes in hospital volume., Results: Lumbar spine surgery recipients are widely distributed throughout the state. Procedures are regionalized on a select few metropolitan centers. The total number of procedures grew 2.5% over the entire 10-year-period. High-volume hospital caseload increased 50%, from 7253 procedures in 2005 to 10,915 procedures in 2014. The number of procedures at medium and low-volume hospitals decreased 30% and 13%, respectively., Conclusions: Despite any concerted effort aimed at moving orthopedic patients to high-volume hospitals, migration to high-volume centers occurred. Public interest in quality outcomes and cost, as well as financial incentives among medical centers to increase market share, potentially influence the migration of patients to high-volume centers. Further regionalization has the potential to exacerbate the current level of disparities among patient populations at low and high-volume hospitals., Level of Evidence: 3.

Ghrelin system comprises a complex family of peptides, receptors (GHSRs), and modifying enzymes [e.g. ghrelin-O-acyl-transferase (GOAT)] that control multiple pathophysiological processes. Aberrant alternative splicing is an emerging cancer hallmark that generates altered proteins with tumorigenic capacity. Indeed, In1-ghrelin and truncated-GHSR1b splicing variants can promote development/progression of certain endocrine-related cancers. Here, we determined the expression levels of key ghrelin system components in neuroendocrine tumor (NETs) and explored their potential functional role. Twenty-six patients with NETs were prospectively/retrospectively studied [72 samples from primary and metastatic tissues (30 normal/42 tumors)] and clinical data were obtained. The role of In1-ghrelin in aggressiveness was studied in vitro using NET cell lines (BON-1/QGP-1). In1-ghrelin, GOAT and GHSR1a/1b expression levels were elevated in tumoral compared to normal/adjacent tissues. Moreover, In1-ghrelin, GOAT, and GHSR1b expression levels were positively correlated within tumoral, but not within normal/adjacent samples, and were higher in patients with progressive vs. with stable/cured disease. Finally, In1-ghrelin increased aggressiveness (e.g. proliferation/migration) of NET cells. Altogether, our data strongly suggests a potential implication of ghrelin system in the pathogenesis and/or clinical outcome of NETs, and warrant further studies on their possible value for the future development of molecular biomarkers with diagnostic/prognostic/therapeutic value.

Cutaneous manifestation as the first sign of Hodgkin lymphoma (HL) is very rare and diagnostically challenging; especially, because the clinical presentation of specific skin involvement by HL is polymorphous. We present a 44-year-old man with erythematous indurate papules and plaques in the right forearm and arm where skin biopsy showed an HL. He also has an enlarged epitrochlear node, and later histopathologic study confirmed the diagnosis of HL subtype-mixed cellularity. Immunohistochemical stains in both biopsies showed that the atypical cells were positive for CD30 and CD15, and negative for CD20 and CD3. PAX5 stained the nuclei of the atypical large lymphoid cells weakly and Oct-2 staining was negative in the atypical cells. EBER and LMP1 protein were negative in both biopsies. Epitrochlear involvement in HL, like in our case, is a rare event (<1%). We reviewed data about prognosis, clinical appearance, and treatment of all the cases of HL specific skin involvement published after Sioutos et al, emphasizing the cases where HL specific skin involvement was the first sign of the disease as in our patient.

We explored the average cost of 94,197 total knee and 78,541 total hip arthroplasties (TKA and THA) using the New York State Hospital Inpatient Cost Transparency database to evaluate the effect of beneficiary health status on hospital reported cost for the two operations. Using the 3M APR-DRG severity of illness index as a measure of patient's health status, we found a significant increase in cost for both TKA and THA for patients with higher severity of illness index. This study confirms the greater cost and variability of TKA and THA for patients with increased severity of illness and illustrates the inherent unpredictability in cost forecasting and budgeting for these same patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To analyze the expression of hypoxia inducible factor 1 alpha (HIF1A) and its correlation with clinical outcome in men with localized prostate cancer (PC) treated with dose escalation radiotherapy (RT) and androgen deprivation (AD)., Methods: Between 1996 and 2004, 129 PC patients who had diagnostic biopsies pre-treatment and 24-36 months following RT were enrolled in this study. Median follow-up was 129 months. Suitable archival diagnostic tissue was obtained from 86 patients. Correlation analysis was done to assess association between HIF1A expression and clinical outcome., Results: HIF1A expression was observed in 25/86 (29%) of diagnostic biopsies, and in 5/14 (36%) of post-RT biopsies. No significant association was noted between HIF1A expression and clinical and treatment parameters. We also failed to show a significant correlation between HIF1A overexpression and outcome. A borderline significant relationship was observed between expression of HIF1A and overall survival (OS) (HR 0.03, p=0.08)., Conclusion: To our knowledge this is the first study assessing the pattern of change of HIF1A staining in biopsies of patients prior and following treatment. While we did not find significant variations in the expression of HIF1A following radio-hormone therapy, a high HIF1A expression was unexpectedly associated with a borderline improved OS.

Purpose: The present study analyzed the expression by immunochemistry of the novel markers P21-activated protein kinase 6 (PAK6) and proteasome beta-4 subunit (PSMB4) in men with localized prostate cancer (PC) who were treated with dose-escalation radiotherapy (RT) and androgen deprivation therapy., Materials and Methods: Between 1996 and 2004, a cohort of 129 patients with PC who underwent diagnostic biopsies pretreatment and 24 to 36 months following RT were enrolled in this study. Suitable archival diagnostic tissue was obtained from 89 patients. Median follow-up was 129 months (48-198). Correlation analysis was done to assess association between PAK6 and PSMB4 expression and clinical outcome., Results: PAK6 and PSMB4 were expressed in the cytoplasm in 62% and 96.7% of diagnostic biopsies, respectively. Increased staining for PAK6 was significantly (P = 0.04) correlated with higher Gleason scores. In the multivariate analysis, the intensity of PSMB4 staining was an independent predictor of local relapse (hazard ratio = 8.6, P = 0.04)., Conclusions: To our knowledge, this is the first description of PAK6 and PSMB4 expression in the diagnostic specimens of men with PC who were treated with RT. If confirmed by further studies, increased expression of these genes could be used to identify patients at a high risk of developing local failure following high-dose RT, thus better tailoring treatments for the individual patient., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In this work, a reliable methodology for the simultaneous analysis of PCDD/PCDF and dioxin-like PCB (dl-PCB) in flue gas emissions collected using continuous sampling devices is proposed. The analytical scheme followed the minimum requirements described in the EU standard EN-1948:1,2,3,4 according to samples containing large amounts of dioxins and dl-PCBs or samples collected over a long period of time of about 4 weeks. Parameters, such as reproducibility, precision, limits of detection (LOD), limits of quantification (LOQ), extract aliquot size, analytical blanks, extraction efficiency, as well as the amount of internal standards required for an accurate determination, were assessed. The findings demonstrate the suitability of the proposed analytical scheme for the analysis of PCDD/PCDF and PCB in samples collected using long-term sampling devices. The analysis of five different 5% v/v sample aliquots reported %RSD values lower than 10% for all of the 29 congeners at both low and high levels. Similarly, %RSD values were 3.2 and 2.0 for the low level samples and 0.9 and 1.1%RSD for the high level extracts for PCDD/PCDF and dl-PCB, respectively expressed in total TEQ units. Re-extraction provided values less than 3%, expressed in TEQ. Based on blank analyses, LOD values of 100 pg I-TEQ for PCDD/PCDF and 10 pg WHO-TEQ for dl-PCB were achieved when 5% v/v aliquots were analyzed. Finally, the proposed analytical approach was tested with samples from a wide range of combustion processes such as hazardous and municipal waste incinerators, as well as cement kilns (with and without waste co-incineration)., (Copyright © 2012 Elsevier B.V. All rights reserved.)

KRAS mutation status is being used as the sole biomarker to predict therapeutic efficacy of cetuximab in metastatic colorectal cancer (mCRC). A significant number of mCRC patients with KRAS wild-type (WT) tumors, however, do not benefit from cetuximab. We are also lacking efficacy predictors in head and neck squamous cell carcinomas with an intact KRAS signaling and in non-small cell lung cancer in which KRAS mutations do not predict cetuximab efficacy. We recently established pre-clinical models of EGFR gene-amplified KRAS WT A431 squamous carcinoma cells chronically adapted to grow in the presence of cetuximab. We employed the ingenuity pathway analysis software to functionally interpret data from Agilent's whole human genome arrays in the context of biological processes, networks, and pathways. Cetuximab-induced activation of the interferon (IFN)/STAT1 appeared to switch from 'growth inhibitory' in acutely-treated cells to 'pro-survival' in chronically-adapted cells. Cetuximab treatment appeared to negatively select initially dominant IFN-sensitive clones and promoted selection of IFN- and cetuximab-refractory tumor clones constitutively bearing an up-regulated IFN/STAT1 signaling. High-levels of mRNAs coding for the EGFR ligands amphiregulin (AREG), epiregulin (EREG), and neuregulin-1/heregulin (NRG1) predicted for acute cetuximab's functioning. Chronic cetuximab, however, appeared to negatively select initially dominant AREG/EREG/NRG1-positive clones to promote selection of cetuximab-refractory clones exhibiting a knocked-down neuregulin signaling. Our current evolutionary mapping of the transcriptomic changes that occur during cetuximab-induced chronic blockade of EGFR/KRAS WT signaling strongly suggests that mRNAs coding for IFN/STAT1- and EGFR ligands-related genes can be evaluated as novel predictors of efficacy in KRAS WT squamous cancer patients being treated with cetuximab.

Aims: Amplification of the human epidermal growth factor receptor 2 (HER2) gene has been reported in gastric carcinoma (GC). Accordingly, trastuzumab plus chemotherapy has recently become the new standard treatment for HER2-positive advanced GCs. The aim was to compare the alleged gold standard for hybridization [fluorescence in-situ hybridization (FISH)] with a novel, fully automated brightfield dual-colour silver-enhanced in-situ hybridization (SISH) method., Methods and Results: The studies series was comprised of 166 GC samples. Additionally, tumours with discordant results obtained by FISH and SISH were analysed by real-time quantitative polymerase chain reaction (PCR) with the LightMix kit HER-2/neu. Of the samples, 17.5% and 21% were amplified by FISH and SISH, respectively. Heterogeneity was identified in up to 52% of cases. In 96.4% of cases, FISH showed the same results as SISH. All six discordant cases were positive by SISH and negative by FISH. On review of the FISH slides, all contradictory cases were polysomic and were confirmed to be negative for amplification by real-time PCR. Interestingly, all ratios in this latter group were between 2.06 and 2.50, so setting the cut-off for amplification at ≥3 resulted in perfect concordance., Conclusions: Dual-colour SISH represents a novel method for the determination of HER2 status in GC., (© 2011 Blackwell Publishing Limited.)

Proton magnetic resonance spectroscopic imaging ((1) H-MRSI) has been advocated as a valuable tool for prostate cancer diagnosis. However, a barrier to widespread clinical use of this technique is the lack of robust quantification methods that yield reproducible results in an institution-independent manner. The main goal of this study was to develop a standardized and fully automated approach (LCModel-based) for quantitative prostate (1) H-MRSI. To this end, a dedicated basis set was constructed by the combination of simulated (citrate, Cit; choline, Cho, and creatine, CR) and experimentally acquired (spermine, Spm) spectra. The overlapping Spm, Cho, and Cr could be resolved and quantified individually, thus allowing for the independent assessment of glandular (Cit and Spm) and proliferative (Cho) components. Several metabolite ratios were calculated and compared to the histologic findings of prostatectomy specimens from 10 prostate cancer patients with Gleason scores (3 + 3) and (3 + 4). The Cho mole fraction and the Cho/(Cit + Spm) ratio were found to best discriminate between prostate cancer and healthy tissue. The comparison between the quantitative MRSI results and the histologic findings suggests that no correlation exists between the detected metabolic alterations and the Gleason score of low-grade tumors., (Copyright © 2010 Wiley-Liss, Inc.)

The aim of this work is to evaluate the performance of a continuous monitoring system for the analysis of the mass concentration of PCDD/Fs from stationary sources. Data was acquired from a modern, state of the art, hazardous waste thermal treatment plant for a period of more than 2 years using a commercial available continuous monitoring system. The study consisted of a total of 16 samples, collected in periods from 1 week to 2 months resulting in an average of 360 m³ sampled flue gas per sample. The study showed the system was able to confirm that for a period of more than 2 years the plant was complying with the limit of 0.1 ng I-TEQ/Nm(3). In addition, the data showed the typical fingerprint of such installations which is useful for example in impact studies. Long-term samples were compared to five short-term samples (6 h) collected every 6 months during the study period. Principal component analysis was applied to PCDD/Fs obtained data as useful statistical tool to find out trends and similarities between different samples. Improvement in terms of representativeness of data was achieved through continuous assessment since the starts of the project. The obtained data was further used to determine the emission factor for this activity and the total annual PCDD/Fs release to the atmosphere., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The aim of this study was to explore the possible involvement of the angiopoietin (Ang)-1, -2/Tie-2 system in the development, growth, and metastases evolution of gastroenteropancreatic-neuroendocrine tumors (GEP-NETs). We prospectively examined the serum levels of Tie-2, Ang-1, and Ang-2 by ELISA in 42 patients with proven GEP-NETs and 27 controls. We also determined the expression of the Ang/Tie-2 system in freshly isolated peripheral blood monocytes and in tumor cells from malignant primary tumors and/or liver metastases samples from GEP-NET patients by flow cytometry and/or RT-PCR. Furthermore, the function of the Ang/Tie-2 system in monocytes from controls and patients was assessed by a chemotaxis assay. GEP-NET patients showed enhanced serum levels of soluble form of Tie-2 (sTie-2), Ang-1, and Ang-2 (P<0.05 in all cases), compared to controls. sTie-2 and Ang-2 levels were significantly higher in GEP-NETs with metastases compared to those with no metastases. In addition, a significant correlation was detected between Ang-2 levels and chromogranin A or sTie-2 concentrations or 5-hydroxy-indole acetic acid excretion (r=0.71, r=0.60, and r=0.81 respectively, P<0.01 in all cases). Furthermore, we observed an enhanced expression of Ang-1, Ang-2, and Tie-2 in freshly isolated tumor cells from GEP-NET both by immunohistochemistry and by RT-PCR. Interestingly, an enhanced expression and function of Tie-2 was detected in monocytes from GEP-NET patients. Our data suggest that the Ang/Tie-2 system is involved in the growth and development of metastases of GEP-NETs, and that favors the recruitment of Tie-2(+) monocytes to the tumor site, where they can promote inflammation and angiogenesis.