Background and objectives: Performance on implicit measures of suicidality has been associated with suicidal and nonsuicidal self-injury. Despite the high prevalence of self-harm in patients with borderline personality disorder (BPD), no previous study has assessed implicit measures in this patient group. Methods: Forty patients with BPD and 25 healthy controls completed three implicit association tests (IATs) (Death words - Me/Others words, Self-Harm pictures - Me/Others, and Self-Harm pictures - Good/Bad words) and a subliminal priming task (effect of the primes "dying"/"growing" on the categorization speed of positive/negative adjectives) as well as measures of psychopathology (suicidal ideation, previous nonsuicidal self-injury, borderline symptomatology, depression, and hopelessness). Results: Patients with BPD had higher scores on all three IATs than healthy controls. The subliminal priming procedure did not reveal group differences. Correlations between implicit measures and psychopathology among patients with BPD were mostly weak and nonsignificant with a few exceptions: Positive correlations were observed between IAT Self-Harm - Good/Bad and lifetime frequency of nonsuicidal self-injury, between IAT Self-Harm - Me/Others and depression, and between IAT Death - Me/Others and depression. Correlations between implicit measures were weak to moderate. Limitations: The study was cross-sectional only, and the study had reduced power as the sample size was limited. Conclusions: As expected, patients with BPD had higher scores than healthy controls on the IATs, which indicates higher implicit self-identification with self-harm and death as well as stronger implicit positive attitudes towards self-harm. The mostly weak correlations between implicit and explicit measures speak against the discriminative value of IATs in patients with BPD.
Just like in humans vision plays a fundamental role in guiding adaptive locomotion, when designing the control strategy for a walking assistive technology, the use of Computer Vision may substantially improve modulation of the assistance based on the external environment. In this work, we developed a hip exosuit controller able to distinguish among three different walking terrains through the use of an RGB camera and to adapt the assistance accordingly. The system was tested with seven healthy participants walking throughout an overground path comprising of staircases and level ground. Subjects performed the task with the exosuit disabled ( Exo Off ), constant assistance profile ( Vision Off ), and with assistance modulation ( Vision On ). Our results showed that the controller was able to classify in real-time the path in front of the user with an overall accuracy per class above the 85%, and to perform assistance modulation accordingly. Evaluation related to the effects on the user showed that Vision On was able to outperform the other two conditions: we obtained significantly higher metabolic savings than Exo Off , with a peak of $\approx$ $-20\%$ when climbing up the staircase and $\approx$ $-16\%$ in the overall path, and than Vision Off when ascending or descending stairs. Such advancements in the field may yield to a step forward for the exploitation of lightweight walking assistive technologies in real-life scenarios.
Cardiogenic shock is a life-threatening syndrome of peripheral hypoperfusion and organ dysfunction due to primary cardiac disease. Few adequately designed randomized clinical trials provide guidance on the optimal management strategies, which frequently includes vasoactive drugs, circulatory and ventilatory support, and reversal of any underlying cause, including coronary revascularization in case of acute myocardial infarction. Management is largely based on experience rather than evidence-based recommendations and patient outcomes remain poor. Particular attention is currently given to refractory patients (i.e., not responding to medical treatment) with a growing number of studies investigating various modalities of mechanical circulatory support. This consensus document summarizes the output from the third Critical Care Clinical Trialists Workshop, where a group of experts convened to discuss, debate, and reflect on approaches related to trials in refractory cardiogenic shock, to provide recommendations for the design of future trials. Invited participants included clinical trialists, clinicians (including cardiologists, intensive care specialists, anaesthesiologists, and cardiac surgeons), epidemiologists, patient representatives, regulators from the United States and Europe, United States federal grant managers, and industry representatives. Special attention is given to current and future definitions of cardiogenic shock including refractory states, recent and ongoing clinical trials in refractory cardiogenic shock and future directions in light of the most recent literature.
Objectives The aim of this study was to evaluate the effectiveness of brief psychosocial support for patients with cancer and their relatives regarding their mental health. Design Quasi-experimental controlled trial with measurements at three time points (baseline, after 2 weeks and after 12 weeks). Setting The intervention group (IG) was recruited at two cancer counselling centres in Germany. The control group (CG) included patients with cancer or relatives who did not seek support. Participants In total, n=885 participants were recruited and n=459 were eligible for the analysis (IG, n=264; CG, n=195). Intervention One to two psychosocial support sessions (approximately hour) provided by a psycho-oncologist or social worker. Primary and secondary outcome measures The primary outcome was distress. The secondary outcomes were anxiety and depressive symptoms, well-being, cancer-specific and generic quality of life (QoL), self-efficacy and fatigue. Results The linear mixed model analysis showed significant differences between IG and CG at follow-up for distress (d=0.36), p=0.001), depressive (d=0.22), p=0.005) and anxiety symptoms (d=0.22), p=0.003), well-being (d=0.26, p=0.002), QoL (QoL mental; d=0.26, p=0.003), self-efficacy (d=0.21, p=0.011) and QoL (global; d=0.27, p=0.009). The changes were not significant for QoL (physical; d=0.04, p=0.618), cancer-specific QoL (symptoms; d=0.13, p=0.093), cancer-specific QoL (functional; d=0.08, p=0.274) and fatigue (d=0.04, p=0.643). Conclusion The results suggest that brief psychosocial support is associated with the improvement of mental health of patients with cancer and their relatives after 3 months. Trial registration number DRKS00015516.
PurposeThe purpose of this study was to evaluate the osseointegration and radiological outcomes in patients after total hip arthroplasty, hypothesizing different load patterns with one cementless stem design and different CCD angles (CLS Spotorno femoral stem 125° vs 135°).Methods All cases of degenerative hip osteoarthritis fulfilling strict inclusion criteria were treated with cementless hip arthroplasty between 2008 and 2017. Ninety-two out of one hundred six cases were clinically and radiologically examined three and 12 months after implantation. Two groups with each 46 patients were rendered prospectively and compared in clinical (Harris Hip Score) and radiological outcome.ResultsAt final follow-up, no significant difference regarding Harris Hip Score was detected between the two groups (mean 99.2 ± 3.7 vs. 99.3 ± 2.5; p = 0.73). Cortical hypertrophy was found in none of the patients. Stress shielding was seen in a total of 52 hips (n = 27 vs. n = 25; 57% of the 92 hips). No significant difference regarding stress shielding was detected when comparing both groups (p = 0.67). Significant bone density loss was detected in Gruen zone one and two in the 125° group. The 135° group showed significant radiolucency in Gruen zone seven. No overall radiological loosening or subsidence of the femoral component was observed.Conclusion According to our results, the use of a femoral component with a 125° CCD angle versus a 135° CCD did not result in a different osseointegration and load transfer with a clinically relevant significance.
Background Prolyl hydroxylase 1 (PHD1) is a prognostic marker in several cancers. Aims and scopes This study was undertaken to elucidate the clinical relevance of PHD1 in colorectal cancer (CRC) prognosis. Materials and methods We compared PHD1 expression on a tissue microarray (TMA) containing samples from 1800 CRCs with corresponding clinicopathological tumor variables and patient survival. Results While PHD1 staining was always high in benign colorectal epithelium, high PHD1 staining was detectable in only 71.8% of CRCs. Low PHD1 staining was associated with advanced tumor stage (p = 0.0101) and shortened overall survival in CRC patients (p = 0.0011). In a multivariable analysis including tumor stage, histological type and PHD1 staining revealed tumor stage and histological type (p < 0.0001 each), but also PHD1 staining (p = 0.0202) to be independent prognostic markers for CRC. Conclusions In our cohort, loss of PHD1 expression independently identified a subset of CRC patients with poor overall survival and might, thus, be a promising prognostic marker. PHD1 targeting may even allow for specific therapeutic approaches for these patients.
Multiplex fluorescence immunohistochemistry (mfIHC) approaches were yet either limited to 6 markers or limited to a small tissue size that hampers translational studies on large tissue microarray cohorts. Here we have developed a BLEACH&STAIN mfIHC method that enabled the simultaneous analysis of 15 biomarkers (PD-L1, PD-1, CTLA-4, panCK, CD68, CD163, CD11c, iNOS, CD3, CD8, CD4, FOXP3, CD20, Ki67, CD31) in 3098 tumor samples from 44 different carcinoma entities within one week. To facilitate automated immune checkpoint quantification on tumor and immune cells and study its spatial interplay an artificial intelligence-based framework -incorporating 17 different deep-learning systems- was established. Unsupervised clustering showed that the three PD-L1 phenotypes (PD-L1+tumor and immune cells, PD-L1+immune cells, PD-L1 negative) were either inflamed or non-inflamed. In the inflamed PD-L1+patients, spatial analysis revealed that an elevated intratumoral M2-macrophages as well as CD11c+dendritic cell infiltration (p<0.001 each) was associated with a high CD3+CD4±CD8±FOXP3±T-cell exclusion and a high PD-1 expression on T-cells (p<0.001 each). In breast cancer, the PD-L1 fluorescence intensity on tumor cells showed a significantly higher predictive performance for overall survival (AUC: 0.72, p<0.001) compared to the commonly used percentage of PD-L1+ tumor cells (AUC: 0.54). In conclusion, our deep learning-based BLEACH&STAIN framework facilitates rapid and comprehensive assessment of more than 60 spatially orchestrated immune cell subpopulations and its prognostic relevance. Implications: The development of an easy-to-use high-throughput 15+1 multiplex fluorescence approach facilitates the in-depth understanding of the immune tumor microenvironment and enables to study the prognostic relevance of more than 130 immune cell subpopulations.
Cutibacterium acnes, formerly known as Propionibacterium acnes, is a commensal of the human pilosebaceous unit but also causes deep-seated infection, especially in the context of orthopedic and neurosurgical foreign materials. Interestingly, little is known about the role of specific pathogenicity factors for infection establishment. Here, 86 infection-associated and 103 commensalism-associated isolates of C. acnes were collected from three independent microbiology laboratories. We sequenced the whole genomes of the isolates for genotyping and a genome-wide association study (GWAS). We found that C. acnes subsp. acnes IA1 was the most significant phylotype among the infection isolates (48.3% of all infection isolates; odds ratio [OR] = 1.98 for infection). Among the commensal isolates, C. acnes subsp. acnes IB was the most significant phylotype (40.8% of all commensal isolates; OR = 0.5 for infection). Interestingly, C. acnes subsp. elongatum (III) was rare overall and did not occur at all in infection. The open reading frame-based GWAS (ORF-GWAS) did not show any loci with a strong signal for infection association (no P values of ≤0.05 after adjustment for multiple testing; no logarithmic OR [logOR] of ≥|2|). We concluded that all subspecies and phylotypes of C. acnes, possibly with the exception of C. acnes subsp. elongatum, are able to cause deep-seated infection given favorable conditions, most importantly related to inserted foreign material. Genetic content appears to have a small effect on the likelihood of infection establishment, and functional studies are needed to understand the individual factors contributing to deep-seated infections caused by C. acnes. IMPORTANCE Opportunistic infections emerging from human skin microbiota are of ever-increasing importance. Cutibacterium acnes, being abundant on the human skin, may cause deep-seated infections (e.g., device-associated infections). Differentiation between invasive (i.e., clinically significant) C. acnes isolates and sole contaminants is often difficult. Identification of genetic markers associated with invasiveness not only would strengthen our knowledge related to pathogenesis but also could open ways to selectively categorize invasive and contaminating isolates in the clinical microbiology lab. We show that in contrast to other opportunistic pathogens (e.g., Staphylococcus epidermidis), invasiveness is apparently a broadly distributed ability across almost all C. acnes subspecies and phylotypes. Thus, our work strongly supports an approach in which clinical significance is judged from clinical context rather than by detecting specific genetic traits.
Biliary tract cancers (BTCs) are rare and heterogeneous malignant tumours including cholangiocarcinoma and gallbladder cancer. They are very aggressive, often refractory to chemotherapy and associated with an overall poor prognosis. Surgical resection remains the only potentially curative treatment option but less than 35% present with resectable disease. Adjuvant treatments have been widely used but until recently, supportive data were limited to non-randomised, non-controlled retrospective studies. Recent evidence from the BILCAP trial has established adjuvant capecitabine as the standard of care. But there are still unanswered questions as to the role of adjuvant therapy. Further prospective data and translational research with reproducible evidence of clinical benefit are needed. In this review of adjuvant therapy in resectable BTCs, we will summarise the latest evidence setting current treatment standards and highlight future prospects.
Introduction Several studies have reported good to excellent outcomes of revision total hip arthroplasty (rTHA) using allografts for treating severe acetabular bone defects. However, precise information on the impact of allograft type and reconstruction method is not available. Material and methods Systematic literature search was performed in Medline and Web of Science including patients with acetabular bone loss classified according to the Paprosky classification who underwent rTHA involving the use of allografts. Studies with a minimum follow-up of 2 years published between 1990 and 2021 were included. Kendall correlation was applied to determine the relationship between Paprosky grade and allograft type use. Proportion meta-analyses with 95% confidence interval (CI) were performed to summarize the success of various reconstruction options, including allograft type, fixation method, and reconstruction system. Results Twenty-seven studies met the inclusion criteria encompassing 1561 cases from 1491 patients with an average age of 64 years (range 22–95). The average follow-up period was 7.9 years (range 2–22). Structural bulk and morselized grafts were used in equal proportions for all Paprosky acetabular defect types. Their use increased significantly with the type of acetabular defect (r = 0.69, p = 0.049). The overall success rate ranged from 61.3 to 98.3% with a random effect pooled estimate of 90% [95% CI 87–93]. Trabecular metal augments (93% [76–98]) and shells (97% [84–99]) provided the highest success rates. However, no significant differences between reconstruction systems, allograft types and fixation methods were observed (p > 0.05 for all comparisons). Conclusion Our findings highlight the use of bulk or morselized allograft for massive bone loss independent of Paprosky classification type and indicate similar good mid- to long-term outcomes of the different acetabular reconstruction options using allografts. Clinical trial registration PROSPERO: CRD42020223093.
Chronic, or persistent pain affects more than 10% of adults in the general population. This makes it one of the major physical and mental health care problems. Although pain is an important acute warning signal that allows the organism to take action before tissue damage occurs, it can become persistent and its role as a warning signal thereby inadequate. Although per definition, pain can only be labeled as persistent after 3 months, the trajectory from acute to persistent pain is likely to be determined very early and might even start at the time of injury. The biopsychosocial model has revolutionized our understanding of chronic pain and paved the way for psychological treatments for persistent pain, which routinely outperform other forms of treatment. This suggests that psychological processes could also be important in shaping the very early trajectory from acute to persistent pain and that targeting these processes could prevent the development of persistent pain. In this review, we develop an integrative model and suggest novel interventions during early pain trajectories, based on predictions from this model.
Aims: The randomized, controlled EAST-AFNET 4 trial showed that early rhythm control (ERC) reduces the rate of a composite primary outcome (cardiovascular death, stroke, or hospitalization for worsening heart failure or acute coronary syndrome) by ∼20%. The current study examined the cost-effectiveness of ERC compared to usual care. Methods and results: This within-trial cost-effectiveness analysis was based on data from the German subsample of the EAST-AFNET 4 trial (n = 1664/2789 patients). Over a 6-year time horizon and from a healthcare payer's perspective, ERC was compared to usual care regarding costs (hospitalization and medication) and effects (time to primary outcome; years survived). Incremental cost-effectiveness ratios (ICERs) were calculated. Cost-effectiveness acceptability curves were constructed to visualize uncertainty. Early rhythm control was associated with higher costs [+€1924, 95% CI (-€399, €4246)], resulting in ICERs of €10 638 per additional year without a primary outcome and €22 536 per life year gained. The probability of ERC being cost-effective compared to usual care was ≥95% or ≥80% at a willingness-to-pay value of ≥€55 000 per additional year without a primary outcome or life year gained, respectively. Conclusion: From a German healthcare payer's perspective, health benefits of ERC may come at reasonable costs as indicated by the ICER point estimates. Taking statistical uncertainty into account, cost-effectiveness of ERC is highly probable at a willingness-to-pay value of ≥€55 000 per additional life year or year without a primary outcome. Future studies examining the cost-effectiveness of ERC in other countries, subgroups with higher benefit from rhythm control therapy, or cost-effectiveness of different modes of ERC are warranted.
Persistent somatic and neuropsychiatric symptoms have been frequently described in patients after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) even after a benign clinical course of the acute infection during the early phases of the coronavirus SARS-CoV-2 (COVID-19) pandemic and are part of Long COVID. The Omicron variant emerged in November 2021 and has rapidly become predominant due to its high infectivity and suboptimal vaccine cross-protection. The frequency of neuropsychiatric post-acute sequelae after infection with the SARS-CoV-2 Omicron and adequate vaccination status is not known. Here, we aimed to characterize post-acute symptoms in individuals with asymptomatic or mildly symptomatic breakthrough infection with SARS-CoV-2. These individuals had either proven infection with the Omicron variant (n = 157) or their infection occurred in 2022 where Omicron was the predominant variant of SARS-CoV-2 in Germany (n = 107). This mono-centric cross-sectional study was conducted at the University Medical Center Hamburg-Eppendorf between February 11, 2022, and April 11, 2022. We employed questionnaires addressing self-reported somatic symptom burden (Somatic Symptoms Scale 8 = SSS-8), and neuropsychiatric symptoms including mood (Patient Health Questionnaire 2 = PHQ-2), anxiety (Generalized Anxiety Disorder Scale 7 = GAD-7), attention (Mindful Attention Awareness Scale = MAAS), and fatigue (Fatigue Assessment Scale = FAS) in a cohort of hospital workers. Scores were compared between 175 individuals less than four weeks after positive testing for SARS-CoV-2, 88 individuals more than four weeks after positive testing, and 87 SARS-CoV-2 uninfected controls. The majority (n = 313; 89·5%) of included individuals were vaccinated at least three times. After recovery from infection, no significant difference in scores assessing neuropsychiatric and somatic symptoms were detected between the three groups (SARS-CoV-2 uninfected controls, individuals less and more than four weeks after positive testing) independent of age, sex, preconditions, and vaccination status. In addition, self-reported symptom burden did not significantly correlate with the number of vaccinations against SARS-CoV-2, time from recovery, or the number of infections. Notably, in all three groups, the mean scores for each item of our questionnaire lay below the pathological threshold. Our data shows that persistent neuropsychiatric and somatic symptoms after recovery from SARS-CoV-2 infection in fully vaccinated hospital workers do not occur more frequently than in uninfected individuals. This will guide healthcare professionals in the clinical management of patients after recovery from breakthrough infections with SARS-CoV-2.
DICER1 syndrome is a tumor predisposition syndrome that is associated with up to 30 different neoplastic lesions, usually affecting children and adolescents. Here we identify a group of mesenchymal tumors which is highly associated with DICER1 syndrome, and molecularly distinct from other DICER1-associated tumors. This group of DICER1-associated mesenchymal tumors encompasses multiple well-established clinicopathological tumor entities and can be further divided into three clinically meaningful classes designated “low-grade mesenchymal tumor with DICER1 alteration” (LGMT DICER1), “sarcoma with DICER1 alteration” (SARC DICER1), and primary intracranial sarcoma with DICER1 alteration (PIS DICER1). Our study not only provides a combined approach to classify DICER1-associated neoplasms for improved clinical management but also suggests a role for global hypomethylation and other recurrent molecular events in sarcomatous differentiation in mesenchymal tumors with DICER1 alteration. Our results will facilitate future investigations into prognostication and therapeutic approaches for affected patients.
Existing guidelines recommend psychopharmacological treatment for the management of schizophrenia and bipolar disorder as part of holistic treatment concepts. About half of the patients do not take their medication regularly, although treatment adherence can prevent exacerbations and re-hospitalizations. To date, the relationship between medication adherence and cognitive performance is understudied. Therefore, this study investigated the relationship between medication adherence and cognitive performance by analyzing the data of 862 participants with schizophrenia-spectrum and bipolar disorders (mean [SD] age, 41.9 [12.48] years; 44.8% female) from a multicenter study (PsyCourse Study). Z-scores for three cognitive domains were calculated, global functioning was measured with the Global Assessment of Functioning Scale, and adherence was assessed by a self-rating questionnaire. We evaluated four multiple linear regression models and built three clusters with hierarchical cluster analyses. Higher adherence behavior (p < 0.001) was associated with better global functioning but showed no impact on the cognitive domains learning and memory, executive function, and psychomotor speed. The hierarchical cluster analysis resulted in three clusters with different cognitive performances, but patients in all clusters showed similar adherence behavior. The study identified cognitive subgroups independent of diagnoses, but no differences were found in the adherence behavior of the patients in these new clusters. In summary, medication adherence was associated with global but not cognitive functioning in patients with schizophrenia-spectrum and bipolar disorders. In both diagnostic groups, cognitive function might be influenced by various factors but not medication adherence.
Acute graft-versus-host disease (aGVHD) is a life-threatening complication after allogeneic haematopoietic cell transplantation, with gastrointestinal (GI) tract involvement (GI aGVHD) being one of the leading causes of morbidity and mortality. Whilst systemic steroids are the standard first-line treatment for aGVHD, approximately 50% of patients become steroid refractory (SR), which is associated with poor outcomes. Existing options for SR-GVHD are limited, and there is a significant unmet need for new non-immunosuppressive treatment approaches in patients with GI aGVHD. Here, we review newer concepts in the pathogenesis of GI aGVHD and present the evidence for the role of glucagon-like peptide 2 (GLP-2) in maintaining and protecting GI epithelial cells, including the enterocytes, intestinal stem cells and Paneth cells, which are direct targets of aGVHD. Finally, we discuss the therapeutic rationale for GLP-2 treatment as a tissue regeneration approach and the potential use of the novel GLP-2 analogue apraglutide as an adjunctive treatment for GI aGVHD.
Purpose Previous research on genital gender-affirming surgery lacked to build a framework that took various surrounding factors into account. E.g., transgender health care services are delivered in both centralized (by one interdisciplinary institution) and decentralized settings (by different medical institutions spread over several locations). The present study investigated the effects of different structural and clinical aspects of gender-affirming genital surgery on psychosocial outcomes. Methods We surveyed former transgender and gender-diverse people who completed a vaginoplasty between 2014 and 2018. 45 participants were included in the study. We calculated hierarchical linear regression analyses to assess the relationship between psychosocial outcome measures (gender congruence, mental health, quality of life) and different aspects of gender-affirming genital surgery (e.g., setting of service delivery). To address shortcomings regarding the small sample size, we applied a rigorous statistical approach (e.g., Bonferroni correction) to ensure that we only identify predictors that are actually related to the outcomes. Results A non-responder analysis revealed no systematic bias in the recruitment procedure. Treatment satisfaction was a significant predictor for gender congruence. Moreover, we found the setting of service delivery (centralized, decentralized) to predict psychological health and the physical health dimension of quality of life. The effect sizes of our models were moderate to high, and models explained up to 26% of the total variance with a power up to 0.83. Conclusion The present study is an exploratory attempt into the manifold relationships between treatment-related factors (e.g., aesthetic outcome), the setting of service delivery, and their effects on gender-affirming genital surgery.
Background Psychosocial support is a crucial component of adequate rare disease care, but to date psychosocial support needs of this patient population are insufficiently met. Within Q.RARE.LI, we strive to evaluate the effectiveness of a structured, transdiagnostic, and location-independent psychosocial support intervention in routine care of patients with rare autoimmune liver diseases in five countries and prepare its implementation. Methods Within an effectiveness-implementation hybrid trial, we aim to a) investigate the effectiveness of the intervention in routine care in five diverse healthcare systems and b) assess implementation outcomes, examine and prepare the implementation context, and develop country-specific implementation strategies. To assess effectiveness, we will include N = 240 patients with rare autoimmune liver diseases. Within a two-armed randomized controlled trial (allocation ratio 1:1), we will compare structured and peer-delivered psychosocial support in addition to care-as-usual (CAU) with CAU alone. Outcomes will be assessed via electronic database entry prior to intervention, directly after, and at a three-month follow-up. Our primary effectiveness outcome will be mental health-related quality of life at post-assessment. Secondary outcomes include depression and anxiety severity, perceived social support, helplessness, and disease acceptance. Implementation outcomes will be assessed within a mixed-methods process evaluation. In a quantitative cross-sectional survey, we will examine perceived acceptability and feasibility in patients, peer-counselors, and healthcare providers involved in delivery of the intervention. In qualitative focus groups, we will analyze the implementation context and determine barriers and facilitators for implementation with different stakeholders (patients and/or representatives, peer-counselors, healthcare providers, health insurers). Based on these results, we will derive country-specific implementation strategies and develop a concrete implementation plan for each country. Discussion The intervention is expected to help patients adjust to their disease and improve their mental quality of life. The transdiagnostic and location-independent program has the potential to reach patients for psychosocial support who are usually hard to reach. By preparing the implementation in five countries, the project can help to make low-threshold psychosocial support available to many patients with rare diseases and improve comprehensive healthcare for an often neglected group. Trial registration ISRCTN15030282
Introduction: Patients with triple-class-exposed relapsed/refractory multiple myeloma (TCE-RRMM) have a poor prognosis and limited treatment options. Teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, was studied in patients with TCE-RRMM in the single-arm MajesTEC-1 study. To assess the relative effectiveness of teclistamab versus real-world physician's choice of therapy (RWPC), adjusted comparisons were performed using individual patient data from MajesTEC-1 and LocoMMotion, a prospective study of patients with TCE-RRMM. Methods: An external control arm for MajesTEC-1 was created from patients in LocoMMotion (n = 248; clinical cut-off: November 2, 2021) and compared with treated patients (n = 165) from MajesTEC-1 (teclistamab 1.5 mg/kg weekly; clinical cut-off: March 16, 2022). Inverse probability weighting was used to adjust for imbalances in baseline covariates. For binary endpoints [overall response rate (ORR), very good partial response or better (≥ VGPR) rate, complete response or better (≥ CR)], relative effect of teclistamab versus RWPC was estimated with an odds ratio and relative response rate and 95% confidence interval (CI), derived from weighted logistic regression. Weighted Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% CIs for time-to-event endpoints [duration of response (DOR), progression-free survival (PFS), and overall survival (OS)]. Results: After weighting, baseline characteristics were balanced across cohorts. In adjusted comparisons, teclistamab-treated patients were 2.3-fold, 5.2-fold and 148.3-fold, more likely to reach ORR [response-rate ratio (RR) = 2.31, 95% CI 1.77-2.85, p < 0.0001], ≥ VGPR (RR = 5.19, 95% CI 3.26-7.12, p < 0.0001) and ≥ CR (RR = 148.25, 95% CI 20.63-1065.40, p < 0.0001), respectively, versus patients receiving RWPC. Following adjustment, DOR (HR 0.32, 95% CI 0.19-0.54, p < 0.0001) and PFS (HR 0.48, 95% CI 0.35-0.65, p < 0.0001) were significantly longer with teclistamab versus RWPC. OS was numerically better with teclistamab versus RWPC [HR 0.77 (0.55-1.09), p = 0.1419]. Conclusion: Teclistamab demonstrated improved effectiveness versus RWPC, highlighting its clinical benefit as a novel and effective treatment for patients with TCE-RRMM. Trial registration: Majest TEC-1, ClinicalTrials.gov NCT04557098; LocoMMotion, ClinicalTrials.gov NCT04035226.
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Martinistrasse 52, 20246, Hamburg, Hamburg, Germany
Head of institution
Prof. Dr. Burkhard Göke, Medical director