The review of A. Zeller reflects perfectly the status of monoamine oxidase (MAO) and its inhibitors as of 1983. He reviews especially the role of MAO and MAO-I with regard to schizophrenia and depression syndrome. Since that time, both clinical and experimental studies have led to the development of new compounds, which are more selective and safer in their clinical applications for the treatment of depression syndrome. However, the use of MAO-I for schizophrenia has not been further developed. In contrast, patients with schizophrenia nowadays are treated with antipsychotic drugs, which inhibit a variety of receptors. As such, the status reviewed by A. Zeller has been a starting point for more detailed basic research leading to development of new drugs, which are more specific, safer and more tolerable for the patients.
The review by Ted Sourkes and Serge Gauthier describe the status quo of drug developments in Parkinson's disease (PD) as of 1983. Remarkably, levodopa is still the most effective medication for the treatment of this devastating disorder. Progress has been made since then, though, in developing new formulations of levodopa in order to treat patients with more severe symptomology. In addition, inhibitors of monoamine oxidase, selegiline and rasagiline, have been synthesized and together with inhibitors of catechol-O-methyltransferase, tolcapone, entacapone, opicapone, allow reduction of the dose of daily levodopa. In addition, these compounds contribute to reduce oxidative stress. In contrast to 1983, as only piribedil is mentioned in the original review, a number of dopamine receptor agonists have been marketed, but only apomorphine, pramipexol, ropinirol, rotigotine and piripedil are of major importance today. The mode of action of amantadine has been discovered and since then, this drug has become a valuable addition to treatment strategies for early PD, mild symptomology and therapy of levodopa-induced dyskinesias. As such, the groundbreaking developments in PD therapy as described by Sourkes and Gauthier have been further elucidated and extended, but we are waiting for the next breakthrough in therapy to cure or at least to halt the degenerative processes underlying PD.
Introduction The aim of this study was to evaluate the influence of a noise optimized virtual monoenergetic reconstruction algorithm (VMI+) on the image quality and assessability of dual energy (DE) computed tomography angiography (CTA) of the lower extremity runoff. Methods A total of 118 lower extremity runoff CTA performed on a 3rd generation DE-CT scanner in 109 patients (54 females; 75.6 ± 9.5 years) were included in this retrospective study. Axial image stacks were reconstructed with a standard 120 kV setting and VMI+ of different keV levels. Objective image quality criteria (contrast attenuation, signal-to-noise [SNR] and contrast-to-noise ratio [CNR]) were measured. Two radiologists evaluated subjective image quality regarding intraluminal attenuation and image noise using a 5-point Likert scale. Diagnostic accuracy for significant stenosis (>75%) and vessel occlusion was assessed for 120 kV and 50 keV VMI+ images rated by two radiologists. In all patients, a digital subtraction angiography (DSA) rated by on board-certified radiologist served as the standard of reference. Results Intraluminal attenuation was highest in 40/50 keV VMI+ while SNR were similar to 120 kV images. In subjective assessment, intraluminal contrast of 50 keV images was deemed superior compared to 120 kV despite higher image noise. Sensitivity, specificity, and accuracy for detection of a vessel occlusion were similar in 50 keV VMI+ compared to 120 kV (70%/92%/84%; 70%/91%/83%; p < 0.001) but 13 of 118 (11%) lower leg runoffs were only assessable with 50 keV VMI+. Conclusion VMI+ reconstructions improve assessability of DE-CTA by increased luminal attenuation with consistent image noise, also allowing the evaluation of lower leg arterial segments inassessable with standard reconstructions. Implications for practice Providing higher intraluminal attenuation and similar image noise compared with conventional reconstructions, 50 keV VMI+ may be appropriate for routine evaluation of DE-CTA.
Testing based on multiple choice questions (MCQ) is one of the most established forms of assessment, not only in the medical field. Extended matching questions (EMQ) represent a specific type of MCQ designed to require higher levels of cognition, such as problem-solving. The purpose of this evaluation was to assess the suitability and efficiency of EMQ as an assessment method. EMQ were incorporated into the end-of-semester examination in internal medicine, in which 154 students participated, and compared with three established MCQ types. Item and examination quality were investigated, as well as readability and processing time. EMQ were slightly more difficult to score; however, both item discrimination and discrimination index were higher when compared to other item types. EMQ were found to be significantly longer and required more processing time, but readability was improved. Students judged EMQ as clearly challenging, but attributed significantly higher clinical relevance when compared to established MCQ formats. Using the Spearman-Brown prediction, only ten EMQ items would be needed to reproduce the Cronbach’s alpha value of 0.75 attained for the overall examination. EMQ proved to be both efficient and suitable when assessing medical students, demonstrating powerful characteristics of reliability. Their expanded use in favor of common MCQ could save examination time without losing out on statistical quality.
Inflammation and oxidative stress represent physiological response mechanisms to different types of stimuli and injury during critical illness. Its proper regulation is fundamental to cellular and organismal survival and are paramount to outcomes and recovery from critical illness. A proper maintenance of the delicate balance between inflammation, oxidative stress, and immune response is crucial for resolution from critical illness with important implications for patient outcome. The extent of inflammation and oxidative stress under normal conditions is limited by the antioxidant defense system of the human body, whereas the antioxidant capacity is commonly significantly compromised, and serum levels of micronutrients and vitamins significantly depleted in patients who are critically ill. Hence, the provision of antioxidants and anti‐inflammatory nutrients may help to reduce the extent of oxidative stress and therefore improve clinical outcomes in patients who are critically ill. As existing evidence of the beneficial effects of antioxidant supplementation in patients who are critically ill is still unclear, actual findings about the most promising anti‐inflammatory and antioxidative candidates selenium, vitamin C, zinc, and vitamin D will be discussed in this narrative review. The existing evidence provided so far demonstrates that several factors need to be considered to determine the efficacy of an antioxidant supplementation strategy in patients who are critically ill and indicates the need for adequately designed multicenter prospective randomized control trials to evaluate the clinical significance of different types and doses of micronutrients and vitamins in selected groups of patients with different types of critical illness.
Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is associated with risk-taking behaviour, leading to accidents and unintentional injuries (summarized here as incidents). Main aim: determine if men and women with and without ADHD differ in the risk of mild (treated outpatient) and severe (treated inpatient) incidents across the adult lifespan (age groups 18-29y; 30-59y, ≥60y.). Secondary aim: investigate the role of comorbid mental disorders and drugs for the treatment of these comorbidities, and ADHD-medication. Methods: Using anonymized German claims data (N=4,575,027), adults with ADHD diagnosis during 2016-2019 (N=17,041) were compared with a 1:4 age and sex-matched group without ADHD diagnosis. Regression analyses statistically tested group differences. Results: Incidents occur in a U-shaped form across the adult lifespan. Individuals with ADHD show the same pattern but at a substantially increased risk of both mild and severe incidents throughout the lifespan. Women without ADHD are at lower risk in young adulthood than men but at higher risk in older adulthood. Women with ADHD show the same pattern for severe incidents, but for mild incidents they have the highest risk throughout the lifespan. Co-occurring anxiety disorder and the use of psycholeptics and ADHD-medication decreased the incident risk. Conclusion: We extend available knowledge which has hitherto focused on young adult males and traffic accidents. ADHD is associated with increased incidents across the adult lifespan, with distinct patterns regarding age, sex and incident severity. An accurate diagnosis of ADHD in adulthood provides the first step towards prevention of accidents and unintentional injuries.
Background Invasive mold infections are a well-known and life-threatening condition after allogeneic hematopoietic stem cell transplantation (HSCT). While Aspergillus species are recognized as predominant pathogens, Fusarium species should also be considered due to their broad environmental distribution and the expected poor outcome of invasive fusariosis. Particularly, splenic rupture as a complication of disseminated disease has not been reported yet.Case presentationTwo weeks after allogeneic HSCT for severe aplastic anemia, a 16-year-old boy presented with painful, erythematous skin nodules affecting the entire integument. As disseminated mycosis was considered, treatment with liposomal amphotericin B and voriconazole (VCZ) was initiated. Invasive fusariosis was diagnosed after histological and previously unpublished polymerase chain reaction-based examination of skin biopsies. Microbiological tests revealed Fusarium solani species. Despite stable neutrophil engraftment and uninterrupted treatment with VCZ, he developed mold disease-associated splenic rupture with hypovolemic shock and fungal endocarditis. The latter induced a cardiac thrombus and subsequent embolic cerebral infarctions with unilateral hemiparesis. Following cardiac surgery, the patient did not regain consciousness because of diffuse cerebral ischemia, and he died on day +92 after HSCT.Conclusion Invasive fusariosis in immunocompromised patients is a life-threatening condition. Despite antimycotic treatment adapted to antifungal susceptibility testing, the patient reported here developed uncommon manifestations such as splenic rupture and fungal endocarditis.
Background Children experiencing unfavorable family circumstances have an increased risk of developing externalizing symptoms. The present study examines the direct, indirect and total effects of family adversity, parental psychopathology, and positive and negative parenting practices on symptoms of attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) in children with ADHD. Methods Data from 555 children ( M = 8.9 years old, 80.5% boys) who participated in a multicenter study on the treatment of ADHD (ESCAschool) were analyzed using structural equation modeling (SEM). Results The SEM analyses revealed that (a) family adversity and parental psychopathology are associated with both child ADHD and ODD symptoms while negative parenting practices are only related to child ODD symptoms; (b) family adversity is only indirectly associated with child ADHD and ODD symptoms, via parental psychopathology and negative parenting practices; (c) the detrimental effect of negative parenting practices on child ADHD and ODD symptoms is stronger in girls than in boys (multi-sample SEM); (d) there are no significant associations between positive parenting practices and child ADHD or ODD symptoms. Conclusions Family adversity, parental psychopathology, and negative parenting practices should be routinely assessed by clinicians and considered in treatment planning. Trial registration (18th December 2015): German Clinical Trials Register (DRKS) DRKS00008973.
Positional plagiocephaly (PP) is the most common skull deformity in infants. Different classification systems exist for graduating the degree of PP, but all of these systems are based on two-dimensional (2D) parameters. This limitation leads to several problems stemming from the fact that 2D parameters are used to classify the three-dimensional (3D) shape of the head. We therefore evaluate existing measurement parameters and validate a newly developed 3D parameter for quantifying PP. Additionally, we present a new classification of PP based on a 3D parameter. 210 patients with PP and 50 patients without PP were included in this study. Existing parameters (2D and 3D) and newly developed volume parameters based on a 3D stereophotogrammetry scan were validated using ROC curves. Additionally, thresholds for the new 3D parameter of a 3D asymmetry index were assessed. The volume parameter 3D asymmetry index quantifies PP equally as well as the gold standard of 30° diagonal difference . Moreover, a 3D asymmetry index allows for a 3D-based classification of PP. The 3D asymmetry index can be used to define the degree of PP. It is easily applicable in stereophotogrammetric datasets and allows for comparability both intra- and inter-individually as well as for scientific analysis.
Background Major efforts have been made in the last decade to develop and improve therapies for proximal spinal muscular atrophy (SMA). The introduction of Nusinersen/Spinraza™ as an antisense oligonucleotide therapy, Onasemnogene abeparvovec/Zolgensma™ as an AAV9-based gene therapy and Risdiplam/Evrysdi™ as a small molecule modifier of pre-mRNA splicing have set new standards for interference with neurodegeneration. Main body Therapies for SMA are designed to interfere with the cellular basis of the disease by modifying pre-mRNA splicing and enhancing expression of the Survival Motor Neuron (SMN) protein, which is only expressed at low levels in this disorder. The corresponding strategies also can be applied to other disease mechanisms caused by loss of function or toxic gain of function mutations. The development of therapies for SMA was based on the use of cell culture systems and mouse models, as well as innovative clinical trials that included readouts that had originally been introduced and optimized in preclinical studies. This is summarized in the first part of this review. The second part discusses current developments and perspectives for amyotrophic lateral sclerosis, muscular dystrophies, Parkinson's and Alzheimer's disease, as well as the obstacles that need to be overcome to introduce RNA-based therapies and gene therapies for these disorders. Conclusion RNA-based therapies offer chances for therapy development of complex neurodegenerative disorders such as amyotrophic lateral sclerosis, muscular dystrophies, Parkinson’s and Alzheimer’s disease. The experiences made with these new drugs for SMA, and also the experiences in AAV gene therapies could help to broaden the spectrum of current approaches to interfere with pathophysiological mechanisms in neurodegeneration.
Background In individuals suffering from a rare disease the diagnostic process and the confirmation of a final diagnosis often extends over many years. Factors contributing to delayed diagnosis include health care professionals' limited knowledge of rare diseases and frequent (co-)occurrence of mental disorders that may complicate and delay the diagnostic process. The ZSE-DUO study aims to assess the benefits of a combination of a physician focusing on somatic aspects with a mental health expert working side by side as a tandem in the diagnostic process. Study design This multi-center, prospective controlled study has a two-phase cohort design. Methods Two cohorts of 682 patients each are sequentially recruited from 11 university-based German Centers for Rare Diseases (CRD): the standard care cohort (control, somatic expertise only) and the innovative care cohort (experimental, combined somatic and mental health expertise). Individuals aged 12 years and older presenting with symptoms and signs which are not explained by current diagnoses will be included. Data will be collected prior to the first visit to the CRD’s outpatient clinic (T0), at the first visit (T1) and 12 months thereafter (T2). Outcomes Primary outcome is the percentage of patients with one or more confirmed diagnoses covering the symptomatic spectrum presented. Sample size is calculated to detect a 10 percent increase from 30% in standard care to 40% in the innovative dual expert cohort. Secondary outcomes are (a) time to diagnosis/diagnoses explaining the symptomatology; (b) proportion of patients successfully referred from CRD to standard care; (c) costs of diagnosis including incremental cost effectiveness ratios; (d) predictive value of screening instruments administered at T0 to identify patients with mental disorders; (e) patients’ quality of life and evaluation of care; and f) physicians’ satisfaction with the innovative care approach. Conclusions This is the first multi-center study to investigate the effects of a mental health specialist working in tandem with a somatic expert physician in CRDs. If this innovative approach proves successful, it will be made available on a larger scale nationally and promoted internationally. In the best case, ZSE-DUO can significantly shorten the time to diagnosis for a suspected rare disease. Trial registration ClinicalTrials.gov; Identifier: NCT03563677; First posted: June 20, 2018, https://clinicaltrials.gov/ct2/show/NCT03563677 .
Background Penicillin allergy labels frequently impede guideline-directed treatment with a penicillin or other β-lactam antibiotics. Despite presumed allergy, targeted questioning may indicate a low probability of sensitization and permit reasonably safe administration of the antibiotic in question. In this study, we evaluated a standardized algorithm aiming to differentiate non-allergic patients from those with true allergic β-lactam hypersensitivity. Methods We retrospectively applied a de-labelling algorithm in 800 consecutive patients with suspected β-lactam hypersensitivity. All had undergone complete allergy work-up permitting to definitely exclude or diagnose β-lactam allergy between 2009 and 2019. Results In 595 (74.4%) out of 800 cases evaluated, β-lactam allergy could be excluded by negative challenge testing. IgE-mediated anaphylaxis was diagnosed in 70 (8.7%) patients, delayed-type hypersensitivity in 135 (16.9%). In 62 (88.6%) anaphylaxis cases, the algorithm correctly advised to use an alternative antibiotic. Accuracy was higher in patients with moderate to severe anaphylaxis (97.7%) compared to those with a history of mild reactions (73.1%). The algorithm correctly identified 122 (90.4%) patients with proven delayed-type hypersensitivity. It permitted de-labelling in 330 (55.5%) out of 595 patients with diagnostic exclusion of penicillin hypersensitivity, but failed to identify the remaining 265 (44.5%) as low-risk cases. Conclusions The algorithm detected 89.8% of cases with penicillin (β-lactam) allergy, sensitivity was optimal for moderate to severe anaphylaxis. Study data justify the implementation of a standardized de-labelling algorithm under close supervision in order to permit guideline-directed treatment and reduce the use of broad-spectrum antibiotics as part of an antibiotic stewardship program.
Background In severe cases, SARS-CoV-2 infection leads to acute respiratory distress syndrome (ARDS), often treated by extracorporeal membrane oxygenation (ECMO). During ECMO therapy, anticoagulation is crucial to prevent device-associated thrombosis and device failure, however, it is associated with bleeding complications. In COVID-19, additional pathologies, such as endotheliitis, may further increase the risk of bleeding complications. To assess the frequency of bleeding events, we analyzed data from the German COVID-19 autopsy registry (DeRegCOVID). Methods The electronic registry uses a web-based electronic case report form. In November 2021, the registry included N = 1129 confirmed COVID-19 autopsy cases, with data on 63 ECMO autopsy cases and 1066 non-ECMO autopsy cases, contributed from 29 German sites. Findings The registry data showed that ECMO was used in younger male patients and bleeding events occurred much more frequently in ECMO cases compared to non-ECMO cases (56% and 9%, respectively). Similarly, intracranial bleeding (ICB) was documented in 21% of ECMO cases and 3% of non-ECMO cases and was classified as the immediate or underlying cause of death in 78% of ECMO cases and 37% of non-ECMO cases. In ECMO cases, the three most common immediate causes of death were multi-organ failure, ARDS and ICB, and in non-ECMO cases ARDS, multi-organ failure and pulmonary bacterial ± fungal superinfection, ordered by descending frequency. Interpretation Our study suggests the potential value of autopsies and a joint interdisciplinary multicenter (national) approach in addressing fatal complications in COVID-19.
The 7th Cardiovascular Outcome Trial (CVOT) Summit on Cardiovascular, Renal, and Glycemic Outcomes, was held virtually on November 18–19, 2021. Pursuing the tradition of the previous summits, this reference congress served as a platform for in-depth discussion and exchange on recently completed CVOTs. This year’s focus was placed on the outcomes of EMPEROR-Preserved, FIGARO-DKD, AMPLITUDE-O, SURPASS 1–5, and STEP 1–5. Trial implications for diabetes and obesity management and the impact on new treatment algorithms were highlighted for endocrinologists, diabetologists, cardiologists, nephrologists, and general practitioners. Discussions evolved from outcome trials using SGLT2 inhibitors as therapy for heart failure, to CVOTs with nonsteroidal mineralocorticoid receptor antagonists and GLP-1 receptor agonists. Furthermore, trials for glycemic and overweight/obesity management, challenges in diabetes management in COVID-19, and novel guidelines and treatment strategies were discussed. Trial registration The 8th Cardiovascular Outcome Trial Summit will be held virtually on November 10–11, 2022 ( http://www.cvot.org )
Background Despite advances in treatment of patients with non-small cell lung cancer, carriers of certain genetic alterations are prone to failure. One such factor frequently mutated, is the tumor suppressor PTEN. These tumors are supposed to be more resistant to radiation, chemo- and immunotherapy. Results We demonstrate that loss of PTEN led to altered expression of transcriptional programs which directly regulate therapy resistance, resulting in establishment of radiation resistance. While PTEN-deficient tumor cells were not dependent on DNA-PK for IR resistance nor activated ATR during IR, they showed a significant dependence for the DNA damage kinase ATM. Pharmacologic inhibition of ATM, via KU-60019 and AZD1390 at non-toxic doses, restored and even synergized with IR in PTEN-deficient human and murine NSCLC cells as well in a multicellular organotypic ex vivo tumor model. Conclusion PTEN tumors are addicted to ATM to detect and repair radiation induced DNA damage. This creates an exploitable bottleneck. At least in cellulo and ex vivo we show that low concentration of ATM inhibitor is able to synergise with IR to treat PTEN-deficient tumors in genetically well-defined IR resistant lung cancer models.
Background Severe COVID-19 induced acute respiratory distress syndrome (ARDS) often requires extracorporeal membrane oxygenation (ECMO). Recent German health insurance data revealed low ICU survival rates. Patient characteristics and experience of the ECMO center may determine intensive care unit (ICU) survival. The current study aimed to identify factors affecting ICU survival of COVID-19 ECMO patients. Methods 673 COVID-19 ARDS ECMO patients treated in 26 centers between January 1st 2020 and March 22nd 2021 were included. Data on clinical characteristics, adjunct therapies, complications, and outcome were documented. Block wise logistic regression analysis was applied to identify variables associated with ICU-survival. Results Most patients were between 50 and 70 years of age. PaO 2 /FiO 2 ratio prior to ECMO was 72 mmHg (IQR: 58–99). ICU survival was 31.4%. Survival was significantly lower during the 2nd wave of the COVID-19 pandemic. A subgroup of 284 (42%) patients fulfilling modified EOLIA criteria had a higher survival (38%) ( p = 0.0014, OR 0.64 (CI 0.41–0.99)). Survival differed between low, intermediate, and high-volume centers with 20%, 30%, and 38%, respectively ( p = 0.0024). Treatment in high volume centers resulted in an odds ratio of 0.55 (CI 0.28–1.02) compared to low volume centers. Additional factors associated with survival were younger age, shorter time between intubation and ECMO initiation, BMI > 35 (compared to < 25), absence of renal replacement therapy or major bleeding/thromboembolic events. Conclusions Structural and patient-related factors, including age, comorbidities and ECMO case volume, determined the survival of COVID-19 ECMO. These factors combined with a more liberal ECMO indication during the 2nd wave may explain the reasonably overall low survival rate. Careful selection of patients and treatment in high volume ECMO centers was associated with higher odds of ICU survival. Trial registration Registered in the German Clinical Trials Register (study ID: DRKS00022964, retrospectively registered, September 7th 2020, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00022964 . Graphical abstract
Background: Neurologic manifestations are increasingly reported in patients with coronavirus disease 2019 (COVID-19). Yet, data on prevalence, predictors and relevance for outcome of neurological manifestations in patients requiring intensive care are scarce. We aimed to characterize prevalence, risk factors and impact on outcome of neurologic manifestations in critically ill COVID-19 patients. Methods: In the prospective, multicenter, observational registry study PANDEMIC (Pooled Analysis of Neurologic DisordErs Manifesting in Intensive care of COVID-19), we enrolled COVID-19 patients with neurologic manifestations admitted to 19 German intensive care units (ICU) between April 2020 and September 2021. We performed descriptive and explorative statistical analyses. Multivariable models were used to investigate factors associated with disorder categories and their underlying diagnoses as well as to identify predictors of outcome. Results: Of the 392 patients included in the analysis, 70.7% (277/392) were male and the mean age was 65.3 (SD ± 3.1) years. During the study period, a total of 2681 patients with COVID-19 were treated at the ICUs of 15 participating centers. New neurologic disorders were identified in 350 patients, reported by these centers, suggesting a prevalence of COVID-19-associated neurologic disorders of 12.7% among COVID-19 ICU patients. Encephalopathy (46.2%; 181/392), cerebrovascular (41.0%; 161/392) and neuromuscular disorders (20.4%; 80/392) were the most frequent categories identified. Out of 35 cerebrospinal fluid analyses with reverse transcriptase PCR for SARS-COV-2, only 3 were positive. In-hospital mortality was 36.0% (140/389), and functional outcome (mRS 3 to 5) of surviving patients was poor at hospital discharge in 70.9% (161/227). Intracerebral hemorrhage (OR 6.2, 95% CI 2.5-14.9, p < 0.001) and acute ischemic stroke (OR 3.9, 95% CI 1.9-8.2, p < 0.001) were the strongest predictors of poor outcome among the included patients. Conclusions: Based on this well-characterized COVID-19 ICU cohort, that comprised 12.7% of all severe ill COVID-19 patients, neurologic manifestations increase mortality and morbidity. Since no reliable evidence of direct viral affection of the nervous system by COVID-19 could be found, these neurologic manifestations may for a great part be indirect para- or postinfectious sequelae of the infection or severe critical illness. Neurologic ICU complications should be actively searched for and treated.
Objective: To evaluate a new methodological approach of applying anatomy-based fitting (ABF) in experienced cochlear implant (CI) users. Participants: Three experienced unilateral and bilateral CI users with postlingual hearing loss. Intervention: Postoperative imaging, via a high-volume Dyna computed tomography, and exact electrode measurement positions were integrated into the clinical fitting software following a new procedure, which adapted individual frequency bandwidths within the audio processor. Main outcome measures: Speech perception in quiet and noise, clinical mapping, and self-perceived level of auditory benefit were assessed. Results: For each CI user, ABF mapping provided better speech perception in quiet and in noise compared with the original clinical fitting mapping. In addition, ABF mapping was accepted in CI users despite unequal bilateral array insertion depths and lengths; however, acceptance was only established if the point of first electrode contact was less than 230 Hz. Conclusions: ABF mapping increased the acceptance in CI users with longer electrode arrays and in bilateral CI users who were unsatisfied with their device experience. A larger prospective, randomized investigation is currently underway to assess longitudinal outcomes with ABF mapping.
Infektionen gehören zu den häufigsten Komplikationen bei Tumorpatienten und werden in Fieber unbekannter Ursache („fever of unknown origin“, FUO) sowie klinisch bzw. mikrobiologisch dokumentierte Infektionen eingeteilt. Einer der wichtigsten Risikofaktoren für das Auftreten und einen komplizierten Verlauf von Infektionen ist die Neutropenie. Patienten mit Hochrisiko-Neutropenie (absolute Neutrophilenzahl <0,5 × 109/l für ≥8 Tage) und Fieber sollen empirisch ein Pseudomonas-aktives β-Lactam-Antibiotikum (z. B. Piperacillin/Tazobactam oder Ceftazidim) erhalten. Eine Kombination mit einem Glykopeptid (z. B. Vancomycin) oder einem Aminoglykosid (z. B. Tobramycin) sollte in der klinischen Routine nicht erfolgen. Aktuelle Leitlinien empfehlen bei klinischer Stabilität auch bei Patienten mit Hochrisiko-Neutropenie und persistierendem Fieber nach 72–96 Stunden die primäre empirische Antibiotikatherapie fortzusetzen. Weiterhin ist es bei klinisch stabilen Patienten mit febriler Neutropenie und anhaltendem Fieber gerechtfertigt, ein Schimmelpilz-wirksames Antimykotikum (z. B. liposomales Amphotericin B) erst einzusetzen, wenn sich klinisch, serologisch (z. B. Nachweis von Galactomannan oder 1➔3-β-D-Glucan im Serum) oder bildgebend Hinweise für das Vorliegen einer invasiven Pilzinfektion zeigen (präemptiver Therapieansatz). Als wichtiger Hinweis für das Vorliegen einer pulmonalen Aspergillose gilt hierbei das Halo-Zeichen in der Thorax-Computertomografie. Bei Patienten mit drohender oder manifester klinischer Instabilität sollte ein frühzeitiger Einsatz eines Schimmelpilz-wirksamen Antimykotikums immer in Erwägung gezogen werden, d. h. auch wenn sich keine Hinweise für das Vorliegen einer invasiven Pilzinfektion ergeben (empirischer Therapieansatz). Neben FUO treten klinisch oder mikrobiologisch dokumentierte Infektionen unabhängig vom Vorliegen einer Neutropenie bei Tumorpatienten häufig auf. Blutstrominfektionen, Infektionen des Respirationstrakts und die Clostridioides-difficile-assoziierte Diarrhö gehören hierbei zu den häufigsten Formen.
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