Correction to: Translation and cross-cultural adaptation of eight pediatric PROMIS® item banks into Spanish and German.

In the original publication of the article, two of the author names "L. A. Schröder, F. Metzner" and email address of the authors "J. Devine, J. Moon, A. C. Haller" were missed out. The correct author group with affiliations are provided in this correction.

Translation and cross-cultural adaptation of eight pediatric PROMIS® item banks into Spanish and German.

PURPOSE: The Patient-Reported Outcome Measurement Information System (PROMIS®) is a National Institutes of Health (NIH)-funded initiative to develop reliable, valid, and normed item banks to measure health. We describe the first large-scale translation and cross-cultural adaptation effort to German and Spanish of eight pediatric PROMIS item banks: Physical activity (PAC), subjective well-being (SWB), experiences of stress (EOS), and family relations (FAM). METHODS: We utilized methods outlined in the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) PRO Translation Task Force recommendations. Ten professional translators performed a translatability assessment and generated forward translations. Forward Translations were compared within a country and cross-culturally to identify problems and to produce a consensus-derived version, which was then back translated, evaluated, and revised where necessary. Reconciled versions were evaluated in cognitive interviews with 126 children before finalization. RESULTS: Eight resulting pediatric PROMIS® item banks were translated: Two PAC banks (22 total items), three SWB banks (125 total items), two EOS banks (45 total items), and one FAM bank (47 total items). Up to 92% of all items raised no or only minor translation difficulties, 0-5.6% were difficult to translate. Up to 20% item revisions were necessary to ensure conceptual equivalence and comprehensibility. Cognitive interviews indicated that 91-94% of the final items were appropriate for children (8-17 years). CONCLUSIONS: German and Spanish translations of eight PROMIS Pediatric item banks were created for clinical trials and routine pediatric health care. Initial translatability assessment and rigorous translation methodology helped to ensure conceptual equivalence and comprehensibility. Next steps include cross-cultural validation and adaptation studies.

Toxicity Assessment of a Phase III Study Evaluating FEC-Doc and FEC-Doc Combined with Gemcitabine as an Adjuvant Treatment for High-Risk Early Breast Cancer: the SUCCESS-A Trial.

Introduction: This paper aims to evaluate the toxicity profile of additive gemcitabine to adjuvant taxane-based chemotherapy in breast cancer patients. Methods: Patients enrolled in this open-label randomized controlled Phase III study were treated with 3 cycles of epirubicin-fluorouracil-cyclophosphamide (FEC) chemotherapy followed by 3 cycles of docetaxel with those receiving 3 cycles of FEC followed by 3 cycles of gemcitabine-docetaxel (FEC-DG). 3690 patients were evaluated according to National Cancer Institute (NCI) toxicity criteria (CTCAE). The study medications were assessed by the occurrence of grade 3-4 adverse events, dose reductions, postponements of treatment cycles and granulocyte colony-stimulating factor (G-CSF) support. Results: No differences in neutropenia or febrile neutropenia were demonstrated. However, thrombocytopenia was significantly increased with FEC-DG treatment (2.0 vs. 0.5 %, p < 0.001), as was leukopenia (64.1 vs. 58.5 %, p < 0.001). With FEC-DG significantly more G-CSF support in cycles 4 to 6 (FEC-DG: 57.8 %, FEC-D: 36.3 %, p < 0.001) was provided. Transaminase elevation was significantly more common with FEC-DG (SGPT: 6.3 %, SGOT: 2 %), whereas neuropathy (1.2 %), arthralgia (1.6 %) and bone pain (2.6 %) were more common using FEC-D. Dose reductions > 20 % (4 vs. 2.4 %) and postponement of treatment cycles (0.9 vs. 0.4 %) were significantly more frequent in the FEC-DG arm. Eight deaths occurred during treatment in the FEC-DG arm and four in the FEC-D arm. Conclusion: The addition of gemcitabine increased hematological toxicity and was associated with more dose reductions and postponements of treatment cycles.

Facial emotion recognition and its relationship to cognition and depressive symptoms in patients with Parkinson's disease.

BACKGROUND: Impairments in facial emotion recognition (FER) have been detected in patients with Parkinson disease (PD). Presently, we aim at assessing differences in emotion recognition performance in PD patient groups with and without mild forms of cognitive impairment (MCI) compared to healthy controls. METHODS: Performance on a concise emotion recognition test battery (VERT-K) of three groups of 97 PD patients was compared with an age-equivalent sample of 168 healthy controls. Patients were categorized into groups according to two well-established classifications of MCI according to Petersen's (cognitively intact vs. amnestic MCI, aMCI, vs. non-amnestic MCI, non-aMCI) and Litvan's (cognitively intact vs. single-domain MCI, sMCI, vs. multi-domain MCI, mMCI) criteria. Patients and controls underwent individual assessments using a comprehensive neuropsychological test battery examining attention, executive functioning, language, and memory (Neuropsychological Test Battery Vienna, NTBV), the Beck Depression Inventory, and a measure of premorbid IQ (WST). RESULTS: Cognitively intact PD patients and patients with MCI in PD (PD-MCI) showed significantly worse emotion recognition performance when compared to healthy controls. Between-groups effect sizes were substantial, showing non-trivial effects in all comparisons (Cohen's ds from 0.31 to 1.22). Moreover, emotion recognition performance was higher in women, positively associated with premorbid IQ and negatively associated with age. Depressive symptoms were not related to FER. CONCLUSIONS: The present investigation yields further evidence for impaired FER in PD. Interestingly, our data suggest FER deficits even in cognitively intact PD patients indicating FER dysfunction prior to the development of overt cognitive dysfunction. Age showed a negative association whereas IQ showed a positive association with FER.

Persistent CMV infection after allogeneic hematopoietic stem cell transplantation in a CMV-seronegative donor-to-positive recipient constellation: Development of multidrug resistance in the absence of anti-viral cellular immunity.

We describe a case of persistent cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with discordant and high-risk (D-/R+) constellation of CMV serostatus. Despite the use of different and innovative antiviral strategies, viral replication could not be suppressed successfully promoting a protracted CMV colitis associated with severe gastrointestinal graft-versus-host disease (GI GVHD). We illustrate that the development of multidrug viral resistance, the failure to mount a CMV-specific cellular immune response, as confirmed by QuantiFERON(®)-CMV (Qiagen) assay, and the refractory GVHD requiring prolonged immunosuppression were the main factors contributing to persistent viral replication and the fulminant unfavorable course.

Quantitative chemical exchange saturation transfer with hyperpolarized nuclei (qHyper-CEST): sensing xenon-host exchange dynamics and binding affinities by NMR.

The reversible binding of xenon to host molecules has found numerous applications in nuclear magnetic resonance studies. Quantitative characterization of the Xe exchange dynamics is important to understand and optimize the physico-chemical behavior of such Xe hosts, but is often challenging to achieve at low host concentrations. We have investigated a sensitive quantification technique based on chemical exchange saturation transfer with hyperpolarized nuclei, qHyper-CEST. Using simulated signals we demonstrated that qHyper-CEST yielded accurate and precise results and was robust in the presence of large amounts of noise (10%). This is of particular importance for samples with completely unknown exchange rates. Using these findings we experimentally determined the following exchange parameters for the Xe host cryptophane-A monoacid in dimethyl sulfoxide in one type of experiment: the ratio of bound and free Xe, the Xe exchange rate, the resonance frequencies of free and bound Xe, the Xe host occupancy, and the Xe binding constant. Taken together, qHyper-CEST facilitates sensitive quantification of the Xe exchange dynamics and binding to hydrophobic cavities and has the potential to analyze many different host systems or binding sites. This makes qHyper-CEST an indispensable tool for the efficient design of highly specific biosensors.

Observing and preventing rubidium runaway in a direct-infusion xenon-spin hyperpolarizer optimized for high-resolution hyper-CEST (chemical exchange saturation transfer using hyperpolarized nuclei) NMR.

Xenon is well known to undergo host-guest interactions with proteins and synthetic molecules. As xenon can also be hyperpolarized by spin exchange optical pumping, allowing the investigation of highly dilute systems, it makes an ideal nuclear magnetic resonance probe for such host molecules. The utility of xenon as a probe can be further improved using Chemical Exchange Saturation Transfer using hyperpolarized nuclei (Hyper-CEST), but for highly accurate experiments requires a polarizer and xenon infusion system optimized for such measurements. We present the design of a hyperpolarizer and xenon infusion system specifically designed to meet the requirements of Hyper-CEST measurements. One key element of this design is preventing rubidium runaway, a chain reaction induced by laser heating that prevents efficient utilization of high photon densities. Using thermocouples positioned along the pumping cell we identify the sources of heating and conditions for rubidium runaway to occur. We then demonstrate the effectiveness of actively cooling the optical cell to prevent rubidium runaway in a compact setup. This results in a 2-3-fold higher polarization than without cooling, allowing us to achieve a polarization of 25% at continuous flow rates of 9 ml/min of (129)Xe. The simplicity of this design also allows it to be retrofitted to many existing polarizers. Combined with a direction infusion system that reduces shot-to-shot noise down to 0.56% we have captured Hyper-CEST spectra in unprecedented detail, allowing us to completely resolve peaks separated by just 1.62 ppm. Due to its high polarization and excellent stability, our design allows the comparison of underlying theories of host-guest systems with experiment at low concentrations, something extremely difficult with previous polarizers.

[Chronic pruritus in autoimmune dermatoses : results of a comparative survey]. / Chronischer Pruritus bei Autoimmundermatosen : Ergebnisse einer vergleichenden Fragebogenstudie.

As the frequency and characteristics of chronic pruritus in autoimmune dermatoses (AID) have not yet been investigated, the present study aimed at characterizing pruritus in a representative group of patients with AID. A total of 35 patients (80% women) with AID were included, divided into 3 main groups (group 1; n = 19: bullous pemphigoid (BP), pemphigus vulgaris (PV); group 2; n = 9: scleroderma (SSc), morphea (Mo); group 3; n = 7: lupus erythematosus (LE), dermatomyositis (DM). Demographic data and pruritus characteristics were obtained by standardized questionnaires and statistically evaluated by SPSS 20.0. In group 1 (BP/PV) and group 3 (LE/DM), pruritus preceded the initial diagnosis of AID (2.1 ± 7.6 years and 9.5 ± 16.0 years). Patients in group 2 (SSc/Mo) reported pruritus initially 2.8 ± 8.6 years after the initial diagnosis. In group 1 (BP/PV) significantly (p < 0.05) more excoriations and relief by scratching were observed than in groups 2 (SSc/Mo) and 3 (LE/DM). While pruritus occurred as a prodromal symptom of BP/PV and LE/DM, it was only detected once the initial diagnosis of SSc/Mo was made. In contrast to BP/PV, the other forms of AID were associated with mechanically inducible pruritus with dysesthetic qualities. All forms of AID were associated with intensive pruritus which had a significant impact on quality of life.

Delayed operative management of fractures of the scapula.

Between 1998 and 2007, 22 patients with fractures of the scapula had operative treatment more than three weeks after injury. The indications for operation included displaced intra-articular fractures, medialisation of the glenohumeral joint, angular deformity, or displaced double lesions of the superior shoulder suspensory complex. Radiological and functional outcomes were obtained for 16 of 22 patients. Disabilities of the Arm, Shoulder, Hand (DASH) and Short form-36 scores were collected for 14 patients who were operated on after March 2002. The mean delay from injury to surgery was 30 days (21 to 57). The mean follow-up was for 27 months (12 to 72). At the last review the mean DASH score was 14 (0 to 41). Of the 16 patients with follow-up, 13 returned to their previous employment and recreational activities without restrictions. No wound complications, infection or nonunion occurred. Malunion of the scapula can be prevented by surgical treatment of fractures in patients with delayed presentation. Surgery is safe, effective, and gives acceptable functional results.

Validation of the in vitro gastrointestinal (IVG) method to estimate relative bioavailable lead in contaminated soils.

The effect of the dosing vehicle (e.g., dough) on the ability of an in vitro gastrointestinal (IVG) method to predict relative bioavailable Pb associated with soil ingestion was evaluated. Bioaccessible Pb determined by the IVG method was compared with relative bioavailable Pb measured from dosing trials using juvenile swine for 18 contaminated soils ranging from 1270 to 14200 mg Pb kg(-1). Bioaccessible Pb was measured in the IVG gastric extraction (GE) and intestinal extraction (IE) solutions. Mean bioaccessible Pb values were 32.2% for GE without dough, 23.0% for GE with dough, 1.06% for IE without dough, and 0.56% for IE with dough. It is possible that phytic acid associated with the dough addition decreased bioaccessible Pb. In vivo relative bioavailable Pb ranges for different swine tissues were 1 to 87% for blood, 0 to 110% for liver, 1 to 124% for kidney, and 0.04 to 94% for bone. Strong linear relationships between IVG GE Pb with dough (r > 0.76, P < 0.0002), IVG IE Pb with dough (r > 0.56, P < 0.015), and IVG GE Pb without dough (r > 0.81, P < 0.0001) and in vivo bioavailable Pb as estimated with blood, kidney, liver, and bone were found. Inexpensive in vitro methods may be useful in providing an estimate of the variability in relative bioavailable Pb at a single study site. The IVG method can be used to estimate relative bioavailable Pb, As, and Cd in contaminated soil.

[Magnetic resonance imaging spectroscopy. Part 1: Basics]. / Magnetresonanzspektroskopie. Teil 1: Grundlagen.

A century after the discovery of X-rays, the low-energy range of the electromagnetic spectrum also attained broad application in radiology. Radiofrequency waves allow excitation in a magnetic field of the magnetic resonance of spin-bearing nuclei in tissue. Using the intense signal of the water protons, morphological images of the human body can be obtained, while at a higher frequency resolution also endogenous metabolites as well as pharmaceuticals, which contain MR-visible nuclei (e.g., 1H, 13C, 19F, 31P), can be detected noninvasively and in vivo. Accordingly, in vivo MR spectroscopy is a technique which is sensitive to molecules and molecular properties and which can be applied to repeated examinations. Its major limitation is the low signal intensity vs noise, which implies long measurement times and poor spatial resolution. Using spectroscopic imaging, the distribution of metabolites within an organ can be monitored selectively and displayed as a molecular image.

Allergic granulomatosis secondary to a limited form of Churg-Strauss syndrome.

Allergic granulomatosis is a disorder of obscure etiology characterized by infiltration of lymph nodes with histiocytic granulomas and eosinophils. In this report, we describe a case of allergic granulomatosis that is consistent with Churg-Strauss disease limited to lymph nodes. The histologic findings of this patient's lymph nodes demonstrated eosinophilic abscesses and ring-shaped necrotizing and nonnecrotizing granulomas surrounding hyperplastic germinal centers. We report herein a rare type of reactive lymphadenopathy and present its histologic, immunohistochemical, and flow cytometric findings, which may allow its distinction from other lymphadenopathies.

Phase II evaluation of suramin in advanced renal cell carcinoma. A Southwest Oncology Group study.

Twenty-two eligible patients with advanced renal carcinoma were treated with suramin utilizing a fixed dose regimen. Therapy was reasonably well tolerated with 3 of 22 patients (14%) developing grade 4 toxicity and 11 of 22 patients (50%) having a maximum toxicity of grade 3. There were no responders; median survival was 10 months. Suramin is not an active agent in advanced renal carcinoma.

Oligoclonal T-cell receptor usage of melanocyte differentiation antigen-reactive T cells in stage IV melanoma patients.

Ex vivo ELISPOT analysis of peripheral blood lymphocytes obtained from stage IV melanoma patients demonstrated reactivity against peptides derived from MART-1 and gp100. However, the number of reactive T cells was < 1% that of total lymphocytes as detected by flow cytometry using tetrameric MHC/peptide complexes. Despite this low frequency, we were able to directly isolate these populations ex vivo by means of magnetic beads coated with MHC/peptide complexes and to subject these cells to T-cell receptor clonotype mapping. This analysis revealed that the MART-1/A*0201- and gp100/A*0201-reactive T-cell populations are composed of oligoclonal T cells that engage several T-cell receptor beta chain families. Longitudinal studies using this approach may result in a better correlation between T-cell reactivity and the course of neoplastic disease.

A phase II trial of etoposide, leucovorin, 5-FU, and interferon alpha 2b (ELFI) + G-CSF for patients with pancreatic adenocarcinoma: a Southwest Oncology Group study (SWOG 9413).

BACKGROUND: Chemotherapeutic treatments using combinations of etoposide, leucovorin and 5-FU (ELF) have shown activity in the treatment of gastrointestinal malignancies. Interferon alpha 2b is known to have antiproliferative effects on several cell lines and has well documented in vitro evidence of synergism with 5-FU. It was postulated that the combination of ELF and interferon alpha 2b would improve response rates and survival in patients with pancreas cancer. METHODS: Fifty-five eligible patients with locally-advanced or metastatic pancreatic adenocarcinoma received a regimen consisting of: i.v. leucovorin at 300 mg/m2/day on Days 1-3 (of 28-day cycle), i.v. etoposide at 80 mg/m2/day on Days 1-3, i.v. 5-FU at 500 mg/m2/day on Days 1-3, subcutaneous interferon alpha 2b at 3 million units TIW, and subcutaneous G-CSF at 5 microg/kg/day on Days 4-14 (or until WBC exceeds 10,000/microl). Patients with no evidence of disease progression continued on treatment for a total of 6 cycles. RESULTS: Complete response was demonstrated in 1 patient, partial response in 5 patients (11% confirmed response rate). The median survival was 5 months, and the six-month survival rate was 40%. Ten patients completed all 6 cycles of treatment. Toxicity-related dose delays and reductions were necessary for most patients. CONCLUSIONS: Although the combination of ELF and interferon alpha 2b (ELFI) has modest activity in pancreatic cancer, it is a toxic and complex regimen that is not superior to other currently available approaches for the chemotherapeutic management of pancreatic cancer. ELFI cannot be recommended as a standard therapy.

Complexes of serum amyloid P component and DNA in serum from healthy individuals and systemic lupus erythematosus patients.

Serum amyloid P component (SAP) binds in vitro to DNA; based on findings in SAP-deficient mice it was proposed that SAP's role is to handle chromatin and DNA, thereby preventing formation of anti-DNA antibodies. For the first time we have shown the presence of Ca2+-dependent SAP-DNA complexes, measured by ELISA, in sera from both healthy volunteers and systemic lupus erythematosus patients (SLE). The concentration of SAP-DNA complexes in SLE sera was significantly lower than in normal sera and particularly low in sera from patients with anti-DNA titers exceeding 50. The complexes were dissociated by the SAP ligand heparin and were not demonstrable in EDTA plasma. Normal sera showed similar capacity to form SAP-DNA complexes with both thymus and Escherichia coli DNA, whereas significantly lower amounts of complexes, in particular with E. coli DNA, were formed in SLE sera. SLE patients with moderate to high anti-DNA titers showed a significant negative correlation between serum SAP's binding of E. coli DNA and the anti-DNA titer.

Treatment of poor-prognosis extensive disease small-cell lung cancer with an all-oral regimen of etoposide and cyclophosphamide - a Southwest Oncology Group clinical and pharmacokinetic study.

PURPOSE: An all-oral regimen of etoposide and cyclophosphamide was developed for use in poor-prognosis extensive disease small-cell lung cancer. Limited pharmacokinetic sampling was used to derive a pharmacodynamic model predictive of myelosuppression early in the course of therapy. PATIENTS AND METHODS: Eligible patients were chemotherapy-naive and had extensive disease small-cell lung cancer with either SWOG performance status 2 or serum albumin <3.5 g/dl. The first cohort (n = 18) received etoposide orally at 50 mg daily and cyclophosphamide orally at 50 mg daily days 1-14 every 28 days. Due to good hematologic tolerance, the second cohort (n = 39) received both agents orally at 50 mg twice daily days 1-14 every 28 days. Plasma etoposide levels were determined in samples drawn at baseline, and at 1 h, 2 h, and 23.5 h (trough) after the first dose. Linear regression analysis was used to determine pharmacokinetic and demographic parameters predictive of myelosuppression. RESULTS: A total of 173 treatment cycles were delivered. Patients on the daily regimen had a 22% response rate (complete and partial), a 22% unconfirmed response rate, and a 5-month median survival, while patients on the twice-daily regimen had a 28% response rate (complete and partial), a 13% unconfirmed response rate, and a 7-month median survival. Granulocytopenia and alopecia were the most common toxicities seen. Significant granulocytopenia could be predicted for the twice-daily regimen according to the formula ln(AGC nadir)=7.80 - 1.88(trough), with an increased incidence of granulocytopenia if the etoposide trough value was >/=1.49 microg/ml. CONCLUSION: Oral etoposide and oral cyclophosphamide given days 1-14 every 28 days is well tolerated and results in an acceptable response rate and median survival in poor-prognosis (poor performance status or low serum albumin) extensive disease small-cell lung cancer. A trough etoposide level obtained within 24 h of starting therapy can predict severe granulocytopenia.

Rhenium-188(Sn)HEDP for treatment of osseous metastases.

UNLABELLED: Rhenium-188 (tin) hydroxyethylidine diphosphonate [188Re(Sn)HEDP] is a new radiopharmaceutical that localizes in skeletal metastases and emits beta particles that may be therapeutically beneficial. METHODS: It was evaluated by in vitro and in vivo testing in the laboratory, in animals and in humans using 188Re from a variety of sources. It may be produced by a desk-top method developed previously for 186Re(Sn)HEDP using 188Re produced through neutron irradiation of either enriched 187Re or naturally occurring rhenium targets or the use of a 188W/188Re generator. RESULTS: So long as the mass of rhenium in the 188Re-perrhenate to be processed into 188Re(Sn)HEDP is at least 100 microg, satisfactory radiochemical yields and purity may be obtained by all methods. The 188Re(Sn)HEDP has biodistribution and radiation dosimetry characteristics that are similar to those noted previously for 186Re(Sn)HEDP and appears to result in similar benefits and toxicities in patients with skeletal metastases. External radiation exposure monitoring indicates that, only 4 hr after a therapeutic administration of 1110 MBq (30 mCi) of 188Re(Sn)HEDP, average exposure rates at 1 meter from the patient would be only 0.5 mR/hr. CONCLUSION: Same-day, on-demand, outpatient therapy of disseminated skeletal metastases appears to be feasible with 188Re(Sn)HEDP.

Determination of biotransformation products of platinum drugs in rat and human urine.

Cisplatin is an extremely effective cancer chemotherapeutic agent, but its use is often accompanied by toxicity. Second generation drugs such as carboplatin are becoming more widely used because of reduced toxicity. Since biotransformation products have been implicated in the toxic responses, we have begun to investigate the reactions of cisplatin and carboplatin with potential biological ligands. Reaction products were characterized using HPLC with inductively coupled plasma - mass spectrometry (HPLC-ICP-MS), (1)H and (13)C NMR and fast atom bombardment - mass spectrometry (FAB-MS). Three Pt-creatinine complexes, cis-[Pt(NH(3))(2)Cl(Creat)](+), cis-[Pt(NH(3))(2)(H(2)O)(Creat)](2+) and cis-[Pt(NH(3))(2)(Creat)(2)](2+), were synthesized and the platinum was shown to coordinate to the ring nitrogen, N(3). Human urine samples from patients on cisplatin chemotherapy were shown to contain cisplatin, its hydrolysis product and biotransformation products containing Pt-creatinine, Pt-urea and Pt-uric acid complexes. Urine from carboplatin patients shows fewer biotransformation products. Studies with control and diabetic (protected against cisplatin toxicity) rats showed systematic differences in the biotransformation products formed on administration of cisplatin.

Phase II evaluation of doxorubicin/vinblastine combined with inhibitors trifluoperazine/verapamil of P-glycoprotein in patients with advanced renal carcinoma.

Doxorubicin/vinblastine combined with the P-glycoprotein inhibitors trifluoperazine and verapamil was evaluated in the treatment of patients with metastatic renal carcinoma. Patients were treated with starting doses of doxorubicin/vinblastine of 30 mg/m(2) (doxorubicin) and 3 mg/m(2) (vinblastine) intravenously every 2 weeks, combined with 4 days of oral trifluoperazine/verapamil at 2 mg tid (trifluoperazine) and 160 mg tid (verapamil) administered I day before the chemotherapy was initiated. Response was assessed every three cycles of treatment. Of 26 evaluable patients, there were no responders. Six patients had stable disease for greater than 6 months on treatment. Therapy was generally well tolerated but 7 of 26 patients developed grade 4 granulocytopenia, including one patient who died due to sepsis. The possible reasons for the failure of P-glycoprotein inhibitors to enhance the effect of chemotherapy are discussed.