Quality of teaching radiation oncology in Germany-where do we stand? : Results from a 2019 survey performed by the working group "young DEGRO" of the German Society of Radiation Oncology.

PURPOSE: Medical students' knowledge of radiation oncology (RO) is of increasing importance with a rising prevalence of malignancies. However, RO teaching in medical schools is heterogeneous and has not been analyzed at a federal level yet. Therefore, the following survey aims to provide a national overview of RO teaching in Germany. METHODS: A questionnaire containing multiple-choice and free-text questions covering the extent and topics of RO teaching was sent to RO departments of all university hospitals in Germany and was answered by the heads of department/main lecturers. RESULTS: 24/35 (68.6%) RO departments returned completed forms. Most faculties employ lectures (91.7%), seminars (87.5%), and practical/bedside training (75.0%), whereas training in radiation biology and medical physics are rare (25% and 33.3%, respectively). Main topics covered are general RO (100%), radiation biology (91.7%), and side effects (87.5%). Regarding RO techniques and concepts, image-guided and intensity-modulated radiotherapy are taught at all faculties, followed by palliative and stereotactic techniques (87.5% each). Notably, all departments offered at least a partial rotation in RO in conjunction with radiology and/or nuclear medicine departments in the last year of medical school, while only 70.8% provided a complete rotation in RO. In addition, 57.1% of the departments have taken measures concerning the upcoming National Competence-Based Learning Objectives Catalogue (NKLM) for medical education. CONCLUSION: RO plays an integral but underrepresented role in clinical medical education in Germany, but faces new challenges in the development of practical and competence-based education, which will require further innovative and interdisciplinary concepts.

Unpredictable episodic breathlessness in patients with advanced chronic obstructive pulmonary disease and lung cancer: a qualitative study.

PURPOSE: The internationally consented definition and categorization describe two categories of episodic breathlessness: predictable (with known triggers) and unpredictable. The link of known triggers only to predictable episodes can be read that unpredictable episodes have none known trigger. Our aim was to illuminate patients' experiences with episodes of unpredictable breathlessness, to collect descriptions of the episodes' impact on the patients' lives, and, in turn, the patients' individual coping strategies in this connection. DESIGN: Qualitative study using semi-structured in-depth interviews with patients suffering from unpredictable episodes of breathlessness and chronic obstructive pulmonary disease (COPD; Global Initiative for Obstructive Lung Disease III and IV) or lung cancer (all stages). Interviews were audio-recorded, transcribed verbatim, and analyzed using Framework Analysis. RESULTS: One hundred one patients were screened in a large university hospital; ten participants fulfilled the inclusion criteria and provided consent. The experienced episodes were evaluated as unpleasant and with higher intensity compared to predictable episodes. Non-pharmacological interventions were identified as useful coping strategies. Interestingly, although patients experienced the episodes in an unpredictable manner, a trigger could be detected retrospectively for the majority of cases (mostly emotions (especially panic) and, occasionally, physical exertion). Unpredictable episodes are less frequent than previously assumed. CONCLUSION: The unpredictability of unpredictable breathless episodes refers to the patients' experience that these episodes occur "out-of-the-blue." However, a known trigger can be identified for the majority of unpredictable breathless episodes. These are therefore triggered as well. Further research needs to describe more possible triggers, to inquire the prevalence of unpredictable episodic breathlessness, and to develop effective management strategies.

The safety of flecainide treatment of atrial fibrillation: long-term incidence of sudden cardiac death and proarrhythmic events.

OBJECTIVE: To assess the safety of long-term treatment with flecainide in patients with atrial fibrillation (AF), particularly with regard to sudden cardiac death (SCD) and proarrhythmic events. DESIGN: Retrospective, observational cohort study. SETTING: Single-centre study at Örebro University Hospital, Sweden. Subjects. A total of 112 patients with paroxysmal (51%) or persistent (49%) AF (mean age 60 ± 11 years) were included after identifying all patients with AF who initiated oral flecainide treatment (mean dose 203 ± 43 mg per day) between 1998 and 2006. Standard exclusion/inclusion criteria for flecainide were used, and flecainide treatment was usually combined with an atrioventricular-blocking agent (89%). MAIN OUTCOME MEASURE: Death was classified as sudden or nonsudden according to standard definitions. Proarrhythmia was defined as cardiac syncope or life-threatening arrhythmia. RESULTS: Eight deaths were reported during a mean follow-up of 3.4 ± 2.4 years. Compared to the general population, the standardized mortality ratios were 1.57 (95% confidence interval (CI) 0.68-3.09) for all-cause mortality and 4.16 (95% CI 1.53-9.06) for death from cardiovascular disease. Three deaths were classified as SCDs. Proarrhythmic events occurred in six patients (two each with wide QRS tachycardia, 1 : 1 conducted atrial flutter and syncope during exercise). CONCLUSION: We found an increased incidence of SCD or proarrhythmic events in this real-world study of flecainide used for the treatment of AF. The findings suggest that further investigation into the safety of flecainide for the treatment of patients with AF is warranted.

Selective unresponsiveness to beta cell autoantigens after induction immunosuppression in pancreas transplantation with anti-interleukin-2 receptor antibody versus anti-thymocyte globulin.

Pancreas transplantation in type 1 diabetes patients could result in (re)activation of allo- and autoreactive T lymphocytes. Anti-thymocyte globulin (ATG) induction treatment is a successful, but broadly reactive anti-lymphocyte therapy used in pancreas and islet transplantation. A more selective alternative is daclizumab, a monoclonal antibody directed against the interleukin-2 receptor (CD25) on activated lymphocytes. We tested the hypothesis that daclizumab is more selective and has less immunological side effects than ATG. Thirty-nine simultaneous pancreas-kidney transplantation patients with type 1 diabetes were randomized for induction therapy with ATG or daclizumab. Auto- and recall immunity was measured cross-sectionally by lymphocyte stimulation tests with a series of auto- and recall antigens in 35 successfully transplanted patients. T cell autoimmunity to islets was low in both groups, except for a marginal but significantly higher reactivity against glutamic acid decarboxylase (GAD)65 in daclizumab-treated patients. The memory responses to recall antigens were significantly higher in the daclizumab-treated group compared to ATG-treated patients, specifically against purified protein derivative (PPD) (anti-bacterial immunity), Haemophilus influenzae virus matrix protein-1 (anti-viral immunity) and p53 [anti-tumour (auto)immunity]. These data imply that daclizumab is more specifically affecting diabetes-related immune responses than ATG. The autoimmunity is affected effectively after daclizumab induction, while memory responses towards bacterial, viral and tumour antigens are preserved.

Mechanisms of antibody immunotherapy on clonal islet reactive T cells.

Clinical intervention trials evaluating the efficacy of antibody immunotherapy in type 1 diabetes are in progress. We tested effects on prediabetic islet antigen-specific autoreactive T cells of antithymocyte globulin (ATG) and humanized monoclonal antibodies against CD3 (ChAglyCD3) or CD25 (daclizumab) with regard to downmodulation of the target protein, proliferation, cytokine production, complement-dependent cytotoxicity (CDC), antibody-dependent cell cytotoxicity (ADCC), and survival. ATG leads to depletion of autoreactive CD4+ T cells by ADCC, CDC, and apoptosis, whereas anti-CD3 and anti-CD25 inhibited T-cell autoreactivity in a nondepleting fashion. ATG treatment led to a cytokine burst of Th1- and Th2-associated cytokines. Modulation of cytokine release through humanized monoclonal antibodies was moderate and selective: anti-CD25 led to increased release of IL-2 and reduced production of TNFalpha, whereas anti-CD3 decreased release of interferon-y and IL-5 and increased secretion of IL-10. ATG and the humanized monoclonal antibodies displayed contrasting mechanisms of action.

High-resolution resonance measurements of the physisorption interaction.

Narrow selective adsorption resonances, with line widths given by the natural lifetime of the intermediate resonance state, have been observed directly in the angular distributions of Ne nozzle beams diffracted from a 20 K Cu(110) surface. Using beams of 20Ne and 22Ne isotopes we show that this high-resolution mode of resonance detection permits, even in a case of a small isotope effect, unique assignment of bound level sequences compatible with a single gas-surface potential curve.

Selective adsorption, bound states, and potential parameters for He, Ne, and Ar interacting with a Cu(110) surface.

Using nozzle beams of He, Ne, and Ar, we have measured diffractive selective adsorption resonances from a Cu(110) surface kept at 20 K. Bound state energies of the atom-surface potentials have been determined from plots of the measured resonance energies versus incident angle and their fits to calculated kinematical dispersion relations. For 3He and 4He we have found a unique level assignment that is compatible with a single gas-surface potential curve with a well depth of 6.05 meV of the He-Cu(110) potential. This value is about 10% larger than the prediction of 5.55 meV from the current physisorption theory. The Ne and Ar data reveal a large number of closely spaced levels with level separations and estimated van der Waals coefficients that are compatible with available theoretical data.

Allele-specific quantification of tumor necrosis factor alpha (TNF) transcription and the role of promoter polymorphisms in rheumatoid arthritis patients and healthy individuals.

Interindividual variation in the expression of tumor necrosis factor alpha (TNF) suggests the existence of functionally distinct TNF alleles that could play a role in susceptibility to TNF associated diseases such as rheumatoid arthritis (RA). To determine whether differential expression of TNF alleles exists, the relative contribution of TNF alleles in total TNF RNA production in peripheral blood mononuclear cells (PBMC) of healthy individuals and synovial tissue of RA patients was analyzed. By using a Tai I restriction fragment length polymorphism (RFLP) located at position +489 in the first intron of the gene, the relative contribution of each allele in precursor transcript production in heterozygous individuals could be measured. By means of this method we studied whether differences exist between TNF alleles in TNF pre-mRNA production. The relative contribution of TNF alleles to the non-spliced RNA pool was measured in PBMC of healthy individuals which were stimulated with LPS, PMA and anti-CD3 and anti-CD28 monoclonal antibodies for different time periods. Moreover, synovial biopsy material of RA patients was analyzed. The results of this study do not reveal a difference in the contribution of distinct TNF alleles in TNF pre-mRNA production upon in vitro and physiological stimulation conditions in healthy individuals and RA patients. Since some of the individuals whose PBMC were tested were also heterozygous for either -308, -1031, -863, -857 TNF promoter/enhancer single nucleotide polymorphisms (SNPs), the data argue against functional relevance of these TNF promoter/enhancer SNPs in the regulation of transcription. In conclusion, the data do not provide evidence for the existence of transcriptionally distinct TNF alleles to explain interindividual variation in TNF expression.

Association of the TNF +489 polymorphism with susceptibility and radiographic damage in rheumatoid arthritis.

Multiple genetic factors contribute to susceptibility to rheumatoid arthritis (RA). The extent of variability in disease presentation in RA may be related to genetic heterogeneity. In this study we investigated the association of the TNF gene polymorphism at position +489 with susceptibility to and severity of RA. Analysis of the frequency of the +489 A and G alleles in a group of 293 consecutive RA patients and 138 healthy controls revealed a significant decrease of the A allele. The +489 GA patients had a 3.9 times decreased chance of having erosive disease than +489 GG patients. These results were confirmed in a prospective study using a cohort of 112 patients who were followed for 12 years. The progression rate of the erosion score over 12 years expressed as Sharp score for X-rays of hands and feet was 3.4 per year for the GA-genotyped patients and 12.1 for the GG-genotyped patients. These associations were independent of rheumatoid factor and HLA-shared epitope positivity. In conclusion, these data suggest that the intron TNF +489 polymorphism is associated with susceptibility to and disease severity of RA independently of HLA-shared epitope-positive alleles.

A bewitching case of factitious disorder in Zimbabwe.

A rural Zimbabwean man attributed the appearance of needles in his leg to witchcraft, but medical practitioners suspected that the needles were self-introduced. Psychiatric evaluation revealed no major mental illness. The patient met criteria for the Euro-American diagnosis of factitious disorder, persisting in his claim that he had been the victim of witchcraft. The patient's claim cannot be considered delusional because belief in witchcraft is culturally sanctioned within Shona culture. The case appears to be one of factitious disorder with both physical and psychological symptoms. Differential diagnoses must be broadened to consider culturally specific phenomena such as witchcraft.

A case of psychotic mood disorder in an AIDS patient.

The following case is reported not because it is uncommon, but rather because cases like it will become more common as the AIDS endemic in sub-Saharan Africa progresses. This is a case of a young woman previously undiagnosed as being HIV positive who was admitted to a psychiatric unit. She clinically presented with a manic episode. The case is remarkable in that it demonstrates the complicated differential diagnosis that needs to be considered in evaluating immune-compromised patients who present primarily with disturbances of mood, cognition, or behaviour.

Late complications after aortic surgery.

The incidence of false aneurysms, anastomotic stenoses, and ureteric obstruction is reported to be low in patients who have undergone aortic surgery. The use of intravenous peripheral digital subtraction angiography (IVDSA) with completion excretory urography (CEU) may provide a more sensitive means of long-term detection of these complications. The aim of this study was to (1) establish the incidence of anastomotic aneurysms, anastomotic stenoses, and ureteric obstruction after aortic surgery; (2) identify local and systemic factors that predispose to these complications; and (3) evaluate IVDSA as a single radiologic investigation to diagnose these complications. Forty-four patients who had undergone aortic surgery 1 to 12.3 years previously agreed to undergo IVDSA and CEU. False aneurysms were found at 10 distal anastomoses (none at the aorta), for an anastomotic incidence of 11.2% and a patient incidence of 15.9%. Endarterectomy and the femoral artery as a site of distal anastomosis were important factors in the development of anastomotic aneurysms, as were detected radiologically at eight aortic anastomosis (18%). There were no distal anastomotic stenoses. Hypercholesterolemia was more common in this group (62.5%) than in the overall group (21.2%). Three asymptomatic ureteric obstructions were diagnosed in two patients, both of whom had emergency surgery for ruptured aortic aneurysms. The higher incidence of anastomotic aneurysms, anastomotic stenoses, and asymptomatic ureteric obstruction sound merits careful follow-up. IVDSA with CEU may be a simple and effective method of detection.

Dust in buildings with man-made mineral fiber ceiling boards.

Man-made mineral fibers (MMMF) and other airborne dusts were measured in 105 rooms in a representative sample of public buildings, excluding rooms with physically damaged boards or buildings with notable indoor climate problems. There were no differences in the MMMF concentrations with respect to the type of binder. The average concentrations ranged from 17 to 210 respirable MMMF/m3. The average concentrations of the reference group was intermediate and therefore indicated that sources other than ceiling boards contributed to the obtained values. No grouping by concentration of MMMF on cupboards was possible. Airborne concentrations of respirable MMMF were 2.7 times lower in rooms with mechanical ventilation than in rooms with natural ventilation. For nonrespirable MMMF, the most important factor was the quality of the cleaning. The concentration in poorly cleaned rooms was 5.5 times that of well-cleaned rooms. Ventilation, quality of cleaning, and number of persons affected the non-MMMF and total dust concentrations.

[Meteorologic effects on hemorrhagic diathesis in hemophilia. 1. Demonstrating weather effects based on a complex weather phase scheme]. / Meteorologische Einflüsse auf die Blutungsneigung bei der Hämophilie.1. Mitteilung: Darstellung der Meteorotropie anhand eines komplexen Wetterphasenschemas.

In haemophilia frequently spontaneous haemorrhages occur without recognition of an evoking cause. Various bleeding-disposing factors are discussed, among others also influences of weather. For the investigation of the meteorotropic relations 1,802 episodes of haemorrhages in 223 haemophiliacs were coordinated to a complex scheme of weather phases. An undisturbed course of the weather was in general connected with a decrease of bleeding, whereas in an influence of low pressure with advection of cold air an increase of the haemorrhages was established. Conspicuous was furthermore the negative biotropism of the radiation-intensive sunny fine weather in summer, which is probably to be traced back to the thermic load in this weather situation.

[Meteorologic effects on hemorrhagic diathesis in hemophilia. 2. Weather effects on hemophilia with special reference to the atmospheric temperature-humidity complex]. / Meteorologische Einflüsse auf die Blutungsneigung bei der Hämophilie. 2. Mitteilung: Die Meteorotropie der Hämophilie unter besonderer Berücksichtigung des atmosphärischen Temperatur-Feuchte-Komplexes.

The meteotropism of haemophilic haemorrhages was investigated for 1,802 episodes of bleeding in 223 patients with the help of selected parameters of the atmospheric temperature-humidity complex and the air pressure. The accumulation of haemorrhages under the influence of tropic air masses was particularly conspicuous. In low blood pressure the frequency of bleeding also increased, whereas high-pressure conditions showed a decrease of bleeding. The study clearly confirms that the haemorrhagic tendency in haemophilia is influenced by weather. Therefore a medico-meteorologic forecast should be taken into consideration for haemophiliacs.

Medication compliance, antidepressant blood levels, and side effects in Southeast Asian patients.

A study of medication compliance, side effects, and clinical change with the use of antidepressants in 32 Southeast Asian refugee patients seen at an urban mental health center is reported. Patients met criteria for either major depressive episode, posttraumatic stress disorder, or both. Only five of the 32 patients who stated that they were taking their medications regularly had antidepressant blood levels in the therapeutic range. Another 10 patients had subtherapeutic levels and the remaining 17 had undetectable blood levels. Patients with therapeutic blood levels had fewer side effects (p = 0.049) than patients with undetectable blood levels. Blood levels tended (p = 0.070) to be correlated with clinical improvement. The authors discuss cultural attitudes of Southeast Asian refugee patients toward medication use and side effects that appear to influence medication compliance.

[One-year analysis of bleeding events in 223 hemophiliacs in the DDR]. / Ein-Jahresanalyse von Blutungsereignissen bei 233 Hämophilen der DDR.

The reports of 223 haemophiliacs living in the districts Halle, Leipzig, Karl-Marx-Stadt, and Gera had been analyzed for bleeding events in 1986. There were suffering from haemophilia A 185, from haemophilia B 36 and 2 persons from a complex disorder. In each case 73 patients suffer from a severe and a moderate type of haemophilia. In 55 patients the diagnosis was mild form of haemophilia and in 22 subhaemophilia. Altogether 1802 bleeding episodes had been registered with the following locations: elbow joint 21.0%, knee joint 17.9%, ankle 14.2%, shoulder 4.3%. In 5% of all cases multiple joints had been affected at the same time. Soft tissue bleedings occurred in 16.7% of all cases. For substitution treatment of these 1802 bleeding events altogether 9020 transfusion units were needed, appropriate to 40.4 per year and 52.4 per year and bleeding patient respectively. Expense and duration of treatment depend on the bleeding location. Conclusions for the clinics and the transfusion service are possible.

[Recommendations for a medical-meteorologic prognosis for hemophilia]. / Empfehlungen für eine medizin-meteorologische Vorhersage für Hämophile.

A one year lasting study about the relation between bleedings in haemophiliacs and weather was performed. There had been included 1802 bleeding events. The influence of meteorologic factors to bleeding was proved. The influx of warm air proved inopportune. The decrease in atmospheric pressure as well as winter cold fronts lead to increase of bleeding tendency. Haemophiliacs should avoid physical and psychical stress in such unconvenient atmospheric situations. The replacement therapy should be adapted to the weather situation.