Ludwig-Maximilians University Munich Research Articles

Transforming Care in SEA: Evidence and Considerations for Evolution of the Current Treatment Paradigm

This article reviews an industry symposium held on 8 September 2024 as part of the European Respiratory Society (ERS) Congress 2024 in Vienna, Austria, which brought together four experts to discuss the current treatment paradigm for severe eosinophilic asthma (SEA), including the role of biologics and background medication tapering. Katrin Milger-Kneidinger, Professor of Respiratory Medicine at the University Hospital of the Ludwig Maximilian University Munich (LMU), in Germany, and the MedUni Graz, in Austria, explored the critical role eosinophils play in SEA pathology and how biologic therapies targeting eosinophils can address key disease features, including airway remodelling, airway hyperresponsiveness (AHR), and mucus production. Felix Herth, Professor of Pulmonary and Critical Care Medicine at Thoraxklinik Heidelberg, Heidelberg University Hospital, in Germany, discussed persistent airflow obstruction (PAO) in patients with SEA, focusing on a typical patient profile to understand the clinical manifestation and opportunities for management. Stephanie Korn, Professor of Pulmonary and Respiratory Medicine at Thoraxklinik Heidelberg, Heidelberg University Hospital, in Germany, and Head of the Clinical Research Centre, Institute für Klinische Forschung (IKP) Pneumologie in Mainz, Germany, presented on remission as a clinical target in SEA, focusing on how biologics can help achieve remission in some patients. Lastly, in a discussion led by symposium chair Stefano Del Giacco, Professor of Medicine, Allergy, and Clinical Immunology, at the University of Cagliari, Sardinia, in Italy, the experts agreed that a positive practice change would be to get more patients with relevant clinical manifestations on biologics, and that background medication tapering, when appropriate, could lead to improved patient outcomes and quality of life (QoL) in SEA.

Two decades of the International Classification of Functioning, Disability and Health (ICF) in health research: a bibliometric analysis

Introduction: We conducted a twenty-year bibliometric analysis of scientific literature, focusing on the trends of The International Classification of Functioning, Disability and Health (ICF) use in health research. Methods: We retrieved 3’467 documents published between 2002 and 2022, sourced from the Web of Science Core Collection database. We used the Bibliometrix and VoSviewer tools for descriptive analyses and data visualization. Results: Our findings indicate a significant increase in ICF application since 2011, with an average annual growth rate of 13.19%. Prominent contributions were observed globally, with notable outputs from the U.S., Canada, Germany, the Netherlands, and Switzerland. The Ludwig Maximilian University Munich, Swiss Paraplegic Research, and McMaster University authored a quarter of the documents (24.6%). Collaboration networks of countries and institutions revealed robust partnerships, particularly between Germany and Switzerland. "Rehabilitation" was the most frequently occurring keyword, although a thematic shift towards epidemiology, aging, and health-related quality of life was observed post-2020. While rehabilitation remained the primary thematic focus, literature post-2020 highlighted epidemiology as a growing area of interest. Conclusions: A steady increase in ICF-based research mirrors the rising interest in a biopsychosocial and person-centered approach to healthcare. However, the literature is primarily produced by high-resource countries, with underrepresentation from low and middle-resource countries, suggesting an area of future research to address this discrepancy.

CD19-directed T cell-engaging antibodies for the treatment of autoimmune disease.

Jennifer S. Michaelson, Chief Scientific Officer at Cullinan Oncology, and Patrick A. Baeuerle, scientific advisor to Cullinan Oncology and honorary professor in immunology at Ludwig Maximilians University Munich, discuss the use of CD19-specific T cell-engaging antibody therapies (TCEs) as therapeutics for autoimmune diseases.

Outcome, predictors and longitudinal trajectories of subjects with critical illness polyneuropathy and myopathy (CINAMOPS): study protocol of an observational cohort study in a clinical and post-clinical setting

IntroductionCritical illness polyneuropathy and myopathy (CIP/CIM) are frequent complications in the intensive care unit (ICU) with major consequences for the progress and outcome of subjects. CIP/CIM delays the weaning process,...

Cell scientist to watch – Jörg Renkawitz

ABSTRACT Jörg Renkawitz is an endowed Peter Hans Hofschneider Professor in Molecular Medicine at Ludwig Maximilians-University Munich, Germany. Following his bachelor and Master's degrees in biochemistry, during which he was first introduced to the field of cell motility, he completed his doctoral work with Prof. Dr Stefan Jentsch at the Max Planck Institute of Biochemistry in Martinsried, Germany, studying the mechanisms of DNA repair. Still intrigued by the mechanics of migrating cells, he moved to the Institute of Science and Technology in Vienna, Austria for his postdoc with Prof. Dr Michael Sixt, which cemented his passion for understanding how motile cells navigate their environments. In 2018, he started his own lab at Ludwig Maximilians-University Munich, and now applies his molecular expertise to unravel the mechanobiology of the immune system by combining omics approaches with engineered microenvironments and high-throughput imaging. We spoke with Jörg over Zoom to learn about his career path, rigorous approaches to experimental design and mentorship philosophy.

Development and Validation of a Simple Tool for Predicting Pandemic-Related Psychological Distress Among Health Care Workers

We aimed to develop a simple predictive model that enables health care workers (HCWs) to self-assess pandemic-related psychological distress in order to assist them to find psychological support to avert adverse distress-related outcomes. In a pilot study, we recruited and followed longitudinally 220 HCWs at the Hospital of the Ludwig Maximilian University Munich (H-LMU) during the first wave of the COVID-19 pandemic (March–July 2020). In this sample, we evaluated whether a machine-learning model with sociodemographic, epidemiological, and psychological data could predict levels of pandemic-related psychological distress. To maximise clinical utility, we derived a brief, 10-variable model to monitor distress risk and inform about the use of individualised preventive interventions. The validity of the model was assessed in a subsequent cross-sectional study cohort (May–August 2020) consisting of 7554 HCWs at the H-LMU who were assessed for depressiveness after the first wave of the pandemic.The model predicted psychological distress at 12 weeks with a balanced accuracy (BAC) of 75.0% (sensitivity, 73.2%; specificity, 76.8%) and an increase in prognostic certainty of 41%. In the derivation cohort, the brief model maintained a BAC of 75.6% and predicted depressiveness (P < .001), resilience (p.001), and coping (p < .001). Furthermore, it accurately stratified HCWs’ psychological trajectories of global and affective burden as well as behavioural adaptation over the 12-week follow-up period. Our clinically scalable, 10-variable model predicts individual COVID-19 pandemic-related psychological distress outcomes. HCWs may use our associated predictive tool to monitor personal and team-based risk and learn about risk preventive interventions based on an intuitive risk stratification.

Histology-Based Prediction of Therapy Response to Neoadjuvant Chemotherapy for Esophageal and Esophagogastric Junction Adenocarcinomas Using Deep Learning.

Quantifying treatment response to gastroesophageal junction (GEJ) adenocarcinomas is crucial to provide an optimal therapeutic strategy. Routinely taken tissue samples provide an opportunity to enhance existing positron emission tomography-computed tomography (PET/CT)-based therapy response evaluation. Our objective was to investigate if deep learning (DL) algorithms are capable of predicting the therapy response of patients with GEJ adenocarcinoma to neoadjuvant chemotherapy on the basis of histologic tissue samples. This diagnostic study recruited 67 patients with I-III GEJ adenocarcinoma from the multicentric nonrandomized MEMORI trial including three German university hospitals TUM (University Hospital Rechts der Isar, Munich), LMU (Hospital of the Ludwig-Maximilians-University, Munich), and UME (University Hospital Essen, Essen). All patients underwent baseline PET/CT scans and esophageal biopsy before and 14-21 days after treatment initiation. Treatment response was defined as a ≥35% decrease in SUVmax from baseline. Several DL algorithms were developed to predict PET/CT-based responders and nonresponders to neoadjuvant chemotherapy using digitized histopathologic whole slide images (WSIs). The resulting models were trained on TUM (n = 25 pretherapy, n = 47 on-therapy) patients and evaluated on our internal validation cohort from LMU and UME (n = 17 pretherapy, n = 15 on-therapy). Compared with multiple architectures, the best pretherapy network achieves an area under the receiver operating characteristic curve (AUROC) of 0.81 (95% CI, 0.61 to 1.00), an area under the precision-recall curve (AUPRC) of 0.82 (95% CI, 0.61 to 1.00), a balanced accuracy of 0.78 (95% CI, 0.60 to 0.94), and a Matthews correlation coefficient (MCC) of 0.55 (95% CI, 0.18 to 0.88). The best on-therapy network achieves an AUROC of 0.84 (95% CI, 0.64 to 1.00), an AUPRC of 0.82 (95% CI, 0.56 to 1.00), a balanced accuracy of 0.80 (95% CI, 0.65 to 1.00), and a MCC of 0.71 (95% CI, 0.38 to 1.00). Our results show that DL algorithms can predict treatment response to neoadjuvant chemotherapy using WSI with high accuracy even before therapy initiation, suggesting the presence of predictive morphologic tissue biomarkers.

Reasons for Discordance Among Imaging‐based Response Criteria In Lymphoma Patients Receiving CAR T‐cell Therapy

Introduction: Chimeric antigen receptor T cell therapy (CART) has emerged as an effective cell-based immunotherapy using patient-derived T cells. Modified CAR T cells are used for the treatment of relapsed or refractory (r/r) lymphoma with expression of a CD19 antigen specific receptor. CART prolongs survival for patients with r/r lymphoma compared to historical controls. In the currently ongoing phase III trials, treatment response is assessed using the Lugano criteria from 2014. In the recent years, new imaging criteria for lymphoma have been published. Discrepancies among these different response criteria for lymphoma under CART were recently shown. We evaluated reasons for discordance among different response criteria and their relation to overall survival (OS). Methods: Consecutive large B-cell lymphoma (LBCL) and mantle-cell lymphoma (MCL) patients with baseline and follow-up imaging 30, and 90 days after CART infusion were included. For each patient, up to 6 Tagret lesions, non-target lesions, and the spleen were 3D-segmented. Overall response was determined based on Lugano criteria, Cheson criteria, response evaluation criteria in lymphoma (RECIL) and lymphoma response to immunomodulatory therapy criteria (LYRIC). Overall response rate (ORR) and rates of progressive disease (PD) were determined. For each criterion reasons for PD were analyzed in detail. Results: 41 patients were included (median age: 64 years, 41% female). ORR was 68%, 68%, 63%, and 68% at FU2 by Lugano, Cheson, RECIL, and LYRIC, respectively. PD rates differed among criteria with 32% by Lugano, 27% by Cheson, 17% by RECIL, and 17% by LYRIC. Dominant reasons for PD according to Lugano were target lesion (TL) progression (84.6%), new appearing lesions (NL; 53.8%), non-TL progression (27.3%), and progressive metabolic disease (PMD; 15.4%). Deviations among the criteria were largely explained by PMD of preexisting lesions that are defined as PD only by Lugano and non-TL progression, which is not defined as PD by RECIL and in some cases classified as indeterminate response by LYRIC. Interestingly, grouping patients according to focality of progressive target lesions showed a significant trend for OS stratification (p = 0.036). The research was funded by: Förderung für Forschung und Lehre (FöFoLe) project number 1147” of the Medical Faculty of Ludwig Maximilian University (LMU) Munich and the Bavarian Cancer Research Center (BZKF) to M.W.. The work was further supported by the Else-Kröner-Fresenius Stiftung (to V.B.) and the German Cancer Consortium DKTK (to V.B.). Keywords: Cellular therapies, Diagnostic and Prognostic Biomarkers, PET-CT Conflicts of interests pertinent to the abstract. V. Blumenberg Consultant or advisory role: Kite/Gilead Honoraria: Kite/Gilead, Janssen, Novartis Research funding: BMS/Celgene, Kite/Gilead, Novartis, Roche, Takeda K. Rejeski Honoraria: Novartis Research funding: Kite/Gilead Educational grants: Kite/Gilead V. Buecklein Honoraria: Amgen, Kite/Gilead, Novartis, Pfizer Research funding: Celgene/BMS, Kite/Gilead C. Schmidt Educational grants: Kite/Gilead M. von Bergwelt-Baildon Consultant or advisory role: Astellas, BMS, Kite/Gilead, Miltenyi, Mologen, MSD Sharp & Dohme, Novartis, Roche Honoraria: Astellas, BMS, Kite/Gilead, Miltenyi, Mologen, MSD Sharp & Dohme, Novartis, Roche Research funding: Astellas, BMS, Kite/Gilead, Miltenyi, Mologen, MSD Sharp & Dohme, Novartis, Roche M. Subklewe Consultant or advisory role: Amgen, Astra Zeneca, Aven Cell, BMS/Celgene, CDR-Life, Gilead, Incyte Biosciences, Janssen, Miltenyi Biotec, Molecular Partners, Novartis, Pfizer, Roche, Takeda Research funding: Amgen, BMS/Celgene, Gilead, Janssen, Miltenyi Biotec, Morphosys, Novartis, Roche, Takeda W. Kunz Consultant or advisory role: Bristol Myers Squibb

Optical coherence tomography-based misdiagnosis and morphological distinction in pachychoroid neovasculopathy vs. polypoidal choroidal vasculopathy

PurposeTo evaluate the rate of misdiagnosis of aneurysmatic pachychoroid type 1 choroidal neovascularization/polypoidal choroidal vasculopathy (PAT1/PCV) among cases diagnosed as non-aneurysmatic pachychoroid neovasculopathy (PNV) and to define optical coherence tomography (OCT) features facilitating their distinction.MethodsThe database of the Department of Ophthalmology, Ludwig-Maximilians University Munich, was screened for patients diagnosed with PNV. Multimodal imaging was screened for the presence of choroidal neovascularization (CNV) and aneurysms/polyps. Imaging features facilitating the diagnosis of PAT1/PCV were analysed.ResultsIn total, 49 eyes of 44 patients with a clinical PNV diagnosis were included, of which 42 (85.7%) had PNV and 7 (14.3%) represented misdiagnosed PAT1/PCV. SFCT was comparable (PNV: 377 ± 92 vs. PAT1/PCV: 400 ± 83 µm; p = 0.39). Whereas no difference was detected in total pigment epithelium detachment (PED) diameter (p = 0.46), maximum PED height was significantly higher in the PAT1/PCV group (199 ± 31 vs. 82 ± 46, p < 0.00001). In a receiver operating characteristic (ROC) analysis, the optimum cutoff for defining “peaking PED” was 158 µm with an area under the curve of 0.969, a sensitivity of 1.0 (95% CI: 0.59–1.0), and a specificity of 0.95 (95% CI: 0.84–0.99). Sub-retinal hyperreflective material (SHRM; p = 0.04), sub-retinal ring-like structures (SRRLS; p < 0.00001), and sub-RPE fluid (p = 0.04) were significantly more frequent in eyes with PAT1/PCV.ConclusionA relevant percentage of eyes diagnosed with PNV might instead suffer from PAT1/PCV. The detection of a maximum PED height (“peaking PED”) exceeding approximately 150 µm, SHRM, SRRLS, and sub-RPE fluid might greatly aid in the production of a more accurate diagnosis.

Chimeric Antigen Receptor T-cell Therapy: Imaging Response Criteria and Relation to Progression-free and Overall Survival.

Chimeric Antigen Receptor T-cell Therapy: Imaging Response Criteria and Relation to Progression-free and Overall Survival.

Advances in Stroke: Genetics, Genomics, Precision Medicine.

Advances in Stroke: Genetics, Genomics, Precision Medicine.

Blood group antigens SLeX, SLeA, and LeY as prognostic markers in endometrial cancer

PurposeEndometrial cancer (EC) is the most common gynecological cancer worldwide. Treatment has been improved in recent years, but, in advanced stages, therapeutical options are still limited. It has been reported that the expression of the blood group antigens Sialyl Lewis X (SLeX), Sialyl Lewis A (SLeA) and Lewis Y (LeY) is associated with prognosis in several tumors. Large studies on endometrial and cervical cancer are still pending.MethodsSpecimens of 234 patients with EC were immunohistochemically stained with antibodies for SLeX, SLeA and LeY. Expression was correlated to histopathological variables.ResultsHigh expression of SLeX was correlated to low pT-stage (p = 0.013), low grade (p < 0.001), low FIGO-stage (p = 0.006) and better overall survival rates (OS; p = 0.023). High expression of SLeA was associated with low pT-stage (p = 0.013), low grade (p = 0.001) and better progression-free survival (PFS; p = 0.043). LeY staining was correlated to pN + (p = 0.038), low grade (p = 0.005) and poorer PFS (p = 0.022).ConclusionThis is the first study examining the expression of SLeX, SLeA and LeY in EC, which can serve as additional future prognostic markers. Further studies are necessary to understand the underlying mechanisms. The study was approved by the local ethics committee of the Ludwig-Maximilians University Munich (reference number 19-249).

Phototherapeutische Keratektomie bei rezidivierenden Hornhauterosionen verschiedener epithelialer Genese: Einfluss der Ablationstiefe auf Pachymetrie und Refraktion

Phototherapeutic keratectomy (PTK) is an established treatment method for patients suffering from either genetic corneal dystrophy or recurrent corneal erosion (RCE) without underlying basement membrane dystrophy, often caused by trauma. This study aimed to describe the changes in manifest subjective refraction and pachymetry after PTK treatment in patients suffering from epithelial basement membrane dystrophy (EBMD) and traumatic or atraumatic RCE without underlying EBMD. This was aretrospective, single-center study performed at the Department of Ophthalmology of the Ludwig-Maximilians University (Munich). Patient data were retrospective collected using the smart-eye database of the Department of Ophthalmology including diagnostic data from an autorefractometer and from the Pentacam HR. All laser treatments were performed with an ablation depth of 10 μm for EBMD patients and 6 μm for RCE patients without EBMD. Both collectives showed adecrease in pachymetry larger than the calculated ablation depths after afollow-up interval of 126days (95% CI 104-147days). While the EBMD collective receiving an ablation of 10 μm showed adecrease of 25.8 μm (N = 74; 95% CI 21.2-30.3; p < 0.001), the non-EBMD collective receiving an ablation of 6 μm showed a decrease of 12.3 μm (N = 44, 95% CI 7.0-17.7; p < 0.001). Both, total corneal refractive power (TCRP) as well as spherical equivalent (SE) offered no significant change in preoperative and postoperative comparison for the EBMD collective. On the other hand, patients without underlying EBMD showed asignificant myopic decrease in SE of 0.4 dpt (±0.7 dpt SD, p < 0.05). The mean follow-up interval was 126 days (95% CI 104-147 days). PTK treatment offers an effective method for patients suffering from either EBMD dystrophy or RCE syndrome without underlying EBMD. The final ablation based on pachymetry at the apex can be estimated at 2.3 to 2.6 times higher compared to the original ablation depth. The reasons for this are on the one hand the laser ablation itself and the influence of the reactive wound healing of the corneal epithelium.

Opportunities for Antibiotic Stewardship Interventions in a Pediatric Hospital

Abstract Objective This study's objective was to assess an antibiotic stewardship intervention, compare pediatric antibiotic usage in a non-university hospital (Children's Hospital Traunstein [TS]) with a university hospital (Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich [MUC]), and assess adherence to national guidelines. Methods Antibiotic usage pre- and post-antibiotic stewardship (ABS) intervention was compared, and antibiotic prescriptions over 4 months were prospectively recorded. ABS intervention consisted of weekly teaching sessions, antibiotic pocket cards, and rounds with pediatric infectious disease staff. Medical records were reviewed to describe antibiotic consumption, antibiotic dosages and length of use, and adherence to national guidelines. Pediatric antibiotic usage was compared between hospitals and patient groups. Results After the ABS intervention, the use of second-generation cephalosporins decreased, while penicillin with β-lactamase inhibitors (BLI) increased. Survey of antibiotic prescriptions over the 4 months study period in the non-university hospital showed a high administration rate of second-generation cephalosporins and extended-spectrum penicillins in the non-intensive care units (ICU) wards (48.53 and 38.93 days of therapy [DoT]/1,000 patient days [PD], respectively) and a high rate of third-generation cephalosporins in the ICU ward (110.33 DoT/1,000PD). A high prescriptions rate was seen in the neonatal intensive care unit (NICU) wards (DoT/ length of therapy [LoT] ratio of 2.185). Reserve group antibiotics were only given in the ICU. Adherence to national guidelines was highest in the NICU and pediatric ICU wards. Striking was the relatively high rate of incorrect usage of second-generation cephalosporins. Comparing the pediatric wards of the non-university hospital (TS) and the university hospital (MUC), the prescription ratio was 11.1% (TS) versus 30.6% (MUC), and DoT/1,000PD 198.9 (TS) versus 483.6 (MUC), p = 0.02. ABS intervention changed the choice of described antibiotics, but not the overall frequency. Conclusion Adherence to national guidelines was highest in fields with standardized therapy recommendations, like in the NICU. In MUC, antibiotics, in particular restricted ones, were prescribed more frequently, probably due to higher severity of illness.These data indicate that the usage of antibiotics and adherence to national guidelines show a wide variety, but ABS interventions were effective in changing prescription behavior.

Introducing our 2022 Early Career Advisory Board Members

Introducing our 2022 Early Career Advisory Board Members

Pachychoroid disease and its association with retinal vein occlusion: a case\u2013control study

The development of a retinal vein occlusion (RVO) is multifactorial. This study investigates pachychoroid as a risk factor for RVO or as an entity sharing common pathophysiology with RVO. A database screening at the University Eye Hospital, Ludwig-Maximilian University Munich, Germany was performed for patients diagnosed with central or branch RVO (CRVO/BRVO). In every patient a complete ophthalmologic examination was performed, including posterior segment enhanced depth spectral domain optical coherence tomography (EDI-SD-OCT). The SD-OCT scans of respective partner eyes without history of RVO were compared to an age- and refraction-matched, randomly recruited normal control group. In total, 312 eyes of 312 patients were included in this study, with 162 eyes in the RVO and 150 eyes in the control group. A significantly higher subfoveal choroidal thickness (SFCT) was found in the RVO (310.3 ± 72.5 (94 to 583) µm) as compared to the control group (237.0 ± 99.0 (62 to 498); p < 0.00001). Moreover, the RVO group showed a significantly higher prevalence of a symptomatic pachychoroid (22 vs. 9 eyes; odds ratio: 2.46; 95 CI: 1.10 to 5.53; p = 0.029). Since pachychoroid disease represents a bilateral entity, it might be a risk factor for RVO, or share risk factors with RVO.

Spectral domain optical coherence tomography-based retinochoroidal cystine crystal score: a window into infantile nephropathic cystinosis

PrécisCystinosis is a lysosomal storage disease leading to an accumulation of cystine crystals in several organs. We aim to comprehensively describe chorioretinal cystine crystals via spectral domain optical coherence tomography...

Trace Amine-Associated Receptor 1 (TAAR1) Is a Positive Prognosticator for Epithelial Ovarian Cancer.

Trace amine-associated receptor 1 (TAAR1) is a Gαs- protein coupled receptor that plays an important role in the regulation of the immune system and neurotransmission in the CNS. In ovarian cancer cell lines, stimulation of TAAR1 via 3-iodothyronamine (T1AM) reduces cell viability and induces cell death and DNA damage. Aim of this study was to evaluate the prognostic value of TAAR1 on overall survival of ovarian carcinoma patients and the correlation of TAAR1 expression with clinical parameters. Ovarian cancer tissue of n = 156 patients who were diagnosed with epithelial ovarian cancer (serous, n = 110 (high-grade, n = 80; low-grade, n = 24; unknown, n = 6); clear cell, n = 12; endometrioid, n = 21; mucinous, n = 13), and who underwent surgery at the Department of Obstetrics and Gynecology, University Hospital of the Ludwig-Maximilians University Munich, Germany between 1990 and 2002, were analyzed. The tissue was stained immunohistochemically with anti-TAAR1 and evaluated with the semiquantitative immunoreactive score (IRS). TAAR1 expression was correlated with grading, FIGO and TNM-classification, and analyzed via the Spearman’s rank correlation coefficient. Further statistical analysis was obtained using nonparametric Kruskal-Wallis rank-sum test and Mann-Whitney-U-test. This study shows that high TAAR1 expression is a positive prognosticator for overall survival in ovarian cancer patients and is significantly enhanced in low-grade serous carcinomas compared to high-grade serous carcinomas. The influence of TAAR1 as a positive prognosticator on overall survival indicates a potential prognostic relevance of signal transduction of thyroid hormone derivatives in epithelial ovarian cancer. Further studies are required to evaluate TAAR1 and its role in the development of ovarian cancer.

Monitoring of Palliative Care Symptoms and Concerns in Specialized Palliative Home Care Using an Electronic Version of the Integrated Palliative care Outcome Scale (Palli-MONITOR): protocol for a mixed-methods study

IntroductionOver the last decades, patient-reported outcome (PRO) measures have been developed to better understand the patient’s perspective and enable patient-centred care. In palliative care, the Integrated Palliative care Outcome Scale...

In celebration of the 70thbirthday of Peter Klüfers

In celebration of the 70^thbirthday of Peter Klüfers