The role of H-H interactions and impurities on the structure and energetics of H/Pd(111).

Understanding hydrogen incorporation into palladium requires detailed knowledge of surface and subsurface structure and atomic interactions as surface hydrogen is being embedded. Using density functional theory (DFT), we examine the energies of hydrogen layers of varying coverage adsorbed on Pd(111). We find that H-H and H-Pd interactions promote the formation of the well-known 3×3 phases but also favor an unreported (3 × 3) phase at high H coverages for which we present experimental evidence. We relate the stability of isolated H vacancies of the (3 × 3) phase to the need of H2 molecules to access bare Pd before they can dissociate. Following higher hydrogen dosage, we observe initial steps of hydride formation, starting with small clusters of subsurface hydrogen. The interaction between H and Pd is complicated by the persistent presence of carbon at the surface. X-ray photoelectron spectroscopy experiments show that trace amounts of carbon, emerging from the Pd bulk despite many surface cleaning cycles, become mobile enough to repopulate the C-depleted surface at temperatures above 200 K. When exposed to hydrogen, these surface carbon atoms react to form benzene, as evidenced by scanning tunneling microscopy observations interpreted with DFT.

Does Medicaid payer status affect patient's shoulder outcomes after shoulder arthroplasty?

BACKGROUND: Low socioeconomic status and Medicaid insurance as a primary payer have been shown to influence resource utilization and risk-adjusted outcomes for total joint arthroplasty. The purpose of this study was to assess the effects of Medicaid primary payer status on outcomes following shoulder arthroplasty (SA). MATERIALS AND METHODS: A retrospective review of shoulder surgery patients was undertaken to identify a matched cohort of 51 patients who underwent SA and were stratified based on insurance type into two cohorts: 28 Medicaid (M) patients and 23 non-Medicaid (NM) patients. Baseline demographics, resource utilization, and outcomes were compared as well as pre-and-postoperative patient-reported outcomes (PRO) and functional scores. PRO scores included the American shoulder and elbow surgeons score (ASES), the Penn shoulder score (PSS), and the subjective shoulder value (SSV). RESULTS: There were no statistically significant differences in demographics, comorbidities, or preoperative baseline scores between the cohorts, except for age (M: 55.3 years; NM: 67.5 years; p ≤ 0.001) and smoking status (M: 13 patients; NM: 4 patients; p = 0.029). Medicaid patients showed a slightly higher rate of missed follow-ups (M: 1.1 vs. NM: 0.9; p = 0.370). All Medicaid and non-Medicaid patients experienced significant improvement on PRO scores and active forward flexion. Medicaid patients demonstrated equivalent final postoperative scores for ASES (M: 65; NM: 57; p = 0.454), PSS (M: 63; NM: 51; p = 0.242), SSV (M: 70; NM: 69; p = 1.0) and range of motion measurements. DISCUSSION: Overall results suggest that Medicaid patients can expect significant improvement after SA and the same level of PRO's compared to non-Medicaid-insured population. LEVEL OF EVIDENCE: Level III, Retrospective Comparative Design, Treatment Study.

Relationship between hospital size and teaching status on outcomes for reverse shoulder arthroplasty.

BACKGROUND: The use of reverse shoulder arthroplasty (RSA) continues to grow with expanding indications and increased surgeon awareness. Previous data for other lower extremity joint replacements indicate that high-volume centers have better outcomes, with lower complication rates, decreased length of stay, and complications for both hemiarthroplasty and total shoulder arthroplasty. The purpose of this study is to evaluate the effects of hospital size and setting on adverse events for RSA. MATERIALS AND METHODS: The National Inpatient Sample database was queried for RSA performed using ICD-9 codes. Primary outcomes included length of stay (LOS), total hospital charges, discharge disposition, and postoperative complications. Odds ratios were used to assess the risk of inpatient postoperative complications. RESULTS: A weighted national estimate of 24,056 discharges for patients undergoing RSA was included in the study. Patients at larger hospitals experienced higher total charges, increased average LOS, and slightly higher complication rates compared to those of small and medium hospitals. Patients in larger hospitals had significantly increased rates of genitourinary and central nervous system complications, while patients in small/medium hospitals experienced higher rates of hematoma/seroma. CONCLUSION: Results from this study indicate that large and non-teaching hospitals overall tend to burden the patients with higher hospital charges, longer hospital stay, and more frequent non-routine discharges. Also, larger hospitals are associated with higher risk of genitourinary and central nervous system complications rates, whereas non-teaching hospitals are associated with lower risk of infection and higher risk of anemia after RSA. With the growth in RSA in the USA, continued attention needs to be placed on improving outcomes and resource utilization for RSA patients even in larger hospitals.

3D preoperative planning for humeral head selection in total shoulder arthroplasty.

BACKGROUND: Recreation of glenohumeral biomechanics and humeral anatomy has been shown to improve outcomes in shoulder arthroplasty. Recent research has focused on utilizing simulation software and intraoperative instrumentation to improve glenoid implant selection and positioning, but no study had evaluated the reliability of new features in 3D preoperative planning software for humeral planning in total shoulder arthroplasty. MATERIALS AND METHODS: Preoperative plans were created for 26 patients using three different simulation software programs: an independent preoperative planning simulation (IPPS) software (OrthoVis) and two automated manufacturers preoperative simulation systems: ArthrexVIP™ (AMPS I) and Tornier Blueprint™ 3D Planning (AMPS II). Preoperative plans were compared for reliability and consistency among different software systems based on available variables including humeral head diameter (HD) and head height (HH). RESULTS: The measured HD was consistent between the three systems with a maximum mean difference of 0.2 mm for HD among IPPS, AMPS I, and AMPS II (p = 0.964). There was a significant difference in measured humeral HH with 1.7 mm difference between IPPS and AMPS II (p ≤ 0.001). The strongest correlation when comparing humeral head measurements (diameter or height) obtained from all systems was seen between IPPS and AMPS I for humeral HD (r = 0.8; p ≤ 0.001). CONCLUSION: There was a high level of consistency between independent and manufacturer preoperative planning software for humeral head measurements. These preoperative planning systems can improve efficiency and workflow during surgery by guiding surgeons on implant size selection to optimally reconstruct the glenohumeral kinematics, in order to improve patient outcomes. LEVEL OF EVIDENCE: Level III, study of nonconsecutive patients and without a universally applied "gold" standard study of diagnostic test.

The effect of Medicaid payer status on patient outcomes following repair of massive rotator cuff tears.

BACKGROUND: The influence of socioeconomic status and insurance type has not been studied extensively for RCR, particularly not in the high risk massive RCT population. The purpose of this study is to identify relationships between Medicaid payer status and patient outcomes following massive RCR. METHODS: A retrospective review of shoulder surgery database identified 29 patients undergoing massive rotator cuff repair. Patients were stratified based on insurance type into two cohorts, Medicaid (14 patients) and non-Medicaid (15 patients). Missed routine follow-up appointments and comorbidities were recorded and compared between groups. Group comparisons were made for pre- and postoperative patient-reported and functional outcomes. Outcome scores included American Shoulder and Elbow Shoulder Score (ASES), the Penn Shoulder Score, and the Subjective Shoulder Value (SSV). A p value of < 0.05 was considered significant for all statistical analyses. RESULTS: Medicaid patients were on average 7.1 years younger than non-Medicaid patients (49.8 vs. 56.9 years, respectively), and remaining demographics were comparable between groups. Preoperative patient-reported outcomes were only significantly different for ASES and ASES pain (p = 0.010, 0.037). There was excellent average improvement for Medicaid patients but no significant differences compared to non-Medicaid patients for ASES (p = 0.630), PENN scores (p = 0.395), and SSV (p = 0.198). Medicaid patients also had a higher number of missed and canceled appointments (28%) compared to non-Medicaid patients (18%). CONCLUSION: Medicaid coverage will expand to millions of uninsured Americans under current healthcare reform. Medicaid patients with massive RCT appear to significantly improve with surgical treatment.

A systematic surveillance programme for infectious salmon anaemia virus supports its absence in the Pacific Northwest of the United States.

In response to reported findings of infectious salmon anaemia virus (ISAV) in British Columbia (BC), Canada, in 2011, U.S. national, state and tribal fisheries managers and fish health specialists developed and implemented a collaborative ISAV surveillance plan for the Pacific Northwest region of the United States. Accordingly, over a 3-1/2-year period, 4,962 salmonids were sampled and successfully tested by real-time reverse-transcription PCR. The sample set included multiple tissues from free-ranging Pacific salmonids from coastal regions of Alaska and Washington and farmed Atlantic salmon (Salmo salar L.) from Washington, all representing fish exposed to marine environments. The survey design targeted physiologically compromised or moribund animals more vulnerable to infection as well as species considered susceptible to ISAV. Samples were handled with a documented chain of custody and testing protocols, and criteria for interpretation of test results were defined in advance. All 4,962 completed tests were negative for ISAV RNA. Results of this surveillance effort provide sound evidence to support the absence of ISAV in represented populations of free-ranging and marine-farmed salmonids on the northwest coast of the United States.

Extremity fractures associated with ATVs and dirt bikes: a 10-year national epidemiologic study.

BACKGROUND: Morbidity and mortality of all-terrain vehicles and dirt bikes have been studied, as well as the association of helmet use and head injury. HYPOTHESIS/PURPOSE: The purpose of this study is to compare and contrast the patterns of extremity fractures associated with ATVs and dirt bikes. We believe there will be unique and potentially preventable injury patterns associated with dirt bikes and three-wheeled ATVs due to the poor stability of these vehicles. STUDY DESIGN: Descriptive epidemiology study. METHODS: The National Electronic Injury Surveillance System (NEISS) was used to acquire data for extremity fractures related to ATV (three wheels, four wheels, and number of wheels undefined) and dirt bike use from 2007 to 2012. Nationwide estimation of injury incidence was determined using NEISS weight calculations. RESULTS: The database yielded an estimate of 229,362 extremity fractures from 2007 to 2012. The incidence rates of extremity fractures associated with ATV and dirt bike use were 3.87 and 6.85 per 1000 participant-years. The largest proportion of all fractures occurred in the shoulder (27.2%), followed by the wrist and lower leg (13.8 and 12.4%, respectively). There were no differences in the distribution of the location of fractures among four-wheeled or unspecified ATVs. However, three-wheeled ATVs and dirt bikes had much larger proportion of lower leg, foot, and ankle fractures compared to the other vehicle types. CONCLUSIONS: While upper extremity fractures were the most commonly observed in this database, three-wheeled ATVs and dirt bikes showed increased proportions of lower extremity fractures. Several organizations have previously advocated for better regulation of the sale and use of these specific vehicles due to increased risks. These findings help illustrate some of the specific risks associated with these commonly used vehicles.

Viral hemorrhagic septicemia IVb status in the United States: inferences from surveillance activities and regional context.

The United States (U.S.) response to viral hemorrhagic septicemia virus (VHSV) IVb emergence in the Laurentian Great Lakes (GL) included risk-based surveillance for cost-effective decision support regarding the health of fish populations in open systems. All U.S. VHSV IVb isolations to date derive from free-ranging fish from GL States. Most originate in the region designated by US Geological Survey hydrologic unit code (HUC) 04, with the exception of two detections in neighboring Upper Mississippi (HUC 05) and Ohio (HUC 07) regions. For States outside the GL system, disease probability was assessed using multiple evidence sources. None substantiated VHSV IVb absence using surveillance alone, in part due to the limited temporal relevance of data in open systems. However, Bayesian odds risk-based analysis of surveillance and population context, coupled with exclusions where water temperatures likely preclude viral replication, achieved VHSV IVb freedom assurance for 14 non-GL States by the end of 2012, with partial evidence obtained for another 17 States. The non-GL region (defined as the aggregate of 4-digit HUCs located outside of GL States) met disease freedom targets for 2012 and is projected to maintain this status through 2016 without additional active surveillance. Projections hinge on continued basic biosecurity conditions such as movement restrictions and passive surveillance. Areas with navigable waterway connections to VHSV IVb-affected HUCs (and conducive water temperatures) should receive priority for resources in future surveillance or capacity building efforts. However, 6 years of absence of detections in non-GL States suggests that existing controls limit pathogen spread, and that even spread via natural pathways (e.g., water movement or migratory fish) appears contained to the Great Lakes system. This report exemplifies the cost-effective use of risk-based surveillance in decision support to assess and manage aquatic animal population health in open systems.

Sexual function and the use of medical devices or drugs to optimize potency after prostate brachytherapy.

PURPOSE: Prospective evaluation of sexual outcomes after prostate brachytherapy with iodine-125 seeds as monotherapy at a tertiary cancer care center. METHODS AND MATERIALS: Subjects were 129 men with prostate cancer with I-125 seed implants (prescribed dose, 145 Gy) without supplemental hormonal or external beam radiation therapy. Sexual function, potency, and bother were prospectively assessed at baseline and at 1, 4, 8, and 12 months using validated quality-of-life self-assessment surveys. Postimplant dosimetry values, including dose to 10% of the penile bulb (D10), D20, D33, D50, D75, D90, and penile volume receiving 100% of the prescribed dose (V100) were calculated. RESULTS: At baseline, 56% of patients recorded having optimal erections; at 1 year, 62% of patients with baseline erectile function maintained optimal potency, 58% of whom with medically prescribed sexual aids or drugs. Variables associated with pretreatment-to-posttreatment decline in potency were time after implant (p = 0.04) and age (p = 0.01). Decline in urinary function may have been related to decline in potency. At 1 year, 69% of potent patients younger than 70 years maintained optimal potency, whereas 31% of patients older than 70 maintained optimal potency (p = 0.02). Diabetes was related to a decline in potency (p = 0.05), but neither smoking nor hypertension were. For patients with optimal potency at baseline, mean sexual bother scores had declined significantly at 1 year (p < 0.01). Sexual potency, sexual function, and sexual bother scores failed to correlate with any dosimetric variable tested. CONCLUSIONS: Erections firm enough for intercourse can be achieved at 1 year after treatment, but most men will require medical aids to optimize potency. Although younger men were better able to maintain erections firm enough for intercourse than older men, there was no correlation between potency, sexual function, or sexual bother and penile bulb dosimetry.

The novel sodium glucose transporter 2 inhibitor dapagliflozin sustains pancreatic function and preserves islet morphology in obese, diabetic rats.

AIMS: To investigate whether glucose lowering with the selective sodium glucose transporter 2 (SGLT2) inhibitor dapagliflozin would prevent or reduce the decline of pancreatic function and disruption of normal islet morphology. METHODS: Female Zucker diabetic fatty (ZDF) rats, 7-8 weeks old, were placed on high-fat diet. Dapagliflozin (1 mg/kg/day, p.o.) was administered for ∼33 days either from initiation of high-fat diet or when rats were moderately hyperglycaemic. Insulin sensitivity and pancreatic function were evaluated using a hyperglycaemic clamp in anaesthetized animals (n = 5-6); ß-cell function was quantified using the disposition index (DI) to account for insulin resistance compensation. Pancreata from a matched subgroup (n = 7-8) were fixed and ß-cell mass and islet morphology investigated using immunohistochemical methods. RESULTS: Dapagliflozin, administered from initiation of high-fat feeding, reduced the development of hyperglycaemia; after 24 days, blood glucose was 8.6 ± 0.5 vs. 13.3 ± 1.3 mmol/l (p < 0.005 vs. vehicle) and glycated haemoglobin 3.6 ± 0.1 vs. 4.8 ± 0.26% (p < 0.003 vs. vehicle). Dapagliflozin improved insulin sensitivity index: 0.08 ± 0.01 vs. 0.02 ± 0.01 in obese controls (p < 0.03). DI was improved to the level of lean control rats (dapagliflozin 0.29 ± 0.04; obese control 0.15 ± 0.01; lean 0.28 ± 0.01). In dapagliflozin-treated rats, ß-cell mass was less variable and significant improvement in islet morphology was observed compared to vehicle-treated rats, although there was no change in mean ß-cell mass with dapagliflozin. Results were similar when dapagliflozin treatment was initiated when animals were already moderately hyperglycaemic. CONCLUSION: Sustained glucose lowering with dapagliflozin in this model of type 2 diabetes prevented the continued decline in functional adaptation of pancreatic ß-cells.

Ewing tumors of the head and neck.

PURPOSE: Retrospective review describing the 40-year University of Florida experience treating Ewing tumors of the head-and-neck region with a summary of the pertinent literature. PATIENTS AND METHODS: Nine patients were diagnosed and treated for Ewing sarcoma of the head and neck at our institution between 1965 and 2007. Primary sites included: mandible (3 patients), calvarium (2 patients), paranasal sinus (2 patients), oral cavity (1 patient), and the extraosseous soft tissue of the neck (1 patient). The median age at diagnosis was 13.0 years (range, 6.3-20.1 years). The median observed follow-up was 10.2 years (range, 1.5-37 years). RESULTS: All patients received multiagent chemotherapy and radiation therapy to a median dose of 55.8 Gy (range, 36-67.2 Gy). Three patients also underwent wide local excision. The actuarial 10-year overall survival, cause-specific survival, event-free survival, and local control probabilities were 66%, 66%, 56%, and 89%, respectively. Late complications included poor dentition, mild xerophthalmia, cataract, and mandibular hypoplasia. A literature search revealed 8 previous series with Ewing tumors of the head and neck analyzed as subsets of larger studies. CONCLUSIONS: In the context of limited data on head and neck Ewing tumors, combined modality therapy provides excellent local control with reasonable acute and late toxicity. Large tumors were associated with poor disease control.

In vitro characterization and pharmacokinetics of dapagliflozin (BMS-512148), a potent sodium-glucose cotransporter type II inhibitor, in animals and humans.

(2S,3R,4R,5S,6R)-2-(3-(4-Ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyl-tetrahydro-2H-pyran-3,4,5-triol (dapagliflozin; BMS-512148) is a potent sodium-glucose cotransporter type II inhibitor in animals and humans and is currently under development for the treatment of type 2 diabetes. The preclinical characterization of dapagliflozin, to allow compound selection and prediction of pharmacological and dispositional behavior in the clinic, involved Caco-2 cell permeability studies, cytochrome P450 (P450) inhibition and induction studies, P450 reaction phenotyping, metabolite identification in hepatocytes, and pharmacokinetics in rats, dogs, and monkeys. Dapagliflozin was found to have good permeability across Caco-2 cell membranes. It was found to be a substrate for P-glycoprotein (P-gp) but not a significant P-gp inhibitor. Dapagliflozin was not found to be an inhibitor or an inducer of human P450 enzymes. The in vitro metabolic profiles of dapagliflozin after incubation with hepatocytes from mice, rats, dogs, monkeys, and humans were qualitatively similar. Rat hepatocyte incubations showed the highest turnover, and dapagliflozin was most stable in human hepatocytes. Prominent in vitro metabolic pathways observed were glucuronidation, hydroxylation, and O-deethylation. Pharmacokinetic parameters for dapagliflozin in preclinical species revealed a compound with adequate oral exposure, clearance, and elimination half-life, consistent with the potential for single daily dosing in humans. The pharmacokinetics in humans after a single dose of 50 mg of [(14)C]dapagliflozin showed good exposure, low clearance, adequate half-life, and no metabolites with significant pharmacological activity or toxicological concern.

(-)-Deprenyl inhibits vascular hyperpermeability after hemorrhagic shock.

Recent studies from our laboratory demonstrated the involvement of endothelial cell reactive oxygen species (ROS) formation and activation of apoptotic signaling in vascular hyperpermeability after hemorrhagic shock (HS). The objective of this study was to determine if (-)-deprenyl, an antioxidant with antiapoptotic properties, would attenuate HS-induced vascular hyperpermeability. In rats, HS was induced by withdrawing blood to reduce the MAP to 40 mmHg for 60 min followed by resuscitation for 60 min. To study hyperpermeability, we injected the rats with fluorescein isothiocyanate--albumin (50 mg/kg), and the changes in integrated optical intensity of the mesenteric postcapillary venules were obtained intravascularly and extravascularly using intravital microscopy. Mitochondrial ROS formation and mitochondrial transmembrane potential (DeltaPsim) were studied using dihydrorhodamine 123 and JC-1, respectively. Mitochondrial release of cytochrome c was determined using enzyme-linked immunosorbent assay and caspase-3 activity by a fluorometric assay. Parallel studies were performed in rat lung microvascular endothelial cells using proapoptotic BAK as inducer of hyperpermeability. Hemorrhagic shock induced vascular hyperpermeability, mitochondrial ROS formation, DeltaPsim decrease, cytochrome c release, and caspase-3 activation (P G 0.05). (-)-Deprenyl (0.15 mg/kg) attenuated all these effects (P < 0.05). Similarly in rat lung microvascular endothelial cells, (-)-deprenyl attenuated BAK peptide-induced monolayer hyperpermeability (P < 0.05), ROS formation, DeltaPsim decrease, cytochrome c release (P<0.05), and caspase-3 activation (P < 0.05). The protective effects of (-)-deprenyl on vascular barrier functions may be due to its protective effects on DeltaPsim, thereby preventing mitochondrial release of cytochrome c and caspase-3--mediated disruption of endothelial adherens junctions.

(-)-Deprenyl inhibits thermal injury-induced apoptotic signaling and hyperpermeability in microvascular endothelial cells.

Burn injury is associated with a significant leak of intravascular fluid into the interstitial space, requiring large amounts of volume resuscitation. Activation of the intrinsic (mitochondrial) apoptotic pathway has been associated with vascular hyperpermeability. We hypothesized that vascular hyperpermeability following burns is also mediated via this pathway. The purpose of this study was to investigate whether (-)-deprenyl, a drug with antioxidant and antiapoptotic properties, could attenuate burn induced-apoptotic signaling and hyperpermeability. Male Sprague-Dawley rats were assigned to sham or experimental groups. The experimental rats underwent a 30 to 40% TBSA full-thickness burn. Serum was collected from all rats at 180 minutes postburn. Rat lung microvascular endothelial cell monolayers were exposed to the sham or burn serum; permeability was determined by fluorescein isothiocyanate-tagged albumin flux. Mitochondrial reactive oxygen species formation was measured with dihydrorhodamine 123. The change in mitochondrial membrane potential was determined with JC-1. Cytosolic cytochrome c was measured by enzyme-linked immunosorbent assay. A group of cells in each series was pretreated with (-)-deprenyl (1 microM). Monolayer permeability increased significantly (P<.05) when treated with burn serum. (-)-Deprenyl significantly attenuated the hyperpermeability induced by burn serum (P<.05). Burn serum increased mitochondrial reactive oxygen species levels and reduced mitochondrial membrane potential; these effects were markedly reduced by (-)-deprenyl. Cytochrome c release was increased by treatment with burn serum (P<.05), and this effect was significantly inhibited by (-)-deprenyl (P<.05). Burn serum induces hyperpemeability and activates intrinsic apoptotic signaling in microvascular endothelial cells. (-)-Deprenyl, an antioxidant and antiapoptotic drug, modulates intrinsic apoptotic signaling and attenuates burn-induced hyperpermeability.

17beta-estradiol mediates protection against microvascular endothelial cell hyperpermeability.

BACKGROUND: Previous work from our laboratory demonstrated the involvement of "intrinsic" mitochondrial apoptotic signaling in vascular hyperpermeability. The objective of this study was to determine if 17beta-estradiol, a known inhibitor of apoptosis, would attenuate microvascular endothelial cell hyperpermeability. METHODS: Rat lung microvascular endothelial cell monolayers were treated with 17beta-estradiol or estrogen-receptor antagonist ICI 182780 after transfection with BAK peptide (5 microg/mL). Fluorescein isothiocyanate (FITC)-albumin was used to determine the change in permeability. Mitochondrial reactive oxygen species (ROS) formation and transmembrane potential were determined using 123 dihydrorhodamine and JC-1, respectively. Cytosolic cytochrome c levels and caspase-3 activity were determined using enzyme-linked immunosorbent assay and fluorometric assay respectively. RESULTS: 17beta-estradiol (10 nm) attenuated BAK-induced hyperpermeability (P < .05), ROS formation, cytochrome c release, and caspase-3 activation. The estrogen receptor antagonist ICI 182780 blocked the protective effect of 17beta-estradiol on hyperpermeability (P < .05). CONCLUSIONS: 17beta-estradiol attenuates BAK-induced hyperpermeability in rat lung microvascular endothelial cells by way of an estrogen-receptor mediated pathway.

The relationship between serum levels of YKL-40 and disease progression in patients with early rheumatoid arthritis.

YKL-40 concentrations in serum were determined by an ELISA at 3 occasions during 19 months for 57 early RA patients. The results were related to biochemical and radiographic measures at each time point. YKL-40 correlated significantly to ESR and CRP throughout the study. Correlations between YKL-40 and radiographic findings scored by the Larsen method were fairly weak both for absolute values at each time point (Rs 0.212-0.319) and for progression over time (Rs 0.152-0.301). Baseline YKL-40 could predict radiographic progression with a specificity and sensitivity of only slightly over 50%. ESR and CRP correlated stronger than YKL-40 to joint damage progression and in a multiple regression model ESR was the only significant variable explaining the variance of this radiographic measure. We conclude that serial measurements of serum YKL-40 did not provide information that could not be obtained by conventional biochemical measures of disease activity.

A medical research council randomized trial in patients with primary cerebral non-Hodgkin lymphoma: cerebral radiotherapy with and without cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy.

BACKGROUND: The role of chemotherapy in the treatment of patients with primary central nervous system lymphoma (PCL) remains unclear, with no randomized trials available to aid in the interpretation of the current data. The Medical Research Council therefore conducted the current randomized trial to assess the impact on survival of postradiotherapy chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in nonimmunocompromised adult patients with pathologically proven PCL. METHODS: After surgery, patients were randomized at a ratio of 1:2 to radiotherapy alone (RT: 40 grays [Gy] in 20 fractions to the whole brain followed by a 14-Gy boost to the tumor plus a 2-cm tumor margin) or to the same radiotherapy followed by six cycles of CHOP chemotherapy given at 3-week intervals (RT-CHOP). The target sample size was 90 patients, which allowed 90% power to detect a doubling of the median survival time. RESULTS: Between 1988 and 1995, 53 patients were randomized: Fifteen patients were randomized to RT, and 38 patients were randomized to RT-CHOP. The trial closed earlier than planned through poor accrual. The median patient age was 57 years, 57% of the patients were male, and 75% of the patients had unifocal disease. The median number of chemotherapy cycles received was 6 (mean, 4 cycles). Forty-three patients have died, and the median follow-up of survivors is 5 years (range, 1-9 years). There was no evidence of a benefit from RT-CHOP with respect to overall survival (hazard ratio [HR], 1.19; 95% confidence interval, 0.51-2.76) after adjustment for prognostic factors (patient age and neurologic performance status) in an analysis in which HR > 1 favored the control (RT) group. CONCLUSIONS: CHOP has no clear role in the postradiotherapy treatment of patients with PCL. Chemotherapy is poorly tolerated and largely palliative in older, less fit patients. In younger patients, initial chemotherapy designed to penetrate the blood-brain barrier warrants further investigation.