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Cirrhosis – the common end-stage of chronic liver disease – is associated with a cascade of events, of which intestinal bacterial overgrowth and dysbiosis are central. Bacterial toxins entering the portal or systemic circulation can directly cause hepatocyte death, while dysbiosis also affects gut barrier function and increases bacterial translocation, leading to infections, systemic inflammation and vasodilation, which contribute to acute decompensation and organ failure. Acute decompensation and its severe forms, pre-acute-on-chronic liver failure (ACLF) and ACLF, are characterised by sudden organ dysfunction (and failure) and high short-term mortality. Patients with pre-ACLF and ACLF present with high-grade systemic inflammation, usually precipitated by proven bacterial infection and/or severe alcoholic hepatitis. However, no precipitant is identified in 30% of these patients, in whom bacterial translocation from the gut microbiota is assumed to be responsible for systemic inflammation and decompensation. Different microbiota profiles may influence the rate of decompensation and thereby outcome in these patients. Thus, targeting the microbiota is a promising strategy for the prevention and treatment of acute decompensation, pre-ACLF and ACLF. Approaches include the use of antibiotics such as rifaximin, faecal microbial transplantation and enterosorbents (e.g. Yaq-001), which bind microbial factors without exerting a direct effect on bacterial growth kinetics. This review focuses on the role of microbiota in decompensation and strategies targeting microbiota to prevent acute decompensation.
Background: Nicolaides-Baraitser syndrome (NCBRS) is a rare disease caused by mutations in the SMRCA2 gene, which affects chromatin remodelling and leads to a wide range of symptoms including microcephaly, distinct facial features, recurrent seizures, and severe mental retardation. Until now, less than 100 cases have been reported. Case presentation: A 22-month old male infant with NCBRS underwent elective cleft palate surgery. The anaesthetists were challenged by the physiological condition of the patient: narrow face, very small mouth, mild tachypnea, slight sternal retractions, physical signs of partial monosomy 9p, and plagiocephalus, midface hypoplasia, V-shaped cleft palate, enhanced muscular hypotension, dysplastic kidneys (bilateral, estimated GFR: approx. 40 ml/m2), nocturnal oxygen demand, and combined apnea. In addition, little information was available about interaction of the NCBRS displayed by the patient and anaesthesia medications. Conclusions: The cleft palate was successfully closed using the bridge flap technique. Overall, we recommend to perform a trial video assisted laryngoscopy in the setting of spontaneous breathing with deep inhalative anaesthesia before administration of muscle relaxation to detect any airway difficulties while remaining spontaneoues breathing and protective reflexes.
Upon infection with SARS-CoV-2, a variety of changes happen inside the host cell. The virus hijacks host cell pathways for driving its own replication, while the host counteracts with response mechanisms. To gain a comprehensive understanding of COVID-19, caused by SARS-CoV-2 infection, and develop therapeutic strategies, it is crucial to observe these systematic changes in their entirety. In our recent studies, we followed the effects of SARS-CoV-2 infection on the human proteome, which led to the identification of several drugs that abolished viral proliferation in cells.
Purpose: To compare swept-source (SS) versus spectral-domain (SD) optical coherence tomography angiography (OCTA) for the detection of macular neovascularization (MNV).
Methods: In this prospective cohort study, 72 eyes of 54 patients with subretinal hyperreflective material (SHRM) and/or pigment epithelial detachment (PED) on OCT possibly corresponding to MNV in at least one eye were included. OCTA scans were acquired using two devices, the PLEX Elite 9000 SS-OCTA and the Spectralis SD-OCTA. Fluorescein angiography (FA) was used as reference. Two graders independently evaluated en face OCTA images using a preset slab as well as a manually modified slab, followed by a combination of en face and cross-sectional OCTA.
Results: Sensitivity (specificity) for the automated slabs was 51.7% (93.0%) for SS-OCTA versus 58.6% (95.3%) for SD-OCTA. Manual modification of segmentation increased sensitivity to 79.3% for SS-OCTA but not for SD-OCTA (58.6%). The combination of en face OCTA with cross-sectional OCTA reached highest sensitivity values (SS-OCTA: 82.8%, SD-OCTA: 86.2%), and lowest number of cases with discrepancies between SS-OCTA and SD-OCTA (4.2%). Fleiss kappa as measure of concordance between FA, SS-OCTA, and SD-OCTA was 0.56 for the automated slabs, 0.60 for the manual slabs, and 0.73 (good agreement) for the combination of en face OCTA with cross-sectional OCTA. Concordance to FA was moderate for the automated slabs and good for manual slabs and combination with cross-sectional OCTA of both devices.
Conclusion: Both devices reached comparable results regarding the detection of MNV on OCTA. Sensitivity for MNV detection and agreement between devices was best when evaluating a combination of en face and cross-sectional OCTA.
Hematopoietic stem cell transplantation (HSCT) is the therapeutic concept to cure the blood/immune system of patients suffering from malignancies, immunodeficiencies, red blood cell disorders, and inherited bone marrow failure syndromes. Yet, allogeneic HSCT bear considerable risks for the patient such as non-engraftment, or graft-versus host disease. Transplanting gene modified autologous HSCs is a promising approach not only for inherited blood/immune cell diseases, but also for the acquired immunodeficiency syndrome. However, there is emerging evidence for substantial heterogeneity of HSCs in situ as well as ex vivo that is also observed after HSCT. Thus, HSC gene modification concepts are suggested to consider that different blood disorders affect specific hematopoietic cell types. We will discuss the relevance of HSC heterogeneity for the development and manufacture of gene therapies and in exemplary diseases with a specific emphasis on the key target HSC types myeloid-biased, lymphoid-biased, and balanced HSCs.
Background: Various studies have been made about the most effective and safest type of treatment for vertebral compression fractures (VCFs). Long-term results are needed for qualitative evaluation.
Purpose: The purpose of the study is to evaluate the effectiveness of percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) procedures for VCFs.
Materials and Methods: Forty-nine patients who received either PVP or PKP between 2002 and 2015 returned a specially developed questionnaire and were included in a cross-sectional outcome analysis. The questionnaire assessed pain development by use of a visual analog scale (VAS). Imaging data (CT scans) were retrospectively analyzed for identification of cement leakage.
Results: Patients’ VAS scores significantly decreased after treatment (7.0 ± 3.4 => 3.7 ± 3.4), (p < 0.001). The average pain reduction in patients treated with PVP was −3.3 ± 3.8 (p < 0.001) (median −3.5) and −4.0 ± 3.9 (p < 0.001) (median −4.5) in patients treated with PKP. Fifteen Patients (41.7%) receiving PVP and four patients (30.7%) receiving PKP experienced recurrence of pain. Cement leakage occurred in 10 patients (22.73%). Patients with cement leakage showed comparable VAS scores after treatment (6.8 ± 3.5 => 1.4 ± 1.6), (p = 0.008). Thirty-nine patients reported an increase in mobility (79.6%) and 41 patients an improvement in quality of life (83.7%).
Conclusion: Pain reduction by means of PVP or PKP in patients with VCFs was discernible over the period of observation. Percutaneous vertebroplasty and PKP contribute to the desired treatment results. However, the level of low pain may not remain constant.
Pathogens possess the ability to adapt and survive in some host species but not in others–an ecological trait known as host tropism. Transmitted through ticks and carried mainly by mammals and birds, the Lyme disease (LD) bacterium is a well-suited model to study such tropism. Three main causative agents of LD, Borrelia burgdorferi, B. afzelii, and B. garinii, vary in host ranges through mechanisms eluding characterization. By feeding ticks infected with different Borrelia species, utilizing feeding chambers and live mice and quail, we found species-level differences in bacterial transmission. These differences localize on the tick blood meal, and specifically complement, a defense in vertebrate blood, and a polymorphic bacterial protein, CspA, which inactivates complement by binding to a host complement inhibitor, Factor H (FH). CspA selectively confers bacterial transmission to vertebrates that produce FH capable of allele-specific recognition. CspA is the only member of the Pfam54 gene family to exhibit host-specific FH-binding. Phylogenetic analyses revealed convergent evolution as the driver of such uniqueness, and that FH-binding likely emerged during the last glacial maximum. Our results identify a determinant of host tropism in Lyme disease infection, thus defining an evolutionary mechanism that shapes host-pathogen associations.
Purpose: Suicidality and suicidal ideation (SI) in oncology has long been an underestimated danger. Although there are cancer-specific distress screening tools available, none of these specifically incorporates items for SI. We examined the prevalence of SI in cancer patients, investigated the relation between SI and distress, and tried to identify additional associated factors. Methods: A cross-sectional study with patients treated for cancer in a primary care hospital was conducted. Psychosocial distress and SI in 226 patients was assessed. An expert rating scale (PO-Bado-SF) and a self-assessment instrument (QSC-R23) were used to measure distress. SI was assessed with item 9 of the PHQ-9. Data was descriptively analyzed, and correlations and group comparisons between clinically distressed and non-distressed patients were calculated. Results: SI was reported by 15% of patients. Classified as clinically distressed were 24.8% (QSC-R23) to 36.7% (PO-Bado-SF). SI was correlated with externally (rτ = 0.19, p < 0.001) and self-rated distress (rτ = 0.31, p < 0.001). Symptoms sufficiently severe for at least a medium major depressive episode were recorded in 23.5% of patients (PHQ-9). Factors associated with SI were feeling bad about oneself, feeling down, depressed, and hopeless, deficits in activities of daily life, psycho-somatic afflictions, social restrictions, and restrictions in daily life. Being in a steady relationship seemed to have a protective effect. Conclusions: SI is common in cancer patients. Distress and associated factors are increased in patients with SI. A distress screening with the ability to assess SI could be an important step in prevention, but more research is necessary.
Purpose: In this study, we examined distress levels and quality of life (QoL) of patients with hematologic malignancies under treatment in an acute setting. We used external- and self-assessment instruments for distress. Additionally, we investigated the relation between distress and QoL as well as whether highly distressed patients differed from less distressed patients concerning their QoL.
Methods: A cross-sectional study with patients of the Medical Clinic II of the University Hospital Frankfurt was conducted. One hundred and nine patients were assessed with an expert rating scale and completed self-report questionnaires. Data were exploratively analyzed and group comparisons between patients who scored above the cut-off of the respective screening instruments and those who did not were conducted.
Results: Patients with hematologic malignancies experience high levels of distress and low QoL. Especially, role and social functioning are affected. Patients suffer most from fatigue, appetite loss, and insomnia. Using established cut-offs, all screening instruments were able to differentiate between patients regarding distress and QoL. Patients scoring above the cut-off were significantly more distressed and had a lower QoL. There was a medium-to-strong correlation between distress and QoL indicators.
Conclusion: Cancer-specific screening instruments seem to be able to identify treatment needs more specifically. They also allowed a better differentiation concerning QoL. The close link between distress and QoL needs to be recognized to enable a holistic approach to treatment and thereby optimize the quality of treatment.
Purpose: The coronavirus disease 2019 (COVID-19) poses major challenges to health-care systems worldwide. This pandemic demonstrates the importance of timely access to intensive care and, therefore, this study aims to explore the accessibility of intensive care beds in 14 European countries and its impact on the COVID-19 case fatality ratio (CFR).
Methods: We examined access to intensive care beds by deriving (1) a regional ratio of intensive care beds to 100,000 population capita (accessibility index, AI) and (2) the distance to the closest intensive care unit. The cross-sectional analysis was performed at a 5-by-5 km spatial resolution and results were summarized nationally for 14 European countries. The relationship between AI and CFR was analyzed at the regional level.
Results: We found national-level differences in the levels of access to intensive care beds. The AI was highest in Germany (AI = 35.3), followed by Estonia (AI = 33.5) and Austria (AI = 26.4), and lowest in Sweden (AI = 5) and Denmark (AI = 6.4). The average travel distance to the closest hospital was highest in Croatia (25.3 min by car) and lowest in Luxembourg (9.1 min). Subnational results illustrate that capacity was associated with population density and national-level inventories. The correlation analysis revealed a negative correlation of ICU accessibility and COVID-19 CFR (r = − 0.57; p < 0.001).
Conclusion: Geographical access to intensive care beds varies significantly across European countries and low ICU accessibility was associated with a higher proportion of COVID-19 deaths to cases (CFR). Important differences in access are due to the sizes of national resource inventories and the distribution of health-care facilities relative to the human population. Our findings provide a resource for officials planning public health responses beyond the current COVID-19 pandemic, such as identifying potential locations suitable for temporary facilities or establishing logistical plans for moving severely ill patients to facilities with available beds.
Improving spatial accessibility to hospitals is a major task for health care systems which can be facilitated using recent methodological improvements of spatial accessibility measures. We used the integrated floating catchment area (iFCA) method to analyze spatial accessibility of general inpatient care (internal medicine, surgery and neurology) on national level in Germany determining an accessibility index (AI) by integrating distances, hospital beds and morbidity data. The analysis of 358 million distances between hospitals and population locations revealed clusters of lower accessibility indices in areas in north east Germany. There was a correlation of urbanity and accessibility up to r = 0.31 (p < 0.001). Furthermore, 10% of the population lived in areas with significant clusters of low spatial accessibility for internal medicine and surgery (neurology: 20%). The analysis revealed the highest accessibility for heart failure (AI = 7.33) and the lowest accessibility for stroke (AI = 0.69). The method applied proofed to reveal important aspects of spatial accessibility i.e. geographic variations that need to be addressed. However, for the majority of the German population, accessibility of general inpatient care was either high or at least not significantly low, which suggests rather adequate allocation of hospital resources for most parts of Germany.
Hintergrund: Parkinson-Syndrome führen im Krankheitsverlauf zur Pflegebedürftigkeit bei den Betroffenen. Zur Prävalenz der Bewohner*innen mit einem Parkinson-Syndrom in Pflegeeinrichtungen, zu ihrer Versorgungssituation und zur vorhandenen Expertise der Pflegefachpersonen in den Einrichtungen ist wenig bekannt.
Ziel der Arbeit: Die vorliegende Studie untersucht die Prävalenzrate der Bewohner*innen mit einem Parkinson-Syndrom in stationären Pflegeeinrichtungen in Deutschland. Die Arbeit exploriert die Zusammenarbeit verschiedener Akteure, deren Koordination sowie Information und Wissen des Pflegepersonals. Ziel ist es, einen möglichen Bedarf an spezialisierter Pflege in Pflegeeinrichtungen aufzuzeigen.
Methode: Die schriftliche Querschnittsbefragung der Wohnbereichsleitungen von 500 zufällig ausgewählten Pflegeeinrichtungen in Deutschland erfolgte von Januar bis Juni 2020. Der eingesetzte Fragebogen wurde vorab literaturbasiert entwickelt. Die Daten wurden deskriptiv analysiert.
Ergebnisse: Aus 57 Einrichtungen wurden Fragebogen von 85 Wohnbereichen analysiert (Rücklaufquote 11,4 %). Die Prävalenzrate von Bewohner*innen mit einem Parkinson-Syndrom in der stationären Altenhilfe beträgt 13,9 %. Mehr als die Hälfte haben zusätzlich eine Demenzdiagnose (52,8 %). In 26 % der Fälle erfolgen Krankenhausaufenthalte infolge von Sturzereignissen. Eine eindeutige Koordination der Versorgung durch ärztliche oder pflegerische Spezialisten gibt es nicht.
Diskussion: Bewohner*innen mit einem Parkinson-Syndrom in der stationären Altenhilfe sind häufig, und sie zeigen komplexe motorische und nichtmotorische Symptome – auch durch die Komorbidität Demenz. Die Häufigkeit von Sturzereignissen mit Krankenhausaufenthalten und die geringe Anzahl Parkinson-Syndrom-spezifischer Hilfsmittel zeigen, dass das Wissen der Pflege vor Ort gesteigert werden kann. Eine zentrale Koordination und Unterstützung hierzu sollten in der stationären Langzeitpflege etabliert werden.
Bloodstream infections (BSI) are a frequent complication in patients with hematological and oncological diseases. However, the impact of different bacterial species causing BSI and of multiple BSI remains incompletely understood. We performed a retrospective study profiling 637 bacterial BSI episodes in hematological and oncological patients. Based on the 30-day (30d) overall survival (OS), we analyzed different types of multiple BSI and grouped BSI-associated bacteria into clusters followed by further assessment of clinical and infection-related characteristics. We discovered that polymicrobial BSI (different organisms on the first day of a BSI episode) and sequential BSI (another BSI before the respective BSI episode) were associated with a worse 30d OS. Different bacterial groups could be classified into three BSI outcome clusters based on 30d OS: favorable (FAV) including mainly common skin contaminants, Escherichia spp. and Streptococcus spp.; intermediate (INT) including mainly Enterococcus spp., vancomycin-resistant Enterococcus spp., and multidrug-resistant gram-negative bacteria (MDRGN); and adverse (ADV) including MDRGN with an additional carbapenem-resistance (MDRGN+CR). A polymicrobial or sequential BSI especially influenced the outcome in the combination of two INT cluster BSI. The presence of a polymicrobial BSI and the assignment into the BSI outcome clusters were identified as independent risk factors for 30d mortality in a Cox multivariate regression analysis. The assignment to a BSI outcome cluster and the differentiated perspective of multiple BSI open new insights into the prognosis of patients with BSI and should be further validated in other patient cohorts.
This focus issue of the European Journal of Trauma and Emergency Surgery compiles a collection of outstanding clinical research using the immense dataset of the German TraumaRegister DGU® (TR-DGU). The TR-DGU of the German Trauma Society (Deutsche Gesellschaft für Unfallchirurgie, DGU) was founded in 1993. Currently, approximately 40,000 cases from more than 600 hospitals are entered into the database every year. The selected articles of this focus on issue highlight the immense value the TR-DGU constitutes for the current, but also for the future trauma research.
Zielsetzung: Die Daten für das Jahr 2019 des Registers „Abdominelles Aortenaneurysma“ (AAA) des Deutschen Instituts für Gefäßmedizinische Gesundheitsforschung (DIGG) der Deutschen Gesellschaft für Gefäßchirurgie und Gefäßmedizin werden vorgestellt.
Methodik: Im Jahr 2019 beteiligten sich an dem Register insgesamt 109 Kliniken. Für die offene Versorgung (OR) des intakten AAA (iAAA) gaben 78 (71,6 %) Kliniken, für die endovaskuläre Versorgung (EVAR) des iAAA 102 (93,6 %) Kliniken Daten ein. Für das rupturierte AAA (rAAA) wurden von 36 Kliniken (33,0 %) (EVAR) bzw. 50 (45,9 %) Kliniken (OR) Patienten gemeldet. Ausgewertet wurden die Daten von 1967 stationär behandelten Patienten. Von den insgesamt 1793 iAAA waren 1501 infrarenal (83,7 %) und 292 (16,3 %) juxtarenal gelegen.
Ergebnisse: 1429 iAAA (79,7 %) wurden endovaskulär und 364 (20,3 %) offen versorgt. Bei den endovaskulär versorgten Patienten mit iAAA verlief der Eingriff in 86,3 % der Fälle komplikationslos. Es verstarben insgesamt 15 Patienten (1,0 %) bis zur Entlassung. Bei den offen versorgten Patienten wiesen 67,0 % der Patienten keine Komplikationen auf. Verstorben sind insgesamt 20 Patienten (5,5 %). Bei EVAR war die Klinikletalität bei Versorgung juxtarenaler AAA mit 3,7 % signifikant höher als bei Versorgung infrarenaler AAA mit 0,6 % (p = 0,002), bei OR konnten hingegen keine signifikanten Unterschiede hinsichtlich der Klinikletalität aufgezeigt werden (juxtarenal 4,8 %, infrarenal 5,8 %; p = 0,470). Von den 174 Patienten mit rAAA wurden 80 (46,0 %) endovaskulär und 94 (54,0 %) offen versorgt. Bei EVAR sind 20,0 % der Patienten während des stationären Aufenthalts verstorben, bei OR 36,2 %.
Schlussfolgerung: Die Ergebnisse des Jahres 2019 zu Klinikletalität und Morbidität bei endovaskulärer und offener Versorgung des iAAA bestätigen weitgehend die publizierten Ergebnisse für die Jahre 2013 bis 2018. Beim rAAA sind die Ergebnisse der einzelnen Jahresberichte hingegen widersprüchlich, die kleinen berichteten jährlichen Fallzahlen erlauben nur Aussagen über größere Zeiträume.
Introduction: The induced membrane technique for the treatment of large bone defects is a two-step procedure. In the first operation, a foreign body membrane is induced around a spacer, then, in the second step, several weeks or months later, the spacer is removed and the Membrane pocket is filled with autologous bone material. Induction of a functional biological membrane might be avoided by initially using a biological membrane. In this study, the effect of a human acellular dermis (hADM, Epiflex, DIZG gGmbH) was evaluated for the treatment of a large (5 mm), plate-stabilised femoral bone defect.
Material and Methods: In an established rat model, hADM was compared to the two-stage induced membrane technique and a bone defect without membrane cover. Syngeneous spongiosa from donor animals was used for defect filling in all groups. The group size in each case was n = 5, the induction time of the membrane was 3–4 weeks and the healing time after filling of the defect was 8 weeks.
Results: The ultimate loads were increased to levels comparable with native bone in both membrane groups (hADM: 63.2% ± 29.6% of the reference bone, p < 0.05 vs. no membrane, induced membrane: 52.1% ± 25.8% of the reference bone, p < 0.05 vs. no membrane) and were significantly higher than the control group without membrane (21.5%). The membrane groups were radiologically and histologically almost completely bridged by new bone formation, in contrast to the control Group where no closed osseous bridging could be observed.
Conclusion: The use of the human acellular dermis leads to equivalent healing results in comparison to the two-stage induced membrane technique. This could lead to a shortened therapy duration of large bone defects.
Aims: SARS-CoV-2 is a single-stranded RNA virus which is part of the ß-coronavirus family (like SARS 2002 and MERS 2012). The high prevalence of hospitalization and mortality, in addition to the lack of vaccines and therapeutics, forces scientists and clinicians around the world to evaluate new therapeutic options. One strategy is the repositioning of already known drugs, which were approved drugs for other indications.
Subject and method: SARS-CoV-2 entry inhibitors, RNA polymerase inhibitors, and protease inhibitors seem to be valuable targets of research. At the beginning of the pandemic, the ClinicalTrials.gov webpage listed n=479 clinical trials related to the antiviral treatment of SARS-CoV-2 (01.04.2020, “SARS-CoV-2,” “COVID-19,” “antivirals,” “therapy”), of which n=376 are still accessible online in January 2021 (10.01.2021). Taking into account further studies not listed in the CTG webpage, this narrative review appraises HIV protease inhibitors and nucleos(t)ide RNA polymerase inhibitors as promising candidates for the treatment of COVID-19.
Results: Lopinavir/ritonavir, darunavir/cobicistat, remdesivir, tenofovir-disoproxilfumarate, favipriravir, and sofosbuvir are evaluated in clinical studies worldwide. Study designs show a high variability and results often are contradictory. Remdesivir is the drug, which is deployed in nearly 70% of the reviewed clinical trials, followed by lopinavir/ritonavir, favipiravir, ribavirine, and sofosbuvir.
Discussion: This review discusses the pharmacological/clinical background and questions the rationale and study design of clinical trials with already approved HIV protease inhibitors and nucleos(t)ide RNA polymerase inhibitors which are repositioned during the SARS-CoV-2 pandemic worldwide. Proposals are made for future study design and drug repositioning of approved antiretroviral compounds.
Background: The prevalence of multimorbidity is increasing in recent years, and patients with multimorbidity often have a decrease in quality of life and require more health care. The aim of this study was to explore the evolution of multimorbidity taking the sequence of diseases into consideration.
Methods: We used a Belgian database collected by extracting coded parameters and more than 100 chronic conditions from the Electronic Health Records of general practitioners to study patients older than 40 years with multiple diagnoses between 1991 and 2015 (N = 65 939). We applied Markov chains to estimate the probability of developing another condition in the next state after a diagnosis. The results of Weighted Association Rule Mining (WARM) allow us to show strong associations among multiple conditions.
Results: About 66.9% of the selected patients had multimorbidity. Conditions with high prevalence, such as hypertension and depressive disorder, were likely to occur after the diagnosis of most conditions. Patterns in several disease groups were apparent based on the results of both Markov chain and WARM, such as musculoskeletal diseases and psychological diseases. Psychological diseases were frequently followed by irritable bowel syndrome.
Conclusions: Our study used Markov chains and WARM for the first time to provide a comprehensive view of the relations among 103 chronic conditions, taking sequential chronology into consideration. Some strong associations among specific conditions were detected and the results were consistent with current knowledge in literature, meaning the approaches were valid to be used on larger data sets, such as National Health care Systems or private insurers.
Das Corona-Update Frankfurt
(2022)
Seit Beginn der Coronapandemie haben die vier Arbeitsgruppen am Institut für Medizinische Virologie ihre Forschungsschwerpunkte innerhalb kürzester Zeit verlagert. Sie haben wichtige Erkenntnisse zu Teststrategien, Impfschutz und Therapieansätzen gewonnen. Dieser Weg wird durch Förderung des Landes Hessen weiter ausgebaut. Eine Bestandsaufnahme.
Aqueous solutions of a nonionic surfactant (either Tween20 or BrijL23) and an anionic surfactant (sodium dodecyl sulfate, SDS) are investigated, using small-angle neutron scattering (SANS). SANS spectra are analysed by using a core-shell model to describe the form factor of self-assembled surfactant micelles; the intermicellar interactions are modelled by using a hard-sphere Percus–Yevick (HS-PY) or a rescaled mean spherical approximation (RMSA) structure factor. Choosing these specific nonionic surfactants allows for comparison of the effect of branched (Tween20) and linear (BrijL23) surfactant headgroups, both constituted of poly-ethylene oxide (PEO) groups. The nonionic–anionic surfactant mixtures are studied at various concentrations up to highly concentrated samples (ϕ ≲ 0.45) and various mixing ratios, from pure nonionic to pure anionic surfactant solutions. The scattering data reveal the formation of mixed micelles already at concentrations below the critical micelle concentration of SDS. At higher volume fractions, excluded volume effects dominate the intermicellar structuring, even for charged micelles. In consequence, at high volume fractions, the intermicellar structuring is the same for charged and uncharged micelles. At all mixing ratios, almost spherical mixed micelles form. This offers the opportunity to create a system of colloidal particles with a variable surface charge. This excludes only roughly equimolar mixing ratios (X≈ 0.4–0.6) at which the micelles significantly increase in size and ellipticity due to specific sulfate–EO interactions.
Objective In rheumatoid arthritis (RA), chronic inflammation can enhance the development of sarcopenia with a depletion of muscle mass, strength and performance. Currently, a consensus definition for sarcopenia and solid results for the prevalence of sarcopenia in patients with RA are lacking.
Methods In this cross-sectional study, 289 patients ≥18 years with RA were recruited. Dual X-ray absorptiometry was performed to measure appendicular lean mass. Assessment of muscle function included grip strength, gait speed and chair rise time. Prevalence of sarcopenia was defined using the updated European Working Group on Sarcopenia in Older People (EWGSOP2) and the Foundation for the National Institutes of Health (FNIH) definition. In addition, the RA study population was compared with existing data of healthy controls (n=280).
Results 4.5% of patients (59.4±11.3 years) and 0.4% of controls (62.9±11.9 years) were affected by sarcopenia according to the EWGSOP2 definition. Body weight (OR 0.92, 95% CI 0.86 to 0.97), body mass index (BMI) (OR 0.70, 95% CI 0.57 to 0.87), C reactive protein (CRP) (OR 1.05, 95% CI 1.01 to 1.10), disease duration (OR 1.08, 95% CI 1.02 to 1.36), current medication with glucocorticoids (OR 5.25, 95% CI 2.14 to 24.18), cumulative dose of prednisone equivalent (OR 1.04, 95% CI 1.02 to 1.05) and Health Assessment Questionnaire (HAQ) (OR 2.50, 95% CI 1.27 to 4.86) were associated with sarcopenia in patients with RA. In contrast, the prevalence was 2.8% in patients compared with 0.7% in controls when applying the FNIH definition, and body height (OR 0.75, 95% CI 0.64 to 0.88), BMI (OR 1.20, 95% CI 1.02 to 1.41), CRP (OR 1.06, 95% CI 1.01 to 1.11) and HAQ (OR 2.77, 95% CI 1.17 to 6.59) were associated with sarcopenia.
Conclusion Sarcopenia is significantly more common in patients with RA compared with controls using the EWGSOP2 criteria. The FNIH definition revealed sarcopenia in individuals with high BMI and fat mass, regardless of the presence of RA.
Trial registration number It was registered at the German Clinical Trials Registry (DRKS) as well as WHO Clinical Trials Registry (ICTRP) (DRKS00011873, registered on 16 March 2017).
Hidradenitis suppurativa/Acne inversa (HS/AI) ist eine chronisch-entzündliche Hauterkrankung, deren Behandlung sowohl konservative als auch chirurgische Behandlungsmöglichkeiten umfasst. In den Hurley-Stadien II und III ist die chirurgische Resektion irreversibel zerstörten Gewebes anzustreben. Hierzu existieren verschiedene Resektionstechniken, die sich vor allem in ihrer Invasivität und Rezidivneigung unterscheiden. Bis heute gibt es keinen allgemein akzeptierten Konsens hinsichtlich verschiedener Resektions- und Rekonstruktionstechniken sowie der Einbeziehung medikamentöser Therapien in das therapeutische Gesamtkonzept.
Omicron is the evolutionarily most distinct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VOC) to date. We report that Omicron BA.1 breakthrough infection in BNT162b2-vaccinated individuals resulted in strong neutralizing activity against Omicron BA.1, BA.2, and previous SARS-CoV-2 VOCs but not against the Omicron sublineages BA.4 and BA.5. BA.1 breakthrough infection induced a robust recall response, primarily expanding memory B (BMEM) cells against epitopes shared broadly among variants, rather than inducing BA.1-specific B cells. The vaccination-imprinted BMEM cell pool had sufficient plasticity to be remodeled by heterologous SARS-CoV-2 spike glycoprotein exposure. Whereas selective amplification of BMEM cells recognizing shared epitopes allows for effective neutralization of most variants that evade previously established immunity, susceptibility to escape by variants that acquire alterations at hitherto conserved sites may be heightened.
Objectives: Immune checkpoint inhibitors have become the standard of care for metastatic non–small-cell lung cancer (NSCLC) progressing during or after platinum-based chemotherapy. Real-world clinical practice tends to represent more diverse patient characteristics than randomized clinical trials. We sought to evaluate overall survival (OS) outcomes in the total study population and in key subsets of patients who received nivolumab for previously treated advanced NSCLC in real-world settings in France, Germany, or Canada.
Materials and methods: Data were pooled from two prospective observational cohort studies, EVIDENS and ENLARGE, and a retrospective registry in Canada. Patients included in this analysis were aged ≥18 years, had stage IIIB/IV NSCLC, and received nivolumab after at least one prior line of systemic therapy. OS was estimated in the pooled population and in various subgroups using the Kaplan-Meier method. Timing of data collection varied across cohorts (2015–2019).
Results: Of the 2585 patients included in this analyses, 1235 (47.8 %) were treated in France, 881 (34.1 %) in Germany, and 469 (18.1 %) in Canada. Median OS for the total study population was 11.3 months (95 % CI: 10.5–12.2); this was similar across France, Germany, and Canada. The OS rate was 49 % at 1 year and 28 % at 2 years for the total study population. In univariable Cox analyses, the presence of epidermal growth factor receptor mutations in nonsquamous disease, liver, or bone metastases were associated with significantly shorter OS, whereas tumor programmed death ligand 1 expression and Eastern Cooperative Oncology Group performance status 0–1 were associated with significantly prolonged OS. Similar OS was noted across subgroups of age and prior lines of therapy.
Conclusion: OS rates in patients receiving nivolumab for previously treated advanced NSCLC in real-world clinical practice closely mirrored those in phase 3 studies, suggesting similar effectiveness of nivolumab in clinical trials and clinical practice.
Die Multiple Sklerose (MS) ist die häufigste nicht-traumatische, autoimmun-vermittelte Erkrankung des zentralen Nervensystems (ZNS), welche vor allem bei jüngeren Patienten mit Invalidisierung und anhaltenden neurologischen Defiziten einhergehen kann.
Im Rahmen eines optimalen Therapiekonzepts wurden deshalb immer neuere und potentere Medikamente eingeführt. Mit den Sphingosin-1-Phosphat-Rezeptor-1 (S1P1) -Agonisten Fingolimod und Siponimod sind seit mehreren Jahren Medikamente auf dem Markt deren Wirksamkeit bewiesen, jedoch die genauen Wirkprinzipien noch nicht vollends verstanden sind. Angenommen wurde bisher eine Lymphozytendepletion aufgrund einer Hemmung der Lymphozyteninfiltation ins ZNS über den ubiquitär exprimierten, G-protein gekoppelten S1P1-Rezeptor. Neben Wirksamkeiten im Bereich des Immunsystems spielt der S1P1-Rezeptor und sein natürliches Substrat, das S1P, in vielen essenziellen Bereichen eine entscheidende Rolle, unter anderem in der Ausbildung und Reifung des vaskulären Systems in der Embryogenese.
Die genaue Untersuchung des S1P1-Signalwegs in-vivo gestaltete sich deshalb erschwert, da S1P1-Knock-Out-Mäuse einen letalen Phänotyp ausbilden. Jedoch deuten immer mehr Untersuchungen auch auf eine direkte S1P1-Rezeptor-vermittelte Wirksamkeit von Fingolimod auf Zellen des ZNS hin, somit eine Wirkung über die bisher bekannte Lymphozytenaffektion hinaus. Eine genaue Darstellung der im ZNS-beteiligten Zellen und ihrer S1P1-Aktivität gelang bisher auf zellulärer Ebene nicht.
Mit dem in dieser Arbeit genutzten Mausmodell der genmodifizierten S1P1-Signaling-Maus sollte erstmals eine lokoregionale und zelluläre Untersuchung der am S1P1-Signalweg beteiligten Zellen im Rahmen von physiologischen und experimentellen autoimmunen Enzephalomyelitis (EAE)-Bedingungen im ZNS erfolgen. Hierbei entspricht die EAE weitgehend einem tierexperimentellen Korrelat der menschlichen MS. Bei Aktivierung eines S1P1-Rezeptors bei der S1P1-Signaling-Maus erfolgt durch eine gekoppelte Signalkaskade eine konsekutive Expression eines Histonproteins, welches an ein grün-fluoreszierendes Protein gekoppelt ist. Es resultiert eine grüne Fluoreszenz des Zellkerns der betroffenen Zelle. Bei der Kontroll-Maus findet sich keine Kopplung zwischen Rezeptor und im Zellkern befindlicher Proteine.
Hierbei konnte mit Hilfe von Immunhistochemie sowie der quantitativen Methode der Durchflusszytometrie ein S1P1-Signaling in peripheren Organen wie beispielweise der im Rahmen der MS bedeutsamen Milz nachgewiesen werden. Dadurch eröffnen sich Einblicke in Migrationsverhalten und Zusammensetzung der Lymphozyten-Subtypen und deren S1P1-Signaling im Rahmen von physiologischen Bedingungen und unter EAE-Bedingungen.
Die Darstellung des S1P1-Signalings im ZNS, als Hauptmanifestationsort der MS, gelang unter Zuhilfenahme der EAE mit dem genmodifizierten Mausmodell jedoch nicht. Da sich keine Unterschiede in der GFP-Expression zwischen der Signaling-Maus und der heterozygoten Kontroll-Maus zeigen, sind keinerlei Rückschlüsse auf ein echtes S1P1-Signaling möglich. Es zeigen sich zwar deutliche Expressionsunterschiede des GFP im Vergleich erkrankter und gesunder Versuchstiere, Rückschlüsse auf eine echte S1P1-Aktivität konnten jedoch nicht getroffen werden.
Zusammenfassend eignet sich das hier genutzte Mausmodell der genmodifizierten S1P1-Maus zur Untersuchung peripherer Organe und ihrem S1P1-Signaling, z.B. zur Untersuchung kardiovaskulärer Fragestellungen oder zur dezidierteren Veranschaulichung peripher lymphatischer Prozesse.
Zur Untersuchung ZNS-eigener Zellen sowie zur Beantwortung der Frage, ob und wie sie über den S1P1-Rezeptor agieren, bedarf es jedoch noch der Entwicklung eines geeigneteren Tiermodells.
Die bereits erprobte Möglichkeit der Biolumineszenz zeigte in vorherigen Untersuchungen zwar eine S1P1-Aktivität in-vivo, jedoch sind hier keinerlei Untersuchungen auf zellulärer Basis möglich, sodass mit dem aktuellen Stand der Forschung ein direkter Nachweis der S1P1-Aktivität auf zellulärer Ebene im ZNS nicht möglich ist.
GATA2 deficiency is a heterogeneous multi-system disorder characterized by a high risk of developing myelodysplastic syndrome (MDS) and myeloid leukemia. We analyzed the outcome of 65 patients reported to the registry of the European Working Group (EWOG) of MDS in childhood carrying a germline GATA2 mutation (GATA2mut) who had undergone hematopoietic stem cell transplantation (HSCT). At 5 years the probability of overall survival and disease-free survival (DFS) was 75% and 70%, respectively. Non-relapse mortality and relapse equally contributed to treatment failure. There was no evidence of increased incidence of graft-versus-host-disease or excessive rates of infections or organ toxicities. Advanced disease and monosomy 7 (−7) were associated with worse outcome. Patients with refractory cytopenia of childhood (RCC) and normal karyotype showed an excellent outcome (DFS 90%) compared to RCC and −7 (DFS 67%). Comparing outcome of GATA2mut with GATA2wt patients, there was no difference in DFS in patients with RCC and normal karyotype. The same was true for patients with −7 across morphological subtypes. We demonstrate that HSCT outcome is independent of GATA2 germline mutations in pediatric MDS suggesting the application of standard MDS algorithms and protocols. Our data support considering HSCT early in the course of GATA2 deficiency in young individuals.
Purpose: Colorectal cancer (CRC) is the second most common cancer in Germany. Around 60,000 people were diagnosed CRC in 2016 in Germany. Since 2019, screening colonoscopies are offered in Germany for men by the age of 50 and for women by the age of 55. It is recently discussed if women should also undergo a screening colonoscopy by the age of 50 and if there are any predictors for getting CRC.
Methods: Colonoscopies of 1553 symptomatic patients younger than 55 years were compared with colonoscopies of 1075 symptomatic patients older than 55 years. We analyzed if there are any significant differences between those two groups in the prevalence of CRC and its precursor lesions or between symptomatic men and women. We evaluated if there is a correlation between abdominal symptoms and the prevalence of CRC.
Results: In 164/1553 symptomatic patients, 194 (12.5%) polyps were detected. In total, six colorectal carcinomas (0.4%) were detected. There were no significant differences between men and women. In symptomatic patients ≥ 55 years, significantly more polyps were found (p<0.0001; 26.6% vs. 12.5%). Totally, 286 polyps (26.6%) were removed in 1075 symptomatic patients older than 55 years. Anorectal bleeding was the only abdominal symptom being a significant indicator for the prevalence of the occurrence of colon and rectum cancer in both groups (p=0.03, OR=2.73 95%-CI [1.11;6.70]), but with only low sensitivity (44%).
Conclusion: Due to no significant differences in men and women, we recommend screening colonoscopies also for women by the age of 50.
Background: This prospective randomized trial is designed to compare the performance of conventional transarterial chemoembolization (cTACE) using Lipiodol-only with additional use of degradable starch microspheres (DSM) for hepatocellular carcinoma (HCC) in BCLC-stage-B based on metric tumor response. Methods: Sixty-one patients (44 men; 17 women; range 44–85) with HCC were evaluated in this IRB-approved HIPPA compliant study. The treatment protocol included three TACE-sessions in 4-week intervals, in all cases with Mitomycin C as a chemotherapeutic agent. Multiparametric magnetic resonance imaging (MRI) was performed prior to the first and 4 weeks after the last TACE. Two treatment groups were determined using a randomization sheet: In 30 patients, TACE was performed using Lipiodol only (group 1). In 31 cases Lipiodol was combined with DSMs (group 2). Response according to tumor volume, diameter, mRECIST criteria, and the development of necrotic areas were analyzed and compared using the Mann–Whitney-U, Kruskal–Wallis-H-test, and Spearman-Rho. Survival data were analyzed using the Kaplan–Meier estimator. Results: A mean overall tumor volume reduction of 21.45% (± 62.34%) was observed with an average tumor volume reduction of 19.95% in group 1 vs. 22.95% in group 2 (p = 0.653). Mean diameter reduction was measured with 6.26% (± 34.75%), for group 1 with 11.86% vs. 4.06% in group 2 (p = 0.678). Regarding mRECIST criteria, group 1 versus group 2 showed complete response in 0 versus 3 cases, partial response in 2 versus 7 cases, stable disease in 21 versus 17 cases, and progressive disease in 3 versus 1 cases (p = 0.010). Estimated overall survival was in mean 33.4 months (95% CI 25.5–41.4) for cTACE with Lipiosol plus DSM, and 32.5 months (95% CI 26.6–38.4), for cTACE with Lipiodol-only (p = 0.844), respectively. Conclusions: The additional application of DSM during cTACE showed a significant benefit in tumor response according to mRECIST compared to cTACE with Lipiodol-only. No benefit in survival time was observed.
Background: Decedents who are repatriated to Germany from abroad are not systematically registered nationwide. In Hamburg, in addition to an epidemic hygienic examination, registration and examination of the content of the documents accompanying the corpses of German citizens has been carried out since 2007. In this way, unclear and non-natural deaths in particular are to be followed up as necessary.
Material and methods: Protocols of external and internal autopsies of German nationals who died abroad and were repatriated to Hamburg via the port or airport between 2007 and 2018 were retrospectively evaluated with respect to numbers, completeness of the autopsy abroad and correctness of manner and cause of death.
Results: Between 2007 and 2018 a total of 703 corpses were repatriated via the port or airport of Hamburg and examined by the Port Medical Service for epidemic hygiene and for anything conspicuous in the documents accompanying the corpse. Of them, 307 corpses were examined at the Institute of Legal Medicine at the University Medical Center Hamburg-Eppendorf. In total, 82.4% of the examined cases had an incorrect, unspecific or incomplete foreign death certificate. Of the deceased, 238 were subjected to a second external autopsy by a forensic pathologist and 69 deceased were autopsied again or for the first time in Hamburg. It was found that 84% of the autopsies performed abroad were not performed according to German and European standards. The most common discrepancy was incomplete preparation of the organs. In almost one quarter of the autopsies performed in Hamburg a different cause of death than abroad was determined at autopsy.
Conclusion: Since the quality of autopsies performed abroad sometimes does not meet the standards in Germany and Europe and many papers accompanying corpses are incomplete or incorrectly filled out, a systematic review procedure in the home country is recommended. Through the system established in Hamburg in 2007, at least a re-evaluation of the cases takes place.
Background: In a phase 3 clinical study, patients from Germany with moderate to severe psoriasis who were naïve to systemic treatment and received risankizumab had greater and more rapid disease improvements compared with those who received fumaric acid esters (FAEs).
Objective: To evaluate patient-reported outcomes (PROs) in patients treated with risankizumab compared with FAEs.
Methods: Adult patients were randomized 1:1 to receive either risankizumab 150 mg subcutaneous injections at weeks 0, 4 and 16 or FAEs (Fumaderm®) provided according to the prescribing label. PRO secondary endpoints assessed were Psoriasis Symptom Scale (PSS), Dermatology Life Quality Index (DLQI), 36-Item Short Form Health Survey, version 2 (SF-36v2), Patient Benefit Index (PBI), Hospital Anxiety and Depression Scale (HADS), Patient Global Assessment (PtGA) and European Quality of Life 5 Dimensions 5 Level (EQ-5D-5L). PROs were assessed at weeks 0, 16 and 24.
Results: Sixty patients each were randomized to receive risankizumab or FAEs. A significant PSS improvement was observed with risankizumab vs. FAEs at weeks 16 and 24 for total and psoriasis-associated redness, itching and burning scores (P < 0.001). DLQI scores were significantly lower (reflecting better health-related quality of life) with risankizumab vs. FAEs, with least squares (LS) mean differences of −7.4 and −7.6 at weeks 16 and 24, respectively (both P < 0.001). Patients randomized to risankizumab also had larger improvements in SF-36 Physical and Mental Component Summary scores, HADS anxiety and depression scores, PtGA, and EQ-5D-5L index and visual analogue scale scores (all P ≤ 0.002) at weeks 16 and 24 compared with FAEs. PBI was significantly higher, indicating greater benefit, with risankizumab vs. FAEs, with an LS mean difference of 1.1 and 1.3 at weeks 16 and 24, respectively (both P < 0.001).
Conclusions: Risankizumab provides significant benefits over FAEs in improving PROs across several dimensions in patients with moderate to severe psoriasis.
Lippen-Kiefer-Gaumenspalten sind häufige, angeborene Fehlbildungen beim Menschen und werden zumeist schon innerhalb des ersten Lebensjahres operativ korrigiert. In 5-11% der Fälle ist das Vorliegen einer solchen Anomalie mit einer schwierigen Laryngoskopie assoziiert und kann ein modifiziertes Vorgehen bei der Sicherung des Atemweges erfordern. Videolaryngoskopische Techniken kommen hierbei vermehrt zum Einsatz und können auch im Kindesalter zu einer Verbesserung der Intubationsbedingungen beitragen.
In der vorliegenden Arbeit wurden die Intubationsbedingungen zwischen der indirekten Laryngoskopie mittels Glidescope® GVL Spatel Gr. 2 und der indirekten sowie direkten Laryngoskopie mittels C-MAC® Miller-Spatel Gr. 1 bei Kindern mit Lippen-Kiefer-Gaumenspalte miteinander verglichen.
Über einen Zeitraum von acht Monaten wurden Kinder mit Lippen-Kiefer-Gaumenspalte prospektiv abwechselnd entweder indirekt mit dem Glidescope® oder direkt und indirekt mit dem C-MAC® laryngoskopiert. Die Visualisierung der Glottisebene nach der modifizierten Cormack und Lehane Klassifikation war das Hauptzielkriterium. Sekundäre Zielparameter waren unter anderem die Zeit bis zur optimalen Sicht und die Zeit bis zur Intubation.
36 Kinder, die sich einer elektiven Korrektur einer Lippen-Kiefer-Gaumenspalte unterzogen, wurden eingeschlossen und erfolgreich intubiert. Jeweils 18 Kinder wurden mit dem C-MAC® Miller-Spatel Gr. 1 und mit dem Glidescope® GVL-Spatel Gr. 2 laryngoskopiert. Im Vergleich zwischen direkter und indirekter Laryngoskopie mit dem C-MAC® zeigte sich bei vier (22%) Kindern eine deutliche Verbesserung der Visualisierung der Glottisebene von einer schlechten Visualisierung (CL2b, 3 und 4) hin zu einer guten Visualisierung (CL2a und 1) der Glottisebene. Bei Verwendung des Glidescope® lag lediglich in einem Fall eine schlechte Visualisierung der Glottisebene vor.
Der Einsatz indirekter videolaryngoskopischer Techniken kann die Visualisierung der Glottisebene verbessern und reduziert die Anzahl an schwierigen Laryngoskopien bei Kindern mit Lippen-Kiefer-Gaumenspalte.
The role and timing of radiotherapy (RT) in prostate cancer (PCa) patients treated with radical prostatectomy (RP) remains controversial. While recent trials support the oncological safety of early salvage RT (SRT) compared to adjuvant RT (ART) in selected patients, previous randomized studies demonstrated that ART might improve recurrence-free survival in patients at high risk for local recurrence based on adverse pathology. Although ART might improve survival, this approach is characterized by a risk of overtreatment in up to 40% of cases. SRT is defined as the administration of RT to the prostatic bed and to the surrounding tissues in the patient with PSA recurrence after surgery but no evidence of distant metastatic disease. The delivery of salvage therapies exclusively in men who experience biochemical recurrence (BCR) has the potential advantage of reducing the risk of side effects without theoretically compromising outcomes. However, how to select patients at risk of progression who are more likely to benefit from a more aggressive treatment after RP, the exact timing of RT after RP, and the use of hormone therapy and its duration at the time of RT are still open issues. Moreover, what the role of novel imaging techniques and genomic classifiers are in identifying the most optimal post-operative management of PCa patients treated with RP is yet to be clarified. This narrative review summarizes most relevant published data to guide a multidisciplinary team in selecting appropriate candidates for post-prostatectomy radiation therapy.
Focal therapy is a modern alternative to selectively treat a specific part of the prostate harboring clinically significant disease while preserving the rest of the gland. The aim of this therapeutic approach is to retain the oncological benefit of active treatment and to minimize the side-effects of common radical treatments. The oncological effectiveness of focal therapy is yet to be proven in long-term robust trials. In contrast, the toxicity profile is well-established in randomized controlled trials and multiple robust prospective cohort studies. This narrative review summarizes the relevant evidence on complications and their management after focal therapy. When compared to whole gland treatments, focal therapy provides a substantial benefit in terms of adverse events reduction and preservation of genito-urinary function. The most common complications occur in the peri-operative period. Urinary tract infection and acute urinary retention can occur in up to 17% of patients, while dysuria and haematuria are more common. Urinary incontinence following focal therapy is very rare (0–5%), and the vast majority of patients recover in few weeks. Erectile dysfunction can occur after focal therapy in 0–46%: the baseline function and the ablation template are the most important factors predicting post-operative erectile dysfunction. Focal therapy in the salvage setting after external beam radiotherapy has a significantly higher rate of complications. Up to one man in 10 will present a severe complication.
Systemic lupus erythematosus (SLE) is a severe autoimmune disease of unknown etiology. The major histocompatibility complex (MHC) class I-related chain A (MICA) and B (MICB) are stress-inducible cell surface molecules. MICA and MICB label malfunctioning cells for their recognition by cytotoxic lymphocytes such as natural killer (NK) cells. Alterations in this recognition have been found in SLE. MICA/MICB can be shed from the cell surface, subsequently acting either as a soluble decoy receptor (sMICA/sMICB) or in CD4+ T-cell expansion. Conversely, NK cells are frequently defective in SLE and lower NK cell numbers have been reported in patients with active SLE. However, these cells are also thought to exert regulatory functions and to prevent autoimmunity. We therefore investigated whether, and how, plasma membrane and soluble MICA/B are modulated in SLE and whether they influence NK cell activity, in order to better understand how MICA/B may participate in disease development. We report significantly elevated concentrations of circulating sMICA/B in SLE patients compared with healthy individuals or a control patient group. In SLE patients, sMICA concentrations were significantly higher in patients positive for anti-SSB and anti-RNP autoantibodies. In order to study the mechanism and the potential source of sMICA, we analyzed circulating sMICA concentration in Behcet patients before and after interferon (IFN)-α therapy: no modulation was observed, suggesting that IFN-α is not intrinsically crucial for sMICA release in vivo. We also show that monocytes and neutrophils stimulated in vitro with cytokines or extracellular chromatin up-regulate plasma membrane MICA expression, without releasing sMICA. Importantly, in peripheral blood mononuclear cells from healthy individuals stimulated in vitro by cell-free chromatin, NK cells up-regulate CD69 and CD107 in a monocyte-dependent manner and at least partly via MICA-NKG2D interaction, whereas NK cells were exhausted in SLE patients. In conclusion, sMICA concentrations are elevated in SLE patients, whereas plasma membrane MICA is up-regulated in response to some lupus stimuli and triggers NK cell activation. Those results suggest the requirement for a tight control in vivo and highlight the complex role of the MICA/sMICA system in SLE.
[Nachruf] Helmut Siefert
(2012)
Wolfgang Schlote : 80 Jahre
(2012)
Das Institut für Medizinische Virologie, untergebracht in dem 100 Jahre alten Gebäude des ehemaligen Frankfurter Gesundheitsamtes direkt neben dem Georg-Speyer-Haus, ist eine wunderbare Kombination von Funktionalität und Schönheit. Von der geschwungenen Holztreppe des historischen Treppenhauses geht der Blick immer wieder in hochmoderne biomedizinische Laboratorien, gesichert hinter dicken Glastüren – ein Blick in eine futuristisch anmutende Welt.
Hausherr ist hier seit April 2012 der mehrfach ausgezeichnete HIV/AIDS-Experte Professor Oliver T. Keppler. Unter seiner Leitung ist das Institut umgehend mit Wirkung zum 1. Oktober 2012 vom Präsidenten des Robert-Koch-Instituts zum „Nationalen Referenzzentrum für Retroviren“ berufen worden. Mit Retroviren sind zu 95 Prozent HI-Viren (Humanes Immundefizienz-Virus) gemeint – die restlichen fünf Prozent umfassen die HTL-Viren (Humanes T-lymphotropes-Virus), mit denen weltweit etwa 20 Millionen Menschen infiziert sind, das jedoch kaum in Deutschland vorkommt. Das Institut ist damit das deutsche Referenzlabor für die Routine- und Spezialdiagnostik von Retroviren, Schwerpunkt HIV-Infektionen, sowie für Stellungnahmen zu Fragen der Krankheitsentstehung und Behandlung.