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Background: Chemotherapy-induced peripheral neuropathy (CIPN) continues to be a substantial problem for many cancer patients. Pursuant to promising appearing pilot data, the current study evaluated the use of vitamin E for the prevention of CIPN.Methods: A phase III, randomized, double-blind, placebo-controlled study was conducted in patients undergoing therapy with neurotoxic chemotherapy, utilizing twice daily dosing of vitamin E (400 mg)/placebo. The primary endpoint was the incidence of grade 2+ sensory neuropathy (SN) toxicity (CTCAE v 3.0) in each treatment arm, analyzed by chi-square testing. Planned sample size was 100 patients per arm to provide 80% power to detect a difference in incidence of grade 2+ SN toxicity from 25% in the placebo group to 10% in the vitamin E group.Results: Two-hundred seven patients were enrolled between December 1, 2006 and December 14, 2007, producing 189 evaluable cases for analysis. Cytotoxic agents included taxanes (109), cisplatin (8), carboplatin (2), oxaliplatin (50), or combination (20). There was no difference in the incidence of grade 2+ SN between the two arms (34%-vitamin E, 29%-placebo; P = 0.43). There were no significant differences between treatment arms for time to onset of neuropathy (P = 0.58), for chemotherapy dose reductions due to neuropathy (P = 0.21), or for secondary endpoints derived from patient-reported neuropathy symptom assessments. The treatment was well tolerated overall.Conclusions: Vitamin E did not appear to reduce the incidence of sensory neuropathy in the studied group of patients receiving neurotoxic chemotherapy. [ABSTRACT FROM AUTHOR]

Abstract Background Aneuploidy has long been recognized to be associated with cancer. A growing body of evidence suggests that tumorigenesis, the formation of new tumors, can be attributed to some extent to errors occurring at the mitotic checkpoint, a major cell cycle control mechanism that acts to prevent chromosome missegregation. However, so far no statistical model has been available quantify the role aneuploidy plays in determining cancer. Methods We develop a statistical model for testing the association between aneuploidy loci and cancer risk in a genome-wide association study. The model incorporates quantitative genetic principles into a mixture-model framework in which various genetic effects, including additive, dominant, imprinting, and their interactions, are estimated by implementing the EM algorithm. Results Under the new model, a series of hypotheses tests are formulated to explain the pattern of the genetic control of cancer through aneuploid loci. Simulation studies were performed to investigate the statistical behavior of the model. Conclusions The model will provide a tool for estimating the effects of genetic loci on aneuploidy abnormality in genome-wide studies of cancer cells.

Abstract Background Contemporary biological research integrates neighboring scientific domains to answer complex questions in fields such as systems biology and drug discovery. This calls for tools that are intuitive to use, yet flexible to adapt to new tasks. Results Bioclipse is a free, open source workbench with advanced features for the life sciences. Version 2.0 constitutes a complete rewrite of Bioclipse, and delivers a stable, scalable integration platform for developers and an intuitive workbench for end users. All functionality is available both from the graphical user interface and from a built-in novel domain-specific language, supporting the scientist in interdisciplinary research and reproducible analyses through advanced visualization of the inputs and the results. New components for Bioclipse 2 include a rewritten editor for chemical structures, a table for multiple molecules that supports gigabyte-sized files, as well as a graphical editor for sequences and alignments. Conclusion Bioclipse 2 is equipped with advanced tools required to carry out complex analysis in the fields of bio- and cheminformatics. Developed as a Rich Client based on Eclipse, Bioclipse 2 leverages on today's powerful desktop computers for providing a responsive user interface, but also takes full advantage of the Web and networked (Web/Cloud) services for more demanding calculations or retrieval of data. The fact that Bioclipse 2 is based on an advanced and widely used service platform ensures wide extensibility, making it easy to add new algorithms, visualizations, as well as scripting commands. The intuitive tools for end users and the extensible architecture make Bioclipse 2 ideal for interdisciplinary and integrative research. Bioclipse 2 is released under the Eclipse Public License (EPL), a flexible open source license that allows additional plugins to be of any license. Bioclipse 2 is implemented in Java and supported on all major platforms; Source code and binaries are freely available at http://www.bioclipse.net.

Abstract Single nucleotide polymorphisms (SNPs) represent the most widespread type of DNA sequence variation in the human genome and they have recently emerged as valuable genetic markers for revealing the genetic architecture of complex traits in terms of nucleotide combination and sequence. Here, we extend an algorithmic model for the haplotype analysis of SNPs to estimate the effects of genetic imprinting expressed at the DNA sequence level. The model provides a general procedure for identifying the number and types of optimal DNA sequence variants that are expressed differently due to their parental origin. The model is used to analyze a genetic data set collected from a pain genetics project. We find that DNA haplotype GAC from three SNPs, OPRKG36T (with two alleles G and T), OPRKA843G (with alleles A and G), and OPRKC846T (with alleles C and T), at the kappa-opioid receptor, triggers a significant effect on pain sensitivity, but with expression significantly depending on the parent from which it is inherited (p = 0.008). With a tremendous advance in SNP identification and automated screening, the model founded on haplotype discovery and statistical inference may provide a useful tool for genetic analysis of any quantitative trait with complex inheritance.

Background: Approximately 50% of patients with congenital scoliosis will require surgical treatment to prevent further progression. Outcomes following congenital scoliosis are sparse in the literature. The purpose of this study was to identify independent risk factors associated with unplanned readmission and prolonged length of stay (LOS) in patients undergoing primary surgical treatment for congenital scoliosis., Methods: The National Surgical Quality Improvement Database-Pediatric was queried for database years 2016-2018 to identify patients with congenital scoliosis who underwent primary posterior fusion of the spine. Patient demographics, comorbidities, and operative variables, such as the number of levels fused and the American Society of Anesthesiologists (ASA) classificaiton, were collected. Univariate and multivariate analyses of patient factors were performed to test for association with readmission within 30 days and prolonged LOS (>4 days)., Results: Eight hundred sixteen patients were identified. The average age was 11.3 ± 4.02 years, and the mean postoperative LOS was 4.64 ± 3.71 days. Forty-three patients (5.40%) were readmitted, and 73 patients (8.96%) had prolonged LOS. Independent risk factors associated with prolonged LOS included chronic lung disease ( P < 0.001), presence of a tracheostomy ( P < 0.001), structural central nervous system abnormality ( P = 0.039), oxygen support ( P < 0.001), and number of levels fused ( P = 0.008). The factors independently associated with unplanned readmission were fusion to the pelvis ( P = 0.004) and LOS >4 days ( P = 0.008)., Conclusions: Prolonged LOS and readmission are widely being used as quality and performance metrics for hospitals. Congenital scoliosis, which often progresses rapidly resulting in significant deformity, frequently requires surgery at an earlier age than idiopathic and neuromuscular deformity. Nevertheless, 30-day outcomes for surgical intervention have not been thoroughly studied. The present study identifies risk factors for prolonged LOS and readmission, which can facilitate preoperative planning, patient/family counseling, and postoperative care., Clinical Relevance: Congenital scoliosis management poses certain challenges that may be mitigated by understanding the risk factors for adverse outcomes following primary fusion surgery., Competing Interests: Declaration of Conflicting Interests : The authors report no conflicts of interest in this work., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2024 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Background: The Internet is an important source of information for patients, but its effectiveness relies on the readability of its content. Patient education materials (PEMs) should be written at or below a sixth-grade reading level as outlined by agencies such as the American Medical Association. This study assessed PEMs' readability for the novel anterior vertebral body tethering (AVBT), distraction-based methods, and posterior spinal fusion (PSF) in treating pediatric spinal deformity., Methods: An online search identified PEMs using the terms "anterior vertebral body tethering," "growing rods scoliosis," and "posterior spinal fusion pediatric scoliosis." We selected the first 20 general medical websites (GMWs) and 10 academic health institution websites (AHIWs) discussing each treatment (90 websites total). Readability tests for each webpage were conducted using Readability Studio software. Reading grade levels (RGLs), which correspond to the US grade at which one is expected to comprehend the text, were calculated for sources and independent t tests compared with RGLs between treatment types., Results: The mean RGL was 12.1 ± 2.0. No articles were below a sixth-grade reading level, with only 2.2% at the sixth-grade reading level. AVBT articles had a higher RGL than distraction-based methods (12.7 ± 1.6 vs 11.9 ± 1.9, P = 0.082) and PSF (12.7 ± 1.6 vs 11.6 ± 2.3, P = 0.032). Materials for distraction-based methods and PSF were comparable (11.9 ± 1.9 vs 11.6 ± 2.3, P = 0.566). Among GMWs, AVBT materials had a higher RGL than distraction-based methods (12.9 ± 1.4 vs 12.1 ± 1.8, P = 0.133) and PSF (12.9 ± 1.4 vs 11.4 ± 2.4, P = 0.016)., Clinical Relevance: Patients' health literacy is important for shared decision-making. Assessing the readability of scoliosis treatment PEMs guides physicians when sharing resources and discussing treatment with patients., Conclusion: Both GMWs and AHIWs exceed recommended RGLs, which may limit patient and parent understanding. Within GMWs, AVBT materials are written at a higher RGL than other treatments, which may hinder informed decision-making and patient outcomes. Efforts should be made to create online resources at the appropriate RGL. At the very least, patients and parents may be directed toward AHIWs; RGLs are more consistent., Competing Interests: Declaration of Conflicting Interests : The authors report no conflicts of interest in this work., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2024 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Background: Posterior cervical decompression with or without fusion (PCD/F) is used to manage degenerative spinal conditions. Malnutrition has been implicated for poor outcomes in spine surgery. The aim of this study was to assess the ability of the Geriatric Nutritional Risk Index (GNRI) as a risk calculator for postoperative complications in patients undergoing PCD/F., Methods: The 2006 to 2018 American College of Surgeons National Surgery Quality Improvement Program Database was queried for patients undergoing PCD/F. Nutritional status was categorized as normal (GNRI greater than 98), moderately malnourished (GNRI 92-98), or severely malnourished (GNRI less than or equal to 92). Complications within 30 days of surgery were compared among the groups. Preoperative data that were statistically significant ( P < 0.05) upon univariate χ 2 analysis were included in the univariate then multivariate binary regression model to calculate adjusted ORs. All ORs were assessed at the 95% CI., Results: Of the 7597 PCD/F patients identified, 15.6% were severely malnourished and 19.1% were moderately malnourished. Severe and moderate malnourishment were independent risk factors for mortality (OR = 3.790, 95% CI 2.492-5.763, P < 0.001; OR = 2.150, 95% CI 1.351-3.421, P = 0.011). Severe malnourishment was an independent risk factor for sepsis/septic shock (OR = 3.448, 95% CI 2.402-4.948, P < 0.001)., Conclusions: In elderly patients undergoing PCD/F, severe malnutrition, as defined by the GNRI, was an independent risk factor for mortality and sepsis/septic shock., Clinical Relevance: The GNRI may be more useful than other indices for risk stratification in elderly patients because it accounts for confounding variables such as hydration status and paradoxical malnourishment in obese patients., Competing Interests: Declaration of Conflicting Interests : The authors report no conflicts of interest in this work., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2023 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Background: s: Psoriasis is a disease of systemic inflammation associated with increased cardiometabolic risk. Epicardial adipose tissue (EAT) and thoracic adipose tissue (TAT) are contributing factors for atherosclerosis and cardiac dysfunction. We strove to assess the longitudinal impact of the EAT and TAT on coronary and cardiac characteristics in psoriasis., Methods: The study consisted of 301 patients with baseline coronary computed tomography angiography (CTA), of which 139 had four-year follow up scans. EAT and TAT volumes from non-contrast computed tomography scans were quantified by an automated segmentation framework. Coronary plaque characteristics and left ventricular (LV) mass were quantified by CTA., Results: When stratified by baseline EAT and TAT volume quartiles, a stepwise significant increase in cardiometabolic parameters was observed. EAT and TAT volumes associated with fibro-fatty burden (FFB) (TAT: ρ = 0.394, P < 0.001; EAT: ρ = 0.459, P < 0.001) in adjusted models. Only EAT had a significant four-year time-dependent association with FFB in fully adjusted models (β = 0.307 P = 0.003), whereas only TAT volume associated with myocardial injury in fully adjusted models (TAT: OR = 1.57 95 % CI = (1.00-2.60); EAT: OR = 1.46 95 % CI = (0.91-2.45). Higher quartiles of EAT and TAT had increased LV mass and developed strong correlation (TAT: ρ = 0.370, P < 0.001; EAT: ρ = 0.512, P < 0.001)., Conclusions: Our study is the first to explore how both EAT and TAT volumes associate with increased cardiometabolic risk profile in an inflamed psoriasis cohorts and highlight the need for further studies on its use as a potential prognostic tool for high-risk coronary plaques and cardiac dysfunction., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Dr. Sorokin is a full-time US government employee., (© 2023 The Authors. Published by Elsevier Ltd.)

APOA-1 is central to the high-density lipoprotein function of reverse cholesterol transport measured by cholesterol efflux capacity. Psoriasis is a systemic inflammatory disease associated with poor cholesterol efflux capacity and accelerated noncalcified coronary burden (NCB) as measured by coronary computed tomographic angiography. In this study, we characterized the relationship between APOA-1, cholesterol efflux capacity, and progression of NCB over 4 years. Consecutively recruited participants with psoriasis underwent coronary computed tomographic angiography for NCB quantification (Medis QAngio, Leiden, The Netherlands) at baseline (n = 310) and at four years (n = 124). Blood was assessed for cardiometabolic biomarkers. The lowest quartile of APOA-1 was associated with cardiometabolic blood markers (insulin, homeostatic model assessment for insulin resistance, and cholesterol efflux capacity) and higher NCB (P < 0.001). The low APOA-1 quartile had higher NCB at 4 years (β = -0.36, P = 0.02) in fully adjusted models. Finally, a 10-unit decrease of APOA-1 was associated with a 16% increase in NCB progression over 4 years (OR = 0.83, 95% confidence interval = 0.70-0.99, P = 0.04). In addition to being associated with cardiometabolic disease, low APOA-1 was associated with more NCB over time. These findings show that low APOA-1 is correlated with initiation and progression of coronary artery disease and may have clinical utility in identifying high-risk populations for development of cardiovascular disease., (Published by Elsevier Inc.)

Background: For patients with back pain from osteoporotic vertebral compression fractures (VCFs), vertebral augmentation remains the most utilized surgical intervention. Previous studies report 30-day readmission and mortality rates of up to 10% and 2%, respectively. These studies, however, have included patients with pathologic fractures and combined patients in different admission settings. We undertook the current study to address such shortcomings, which make risk stratification and appropriate counseling difficult., Methods: Four consecutive years of the National Surgical Quality Improvement Program database were queried. Patients who underwent vertebral augmentation for osteoporotic VCFs were divided into 3 groups: (1) outpatient group (defined as patients with same-day discharge), (2) inpatient group (defined as those who were admitted postoperatively), and (3) preprocedure hospitalized group (defined as those who were already inpatient or were at acute/intermediate care facilities and transferred). Postoperative 30-day complications and readmission rates were compared between different groups and examined using multivariate analyses., Results: A total of 1023 patients underwent outpatient surgery; 503 were admitted on the day of surgery; and 149 patients were already in-hospital or were transferred from other facility. Mortality rates were 0.68%, 0.60%, and 2.68%, and readmission rates were 6.26%, 6.76%, and 12.8%, for outpatient, inpatient, and preprocedure hospitalization cohorts, respectively. Multivariate analyses identified preprocedure hospitalization as an independent risk factor for urinary tract infection (UTI; OR = 3.98, 95% CI = 1.41-11.20, P = 0.028), pneumonia (OR = 19.69, 95% CI = 3.81-101.65, P < 0.001), readmission (OR = 1.86, 95% CI = 1.06-3.26, P = 0.032), and mortality (OR = 4.49, 95% CI = 1.22-16.53, P = 0.024)., Conclusion: Our findings suggest that published rates of complications and mortality are substantially impacted by the cohort of patients who are already hospitalized or transferred from other facilities. Such patients are at a higher risk of UTI, pneumonia, readmission, and mortality. Conversely, we show that a relatively healthy patient being offered outpatient same-day augmentation has a readmission risk 40% lower and a mortality risk 3 times lower than previously reported., Competing Interests: Declaration of Conflicting Interests : The authors report no conflicts of interest in this work., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2023 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Competing Interests: Conflicts of interest Dr Mehta is a full-time US government employee and has served as a consultant for Amgen, Eli Lilly, and Leo Pharma, receiving grants/other payments; as a principal investigator and/or investigator for AbbVie, Celgene, Janssen Pharmaceuticals, Inc, and Novartis receiving grants and/or research funding; and as a principal investigator for the National Institute of Health receiving grants and/or research funding. Dr González- Cantero has served as a consultant for AbbVie, Janssen, Novartis, Almirall, Celgene, and Leo Pharma receiving grants/other payments. All other authors have no disclosures to report.

Purpose: To assess the efficacy and safety of intrawound antibiotics in posterior fusions for adolescent idiopathic scoliosis (AIS)., Methods: The NSQIP-Pediatric databases 2016-2018 were utilized. Patients 10 years of age or older with AIS who underwent posterior fusion were selected and divided into two cohorts based on the receipt of intrawound antibiotics. Patient characteristics and complications were compared. Multivariate analyses were performed to determine the efficacy and safety of intrawound antibiotics., Results: A total of 4203 patients received intrawound antibiotics while 879 patients did not. The intrawound antibiotic group had longer constructs, higher blood loss, and longer operative times, factors historically associated with higher infection rates. Those that received intrawound antibiotics had SSI rate of 0.69%, while its counterpart had 0.57% (p = 0.689). The reoperation rates were 1.12% and 1.25% (p = 0.735), for those with and without intrawound antibiotics, respectively. In multivariate analyses, intrawound antibiotics use was not found to be a significant predictor for SSI, any complications, reoperation and readmission., Conclusion: The current study represents the largest AIS surgery cohort studied to evaluate the efficacy of intrawound antibiotics. Our analysis failed to demonstrate association between the use of intrawound antibiotics and reduction in SSI. While other studies have reported seroma, wound dehiscence and renal failure with the practice, we did not observe an increased rate of such complications. This study highlights the difficulty of understanding the role for individual infection prevention measures in current surgical settings, where the SSI rate for the control group was substantially lower than 1%., (© 2022. The Author(s), under exclusive licence to Scoliosis Research Society.)

Background and Objective: Psoriasis is a systemic inflammatory condition with poor cholesterol transport measured by cholesterol efflux capacity (CEC) that is associated with a heightened risk of cardiovascular disease (CVD). In psoriasis patients, we sought to characterize the lipoprotein profile by size using a novel nuclear magnetic resonance algorithm in patients with low CEC compared to normal CEC., Methods: Lipoprotein profile was assessed using the novel nuclear magnetic resonance LipoProfile-4 deconvolution algorithm. Aortic vascular inflammation (VI) and non-calcified burden (NCB) were characterized via positron emission tomography-computed tomography and coronary computed tomography angiography. To understand the relationship between lipoprotein size and markers of subclinical atherosclerosis, linear regression models controlling for confounders were constructed., Results: Psoriasis patients with low CEC had higher more severe psoriasis ( p = 0.04), VI ( p = 0.04) and NCB ( p = 0.001), concomitant with smaller high-density lipoprotein (HDL) ( p < 0.001) and low-density lipoprotein (LDL) particles ( p < 0.001). In adjusted models HDL size ( β = -0.19; p = 0.02) and LDL size ( β = -0.31; p < 0.001) associated with VI and NCB. Lastly, HDL size strongly associated with LDL size in fully adjusted models ( β = -0.27; p < 0.001)., Conclusion: These findings demonstrate that in psoriasis, low CEC associates with a lipoprotein profile comprised of smaller HDL and LDL particles which correlates with vascular health and may be driving early onset atherogenesis. Further, these results demonstrate a relationship between HDL and LDL size and provide novel insights into the complexities of HDL and LDL as biomarkers of vascular health., Competing Interests: NM has served as a consultant for Amgen, Eli Lilly, and Leo Pharma receiving grants/other payments; as a principal investigator and/or investigator for AbbVie, Celgene, Janssen Pharmaceuticals, Inc., and Novartis receiving grants and/or research funding. AG-C has served as a consultant for Abbie, Janssen, Novartis, Almirall, Celgene and Leo Pharma receiving grants/other payments. TThe remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Berg, Petrole, Li, Sorokin, Gonzalez-Cantero, Playford, Mehta and Teague.)

Psoriasis is a systemic inflammatory disease with an increased risk of atherosclerotic events and premature cardiovascular disease. S100A7, A8/A9, and A12 are protein complexes that are produced by activated neutrophils, monocytes, and keratinocytes in psoriasis. Lipid-rich necrotic core (LRNC) is a high-risk coronary plaque feature previously found to be associated with cardiovascular risk factors and psoriasis severity. LRNC can decrease with biologic therapy, but how this occurs remains unknown. We investigated the relationship between S100 proteins, LRNC, and biologic therapy in psoriasis. S100A8/A9 associated with LRNC in fully adjusted models (β = 0.27, P = 0.009; n = 125 patients with psoriasis with available coronary computed tomography angiography scans; LRNC analyses; and serum S100A7, S100A8, S100A9, S100A12, and S100A8/A9 levels). At 1 year, in patients receiving biologic therapy (36 of 73 patients had 1-year coronary computed tomography angiography scans available), a 79% reduction in S100A8/A9 levels (‒172 [‒291.7 to 26.4] vs. ‒29.9 [‒137.9 to 50.5]; P = 0.04) and a 0.6 mm 2 reduction in average LRNC area (0.04 [‒0.48 to 0.77] vs. ‒0.56 [‒1.8 to 0.13]; P = 0.02) were noted. These results highlight the potential role of S100A8/A9 in the development of high-risk coronary plaque in psoriasis., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Metabolic conditions such as obesity and associated comorbidities are increasing in prevalence worldwide. In chronically inflamed pathologies, metabolic conditions are linked to early onset cardiovascular disease, which remains the leading cause of death despite decades of research. In recent years, studies focused on the interdependent pathways connecting metabolism and the immune response have highlighted that dysregulated cholesterol trafficking instigates an overactive, systemic inflammatory response, thereby perpetuating early development of cardiovascular disease. In this review, we will discuss the overlapping pathways connecting cholesterol trafficking with innate immunity and present evidence that cholesterol accumulation in the bone marrow may drive systemic inflammation in chronically inflamed pathologies. Lastly, we will review the current therapeutic strategies that target both inflammation and cholesterol transport, and how biologic therapy restores lipoprotein function and mitigates the immune response., Competing Interests: NM is a full-time US government employee and has served as a consultant for Amgen, Eli Lilly, and Leo Pharma, receiving grants/other payments; as a principal investigator and/or investigator for AbbVie, Celgene, Janssen Pharmaceuticals, Inc, Novartis, and AstraZeneca receiving grants and/or research funding; and as a principal investigator for the National Institute of Health receiving grants and/or research funding. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 O’Hagan, Berg, Hong, Parel, Mehta and Teague.)

Background: The use of the direct anterior approach, a muscle-sparing technique for THA, has increased over the years; however, this approach is associated with longer procedure times and a more expensive direct cost. Furthermore, studies have shown a higher revision rate in the early stages of the learning curve. Whether the clinical advantages of the direct anterior compared with the posterior approach-such as less soft tissue damage, decreased short-term postoperative pain, a lower dislocation rate, decreased length of stay in the hospital, and higher likelihood of being discharged home-outweigh the higher cost is still debatable. Determining the cost-effectiveness of the approach may inform its utility and justify its use at various stages of the learning curve., Questions/purposes: We used a Markov modeling approach to ask: (1) Is the direct anterior approach more likely to be a cost-effective approach than the posterior approach over the long-term for more experienced or higher volume hip surgeons? (2) How many procedures does a surgeon need to perform for the direct anterior approach to be a cost-effective choice?, Methods: A Markov model was created with three health states (well-functioning THA, revision THA, and death) to compare the cost-effectiveness of the direct anterior approach with that of the posterior approach in five scenarios: surgeons who performed one to 15, 16 to 30, 31 to 50, 51 to 100, and more than 100 direct anterior THAs during a 6-year span. Procedure costs (not charges), dislocation costs, and fracture costs were derived from published reports, and model was run using two different cost differentials between the direct anterior and posterior approaches (USD 219 and USD 1800, respectively). The lower cost was calculated as the total cost differential minus pharmaceutical and implant costs to account for differences in implant use and physician preference regarding postoperative pain management. The USD 1800 cost differential incorporated pharmaceutical and implant costs. Probabilities were derived from systematic review of the evidence as well as from the Australian Orthopaedic Association National Joint Replacement Registry. Utilities were estimated from best available literature and disutilities associated with dislocation and fracture were incorporated into the model. Quality of life was expressed in quality-adjusted life years (QALYs), which are calculated by multiplying the utility of a health state (ranging from 0 to 1) by the duration of time in that health state. The primary outcome measure was the incremental cost-effectiveness ratio, or the change in costs divided by the change in QALYs when the direct anterior approach was used for THA. USD 100,000 per quality-adjusted life years was used as a threshold for willingness to pay. One-way and probabilistic sensitivity analyses were performed for the scenario in which the direct anterior approach is cost-effective to further account for uncertainty in model inputs., Results: At a cost differential of USD 219 (95% CI 175 to 263), the direct anterior approach was associated with lower cost and higher effectiveness compared with the posterior approach for surgeons with an experience level of more than 100 operations during a 6-year span. At a cost differential of USD 1800 (95% CI 1440 to 2160), the direct anterior approach remained a cost-effective strategy for surgeons who performed more than 100 operations. At both cost differentials, the direct anterior approach was not cost-effective for surgeons who performed fewer than 100 operations. One-way sensitivity analyses revealed the model to be the most sensitive to fluctuations in the utility of revision THA, probability of revision after the posterior approach THA, probability of dislocation after the posterior approach THA, fluctuations in the probability of dislocation after direct anterior THA, cost of direct anterior THA, and probability of intraoperative fracture with the direct anterior approach. At the cost differential of USD 219 and for surgeons with a surgical experience level of more than 100 direct anterior operations, the direct anterior approach was still the cost-effective strategy for the entire range of values., Conclusion: For high-volume hip surgeons, defined here as surgeons who perform more than 100 procedures during a 6-year span, the direct anterior approach may be a cost-effective strategy within the limitations imposed by our analysis. For lower volume hip surgeons, performing a more familiar approach appears to be more cost-effective., Competing Interests: All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2022 by the Association of Bone and Joint Surgeons.)

Background and Objectives: Psoriasis is a heterogeneous inflammatory disease that involves the skin, joints, liver, heart, and other organs. Psoriatic arthritis (PsA) is associated with cardiovascular disease (CVD), but the relative contributions of inflammatory and metabolic dysregulation to CVD are incompletely understood. We set out to discover novel potential contributors to CVD in PsA patients by comprehensively phenotyping a cohort of PsA patients using these advanced technologies., Methods: In this cross-sectional analysis of a cohort study, we investigated associations of systemic inflammation and metabolic dysregulation with Coronary CT angiography (CCTA)-proven coronary artery disease (CAD) in 39 subjects with PsA. We measured traditional CVD risk factors [blood pressure, Body Mass Index (BMI), diabetes, age, sex, smoking], serum markers of systemic inflammation (hsCRP, GlycA) and metabolic dysfunction (cholesterol efflux capacity), and inflammatory cytokines (IL-1β, IL-6, IL-12/IL-23, IL-17A, TNF-α, IFN-γ). We also incorporated radiographic measures of metabolic dysfunction (visceral and subcutaneous adipose volume) and tissue-specific inflammation (positron emission tomography-computed tomography, PET-CT). To quantify relative contributions of FDG (fluorodeoxyglucose) uptake and adiposity to coronary plaque, we performed multiple linear regression, controlling for Framingham risk score (FRS) and FRS + visceral adiposity., Results: Compared with non-psoriatic volunteers, subjects with PsA had elevated markers of metabolic and inflammatory disease, which was more pronounced in subjects with moderate-to-severe skin disease. This included visceral (p = 0.005) and subcutaneous (p = 0.004) adiposity, BMI (p = 0.001), hemoglobin A1C (p = 0.037), high sensitivity C-reactive protein (p = 0.005), IL-6 (p = 0.003), IFN-γ (p = 0.006), and liver FDG uptake (p = 0.03). In subjects with PsA, visceral adiposity correlated significantly with subclinical CAD (standardized β = 0.681, p = 0.002), as did FDG uptake in bone marrow (standardized β = 0.488, p = 0.008), liver (standardized β = 0.619, p < 0.001), spleen (standardized β = 0.523, p = 0.004), and subcutaneous adipose (standardized β = 0.524, p = 0.003)., Interpretation: Together, these findings reveal inflammatory and metabolic potential contributors to subclinical CAD in PsA, including adipose inflammation, and suggesting novel targets for CVD prevention and treatment in PsA., Competing Interests: NM has served as a consultant for Amgen, Eli Lilly, and Leo Pharma, receiving grants and other payments. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Schwartz, Parel, Li, Sorokin, Berg, Chen, Dey, Hong, Playford, Sylvester, Teague, Siegel and Mehta.)

Purpose of Review: In this review, we focus on the clinical and epidemiological studies pertaining to systemic and vascular inflammation by positron emission tomography (PET) in patients with chronic inflammatory conditions such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV), and psoriasis to highlight the importance of chronic systemic inflammation on vascular inflammation by PET in these disease states., Recent Findings: Recent clinical and translation advancements have demonstrated the durable relationship between chronic systemic inflammation and cardiovascular disease (CVD). In chronic inflammatory states, this relationship is robustly evident in the form of increased vascular inflammation, yet traditional risk estimates often underestimate the subclinical cardiovascular risk conferred by chronic inflammation. PET has emerged as a novel, non-invasive imaging modality capable of both quantifying the degree of systemic and vascular inflammation and detecting residual inflammation prior to cardiovascular events. We begin by demonstrating the role of inflammation in the pathogenesis of atherosclerosis, discussing how PET has been utilized to measure systemic and vascular inflammation and their effect on subclinical atherosclerosis, and finally reviewing recent applications of PET in constructing improved risk stratification for patients at high risk for stroke and CVD., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

(1) Background: Giant Cell Tumor of the spine remains a difficult tumor to treat. Recent advances in adjuvant therapy such as denosumab and innovations in surgical technique in the last 5 years have given providers new options for treatment after a successful diagnosis of the tumor. (2) Methods: Articles published between 1927 and 2021 were selected from PubMed and Scopus searches using key words "Giant Cell Tumor" AND "Lumbar Spine" AND "Treatment". Relevant articles were reviewed and selected by the authors. (3) Results: A total of 191 articles were discovered. Complete en bloc spondylectomy remains the most definitive treatment option; however, this surgery is challenging and carries a high rate of complication. New adjuvant therapies including denosumab offer a viable alternative to surgery. (4) En bloc spondylectomy remains the gold standard treatment for Giant Cell Tumor of the spine with the lowest published recurrence rate. The use of (neo)adjuvant denosumab improves recurrence rates. More data are needed to determine if denosumab alone is a viable standalone definitive treatment.

Organic microfossils in Meso- and Neoproterozoic rocks are of key importance to track the emergence and evolution of eukaryotic life. An increasing number of studies combine Raman spectroscopy with synchrotron-based methods to characterize these microfossils. A recurring observation is that Raman spectra of organic microfossils show negligible variation on a sample scale and that variation between different samples can be explained by differences in thermal maturation or in the biologic origin of organic precursor material. There is a paucity of work, however, that explores the extent to which the petrographic framework and diagenetic processes might influence the chemical structure of organic materials. We present a detailed Raman spectroscopy-based study of a complex organic microfossil assemblage in the ca. 1 Ga old Angmaat Formation, Baffin Island, Canada. This formation contains abundant early diagenetic chert that preserves silicified microbial mats with numerous, readily identifiable organic microfossils. Individual chert beds show petrographic differences with discrete episodes of cementation and recrystallization. Raman spectroscopy reveals measurable variation of organic maturity between samples and between neighboring organic microfossils of the same taxonomy and taphonomic state. Scanning transmission X-ray microscopy performed on taphonomically similar coccoidal microfossils from the same thin section shows distinct chemical compositions, with varying ratios of aromatic compounds to ketones and phenols. Such observations imply that geochemical variation of organic matter is not necessarily coupled to thermal alteration or organic precursor material. Variation of the Raman signal across single samples is most likely linked to the diagenetic state of analyzed materials and implies an association between organic preservation and access to diagenetic fluids. Variation in the maturity of individual microfossils may be a natural outcome of local diagenetic processes and potentially exceeds differences derived from precursor organic material. These observations stress the importance of detailed in situ characterization by Raman spectroscopy to identify target specimens for further chemical analysis., (© 2021 John Wiley & Sons Ltd.)

Case: Tarsal-carpal coalition syndrome (TCCS) is a disorder identified by fusion of the carpals, tarsals, and phalanges of the hands and feet. We describe a case of an 11-year-old girl who has been followed at our outpatient clinic from the age of 8 months., Conclusion: Although patients with TCCS can experience a wide range of symptoms, the primary complaint arises from the foot deformity and associated pain. Using advanced imaging such as 3D computed tomography reconstruction and genetic testing, this report details the clinical, genetic, and radiographic characteristics of the disorder. We highlight the natural progression and symptomatic management of TCCS., Competing Interests: Disclosure:TheDisclosure of Potential Conflicts of Interestforms are provided with the online version of the article (http://links.lww.com/JBJSCC/B685)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

The medial prefrontal cortex (mPFC) steers goal-directed actions and withholds inappropriate behavior. Dorsal and ventral mPFC (dmPFC/vmPFC) circuits have distinct roles in cognitive control, but underlying mechanisms are poorly understood. Here we use neuroanatomical tracing techniques, in vitro electrophysiology, chemogenetics and fiber photometry in rats engaged in a 5-choice serial reaction time task to characterize dmPFC and vmPFC outputs to distinct thalamic and striatal subdomains. We identify four spatially segregated projection neuron populations in the mPFC. Using fiber photometry we show that these projections distinctly encode behavior. Postsynaptic striatal and thalamic neurons differentially process synaptic inputs from dmPFC and vmPFC, highlighting mechanisms that potentially amplify distinct pathways underlying cognitive control of behavior. Chemogenetic silencing of dmPFC and vmPFC projections to lateral and medial mediodorsal thalamus subregions oppositely regulate cognitive control. In addition, dmPFC neurons projecting to striatum and thalamus divergently regulate cognitive control. Collectively, we show that mPFC output pathways targeting anatomically and functionally distinct striatal and thalamic subregions encode bi-directional command of cognitive control.

Background: Postoperative nausea and vomiting (PONV) after surgery degrades patient experience, tolerance of pain medication, rehabilitation progress, and functional outcomes. Given the importance of early rehabilitation following total joint arthroplasty (TJA), we asked whether transdermal scopolamine is effective in reducing rates of PONV and improving functional outcomes following TJA., Methods: We retrospectively reviewed the charts of 1580 consecutive patients who underwent TJA between 2014 and 2017 and compared patients before the addition of the scopolamine patch (control group) to those after the addition (study group). Patients were given the scopolamine patch in the holding area unless contraindicated. A total of 495 patients were excluded. Charts were reviewed for PONV, demographic information, surgical time, length of stay, distance walked with physical therapy, and Visual Analog Scale pain scores. Student t-test was used to compare continuous data and chi-square was used for categorical variables., Results: The incidence of PONV was significantly lower in the study group compared to the control group (14.4% vs 29.3%, P < .0001). Patients who were given scopolamine had lower Visual Analog Scale pain scores on postoperative days (POD) 0 through 2 (P < .01), were able to walk further distances on POD 0 through 3 (P < .001), and received fewer morphine equivalents on POD 1 and 2 (P < .001). Greater morphine equivalents were received by the study group on POD 0., Conclusion: Use of a scopolamine patch was associated with significant reduction in PONV and improvement in functional outcomes following TJA. These data support the use of transdermal scopolamine as part of a multimodal, perioperative pain protocol in patients undergoing TJA., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The occurrence of microfossiliferous, early diagenetic chert in Proterozoic successions is broadly restricted to peritidal marine environments. Such coastal environments are amongst the most environmentally variable of marine environments, experiencing both enhanced evaporation and potential influx of terrestrial freshwaters. To better understand potential conditions under which silicification occurs, we focus on microfossiliferous early diagenetic chert from the Mesoproterozoic Bylot Supergroup, northern Baffin Island. Spectacular preservation of silicified microbial mats, their associated mineral phases, and the petrographic fabrics of the chert itself require that silicification occurred at the sediment-water interface, penecontemporaneously with mat growth. In some cases, silica is the primary precipitated mineral phase and is not associated with replacement of precursor mineral phases. In other cases, silica deposition includes the mimetic replacement of carbonate, gypsum, and halite mineral phases. These petrographic constraints suggest that silicification potentially occurred under a range of fluid chemistries associated with environmental variability in nearshore peritidal environments. Here we provide the first direct thermodynamic modeling of hypothetical Proterozoic seawater solutions, seawater-derived brines, and mixed seawater-freshwater solutions, and demonstrate that peritidal environments are capable of providing a wide range of fluid chemistries under which early diagenetic silica can both precipitate and replace primary mineralogical phases. Despite the thermodynamic potential for silica deposition under a wide range of fluid compositions, chert is not ubiquitous in Proterozoic nearshore environments, suggesting that the kinetics of silica polymerization exert a primary control over deposition., (© 2017 John Wiley & Sons Ltd.)

This article presents data related to the research article "Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain" (P. Moshayedi, L.R. Nih, I.L. Llorente, A.R. Berg, J. Cinkornpumin, W.E. Lowry et al., 2016) [1] and focuses on the biocompatibility aspects of the hydrogel, including its stiffness and the inflammatory response of the transplanted organ. We have developed an injectable hyaluronic acid (HA)-based hydrogel for stem cell culture and transplantation, to promote brain tissue repair after stroke. This 3D biomaterial was engineered to bind bioactive signals such as adhesive motifs, as well as releasing growth factors while supporting cell growth and tissue infiltration. We used a Design of Experiment approach to create a complex matrix environment in vitro by keeping the hydrogel platform and cell type constant across conditions while systematically varying peptide motifs and growth factors. The optimized HA hydrogel promoted survival of encapsulated human induced pluripotent stem cell derived-neural progenitor cells (iPS-NPCs) after transplantation into the stroke cavity and differentially tuned transplanted cell fate through the promotion of glial, neuronal or immature/progenitor states. The highlights of this article include: (1) Data of cell and bioactive signals addition on the hydrogel mechanical properties and growth factor diffusion, (2) the use of a design of Experiment (DOE) approach (M.W. 2 Weible and T. Chan-Ling, 2007) [2] to select multi-factorial experimental conditions, and (3) Inflammatory response and cell survival after transplantation.

Stem cell therapies have shown promise in promoting recovery in stroke but have been limited by poor cell survival and differentiation. We have developed a hyaluronic acid (HA)-based self-polymerizing hydrogel that serves as a platform for adhesion of structural motifs and a depot release for growth factors to promote transplant stem cell survival and differentiation. We took an iterative approach in optimizing the complex combination of mechanical, biochemical and biological properties of an HA cell scaffold. First, we optimized stiffness for a minimal reaction of adjacent brain to the transplant. Next hydrogel crosslinkers sensitive to matrix metalloproteinases (MMP) were incorporated as they promoted vascularization. Finally, candidate adhesion motifs and growth factors were systemically changed in vitro using a design of experiment approach to optimize stem cell survival or proliferation. The optimized HA hydrogel, tested in vivo, promoted survival of encapsulated human neural progenitor cells (iPS-NPCs) after transplantation into the stroke core and differentially tuned transplanted cell fate through the promotion of glial, neuronal or immature/progenitor states. This HA hydrogel can be tracked in vivo with MRI. A hydrogel can serve as a therapeutic adjunct in a stem cell therapy through selective control of stem cell survival and differentiation in vivo., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Human herpes virus 8 (HHV-8)-associated secondary hemophagocytic lymphohistiocytosis is a rare but critical immuno-hematological entity in immunocompetent patients. Establishing a diagnosis is challenging as is the monitoring of disease activity and therapeutic effects. We report a case of a HHV-8-associated hemophagocytic lymphohistiocytosis in a HIV-negative adult patient with multicentric Castleman's disease. As a novel finding, we report the use of certain inflammatory parameters, primarily interleukin-10 combined with viral load monitoring of the causative infectious agent in this case HHV-8 to monitor the clinical course of the hemophagocytic lymphohistiocytosis in the setting of bacterial septic complications.

Introduction: Partial cystectomy use has historically been limited by stringent selection criteria. We compared outcomes following partial cystectomy at our institution with those in other contemporary series. Also, we specifically characterized outcomes in patients with tumors in bladder locations traditionally considered unamenable to partial cystectomy., Methods: Patients who underwent partial cystectomy for primary bladder cancer from 1990 to 2012 were identified from our database. Clinical and pathological data were reviewed. Survival analyses were performed using Kaplan-Meier methods. Cox regression was done to identify factors associated with survival and recurrence., Results: A total of 55 patients were included in analysis. Five-year overall, disease specific and recurrence-free survival was 70.3%, 77.0% and 39.4%, respectively. When controlling for clinical and pathological covariates, lymphovascular invasion predicted decreased recurrence-free survival (HR 10.6, p = 0.025). Perioperative morbidity and mortality rates were 4% and 5%, respectively. In 8 patients (15%) trigone tumors required ureteral reimplantation. Two of the 8 patients (25%) experienced complications, including hydronephrosis and bladder neck contracture, which were treated conservatively. Cancer recurred in 2 of the 8 patients (25%) and both were treated successfully. None of the 8 patients died of bladder cancer., Conclusions: Patients treated with partial cystectomy for primary bladder cancer had satisfactory cancer control and favorable perioperative morbidity consistent with other contemporary reports. Patients with tumors in the bladder trigone, historically considered poor candidates for partial cystectomy, also had good oncologic outcomes without significant complications related to reimplantation. Our data further support partial cystectomy in select patients with bladder cancer.

Schizophrenia is associated with high prevalence of substance abuse. Recent research suggests that dysregulation of N-methyl-d-aspartate receptor (NMDAR) function may play a role in the pathophysiology of both schizophrenia and drug addiction, and thus, may account for this high comorbidity. Our laboratory has developed two transgenic mouse lines that exhibit contrasting NMDAR activity based on the availability of the glycine modulatory site (GMS) agonists d-serine and glycine. Glycine transporter 1 knockdowns (GlyT1(+/-)) exhibit NMDAR hyperfunction, whereas serine racemase knockouts (SR(-/-)) exhibit NMDAR hypofunction. We characterized the behavior of these lines in a cocaine-induced (20 mg/kg) conditioned place preference (CPP) and locomotor sensitization paradigm. Compared with wild-type mice, GlyT1(+/-) mice displayed hastened extinction of CPP and robust cocaine-induced reinstatement. SR(-/-) mice appeared to immediately "forget" the learned preference, because they did not exhibit cocaine-induced reinstatement and also displayed attenuated locomotor sensitization. Treatment of GlyT1(+/-) mice with gavestinel (10 mg/kg on day 1; 5 mg/kg on days 2-17), a GMS antagonist, attenuated cocaine-induced CPP and caused them to immediately "forget" the learned preference. Treatment of SR(-/-) mice with d-serine (300 mg/kg on day 1; 150 mg/kg on days 2-17) to normalize brain levels caused them to avoid the cocaine-paired side of the chamber during extinction. These results highlight NMDAR dysfunction as a possible neural mechanism underlying comorbid schizophrenia and substance abuse. Also, these findings suggest drugs that directly or indirectly activate the NMDAR GMS could be an effective treatment of cocaine abuse., (Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.)

The lateral-flow immunoassay (LFA) is an inexpensive point-of-care (POC) paper-based diagnostic device with the potential to rapidly detect disease biomarkers in resource-poor settings. Although LFA is inexpensive, easy to use, and requires no laboratory equipment, it is limited by its sensitivity, which remains inferior to that of gold standard laboratory-based assays. Our group is the only one to have previously utilized various aqueous two-phase systems (ATPSs) to enhance LFA detection. In those studies, the sample was concentrated by an ATPS in a test tube and could only be applied to LFA after it had been extracted manually. Here, we bypass the extraction step by seamlessly integrating a polyethylene glycol-potassium phosphate ATPS with downstream LFA detection in a simple, inexpensive, power-free, and portable all-in-one diagnostic device. We discovered a new phenomenon in which the target biomarkers simultaneously concentrate as the ATPS solution flows through the paper membranes, and our device features a 3-D paper well that was designed to exploit this phenomenon. Studies with this device, which were performed at room temperature in under 25 min, demonstrated a 10-fold improvement in the detection limit of a model protein, transferrin. Our next-generation LFA technology is rapid, affordable, easy-to-use, and can be applied to existing LFA products, thereby providing a new platform for revolutionizing the current state of disease diagnosis in resource-poor settings.

The article presents the results of study of association of risk of development and clinical course of cardiomyopathies with polymorphic variants of genes ACE, GSTM1, IL8 and IL10. The purpose of research was to find out molecular genetic markers of risk of development and clinical course of various types of cardiomyopathies. The analysis used the DNA samples extracted from lymphocytes of peripheral venous blood of patients with cardiomyopathies (N = 89) and control group (N = 426). The standard analysis techniques of polymerase chain reaction and restriction fragment length polymorphism were applied to detect polymorphic loci of genes candidates. It is established that genotype of DD-polymorphic locus of I/DgeneACE is a marker of development of ischemic cardiomyopathy. The allele D is a marker of development of increased rate of manifestation of extra-systoles, growth of inter-ventricular septum and reduction of fraction of discharge in patients with cardiomyopathies.

Both the serotonin and glutamate systems have been implicated in the pathophysiology of schizophrenia, as well as in the mechanism of action of antipsychotic drugs. Psychedelic drugs act through the serotonin 2A receptor (5-HT2AR), and elicit a head-twitch response (HTR) in mice, which directly correlates to 5-HT2AR activation and is absent in 5-HT2AR knockout mice. The precise mechanism of this response remains unclear, but both an intrinsic cortico-cortical pathway and a thalamo-cortical pathway involving glutamate release have been proposed. Here, we used a genetic model of NMDAR hypofunction, the serine racemase knockout (SRKO) mouse, to explore the role of glutamatergic transmission in regulating 5-HT2AR-mediated cellular and behavioral responses. SRKO mice treated with the 5-HT2AR agonist (±)-2,5-dimethoxy-4-iodoamphetamine (DOI) showed a clearly diminished HTR and lower induction of c-fos mRNA. These altered functional responses in SRKO mice were not associated with changes in cortical or hippocampal 5-HT levels or in 5-HT2AR and metabotropic glutamate-2 receptor (mGluR2) mRNA and protein expression. Together, these findings suggest that D-serine-dependent NMDAR activity is involved in mediating the cellular and behavioral effects of 5-HT2AR activation., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Shark cartilage has been a popular complementary or alternative medicine intervention. The basis for this popularity is the claim that sharks rarely get cancer because of the high proportion of cartilage in the shark's body. However, early studies were equivocal. Therefore, a clinical trial was conducted to look at the impact of shark cartilage in patients with advanced cancer. The primary goal of this trial was to determine whether a shark cartilage product improved overall survival for patients with advanced cancer who were getting standard care. Secondary research goals were to evaluate toxicities, tolerability, and quality of life associated with this shark cartilage product., Methods: The study was a two-arm, randomized, placebo-controlled, double-blind, clinical trial. Patients with incurable breast or colorectal carcinoma had to have good performance status and organ function. Patients could be receiving chemotherapy. Patients were all to receive standard care and then to be randomly selected to receive either a shark cartilage product or an identical-appearing and smelling placebo 3 to 4 times each day., Results: Data on a total of 83 evaluable patients were analyzed. There was no difference in overall survival between patients receiving standard care plus a shark cartilage product versus standard care plus placebo. Likewise, there was no suggestion of improvement in quality of life for patients receiving the shark cartilage, compared with those receiving placebo., Conclusion: This trial was unable to demonstrate any suggestion of efficacy for this shark cartilage product in patients with advanced cancer.

The unique case of a 60-year-old patient with a non-Hodgkin's B-cell lymphoma of the lymphoplasmacytic type and three associated monoclonal proteins, is described. The patient also exhibited various autoimmune phenomena that were consistent with the diagnoses of Sjögren's syndrome and autoimmune thyroiditis. The evolution from production of a single monoclonal protein (IgM-kappa) to three monoclonal proteins (IgG-kappa, IgA-kappa, and IgM-kappa) suggested that the lymphoplasmacytic cells were at different stages of terminal differentiation within a single neoplastic clone. The chronic antigenic stress imposed on the immune system by the autoimmune disorder may have played a role in the development of lymphoma and in the heavy chain immunoglobulin switching that occurred during the patients' clinical course.

The undifferentiated malignant neoplasm presents a significant problem in the intelligent selection of therapy. Because of advances in chemotherapy, there are cancers that are effectively palliated, and sometimes cured if appropriately treated. Characterization of tumors by immunohistochemical stains drastically reduces the incidence of "undifferentiated" diagnoses and will optimize patient management, as illustrated by two cases of large-cell lymphoma arising in skeletal muscle.