Estimates of protection levels against SARS-CoV-2 infection and severe COVID-19 in Germany before the 2022/2023 winter season: the IMMUNEBRIDGE project.

PURPOSE: Despite the need to generate valid and reliable estimates of protection levels against SARS-CoV-2 infection and severe course of COVID-19 for the German population in summer 2022, there was a lack of systematically collected population-based data allowing for the assessment of the protection level in real time. METHODS: In the IMMUNEBRIDGE project, we harmonised data and biosamples for nine population-/hospital-based studies (total number of participants n = 33,637) to provide estimates for protection levels against SARS-CoV-2 infection and severe COVID-19 between June and November 2022. Based on evidence synthesis, we formed a combined endpoint of protection levels based on the number of self-reported infections/vaccinations in combination with nucleocapsid/spike antibody responses ("confirmed exposures"). Four confirmed exposures represented the highest protection level, and no exposure represented the lowest. RESULTS: Most participants were seropositive against the spike antigen; 37% of the participants ≥ 79 years had less than four confirmed exposures (highest level of protection) and 5% less than three. In the subgroup of participants with comorbidities, 46-56% had less than four confirmed exposures. We found major heterogeneity across federal states, with 4-28% of participants having less than three confirmed exposures. CONCLUSION: Using serological analyses, literature synthesis and infection dynamics during the survey period, we observed moderate to high levels of protection against severe COVID-19, whereas the protection against SARS-CoV-2 infection was low across all age groups. We found relevant protection gaps in the oldest age group and amongst individuals with comorbidities, indicating a need for additional protective measures in these groups.

[Chylous ascites in NSCLC: It is not always malignant]. / Chylöser Aszites bei NSCLC: Nicht alles ist maligne, was maligne aussieht.

The etiology of chylous ascites is multifactorial. Malignant diseases, cirrhosis, trauma, lymphomatic abnormalities and mycobacteriosis are the most common causes. In NSCLC, chylous ascites is observed with peritoneal metastasis or abdominal lymph node metastases.RET alterations occur in 1-2% of NSCLC patients and since recently they can be treated in a targeted fashion.Our case report shows that new targeted therapies revolutionize prognosis, but confront us with the challenge of new and partly unknown side effects.

Clinical and neurophysiological patterns of impairments to emotion attention and empathy in multiple sclerosis.

Patients suffering from multiple sclerosis experience various cognitive and affective impairments, resulting in a negative impact on social behavior and personal independence to differing degrees. According to these often clinically subtle but conflicting cognitive-affective impairments, recordings of these socially relevant issues are still of demand to stratifying clinical and social support in a sophisticated way. Therefore, we studied specific cognitive and affective capacities in eleven patients with a predominant relapsing-remitting type of multiple sclerosis by applying paradigms of event-related potentials and a well-selected neuropsychological test protocol. Thus far, distinct cognitive disturbances of executive and attentional domains and the Wechsler Memory Test's four memory indices were found in multiple sclerosis patients. Concerning affective domains, patients showed discrete impairments of affect discrimination and affected naming as proved by specific testing (Tuebinger Affect Battery). Neurophysiologically, event-related potentials recordings in multiple sclerosis patients, were associated with decreased implicit emotion processing to cues of different emotion arousal at the early processing stage depending on attentional capacities and alterations of implicit emotion modulation at late processing stages. These clinical neurophysiological and neuropsychological data were correlated in part to quantitative magnetic resonance imaging brain lesions. Summarizing our data, our data indicate certain neurocognitive and neuroaffective dysfunctions in patients with multiple sclerosis, thus highlighting the validity of sensitive recording of less apparent neurologic disturbances in multiple sclerosis for optimizing the individual care management in patients.

Patients with severe aortic stenosis and coexisting pulmonary hypertension treated by transapical transcatheter aortic valve replacement-Is there a need for increased attention?

OBJECTIVES: Aim of this study is to elucidate the impact of pulmonary hypertension on patients treated with a transapical aortic valve replacement. BACKGROUND: In patients with aortic stenosis (AS) the coexistence of pulmonary hypertension (PH) is associated with increased peri-operative risk for surgical aortic valve replacement. For transcatheter aortic valve replacement (TAVR), it is unknown whether transapical TAVR (TA-TAVR) is associated with increased peri-interventional risk in PH patients. METHODS: We performed a single center analysis in 189 patients with severe AS with (AS + PH) or without PH (AS - PH) undergoing TA-TAVR. PH was defined by mean pulmonary artery pressure ≥25 mmHg assessed by right heart catheterization (exclusion of 64 patients due to missing results). As the primary endpoint a combination of 30-day mortality or cardiopulmonary resuscitation (CPR) was analyzed. RESULTS: Seventy three patients (58.4%) had PH. Increased peri-interventional risk in AS + PH patients was reflected by an increased rate of the primary endpoint in comparison to AS - PH patients (24.7 vs. 3.8%; p = .002). A higher proportion of acute kidney injury (34.2 vs. 15.7%; p = .025) was found in AS + PH patients while AS - PH patients showed a higher rate of bleeding in comparison AS + PH patients (18.5 vs. 6.8% p = .050). CONCLUSION: Patients with AS + PH treated by TA-TAVR are at increased peri-interventional risk for severe complications in comparison to AS - PH patients. Therefore, the identification of preventive therapeutic strategies is needed. CLASSIFICATIONS: TAVR, transapical, pulmonary hypertension, aortic stenosis.

Axenfeld-Rieger Anomaly and Neuropsychiatric Problems-More than Meets the Eye.

OBJECTIVE: The main purpose of this article is to demonstrate the co-occurrence of Axenfeld-Rieger anomaly and neuropsychiatric problems as clinical signs of genetically determined cerebral small vessel disease in two patients. CASE STUDY: We report on two adolescent individuals with ocular anterior segment dysgenesis (Axenfeld-Rieger anomaly) presenting with neuropsychiatric symptoms. Both patients underwent cerebral magnetic resonance imaging showing white matter T2-hyperintensities involving different brain regions, suspective of cerebral small vessel disease. Genetic analysis revealed pathogenic mutations in the FOXC1 gene (patient 1) and the COL4A1 gene (patient 2), respectively. CONCLUSION: We report on the co-occurrence of ocular anterior segment dysgenesis (Axenfeld-Rieger anomaly) and neuropsychiatric symptoms as clinical signs of genetically determined cerebral small vessel disease in two patients. In both patients, the cerebral lesions involved the frontotemporal regions, brain regions that control social behavior as well as executive and cognitive function, highlighting the fact that neuropsychiatric symptoms may be early clinical presentations of cerebral small vessel disease. We further provide a review of monogenic causes of pediatric cerebral small vessel disease, emphasizing the links to childhood-onset neuropsychiatric disease.

Reduction of sleep-disordered breathing following effective percutaneous mitral valve repair with the MitraClip system.

PURPOSE: This study tested the hypothesis that a reduction of pulmonary congestion achieved by a reduction of mitral regurgitation (MR) severity in heart failure (HF) patients is associated with reduced event lengths of sleep-disordered breathing (SDB). METHODS: We prospectively enrolled 20 consecutive HF patients who underwent MitraClip implantation. Patients underwent cardiorespiratory polygraphic recording prior to and after percutaneous mitral valve repair (PMVR). Beyond routinely established indicators of apneas and hypopneas per hour (respiratory event index), we manually analyzed apnea event lengths. RESULTS: MitraClip implantation led to marked reduction of MR severity and a reduction in left atrial pressure. These hemodynamic changes were accompanied by changes in SDB: the subtype of SDB switched from CSA to OSA in 4 patients. Likewise, quantitative indicators of SDB were altered in both forms of SDB with a reduction in circulatory delay (CSA 38 ± 14 vs. 33 ± 15 s.; p = 0.002 and OSA 34 ± 9 vs. 28 ± 6 s.; p = 0.02) and a corresponding reduction in ventilation lengths in CSA patients (42 ± 15 vs. 37 ± 13 s.; p = 0.05). CONCLUSION: A reduction of pulmonary congestion as achieved by a decrease of left atrial pressure through successful MitraClip implantation is associated with a reduction in respiratory event lengths, further pointing towards a relation between SDB and HF.

Sleep-disordered breathing in patients with newly diagnosed lung cancer.

BACKGROUND: There are currently no data on the prevalence of sleep-disordered breathing (SDB) in patients with newly-diagnosed lung cancer. This might be of interest given that SDB is associated with increased cancer incidence and mortality. Furthermore, intermittent hypoxia has been linked with tumor growth and progression. The aim of the current study was to investigate the prevalence of SDB in patients with newly-diagnosed lung cancer. METHODS: Patients with newly-diagnosed lung cancer from three centers in Germany were screened for SDB using a two-channel screening system (ApneaLink™). SDB was defined as an apnea-hypopnea index of > 5/h, and was classified as mild if the AHI was 5-15/h whereas an AHI ≥15/h was classified as severe SDB. The presence of SDB-related symptoms was assessed using the Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI). RESULTS: A total of 100 patients were included. The overall prevalence of SDB was 49%; 32 patients (32%) had mild SDB with a median AHI of 7.7/h (quartile [Q1 5.4/h, Q3 10.4/h]) and a median oxygen desaturation index of 8.5 [Q1 4.2/h; Q3 13.4/h] and seventeen patients (17%) had moderate to severe SDB with a median AHI of 25.2 [Q1 18/h, Q3 45.5/h] and a median oxygen desaturation index of 20.6/h [Q1 9.6/h, Q3 36.6/h]. Patients with moderate to severe SDB had mild daytime sleepiness (ESS score 8.24 ± 3.96 vs. 5.74 ± 3.53 in those without SDB vs. 6.22 ± 2.72 in those with mild SDB; p = 0.0343). The PSQI did not differ significantly between the three groups (p = 0.1137). CONCLUSIONS: This study showed a high prevalence of SDB in patients with newly-diagnosed lung cancer. In these patients SDB was associated with intermittent hypoxia and increased daytime sleepiness. Additional research is needed to determine whether SDB influences prognosis and morbidity in patients with lung cancer. TRIAL REGISTRATION: NCT02270853 (ClinicalTrials.gov), date of registration: 14th October 2014.

Painful Charcot-Marie-Tooth neuropathy type 2E/1F due to a novel NEFL mutation.

INTRODUCTION: Charcot-Marie-Tooth neuropathy (CMT) 2E/1F is caused by mutations in the neurofilament light-chain polypeptide (NEFL) gene. Giant axons are a histological hallmark frequently seen in nerves of patients with CMT2E. METHODS: We describe the case of a 43-year-old patient with a painful, predominantly sensory neuropathy. RESULTS: The patient's sural nerve biopsy showed multiple giant axons. Genetic sequencing of the NEFL gene revealed that the patient was heterozygous for an altered sequence of the gene, c.816C>G, p.Asn272Lys, which has not yet been described in CMT2E/1F. CONCLUSION: In contrast to other cases of CMT2E/1F, where motor symptoms are predominant, pain was the most disabling symptom in this patient. Muscle Nerve 55: 752-755, 2017.

Chronic obstructive pulmonary disease and diabetes mellitus: a systematic review of the literature.

The objective of this systematic review was to discuss our current understanding of the complex relationship between chronic obstructive pulmonary disease (COPD) and type-2 diabetes mellitus (T2DM). We performed a systematic search of the literature related to both COPD and diabetes using PubMed. Relevant data connecting both diseases were compiled and discussed. Recent evidence suggests that diabetes can worsen the progression and prognosis of COPD; this may result from the direct effects of hyperglycemia on lung physiology, inflammation or susceptibility to bacterial infection. Conversely, it has also been suggested that COPD increases the risk of developing T2DM as a consequence of inflammatory processes and/or therapeutic side effects related to the use of high-dose corticosteroids. In conclusion, although there is evidence to support a connection between COPD and diabetes, additional research is needed to better understand these relationships and their possible implications.

Molecular characterization of exosome-like vesicles from breast cancer cells.

BACKGROUND: Membrane vesicles released by neoplastic cells into extracellular medium contain potential of carrying arrays of oncogenic molecules including proteins and microRNAs (miRNA). Extracellular (exosome-like) vesicles play a major role in cell-to-cell communication. Thus, the characterization of proteins and miRNAs of exosome-like vesicles is imperative in clarifying intercellular signaling as well as identifying disease markers. METHODS: Exosome-like vesicles were isolated using gradient centrifugation from MCF-7 and MDA-MB 231 cultures. Proteomic profiling of vesicles using liquid chromatography-mass spectrometry (LC-MS/MS) revealed different protein profiles of exosome-like vesicles derived from MCF-7 cells (MCF-Exo) than those from MDA-MB 231 cells (MDA-Exo). RESULTS: The protein database search has identified 88 proteins in MDA-Exo and 59 proteins from MCF-Exo. Analysis showed that among all, 27 proteins were common between the two exosome-like vesicle types. Additionally, MDA-Exo contains a higher amount of matrix-metalloproteinases, which might be linked to the enhanced metastatic property of MDA-MB 231 cells. In addition, microarray analysis identified several oncogenic miRNA between the two types vesicles. CONCLUSIONS: Identification of the oncogenic factors in exosome-like vesicles is important since such vesicles could convey signals to non-malignant cells and could have an implication in tumor progression and metastasis.

The influence of fixation and cryopreservation of cerebrospinal fluid on antigen expression and cell percentages by flow cytometric analysis.

The pauci-cellular nature of cerebrospinal (CSF), particularly ventricular CSF, and the rapid cell death following sampling, incumbers the use of flow cytometric analysis of these samples in the investigation of central nervous system (CNS) pathologies. Developing a method that allows long-term storage and batched analysis of CSF samples without compromising cell integrity is highly desirable in clinical research, given that CSF is often sampled after hours creating logistical difficulties for fresh processing. We examined percentages and relative proportion of peripheral and brain-derived immune cells in cryopreserved and transfix-treated CSF, compared to freshly processed CSF. Cell proportions were more comparable between Fresh and Cryopreserved CSF (mean of differences = 3.19), than between fresh and transfix-treated CSF (mean of differences = 14.82). No significant differences in cell percentages were observed in fresh versus cryopreserved CSF; however significantly lower cell percentages were observed in transfix-treated CSF compared to Fresh CSF [(CD11b++ (p = 0.01), CD4+ (p = 0.001), CD8+ (p = 0.007), NK cells (p = 0.04), as well as CD69+ activation marker (p = 0.001)]. Furthermore, loss of marker expression of various lymphocyte sub-populations were observed in transfix-treated CSF. Cryopreservation is a feasible option for long-term storage of ventricular CSF and allows accurate immunophenotyping of peripheral and brain-derived cell populations by flow cytometry.

Prospective dual role of mesenchymal stem cells in breast tumor microenvironment.

Breast cancer tissue is a heterogeneous cellular milieu comprising cancer and host cells. The interaction between breast malignant and non-malignant cells takes place in breast tumor microenvironment (TM), and has a crucial role in breast cancer progression. In addition to cellular component of TM, it mainly consists of cytokines released by tumor cells. The tumor-tropic capacity of mesenchymal stem cells (MSCs) and their interaction with breast TM is an active area of investigation. In the present communication, the interplay between the breast resident adipose tissue-derived MSCs (B-ASCs) and breast TM was studied. It was found that a distinct subset of B-ASCs display a strong affinity for conditioned media (CM) from two breast cancer cell lines, MDA-MB 231 (MDA-CM) and MCF-7 (MCF-CM). The expressions of several cytokines including angiogenin, GM-CSF, IL-6, GRO-α and IL-8 in MDA-CM and MCF-CM have been identified. Upon functional analysis a crucial role for GRO-α and IL-8 in B-ASCs migration was detected. The B-ASC migration was found to be via negative regulation of RECK and enhanced expression of MMPs. Furthermore, transcriptome analysis showed that migratory subpopulation express both pro- and anti-tumorigenic genes and microRNAs (miRNA). Importantly, we observed that the migratory cells exhibit similar gene and miRNA attributes as those seen in B-ASCs of breast cancer patients. These findings are novel and suggest that in breast cancer, B-ASCs migrate to the proximity of tumor foci. Characterization of the molecular mechanisms involved in the interplay between B-ASCs and breast TM will help in understanding the probable role of B-ASCs in breast cancer development, and could pave way for anticancer therapies.

Aneuploidy characterizes adjacent non-malignant mucosa of ulcerative colitis-associated but not sporadic colorectal carcinomas: a matched-pair analysis.

INTRODUCTION: Aneuploidy has been suggested as independent prognostic marker in ulcerative colitis (UC) patients for developing UC-associated colorectal carcinomas (UCCs). UCCs are associated with a poorer prognosis and more frequently present with synchronous carcinomas when compared with sporadic colorectal carcinomas (SCCs). The authors therefore investigated if the adjacent non-malignant mucosa of aneuploid UCCs and aneuploid SCCs shows differences regarding the frequency of aneuploidy and if this aneuploidy is associated with histomorphological alterations. METHODS: Primary tumors of 25 UCCs and 20 SCCs were selected showing exclusively aneuploid DNA patterns and matching DNA stemlines. The UCCs' (n = 82) and SCCs' (n = 40) adjacent non-malignant mucosa were evaluated for histopathology and assessed for DNA ploidy status by image cytometry. RESULTS: UCCs' non-malignant mucosa showed dysplasia in 31.7% and aneuploidy in 89%. In contrast, SCCs' non-malignant mucosa revealed no dysplasia and aneuploidy in only 5%. Irrespective of dysplastic lesions, aneuploidy was observed more frequently in adjacent non-malignant mucosa of UCCs than of SCCs (p < 0.001). Neither a correlation between aneuploidy and inflammation (p = 0.916) nor between aneuploidy and dysplastic lesions (p = 0.159) could be observed. CONCLUSION: Aneuploidy is more frequent in adjacent non-malignant mucosa of aneuploid UCCs than in adjacent non-malignant mucosa of aneuploid SCCs. Furthermore, aneuploidy seems to be irrespective of inflammation or dysplasia. The results therefore emphasize the importance of aneuploidy for UC-associated carcinogenesis and its potential as new diagnostic target.

Inflammatory parameters and prediction of prognosis in infective endocarditis.

BACKGROUND: Procalcitonin (PCT) is widely used in critically ill patients to diagnose clinically significant infection and sepsis. Aim of this study was to evaluate the prognostic value of PCT in comparison to white blood cell count (WBC) and C-reactive protein (CRP) for clinical outcome and its correlation with microbiological etiology in patients with infective endocarditis (IE). METHODS: A retrospective single-center analysis was performed from 2007 till 2009. All patients were diagnosed having IE according to Duke standard criteria. Before starting antibiotic therapy, WBC, CRP and PCT were measured and blood cultures were taken for microbiological diagnosis of the etiological pathogen. Patients were followed up during in-hospital stay for poor outcome, defined as death or serious complications due to IE. RESULTS: During the study period 50 patients (57 ± 17 years, 72% male) fulfilling Duke criteria for IE were identified. In all patients PCT measurements before start of antibiotic therapy were available. In ROC analysis, a cut-off for PCT > 0.5 ng/mL was most accurate for the prediction of poor outcome with a sensitivity of 73% and specificity of 79%, a positive predictive value of 79% and a negative predictive value of 73%. Patients with a PCT > 0.5 ng/mL had an odds ratio of 12.8 (95% CI 2.5-66.2) for finding Staphylococcus aureus in blood cultures. CONCLUSIONS: For the first time, this study shows that in IE, an initial value of PCT > 0.5 ng/mL is a useful predictor of poor outcome, i.e. death or serious infectious complications. PCT > 0.5 ng/mL should raise the suspicion of Staphylococcus aureus as the etiological pathogen, whereas PCT levels < 0.5 ng/mL make staphylococcal infection unlikely.

Effect of antimicrobial therapy on progression-free survival of immunotherapy and chemo-/immunotherapy in patients with non-small cell lung cancer.

BACKGROUND: The choice between immunotherapy with a checkpoint inhibitor (CPI) and chemo-/immunotherapy (CIT) in patients with NSCLC stage IV is often discussed. There are some data that the effect of CPI therapy is impaired by antimicrobial therapy (AMT). Little is known about the influence of AMT on CIT. PATIENTS AND METHODS: We retrospectively analysed 114 patients (age 68 ± 8.5 years) with NSCLC stage IV. Patients were treated according to the guidelines with either CPI alone (pembrolizumab, nivolumab, atezolizumab, cemiplimab) or CIT (Carboplatin/Pemetrexed/Pembrolizumab, Carboplatin/Paclitaxel/Pembrolizumab). We registered patients' characteristics including presence and timing of AMT. Group 1 consisted of 42 patients with AMT in the month before CPI or CIT, group 2 were 49 patients with AMT during CPI or CIT, and group 3 were 64 patients without AMT and CPI or CIT. RESULTS: Group 1-3 showed comparable patients characteristics. Using cox-regression analysis, we found that AMT in the month before CPI resulted in a decreased progression-free survival (PFS) compared to patients with CPI and no AMT (14 ± 1.02 vs. 4 ± 1.02 months, p = 0.002, 95% CI 1.88-9). In patients, who were treated with CIT, there was no difference in PFS in those with or without AMT in the month before therapy (10 ± 2.5 vs. 6 ± 1.2 months, p = 0.7). Interestingly, AMT during CIT or CPI therapy showed no effect on PFS. CONCLUSIONS: In a real-life setting, we found that AMT reduces PFS when given in the month before CIT therapy. AMT before or during CIT does not seem to influence PFS. As a consequence, AMT before start of therapy might be a factor that could lead to a preference of CIT instead of CPI in NSCLC stage IV patients.

[Acute dyspnea]. / Akute Dyspnoe.

ACUTE DYSPNEA: The leading symptom "acute dyspnea" and the causal underlying diseases have a high risk potential for an unfavorable course of treatment with a high letality. This overview of possible causes, diagnostic procedures and guideline-based therapy is intended to help implement a targeted and structured emergency medical care in the emergency department. The leading symptom "acute dyspnea" is present in 10% of prehospital and 4-7% of patients in the emergency department. The most common conditions in the emergency department with the leading symptom "acute dyspnea" are heart failure in 25%, COPD in 15%, pneumonia in 13%, respiratory disorders in 8%, and pulmonary embolism in 4%. In 18% of cases, the leading symptom "acute dyspnea" is sepsis. The in-hospital letality is high and amounts to 9%. In critically ill patients in the non-traumatologic resuscitation room, respiratory disorders (B-problems) are present in 26-29%. In addition to cardiovascular disease, noncardiovascular disease may underlie "acute dyspnea" and requires differential diagnostic consideration. A structured approach can contribute to a high degree of certainty in the clarification of the leading symptom "acute dyspnea".

[Do we need Respiratory Care Units or Respiratory Emergency Centers?] / Brauchen wir Respiratory Care Units oder Atemnotfallzentren?

Although lung and heart diseases often occur together, the focus in acute medical emergency care frequently lies on the treatment of the cardiological symptoms only. This leads to a repeated patient visit and an impaired quality of life. How can this treatment gap be closed?

Older patients with EGFR mutation-positive non-small cell lung cancer treated with afatinib in clinical practice: A subset analysis of the non-interventional GIDEON study.

INTRODUCTION: Lung cancer is most common in older patients; despite this, older patients are historically under-represented in clinical studies. Here we present data from GIDEON, a study undertaken in Germany in patients with epidermal growth factor receptor mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC) receiving first-line afatinib. GIDEON enrolled a high proportion of patients aged ≥70 years, providing an opportunity to study afatinib use in older patients. MATERIALS AND METHODS: In GIDEON (NCT02047903), a prospective non-interventional study, patients with EGFRm+ NSCLC received first-line afatinib in routine clinical practice until disease progression, death or intolerable adverse events. Key objectives were twelve-month progression-free survival (PFS) rate and objective response rate (ORR). Overall survival (OS) and safety were also assessed. This post hoc analysis explores outcomes of patients grouped by age (≥70 and <70 years). RESULTS: In the 152 patients enrolled in GIDEON (69.7% female, 64.5%/22.4%/13.2% with Del19/L858R/other exon 18-21 mutations, 33.6% with brain metastases), the median age was 67 years (range 38-89) and 43.4% were aged ≥70 years. In the ≥70 years age group and the <70 years age group, twelve-month PFS rate was 58.9% and 43.9%, median PFS was 17.2 months and 10.6 months, ORR was 72.0% and 76.5%, twelve-month OS rate was 79.1% and 79.2%, 24-month OS rate was 52.0% and 61.7%, and median OS was 30.4 months and 27.4 months, respectively. In the ≥70 years age group and the <70 years age group, grade ≥3 adverse drug reactions (ADRs) were observed in 34.8% and 40.7% of patients, respectively; the most common were diarrhea (13.6% and 14.0%), acneiform dermatitis (7.6% and 7.0%), stomatitis (1.5% and 4.7%) and maculopapular rash (1.5% and 4.7%). DISCUSSION: Patients with EGFRm+ NSCLC aged ≥70 years showed clinical benefit from first-line afatinib with no unexpected safety signals, supporting the use of afatinib in this setting.

Immunity Against SARS-CoV-2 in the German Population.

BACKGROUND: Early during the SARS-CoV-2 pandemic, national population-based seroprevalence surveys were conducted in some countries; however, this was not done in Germany. In particular, no seroprevalence surveys were planned for the summer of 2022. In the context of the IMMUNEBRIDGE project, the GUIDE study was carried out to estimate seroprevalence on the national and regional levels. METHODS: To obtain an overview of the population-wide immunity against SARS-CoV-2 among adults in Germany that would be as statistically robust as possible, serological tests were carried out using self-sampling dried blood spot cards in conjunction with surveys, one by telephone and one online. Blood samples were analyzed for the presence of antibodies to the S and N antigens of SARS-CoV-2. RESULTS: Among the 15 932 participants, antibodies to the S antigen were detected in 95.7%, and to the N antigen in 44.4%. In the higher-risk age groups of persons aged 65 and above and persons aged 80 and above, anti-S antibodies were found in 97,4% and 98.8%, respectively. Distinct regional differences in the distribution of anti-S and anti-N antibodies emerged. Immunity gaps were found both regionally and in particular subgroups of the population. High anti-N antibody levels were especially common in eastern German states, and high anti-S antibody levels in western German states. CONCLUSION: These findings indicate that a large percentage of the adult German population has formed antibodies against the SARS-CoV-2 virus. This will markedly lower the probability of an overburdening of the health care system by hospitalization and high occupancy of intensive care units due to future SARS-CoV-2 waves, depending on the viral characteristics of then prevailing variants.

Late onset Li-Fraumeni Syndrome with bilateral breast cancer and other malignancies: case report and review of the literature.

BACKGROUND: Li-Fraumeni-Syndrome (LFS) is an autosomal-dominant, inherited tumour predisposition syndrome associated with heterozygous germline mutations in the TP53 gene. Patients with LFS are at a high risk to develop early-onset breast cancer and multiple malignancies, among which sarcomas are the most common. A high incidence of childhood tumours and close to 100% penetrance has been described. Knowledge of the genetic status of the TP53 gene in these patients is critical not only due to the increased risk of malignancies, but also because of the therapeutic implications, since a higher rate of radiation-induced secondary tumours in these patients has been observed. CASE REPORT: We report a patient with LFS harbouring heterozygous, pathogenic TP53 germline mutation, who was affected by four synchronous malignancies at the age of 40: a myxofibrosarcoma of the right upper arm, bilateral breast cancer and a periadrenal liposarcoma. Radiological treatments and a surveillance program were adjusted according to recommendations for LFS patients. CONCLUSION: Management of tumour treatment of patients with LFS is different to the general population because of their risk for secondary cancers in the radiation field. Screening procedures should take a possibly elevated risk for radiation induced cancer into account.