Prognostic factors in seminomas with special respect to HCG: Results of a prospective multicenter study

Objective: In a prospective multicenter trial, it was our intention to elucidate clinical prognostic factors of seminomas with special reference to the importance of human chorionic gonadotropin (HCG) elevations in histologically pure seminomas. Methods: Together with 96 participating urological departments in Germany, Austria, and Switzerland, we recruited 803 seminoma patients between 1986 and 1991. Out of 726 evaluable cases, 378 had elevated, while 348 had normal HCG values in the cubital vein. Histology was reviewed by two reference pathologists. HCG levels were determined in local laboratories and in a study laboratory. Standard therapy was defined as radiotherapy in stages I (30 Gy) and IIA/B (36 Gy) to the paraaortal and the ispilateral (stage I) and bilateral (stage IIA/B) iliac lymph nodes; higher stages received polychemotherapy and surgery in case of residual tumor masses. Statistics included chi-square tests, linear Cox regression, and log-rank test. Results: The HCG elevation is associated with a larger tumor mass (primary tumor and/or metastases). HCG-positive and HCG-negative seminomas had no different prognostic outcome after standard therapy. The overall relapse rate of 6% and the survival rate of 98% after 36 months (median) indicate an excellent prognosis. The calculation of the relative risk of developing a relapse discovered only stage of the disease and elevation of the lactate dehydrogenase concentration and its prolonged marker decay as independent prognostic factors for seminomas. A more detailed analysis of the prognostic significance of the stage revealed that the high relapse rate in stage IIB seminomas after radiotherapy (24%) is responsible for this result. Conclusions: We conclude that HCG-positive seminomas do not represent a special entity. Provided standard therapy is applied, HCG has no influence on the prognosis. Patients with stage IIB disease should be treated with chemotherapy because of the demonstrated higher relapse rate outside the retroperitoneum. Copyright (C) 1999 S. Karger AG. Basel

Improved radiative corrections for (e,e'p) experiments - A novel approach to multi-photon bremsstrahlung

Radiative processes lead to important corrections to (e,e'p) experiments. While radiative corrections can be calculated exactly in QED and to a good accuracy also including hadronic corrections, these corrections cannot be included into data analyses to arbitrary orders exactly. Nevertheless consideration of multi-photon bremsstrahlung above the low-energy cut-off is important for many (e,e'p) experiments. To date, higher-order bremsstrahlung effects concerning electron scattering experiments have been implemented approximately by employing the soft-photon approximation (SPA). In this paper we propose a novel approach to multi-photon emission which partially removes the SPA from (e,e'p) experiments. In this combined approach one hard photon is treated exactly; and additional softer bremsstrahlung photons are taken into account resorting to the soft-photon approximation. This partial removal of the soft-photon approximation is shown to be relevant for the missing-energy distribution for several kinematic settings at MAMI and TJNAF energies.Comment: 10 pages, 21 figure

Operator Method for Nonperturbative Calculation of the Thermodynamic Values in Quantum Statistics. Diatomic Molecular Gas

Operator method and cumulant expansion are used for nonperturbative calculation of the partition function and the free energy in quantum statistics. It is shown for Boltzmann diatomic molecular gas with some model intermolecular potentials that the zeroth order approximation of the proposed method interpolates the thermodynamic values with rather good accuracy in the entire range of both the Hamiltonian parameters and temperature. The systematic procedure for calculation of the corrections to the zeroth order approximation is also considered.Comment: 22 pages, 7 Postscript figures, accepted for publication in Journal of Physics

Improved radiative corrections and proton charge form factor from the Rosenbluth separation technique

We investigate whether the apparent discrepancy between proton electric form factor from measurements using the Rosenbluth separation technique and polarization transfer method is due to the standard approximations employed in radiative correction procedures. Inaccuracies due to both the peaking approximation and the soft-photon approximation have been removed in our simulation approach. In contrast to results from (e,e'p) experiments, we find them in this case to be too small to explain the discrepancy.Comment: 6 pages, 3 figure

Relationship of Genotype, Phenotype, and Treatment in Dopa-Responsive Dystonia: MDSGene Review

Background Pathogenic variants in 5 genes (GCH1, TH, PTS, SPR, and QDPR), involved in dopamine/tetrahydrobiopterin biosynthesis or recycling, have been linked to Dopa-responsive dystonia (DRD). Diagnosis and treatment are often delayed due to high between- and within-group variability. Objectives Comprehensively analyzed individual genotype, phenotype, treatment response, and biochemistry information. Methods 734 DRD patients and 151 asymptomatic GCH1 mutation carriers were included using an MDSGene systematic literature review and an automated classification approach to distinguish between different forms of monogenic DRDs. Results Whereas dystonia, L-Dopa responsiveness, early age at onset, and diurnal fluctuations were identified as red flags, parkinsonism without dystonia was rarely reported (11%) and combined with dystonia in only 18% of patients. While sex was equally distributed in autosomal recessive DRD, there was female predominance in autosomal dominant DYT/PARK-GCH1 patients accompanied by a lower median age at onset and more dystonia in females compared to males. Accordingly, the majority of asymptomatic heterozygous GCH1 mutation carriers (>8 years of age) were males. Multiple other subgroup-specific characteristics were identified, showing high accuracy in the automated classification approach: Seizures and microcephaly were mostly seen in DYT/PARK-PTS, autonomic symptoms appeared commonly in DYT/PARK-TH and DYT/PARK-PTS, and sleep disorders and oculogyric crises in DYT/PARK-SPR. Biochemically, homovanillic acid and 5-hydroxyindoleacetic acid in CSF were reduced in most DRDs, but neopterin and biopterin were increased only in DYT/PARK-PTS and DYT/PARK-SPR. Hyperphenylalaninemia was seen in DYT/PARK-PTS, DYT/PARK-QDPR, and rarely reported in autosomal recessive DYT/PARK-GCH1. Conclusions Our indicators will help to specify diagnosis and accelerate start of treatment. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Societ

Maternal PlGF and umbilical Dopplers predict pregnancy outcomes at diagnosis of early-onset fetal growth restriction

BACKGROUND: Severe, early-onset fetal growth restriction (FGR) causes significant fetal and neonatal mortality and morbidity. Predicting the outcome of affected pregnancies at the time of diagnosis is difficult, thus preventing accurate patient counseling. We investigated the use of maternal serum protein and ultrasound measurements at diagnosis to predict fetal or neonatal death and 3 secondary outcomes: fetal death or delivery at or before 28+0 weeks, development of abnormal umbilical artery (UmA) Doppler velocimetry, and slow fetal growth. // METHODS: Women with singleton pregnancies (n = 142, estimated fetal weights [EFWs] below the third centile, less than 600 g, 20+0 to 26+6 weeks of gestation, no known chromosomal, genetic, or major structural abnormalities) were recruited from 4 European centers. Maternal serum from the discovery set (n = 63) was analyzed for 7 proteins linked to angiogenesis, 90 additional proteins associated with cardiovascular disease, and 5 proteins identified through pooled liquid chromatography and tandem mass spectrometry. Patient and clinician stakeholder priorities were used to select models tested in the validation set (n = 60), with final models calculated from combined data. // RESULTS: The most discriminative model for fetal or neonatal death included the EFW z score (Hadlock 3 formula/Marsal chart), gestational age, and UmA Doppler category (AUC, 0.91; 95% CI, 0.86–0.97) but was less well calibrated than the model containing only the EFW z score (Hadlock 3/Marsal). The most discriminative model for fetal death or delivery at or before 28+0 weeks included maternal serum placental growth factor (PlGF) concentration and UmA Doppler category (AUC, 0.89; 95% CI, 0.83–0.94). // CONCLUSION: Ultrasound measurements and maternal serum PlGF concentration at diagnosis of severe, early-onset FGR predicted pregnancy outcomes of importance to patients and clinicians. // TRIAL REGISTRATION: ClinicalTrials.gov NCT02097667. // FUNDING: The European Union, Rosetrees Trust, Mitchell Charitable Trust