Multiple surgical resections for progressive IDH wildtype glioblastoma-is it beneficial?

PURPOSE: The role of repeat resection for recurrent glioblastoma (rGB) remains equivocal. This study aims to assess the overall survival and complications rates of single or repeat resection for rGB. METHODS: A single-centre retrospective review of all patients with IDH-wildtype glioblastoma managed surgically, between January 2014 and January 2022, was carried out. Patient survival and factors influencing prognosis were analysed, using Kaplan-Meier and Cox regression methods. RESULTS: Four hundred thirty-two patients were included, of whom 329 underwent single resection, 83 had two resections and 20 patients underwent three resections. Median OS (mOS) in the cohort who underwent a single operation was 13.7 months (95% CI: 12.7-14.7 months). The mOS was observed to be extended in patients who underwent second or third-time resection, at 22.9 months and 44.7 months respectively (p < 0.001). On second operation achieving > 95% resection or residual tumour volume of < 2.25 cc was significantly associated with prolonged survival. There was no significant difference in overall complication rates between primary versus second (p = 0.973) or third-time resections (p = 0.312). The use of diffusion tensor imaging (DTI) guided resection was associated with reduced post-operative neurological deficit (RR 0.37, p = 0.002), as was use of intraoperative ultrasound (iUSS) (RR 0.45, p = 0.04). CONCLUSIONS: This study demonstrates potential prolongation of survival for rGB patients undergoing repeat resection, without significant increase in complication rates with repeat resections. Achieving a more complete repeat resection improved survival. Moreover, the use of intraoperative imaging adjuncts can maximise tumour resection, whilst minimising the risk of neurological deficit.

The influence of pain-related comorbidities on pain intensity and pain-related psychological distress in patients presenting with musculoskeletal pain.

BACKGROUND: Musculoskeletal pain (MSP) is the largest contributor to chronic pain and frequently occurs alongside other medical comorbidities. OBJECTIVE: Explore the relationships between the presence of pain-related comorbidities, pain intensity, and pain-related psychological distress in patients with MSP. METHODS: A longitudinal assessment of individuals 18-90 years old in the Midwestern United States beginning a new episode of physical therapy for MSP. Electronic medical records were assessed the full year prior for care-seeking of diagnoses for pain-related comorbidities (anxiety, metabolic disorder, chronic pain, depression, nicotine dependence, post-traumatic stress disorder, sleep apnea, and sleep insomnia). Pain intensity and pain-related psychological distress (Optimal Screening for Prediction of Referral and Outcome - Yellow Flags tool) were captured during the physical therapy evaluation. Generalized linear models were used to assess the association between pain intensity, psychological distress, and pain-related co-morbidities. Models were adjusted for variables shown in the literature to influence pain. RESULTS: 532 participants were included in the cohort (56.4% female; median age of 59 years, Interquartile Range [IQR]:47, 69). Comorbid depression (beta coefficient (ß) = 0.7; 95%CI: 0.2, 1.2), spine versus lower extremity pain ((ß = 0.6; 95%CI: 0.1, 1.1), and prior surgery (ß = 0.8, 95%CI: 0.3, 1.4) were associated with higher pain intensity scores. No pain-related comorbidities were associated with pain-related psychological distress (yellow flag count or number of domains). Female sex was associated with less pain-related psychological distress (ß = -0.2, 95%CI: -0.3, -0.02). CONCLUSIONS: Depression was associated with greater pain intensity. No comorbidities were able to account for the extent of pain-related psychological distress.

Skeletal muscle contributions to reduced fitness in cystic fibrosis youth.

Background: Increased maximal oxygen uptake (V̇O2max) is beneficial in children with cystic fibrosis (CF) but remains lower compared to healthy peers. Intrinsic metabolic deficiencies within skeletal muscle (muscle "quality") and skeletal muscle size (muscle "quantity") are both proposed as potential causes for the lower V̇O2max, although exact mechanisms remain unknown. This study utilises gold-standard methodologies to control for the residual effects of muscle size from V̇O2max to address this "quality" vs. "quantity" debate. Methods: Fourteen children (7 CF vs. 7 age- and sex-matched controls) were recruited. Parameters of muscle size - muscle cross-sectional area (mCSA) and thigh muscle volume (TMV) were derived from magnetic resonance imaging, and V̇O2max obtained via cardiopulmonary exercise testing. Allometric scaling removed residual effects of muscle size, and independent samples t-tests and effect sizes (ES) identified differences between groups in V̇O2max, once mCSA and TMV were controlled for. Results: V̇O2max was shown to be lower in the CF group, relative to controls, with large ES being identified when allometrically scaled to mCSA (ES = 1.76) and TMV (ES = 0.92). Reduced peak work rate was also identified in the CF group when allometrically controlled for mCSA (ES = 1.18) and TMV (ES = 0.45). Conclusions: A lower V̇O2max was still observed in children with CF after allometrically scaling for muscle size, suggesting reduced muscle "quality" in CF (as muscle "quantity" is fully controlled for). This observation likely reflects intrinsic metabolic defects within CF skeletal muscle.

Survey of exercise testing and training in cystic fibrosis clinics in the UK: a decade of progress.

OBJECTIVES: Regular exercise testing is recommended for people with cystic fibrosis (pwCF), as is the provision and regular review of exercise training programmes. A previous survey on exercise testing and training for pwCF in the UK was conducted over a decade ago. With the landscape of CF changing considerably during this time, this survey aimed to evaluate UK-based exercise testing and training practices for pwCF a decade on. DESIGN: Cross-sectional, online survey. PARTICIPANTS: A survey was distributed electronically to UK CF clinics and completed by the individual primarily responsible for exercise services. Descriptive statistics and qualitative analyses were undertaken. RESULTS: In total, 31 CF centres participated, representing ~50% of UK specialist clinics. Of these, 94% reported using exercise testing, 48% of which primarily use cardiopulmonary exercise testing. Exercise testing mostly occurs at annual review (93%) and is most often conducted by physiotherapists (62%). A wide variation in protocols, exercise modalities, normative reference values and cut-offs for exercise-induced desaturation are currently used. All centres reportedly discuss exercise training with pwCF; 94% at every clinic appointment. However, only 52% of centres reportedly use exercise testing to inform individualised exercise training. Physiotherapists typically lead discussions around exercise training (74%). CONCLUSIONS: These data demonstrate that the majority of respondent centres in the UK now offer some exercise testing and training advice for pwCF, representing a marked improvement over the past decade. However, continued efforts are now needed to standardise exercise practices, particularly regarding field testing practices and the translation of test results into personalised training programmes for pwCF.

High risk of relapsed disease in patients with NK/T-cell chronic active Epstein-Barr virus disease outside of Asia.

Chronic active Epstein-Barr virus (EBV) disease (CAEBV) is characterized by high levels of EBV predominantly in T and/or natural killer cells with lymphoproliferation, organ failure due to infiltration of tissues with virus-infected cells, hemophagocytic lymphohistiocytosis, and/or lymphoma. The disease is more common in Asia than in the United States and Europe. Although allogeneic hematopoietic stem cell transplantation (HSCT) is considered the only curative therapy for CAEBV, its efficacy and the best treatment modality to reduce disease severity prior to HSCT is unknown. Here, we retrospectively assessed an international cohort of 57 patients outside of Asia. Treatment of the disease varied widely, although most patients ultimately proceeded to HSCT. Though patients undergoing HSCT had better survival than those who did not (55% vs 25%, P < .01), there was still a high rate of death in both groups. Mortality was largely not affected by age, ethnicity, cell-type involvement, or disease complications, but development of lymphoma showed a trend with increased mortality (56% vs 35%, P = .1). The overwhelming majority (75%) of patients who died after HSCT succumbed to relapsed disease. CAEBV remains challenging to treat when advanced disease is present. Outcomes would likely improve with better disease control strategies, earlier referral for HSCT, and close follow-up after HSCT including aggressive management of rising EBV DNA levels in the blood.

Case of e-cigarette or vaping product use-associated lung injury (EVALI) in London, UK.

We present a case of a 38-year-old man with no medical comorbidities who presented to the hospital with haemoptysis and shortness of breath on a background of vaping home-manufactured cannabis oil. He developed e-cigarette or vaping product use-associated lung injury (EVALI) visible on chest X-ray requiring oxygen, and corticosteroid treatment before making a recovery. Research reports that the contents vitamin E acetate and tetrahydrocannabinol are frequently found in substances acquired from informal sources which increase the likelihood of EVALI developing. Further research into their synergistic effect is ongoing. Although safer than smoking, vaping is not risk free and EVALI should be considered in patients presenting with respiratory disease.

A Malignant Neoplasm From the Jejunum With a MALAT1-GLI1 Fusion and 26-Year Survival History.

The transcription factor GLI1 is a critical effector of the sonic hedgehog pathway. Gene fusions that activate GLI1 have recently been reported in several tumor types including gastroblastoma, plexiform fibromyxoma, a subset of pericytomas, and other soft tissue tumors. These tumors arise in a wide variety of anatomical origins and have variable malignant potentials, morphologies, and immunohistochemistry profiles. In this case report, we describe a malignant tumor from the jejunum with a MALAT1-GLI1 gene fusion that expressed a truncated constitutively active GLI1 protein and GLI1 targets that were detectable by immunohistochemistry. The tumor showed high-grade epithelioid and spindle cell morphology, strongly expressed CD56, and focally expressed other neuroendocrine markers and cytokeratins, but not S100 protein or SMA. The tumor recurred multiple times in liver, soft tissue, and lung over the course of 26 years, the longest reported follow-up for a GLI1 fusion-associated tumor. These metastatic tumors were also composed of epithelioid and spindle cells, but showed lower morphological grade than the primary tumor. The metastatic tumors resembled the recently reported "malignant epithelioid neoplasms with GLI1 rearrangements." The tumor also had a relatively high tumor mutation burden for a sarcoma. This case report expands the sites of origin for GLI1 rearranged neoplasms and shows that despite being associated with high-grade morphology, these malignancies can be associated with very long-term survival.

Quantification of thigh muscle volume in children and adolescents using magnetic resonance imaging.

Abstract Estimating muscle volume (MV) using variable numbers of cross-sectional area (CSA) slices obtained from magnetic resonance imaging (MRI) introduces an error that is known in adults, but not in children and adolescents, whereby body sizes differ due to growth and maturation. Therefore, 15 children and adolescents (11 males, 14.8 ± 2.1 years) underwent MRI scans of the right thigh using a 1.5 T scanner to establish this error. A criterion MV was determined by tracing around and summing all CSAs, with MV subsequently estimated using every second, third, fourth and fifth CSA slice. Bland-Altman plots identified mean bias and limits of agreement (LoA) between methods. Error rates between 1.0 and 10.4% were seen between criterion and estimated MV. Additional analyses identified an impact of formulae selection, with a cylindrical formula preferred to a truncated cone. To counter high error between criterion and estimated MV due to the discrepancies in the number of CSA slices analysed, length-matched criterion volumes were established, with reduced error rates (0.5-2.0%) being produced as a result. CSA at 50% thigh-length also predicted MV, producing a high error (13.8-39.6%). Pearson's correlation coefficients determined relationships between error and measures of body size/composition, with all body size/composition measures being correlated (r = -0.78-0.86, p < 0.05) with the error between criterion and estimated MV. To conclude, MV can be accurately estimated using fewer CSA slices. However, the associated error must be considered when calculating MV in children and adolescents, as body size biases estimates.

Alpha-fetoprotein in pericardial, peritoneal, and pleural fluids: A body fluid matrix evaluation.

OBJECTIVES: Alpha-fetoprotein (AFP) measurement in pericardial, peritoneal (ascites), and pleural fluids is sometimes requested by clinicians as supportive evidence in the evaluation of suspected malignancy. As commercially available, Food and Drug Administration (FDA)-cleared AFP assays are not validated for these fluid types, laboratories must complete additional validation studies to comply with regulatory requirements for body fluid testing. The objective of this study was therefore to conduct a matrix evaluation for these body fluid types using the Beckman Access AFP assay on the UniCel DxI 800 immunoassay system. DESIGN AND METHODS: Using an Institutional Review Board (IRB) approved protocol, previously collected pericardial fluid, peritoneal fluid, pleural fluid, and serum specimens were de-identified and frozen at -20 °C prior to matrix evaluation experiments. Spiked recovery, mixed recovery/linearity, and precision studies were conducted. RESULTS: In spiked and mixed recovery studies, the average percent (%) recovery was within predefined acceptable limits (±15%) for all three body fluids. Linearity was observed over the analytical measurement range (AMR) for all three body fluids (slope, intercept, systematic error): pericardial 0.988, -0.1, 6.1%; peritoneal 0.986, 0.0, 4.1%; and pleural 1.016, 0.0, 1.6%. Imprecision was ≤6.0% CV for all three body fluids at both high and low AFP concentrations. CONCLUSIONS: Matrix interference with AFP testing was not observed for pericardial, peritoneal, or pleural fluids on the Beckman UniCel DxI 800 system.

Aberrant tRNA processing causes an autoinflammatory syndrome responsive to TNF inhibitors.

OBJECTIVES: To characterise the clinical features, immune manifestations and molecular mechanisms in a recently described autoinflammatory disease caused by mutations in TRNT1, a tRNA processing enzyme, and to explore the use of cytokine inhibitors in suppressing the inflammatory phenotype. METHODS: We studied nine patients with biallelic mutations in TRNT1 and the syndrome of congenital sideroblastic anaemia with immunodeficiency, fevers and developmental delay (SIFD). Genetic studies included whole exome sequencing (WES) and candidate gene screening. Patients' primary cells were used for deep RNA and tRNA sequencing, cytokine profiling, immunophenotyping, immunoblotting and electron microscopy (EM). RESULTS: We identified eight mutations in these nine patients, three of which have not been previously associated with SIFD. Three patients died in early childhood. Inflammatory cytokines, mainly interleukin (IL)-6, interferon gamma (IFN-γ) and IFN-induced cytokines were elevated in the serum, whereas tumour necrosis factor (TNF) and IL-1ß were present in tissue biopsies of patients with active inflammatory disease. Deep tRNA sequencing of patients' fibroblasts showed significant deficiency of mature cytosolic tRNAs. EM of bone marrow and skin biopsy samples revealed striking abnormalities across all cell types and a mix of necrotic and normal-appearing cells. By immunoprecipitation, we found evidence for dysregulation in protein clearance pathways. In 4/4 patients, treatment with a TNF inhibitor suppressed inflammation, reduced the need for blood transfusions and improved growth. CONCLUSIONS: Mutations of TRNT1 lead to a severe and often fatal syndrome, linking protein homeostasis and autoinflammation. Molecular diagnosis in early life will be crucial for initiating anti-TNF therapy, which might prevent some of the severe disease consequences.

Scaling the Oxygen Uptake Efficiency Slope for Body Size in Cystic Fibrosis.

PURPOSE: The aim of this study was to describe the relationship between body size and oxygen uptake efficiency slope (OUES) in pediatric patients with cystic fibrosis (CF) and healthy controls (CON), to identify appropriate scaling procedures to adjust the influence of body size upon OUES. METHODS: The OUES was derived using maximal and submaximal points from cardiopulmonary exercise testing in 72 children (36 CF and 36 CON). OUES was subsequently scaled for stature, body mass (BM), and body surface area (BSA) using ratio-standard (Y/X) and allometric (Y/X) methods. Pearson's correlation coefficients were used to determine the relationship between body size and OUES. RESULTS: When scaled using the ratio-standard method, OUES had a significant positive relationship with stature (r = 0.54, P < 0.001) and BSA (r = 0.25, P = 0.031) and significant negative relationship with BM (r = -0.38, P = 0.016) in the CF group. Combined allometric exponents (b) for CF and CON were stature 3.00, BM 0.86, and BSA 1.40. A significant negative correlation was found between OUES and stature in the CF group when scaled allometrically (r = -0.37, P = 0.027). Nonsignificant (P > 0.05) correlations for the whole group were found between OUES and allometrically scaled BM (CF r = -0.25, CON, r = 0.15) and BSA (CF r = -0.27, CON r = 0.13). CONCLUSIONS: Only allometric scaling of either BM or BSA, and not ratio-standard scaling, successfully eliminates the influence of body size upon OUES. Therefore, this enables a more direct comparison of the OUES between patients with CF and healthy controls.

MET-EGFR dimerization in lung adenocarcinoma is dependent on EGFR mtations and altered by MET kinase inhibition.

Advanced lung cancer has poor survival with few therapies. EGFR tyrosine kinase inhibitors (TKIs) have high response rates in patients with activating EGFR mutations, but acquired resistance is inevitable. Acquisition of the EGFR T790M mutation causes over 50% of resistance; MET amplification is also common. Preclinical data suggest synergy between MET and EGFR inhibitors. We hypothesized that EGFR-MET dimerization determines response to MET inhibition, depending on EGFR mutation status, independently of MET copy number. We tested this hypothesis by generating isogenic cell lines from NCI-H1975 cells, which co-express L858R and T790M EGFR mutations, namely H1975L858R/T790M (EGFR TKI resistant); H1975L858R (sensitized) and H1975WT (wild-type). We assessed cell proliferation in vitro and tumor growth/stroma formation in derived xenograft models in response to a MET TKI (SGX523) and correlated with EGFR-MET dimerization assessed by Förster Resonance Energy Transfer (FRET). SGX523 significantly reduced H1975L858R/T790M cell proliferation, xenograft tumor growth and decreased ERK phosphorylation. The same was not seen in H1975L858R or H1975WT cells. SGX523 only reduced stroma formation in H1975L858R. SGX523 reduced EGFR-MET dimerization in H1975L858R/T790M but induced dimer formation in H1975L858R with no effect in H1975WT. Our data suggests that MET inhibition by SGX523 and EGFR-MET heterodimerisation are determined by EGFR genotype. As tumor behaviour is modulated by this interaction, this could determine treatment efficacy.

Liver iron concentration measurements by MRI in chronically transfused children with sickle cell anemia: baseline results from the TWiTCH trial.

Noninvasive, quantitative, and accurate assessment of liver iron concentration (LIC) by MRI is useful for patients receiving transfusions, but R2 and R2* MRI techniques have not been systematically compared in sickle cell anemia (SCA). We report baseline LIC results from the TWiTCH trial, which compares hydroxyurea with blood transfusion treatment for primary stroke prophylaxis assessed by transcranial Doppler sonography in pediatric SCA patients. Liver R2 was collected and processed using a FDA-approved commercial process (FerriScan®), while liver R2* quality control and processing were performed by a Core Laboratory blinded to clinical site and patient data. Baseline LIC studies using both MRI techniques were available for 120 participants. LICR2* and LICR2 results were highly correlated (r(2) = 0.93). A proportional bias of LIC(R2*)/LIC(R2), decreasing with average LIC, was observed. Systematic differences between LICR2* and LICR2 were also observed by MRI manufacturer. Importantly, LICR2* and LICR2 estimates had broad 95% limits of agreement with respect to each other. We recommend LICR2 and LICR2* not be used interchangeably in SCA patients to follow individual patient trends in iron burden.

Performance characteristics of the ARCHITECT Active-B12 (Holotranscobalamin) assay.

BACKGROUND: Vitamin B12 (cobalamin) is a necessary cofactor in methionine and succinyl-CoA metabolism. Studies estimate the deficiency prevalence as high as 30% in the elderly population. Ten to thirty percent of circulating cobalamin is bound to transcobalamin (holotranscobalamin, holoTC) which can readily enter cells and is therefore considered the bioactive form. The objective of our study was to evaluate the analytical performance of a high-throughput, automated holoTC assay (ARCHITECT i2000(SR) Active-B12 (Holotranscobalamin)) and compare it to other available methods. METHODS: Manufacturer-specified limits of blank (LoB), detection (LoD), and quantitation (LoQ), imprecision, interference, and linearity were evaluated for the ARCHITECT HoloTC assay. Residual de-identified serum samples were used to compare the ARCHITECT HoloTC assay with the automated AxSYM Active-B12 (Holotranscobalamin) assay (Abbott Diagnostics) and the manual Active-B12 (Holotranscobalamin) Enzyme Immunoassay (EIA) (Axis-Shield Diagnostics, Dundee, Scotland, UK). RESULTS: Manufacturer's claims of LoB, LoD, LoQ, imprecision, interference, and linearity to the highest point tested (113.4 pmol/L) were verified for the ARCHITECT HoloTC assay. Method comparison of the ARCHITECT HoloTC to the AxSYM HoloTC produced the following Deming regression statistics: (ARCHITECT(HoloTc)) = 0.941 (AxSYM(HoloTC)) + 1.2 pmol/L, S(y/x) = 6.4, r = 0.947 (n = 98). Comparison to the Active-B12 EIA produced: (ARCHITECT(HoloTC)) = 1.105 (EIA(Active-B12)) - 6.8 pmol/L, S(y/x) = 11.0, r = 0.950 (n = 221). CONCLUSIONS: This assay performed acceptably for LoB, LoD, LoQ, imprecision, interference, linearity and method comparison to the predicate device (AxSYM). An additional comparison to a manual Active-B12 EIA method performed similarly, with minor exceptions. This study determined that the ARCHITECT HoloTC assay is suitable for routine clinical use, which provides a high-throughput alternative for automated testing of this emerging marker of cobalamin deficiency.

Body fluid matrix evaluation on a Roche cobas 8000 system.

OBJECTIVES: Chemical analysis of body fluids is commonly requested by physicians. Because most commercial FDA-cleared clinical laboratory assays are not validated by diagnostic manufacturers for "non-serum" and "non-plasma" specimens, laboratories may need to complete additional validation studies to comply with regulatory requirements regarding body fluid testing. The objective of this report is to perform recovery studies to evaluate potential body fluid matrix interferences for commonly requested chemistry analytes. DESIGN AND METHODS: Using an IRB-approved protocol, previously collected clinical body fluid specimens (biliary/hepatic, cerebrospinal, dialysate, drain, pancreatic, pericardial, peritoneal, pleural, synovial, and vitreous) were de-identified and frozen (-20°C) until experiments were performed. Recovery studies (spiking with high concentration serum, control, and/or calibrator) were conducted using 10% spiking solution by volume; n=5 specimens per analyte/body fluid investigated. Specimens were tested on a Roche cobas 8000 system (c502, c702, e602, and ISE modules). RESULTS: In all 80 analyte/body fluid combinations investigated (including amylase, total bilirubin, urea nitrogen, carbohydrate antigen 19-9, carcinoembryonic antigen, cholesterol, chloride, creatinine, glucose, potassium, lactate dehydrogenase, lipase, rheumatoid factor, sodium, total protein, triglycerides, and uric acid), the average percent recovery was within predefined acceptable limits (less than ±10% from the calculated ideal recovery). CONCLUSIONS: The present study provides evidence against the presence of any systematic matrix interference in the analyte/body fluid combinations investigated on the Roche cobas 8000 system. Such findings support the utility of ongoing body fluid validation initiatives conducted to maintain compliance with regulatory requirements.

Congenital hemophagocytic lymphohistiocytosis presenting as thrombocytopenia in a newborn.

Hemophagocytic lymphohistiocytosis (HLH) is a disease caused by dysregulation and hyperactivation of the immune system, and can be familial or acquired. HLH presenting in infancy can be rapidly fatal if not promptly recognized and treated. Congenital HLH can be caused by various genetic mutations or part of immunodeficiency syndromes. We present an infant with Griscelli syndrome and familial HLH with atypical genetic mutations, presenting as thrombocytopenia on the first day of life, cured with chemotherapy and unrelated cord blood transplant.

Copper bromide laser for facial telangiectasia: a dose response evaluation.

Facial telangiectases are small dilated vessels that are visible on the skin surface. They are a cosmetic disfigurement for millions of people, making their treatment one of the most frequently requested procedures in dermatology. Several treatment choices are available, including a variety of lasers. The purpose of this study was to evaluate the results, using a copper bromide laser, of variable energy levels related to vessel size and location, including side effects, and to survey patient assessment of benefit and tolerance. Two groups of 19 patients were treated at 23 J/cm(2) and 28 J/cm(2) , and 32 J/cm(2) and 38 J/cm(2) , respectively. Only facial telangiectasias were treated. Benefit was seen at all energy settings. Little additional benefit was noted with energy increase alone, but it was noted with a second treatment. This study showed that the copper bromide laser is a very effective, safe, and well tolerated treatment for facial telangiectasia at all four tested energy levels.

Blastomycosis presenting as a nonhealing wound.

A 41-year-old man was referred to the wound clinic for an enlarging 9.5 x 14-cm ulceration of the right upper arm of 8 months' duration. A biopsy was obtained, and fungal stains showed broad-based budding spores typical of blastomycosis. He was treated with oral itraconazole, and the ulcer healed in 2 months. Blastomycosis is a systemic fungal infection acquired by inhalation of the spores of the fungus Blastomyces dermatitidis. Initially a pulmonary infection, the skin is the most common secondary site of involvement. More typically presenting as hyperkeratotic nodules, it may occur as ulcerations. Blastomycosis has significant morbidity and mortality, and in unsuspected or asymptomatic cases, the skin lesions may be the key to successful diagnosis and treatment.

Performance characteristics of a new Immulite(®) 2000 system erythropoietin assay.

BACKGROUND: Serum erythropoietin (EPO) measurements are useful for diagnostic evaluations of anemia, polycythemia, and other erythroid disorders. METHODS: We evaluated a new formulation of the chemiluminescent immunoassay for EPO on the Immulite 2000 analyzer (Siemens Healthcare Diagnostics) for limit of blank (LoB), imprecision, linearity, interference, comparison to another commercially available assay, reference interval, and cross-reactivity with 2 recombinant EPO preparations. RESULTS: The LoB was 0.23IU/l. Total imprecision ranged from 4.2 to 12.1%. The assay was linear from 0 to 678IU/l. Hemoglobin caused negative interference at concentrations >17.4g/l. Deming regression from the method comparison study gave a slope of 1.00±0.04, an intercept of 3.9±12.7, and a S(y/x) of 44.9 (r=0.98). The non-parametric reference interval was 3.3 to 23.4IU/l. Epoetin alfa at a1:2000 dilution gave mean results of 541IU/l and 650IU/l for Immulite 2000 and Access 2, respectively. Darbopoetin alfa at a 1:2000 dilution gave mean results of 337IU/l and 579IU/l for the Immulite 2000 and Access 2, respectively, indicating the 2 assays have substantially different cross-reactivities with recombinant EPO preparations. CONCLUSIONS: The new Immulite 2000 EPO assay shows acceptable performance and is suitable for routine clinical use.