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Background: SARS-CoV-2 infection has been and, in some parts, still is a threat to oncologic patients, making it crucial to understand perception of vaccination and immunologic responses in this vulnerable patient segment. SARS-CoV-2 vaccines in relation to malignant disease characteristics and therapies have so far not been studied consecutively in larger oncologic patient populations. This study captures SARS-CoV-2 vaccination willingness and humoral immune response in a large consecutive oncologic patient collective at the beginning of 2021., Methods: 1142 patients were consecutively recruited over 5.5 months at a tertiary department for radiation oncology and were assessed for vaccination willingness via a standardized interview. In already vaccinated patients total SARS-CoV-2 S antibody titres against the spike protein (Anti-SARS-CoV-2 S) and were evaluated 35 days or later after the first dose of SARS-CoV-2 vaccine., Results: Vaccination willingness was high with a rate of 90 %. The most frequent reasons for rejection were: undecided/potential vaccination after therapy, distrust in the vaccine and fear of interaction with comorbidities. Factors associated with lower vaccination willingness were: worse general condition, lower age and female sex. 80 % of the participants had been previously vaccinated, 8 % reported previous infection and 16 % received vaccination during antineoplastic therapy. In 97.5 % of the vaccinated patients Anti-SARS-CoV-2 S was detected. In a univariable analysis parameters associated with non-conversion were: lower performance status, spread to the local lymphatics (N + ), hematologic disease and diffuse metastases. All patients with oligometastatic disease achieved positive Anti-SARS-CoV-2 S titres. For patients with two vaccinations several risk factors were identified, that were associated with low antibody concentrations., Conclusions: SARS-CoV-2 vaccination willingness among oncologic patients was high in the first months after its availability, and most patients had already received one or two doses. Over 97 % of vaccinated patients had measurable anti-SARS-CoV-2 S titres. Our data supports early identification of low humoral responders after vaccination and could facilitate the design of future oncologic vaccine trials (clinicaltrials.gov Identifier: NCT04918888)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Aim: Migraine headache and vestibular-type vertigo co-occur in the general population about three times more often than expected by chance. Attacks of episodic vertigo (eV) are currently not recognized as migraine equivalents or variants in the International Classification of Headache Disorders, 3rd edition (ICHD III). No strong data exist about the prevalence of eV during the phases of a migraine attack. The aim of this study is to analyze the timing association between migraine-related episodic vertigo and the phases of migraine., Methods: The "Migraine and Neck Pain Study" gathered data from nearly 500 adult participants in a questionnaire-based survey. In this prospective, follow-up study we re-analyzed patients with episodic migraine with and without aura who experienced eV anytime around their migraine attacks. For this we defined 3 different time periods., Results: 146/487 (30%) reported eV anytime during the migraine attack; 79/487 (16%) that noticed eV with the start of the headache, 51/487 (10%) within 2 h before the headache and 16/487 (3%) experienced eV 2-48 h before the headache, as a premonitory symptom. 130/487 (26.7%) of our patients can be diagnosed with vestibular or probable vestibular migraine supporting the clinical association of migraine and vertigo., Conclusions: Our results seem to further support the concept that vertigo in migraine is best thought of as an integral manifestation of migraine, rather than a prodromal or aura symptom.

Background: The purpose of this study was to analyze risk factors for ipsilateral in-breast relapse and inferior disease-free survival (DFS) after standard adjuvant whole-breast radiotherapy (± boost and systemic treatment) as part of a multimodal breast-conserving approach., Patients and Methods: Decision trees were built through recursive partitioning analysis (RPA). The median follow-up for all 2161 patients was 114 months (9.5 years)., Results: Local relapse in the treated breast was uncommon (actuarial rates after 5 and 10 years were 2.7% and 5.8%, respectively). In RPA, the first split was related to age (52 years), with younger patients having a significantly higher risk of local relapse. The younger patients were stratified further by lymph node ratio (LNR). In patients older than 52 years, lack of endocrine treatment was associated with significantly higher risk. DFS was 80.7% at 10 years. The first split was caused by LNR, and the group with unfavorable LNR (> 0.20) could not be stratified further. Ten-year DFS in this group was as low as 50.6%. Patients with favorable LNR (0-0.20) could be stratified by additional risk factors, in particular primary tumor size., Conclusion: RPA is a suitable method to assign patients with early stage breast cancer to different risk groups, both regarding local relapse and DFS. Although age was a major risk factor for local relapse after breast-conserving management, LNR was associated with both endpoints. The systemic treatment approaches used in this study failed to provide satisfactory DFS in patients with LNR > 0.20 and 2 other subgroups., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Cluster headache (CH) is a clinically well-defined primary headache disorder, approximately 20% of cluster headache sufferers experience recurrent attacks without periods of significant remission. For the treatment of chronic cluster headache (CCH) only limited therapeutic options are available., Methods: A potential refractory CCH patient group was identified according to the clinical definition of rCCH based on the consensus statement of the European Headache Federation (EHF). Treatment with OnabotulinumtoxinA (BoNT-A; Botox®, 150 Allergan IU) was done according to the PREEMPT study protocol. A standardized headache diary was used for recording frequency, duration of attacks and pain intensity. To assess personal burden the HIT-6 and the Hospital Anxiety and Depression scale was used. Primary outcome measure was a > 50% reduction in headache minutes., Results: Seventeen male patients suffering from rCCH, aged 32 ± 11 (mean ± SD) years, presenting a mean disease duration of 6.6 years completed the study of 28 weeks. The cut-off point of > 50% reduction in headache minutes as positive result was reached in 58.8%, 29.4% experienced an improvement of 30-50%. Mean frequency of headache days dropped from 28.2 to 11.8 days at week 24 (p = 0.0001; 95% CI -21.33 to - 11.61;). Intensity of remaining attacks was also reduced significantly. Headache disability scores showed a trend to improvement after BoNT-A., Conclusions: Encouraging results for the treatment with BoNT-A in rCCH patients were observed in our study population.

Purpose: To demonstrate the unfavorable results in survival rates in patients with medial breast cancer compared to patients with laterally located tumors of the mammary gland., Patients and Methods: Between 1984 and 1995, 1,089 patients presenting with a total of 1,100 pT1-2 invasive carcinomas of the breast were treated at the authors' institution. 707 presented with tumors in the lateral quadrants, 294 with tumors in the medial quadrants, and 99 with tumors in the central quadrant. Treatment protocols involved breast-conserving surgery and whole-breast radiotherapy in all women, followed by a tumor bed boost dose according to risk factors for local recurrence. All axillary node-positive patients underwent systemic therapy (six cycles of classic CMF and/or 2-5 years of tamoxifen 20 mg/day). Rates of actuarial survival and local control were calculated by the Kaplan-Meier method and differences in survival curves were compared by use of the log-rank test., Results: The mean follow-up of survivors was 97 months (range 36-192 months). Comparing patients with medial and lateral tumors, the actuarial survival data were significantly better for patients with lateral tumors. At 10 years, overall survival for patients with medial tumors was 71%, for patients with lateral tumors 81.8% (p < 0.025), disease-specific survival for patients with medial tumors 79.9%, for patients with lateral tumors 89.1% (p < 0.025). There was no significant difference in local tumor control according to tumor location., Conclusion: Medial tumor location is associated with a lower survival rate, but not with inferior local tumor control. Failure to identify nodal metastases confined to the internal mammary chain may lead to undertreatment with systemic/local agents and compromised survival.

Purpose: This retrospective analysis of 1,610 women treated for breast cancer and 88 patients with local relapse aims to show the poor survival parameters after local failure and to evaluate risk factors and compare them with other studies and analyses published., Patients and Methods: Between 1984 and 1997, 1,610 patients presenting with a total of 1,635 pT1-2 invasive and noninvasive carcinomas of the breast were treated at the authors' institution. The mean age was 57.1 years (range 25-85 years). Treatment protocols involved breast-conserving surgery with or without systemic therapy and whole-breast radiotherapy in all women, followed by a boost dose to the tumor bed according to risk factors for local recurrence. All axillary node-positive patients underwent systemic therapy (six cycles of classic CMF or tamoxifen 20 mg/day for 2-5 years). The time of diagnosis of local relapse was defined as time 0 for the survival curves after local failure. The association of clinicopathologic factors was studied using uni- and multivariate analyses. Survival and local control were calculated by the Kaplan-Meier actuarial method and significance by the log-rank test., Results: After a mean follow-up of 104 months, 88 local failures were recorded (5.4%). Calculated from the time of diagnosis of local relapse, 5-year overall survival (OS) was 62.8%, metastasis-free survival 60.6%, and disease-specific survival 64.2%. In patients with failure during the first 5 years after treatment, the survival parameters were worse (OS 50.6%) compared to those who relapsed after 5 years (OS 78.8%; p < 0.028). Significances were also found for initial T- and N-stage and type of failure (solid tumor vs. diffuse spread)., Conclusion: This analysis again shows that the survival parameters are worsening after local relapse, especially in case of early occurrence. In breast cancer treatment, therefore, the goal remains to avoid local failure.

The flow cytometric detection of aberrant antigen expression is one method proposed for the quantification of minimal residual disease (MRD) in acute leukemias. The present study was designed to investigate the stability of the aberrant antigen expression at relapse or at treatment failure of initial chemotherapy. For this purpose, multiparameter immunophenotyping with a panel of 15 monoclonal antibodies was used at diagnosis as well as at relapse (43 patients with overall 65 aberrations) and at treatment failure (35 patients with overall 66 aberrations). There was a significant decrease in the percentage of the initially described aberrant antigen expression on leukemia blasts at relapse (P = 0.001; n = 65) as well as at treatment failure (P = 0.0001; n = 66) considering all aberrations in the whole leukemia population. Concerning only patients with acute myelogenous leukemia (AML), significant decreases in the aberrant expression could be detected at relapse (P = 0.031; n = 42) and at treatment failure (P = 0.0001; n = 52). The changes in patients with acute lymphoblastic leukemia (ALL) were significant only at relapse (P = 0.006; n = 23). Initially, the most informative aberration was not detectable in four patients at relapse and in seven patients at treatment failure. A decrease of under 50% of the initial value was observed in another 8 patients at relapse and in 10 patients at treatment failure. In further studies assessing the detection of aberrant antigen expression for MRD, quantification of the relapses should be explicitly analyzed regarding the persistence of the initially described aberrant antigen expression., (Copyright 2000 Wiley-Liss, Inc.)

Previously we reported the neo-expression of cytokeratin 7 in metaplastic and dysplastic stomach mucosa. In this study using immunohistochemistry and immunoblotting technique, we observed an cytokeratin 7 expression in the fetal and "infantile" human stomach, thus indicating an "oncofetal" behaviour of some simple epithelial type cytokeratins.

Metalaxyl is used to control diseases caused by fungi of the order of the Perenosporales. We investigated the action of this fungicid eon nucleic acid and protein synthesis in liquid cultures of Phytophthora nicotianae. The uptake of 32P, 3H-uridine, 3H-thymidine and 14C-leucine as precursors of nuclei acid and protein synthesis by the mycelium was not inhibited by metalaxyl. RNA synthesis as indicated by 3H-uridine incorporation was strongly inhibited (about 80%) by 0.5 micrograms/ml of metalaxyl. The inhibition was visible already few minutes after addition of the toxicant. Since the inhibition of incorporation of 3H-thymidine into DNA and of 14C-leucine into protein became significant 2-3 hours later, we conclude that metalaxyl primarily interfers with RNA synthesis. Synthesis of ribosomal RNA is more affected (more than 90%) than that of tRNA (about 55%) and poly(A)-containing RNA. Since in the presence of actinomycin, in contrast to metalaxyl, protein synthesis is inhibited immediately as a consequence of complete inhibition of RNA synthesis and of the short life-time of mRNA, it is also evident that mRNA synthesis is less strongly inhibited, at least during the early period of metalaxyl action. The molecular mechanism of metalaxyl inhibition of the transcription process remains open. The fungicide did not inhibit the activity of a partially purified RNA polymerase isolated from the fungus. On the other hand, the RNA synthesis (14C-UTP-incorporation) by a cell homogenate and by isolated nuclear fractions was inhibited significantly. Possibilities of the molecular action of metalaxyl are discussed. The RNA synthesis of some plant systems (cell cultures of Lycopersicon peruvianum, isolated nuclei from the same cell cultures, purified RNA polymerase from Spinacia oleracea chloroplasts) was not inhibited by metalaxyl, not even at high concentrations.