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Recent GWAS allow us to calculate polygenic risk scores for ADHD. At the imaging level, resting-state fMRI analyses have given us valuable insights into changes in connectivity patterns in ADHD patients. However, no study has yet attempted to combine these two different levels of investigation. For this endeavor, we used a dopaminergic challenge fMRI study (L-DOPA) in healthy participants who were genotyped for their ADHD, MDD, schizophrenia, and body height polygenic risk score (PRS) and compared results with a study comparing ADHD patients and healthy controls. Our objective was to evaluate how L-DOPA-induced changes of reward-system-related FC are dependent on the individual polygenic risk score. FMRI imaging was used to evaluate resting-state functional connectivity (FC) of targeted subcortical structures in 27 ADHD patients and matched controls. In a second study, we evaluated the effect of ADHD and non-ADHD PRS in a L-DOPA-based pharmaco-fMRI-challenge in 34 healthy volunteers. The functional connectivity between the putamen and parietal lobe was decreased in ADHD patients. In healthy volunteers, the FC between putamen and parietal lobe was lower in ADHD high genetic risk participants. This direction of connectivity was reversed during L-DOPA challenge. Further findings are described for other dopaminergic subcortical structures. The FC between the putamen and the attention network showed the most consistent change in patients as well as in high-risk participants. Our results suggest that FC of the dorsal attention network is altered in adult ADHD as well as in healthy controls with higher genetic risk.
Changes in glutamatergic neuroplasticity has been proposed as one of the core mechanisms underlying the pathophysiology of depression. In consequence components of the glutamatergic synapse have been explored as potential targets for antidepressant treatment. The rapid antidepressant effect of the NMDA receptor antagonist ketamine and subsequent approval of its S-enantiomer (i.e. esketamine), have set the precedent for investigation into other glutamatergic rapid acting antidepressants (RAADs). In this review, we discuss the potential of the different glutamatergic targets for antidepressant treatment. We describe important clinical outcomes of several key molecules targeting components of the glutamatergic synapse and their applicability as RAADs. Specifically, here we focus on substances beyond (es)ketamine, for which meaningful data from clinical trials are available, including arketamine, esmethadone, nitrous oxide and other glutamate receptor modulators. Molecules only successful in preclinical settings and case reports/series are only marginally discussed. With this review, we aim underscore the critical role of glutamatergic modulation in advancing antidepressant therapy, thereby possibly enhancing clinical outcomes but also to reducing the burden of depression through faster therapeutic effects.
Background: Patients undergoing allogeneic stem cell transplantation (aSCT) are at high risk to develop an invasive fungal disease (IFD). Optimisation of antifungal prophylaxis strategies may improve patient outcomes and reduce treatment costs.
Objectives: To analyse the clinical and economical impact of using continuous micafungin as antifungal prophylaxis.
Patients/Methods: We performed a single-centre evaluation comparing patients who received either oral posaconazole with micafungin as intravenous bridging as required (POS-MIC) to patients who received only micafungin (MIC) as antifungal prophylaxis after aSCT. Epidemiological, clinical and direct treatment cost data extracted from the Cologne Cohort of Neutropenic Patients (CoCoNut) were analysed.
Results: Three hundred and thirteen patients (97 and 216 patients in the POS-MIC and MIC groups, respectively) were included into the analysis. In the POS-MIC and MIC groups, median overall length of stay was 42 days (IQR: 35–52 days) vs 40 days (IQR: 35–49 days; p = .296), resulting in median overall costs of €42,964 (IQR: €35,040–€56,348) vs €43,291 (IQR: €37,281 vs €51,848; p = .993), respectively. Probable/proven IFD in the POS-MIC and MIC groups occurred in 5 patients (5%) vs 3 patients (1%; p = .051), respectively. The Kaplan-Meier analysis showed improved outcome of patients in the MIC group at day 100 (p = .037) and day 365 (p < .001) following aSCT.
Conclusions: Our study results demonstrate improved outcomes in the MIC group compared with the POS-MIC group, which can in part be explained by a tendency towards less probable/proven IFD. Higher drug acquisition costs of micafungin did not translate into higher overall costs.
[Congress abstract P-05-09] Calcium, calcium-sensing receptor and its role in leukaemia progression
(2022)
Introduction: Survival data reported by randomised controlled trials are collected in a highly selected patient population and can thus only be transferred to a limited extent to real-world patients: the patients in routine care are mostly older, present with more comorbidities and a worse general state of health. This so-called efficacy-effectiveness gap typically results in inferior survival data in routine healthcare.
Methods: Six prospective clinical tumour registries recruited a total of 11,679 patients receiving systemic therapy in haemato-oncological practices in Germany between 2006 and 2020. For these patients with advanced colorectal cancer, breast cancer, lung cancer, pancreatic cancer, renal cell cancer, and lymphatic neoplasms, overall survival was analysed. A comprehensive literature search was performed to identify suitable pivotal randomised controlled trials.
Results: Median overall survival of patients treated in German routine care, with advanced colorectal, breast, lung, and pancreatic cancer, as well as with diffuse large B-cell lymphoma and multiple myeloma, is not shorter than the respective survival data reported in trials. Patients with advanced renal cell carcinoma, chronic lymphocytic leukaemia, or indolent non-Hodgkin lymphoma showed slightly lower survival rates compared to clinical trials.
Conclusions: Despite less favourable patient characteristics, survival data from patients with cancer treated in ambulatory routine care in Germany are in range with results from randomised controlled studies.