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Summary: The bendamustine–rituximab (BR) schedule is an efficient first‐line therapy in Waldenström macroglobulinaemia (WM). A previous analysis of 69 patients who received this treatment confirmed a high response rate and good progression‐free (PFS) and overall survival (OS). With a median follow‐up of 76.1 months (95% confidence interval [CI] 69.9–80.6), 5‐year outcome is still excellent at 66.63% (95% CI 56.09–79.17) for PFS and 80.01% (95% CI 70.82–90.41) for OS. The rate of secondary cancers is 17.66% (IQR 7.99–27.64) at 66 months. Relapsed patients who received ibrutinib as second‐line clearly benefited from this schedule. This confirms current recommendations suggesting BR long‐term efficacy as first‐line option in WM. [ABSTRACT FROM AUTHOR]

Background: Culturally sensitive care is integral to effective and equitable healthcare delivery, necessitating an understanding and acknowledgment of patients' cultural needs, preferences, and expectations. This study investigates the perceptions of cultural sensitivity among general practitioners (GPs), focusing on their intentions, willingness and perceived responsibilities in providing care tailored to cultural needs. Methods: In-depth interviews were conducted with 21 Flemish GPs to explore their perspectives on culturally sensitive care. Data analysis followed a conventional qualitative content analysis approach within a constructivist framework. A coding scheme was developed to identify recurring themes and patterns in the GPs' responses. Results: Findings reveal that culturally sensitive care provision is perceived as a multifaceted process, initiated by an exploration phase where GPs inquire about patients' cultural needs and preferences. Two pivotal factors shaping culturally sensitive care emerged: patients' specific cultural expectations and GPs' perceived responsibilities. These factors guided the process of culturally sensitive care towards three distinct outcomes, ranging from complete adaptation to patients' cultural requirements driven by a high sense of responsibility, through negotiation and compromise, to a paternalistic approach where GPs expect patients to conform to GPs' values and expectations. Three typologies of GPs in providing culturally sensitive care were identified: genuinely culturally sensitive, surface-level culturally sensitive, and those perceiving diversity as a threat. Stereotyping and othering persist in healthcare, underscoring the importance of critical consciousness and cultural reflexivity in providing patient-centered and equitable care. Conclusions: This study emphasizes the significance of empathy and underscores the necessity for GPs to embrace the exploration and acknowledgement of patients' preferences and cultural needs as integral aspects of their professional role. It highlights the importance of shared decision-making, critical consciousness, cultural desire and empathy. Understanding these nuances is essential for enhancing culturally sensitive care and mitigating healthcare disparities. [ABSTRACT FROM AUTHOR]

Internalized HIV stigma is prevalent and research on internalized HIV stigma has increased during the past 10 years. The aim of this systematic review was to synthesize research on internalized HIV stigma and relationships with various health-related variables in order to better inform the development of interventions aimed at reducing internalized HIV stigma. We reviewed 176 studies with a quantitative design reporting correlates that were peer-reviewed, published in English before January 2021, drawn from PubMed, PSYCHINFO, Web of Science, EBSCO, and Scopus. Synthesis showed consistent associations between internalized stigma and negative psychological (e.g., depression, anxiety), social (e.g., lack of social support, discrimination, nondisclosure, and intersecting stigmas), and health (e.g., substance use, treatment nonadherence, negative clinical HIV outcomes) variables. We argue for a more socioecological approach to internalized stigma, with greater attention for intersectional stigmas, and more longitudinal research, if we are to effectively develop interventions that reduce internalized stigma. [ABSTRACT FROM AUTHOR]

Keywords: osteoporosis; patient preference; burden of disease; quality of life EN osteoporosis patient preference burden of disease quality of life 107 118 12 02/08/23 20230101 NES 230101 Kyriakos Souliotis, SP 1, sp SP 2 sp Christina Golna, SP 2 sp Christina Poimenidou, SP 2 sp Tatiana Drakopoulou, SP 3 sp Memi Tsekoura, SP 2 sp Damon Willems, SP 4 sp Vasileios Kountouris, SP 5 sp Polyzois Makras SP 6 sp SP 1 sp Department of Social and Education Policy, University of Peloponnese, Corinth, Greece; SP 2 sp Research Department, Health Policy Institute, Maroussi, Greece; SP 3 sp Greek Bone Health Association "Petalouda", Perama, Greece; SP 4 sp Market Access Lead, UCB Pharma, Brussels, Belgium; SP 5 sp External Engagement Lead, UCB Pharma, Athens, Greece; SP 6 sp Department of Endocrinology and Diabetes and Department of Medical Research, 251 Hellenic Air Force & VA General Hospital, Athens, Greece Correspondence: Kyriakos Souliotis, Email [email protected] Plain Language Summary This study aimed to describe patient-reported health status and quality of life in postmenopausal women with severe osteoporosis in Greece, and to understand patient preferences for osteoporosis therapies. Finally, when participants in this study were asked to select their preferred treatment scenario between two unlabeled anabolic treatments, 70% opted for the scenario that shared treatment characteristics with romosozumab over a scenario that shared treatment characteristics with teriparatide. Around half of participants (58%) would consider their osteoporosis treatment to be effective if it led to a 50% reduction in future fracture risk, 10% would consider their osteoporosis treatment to be effective only if it led to an 80% reduction in risk, and almost 20% only if it led to at least a 90% reduction in risk. [Extracted from the article]

Simple Summary: A critical step in the success of immunotherapy is the presentation of tumor-derived peptides by the major histocompatibility complex I (MHC-I) of tumor cells. These neoantigens are potentially immunogenic and trigger immune responses orchestrated by cytotoxic cells. In malignant mesothelioma (MM), tumor development is nevertheless characterized by a low mutation rate despite major structural chromosomal rearrangements driving oncogenesis. In this paper, we propose a paradigm based on the mechanisms of the DNA damage tolerance (DDT) pathways to increase the frequency of non-synonymous mutations. The idea is to transiently activate the error-prone DDT in order to generate neoantigens while preserving a fully competent antitumor immune response. Immunotherapy based on two checkpoint inhibitors (ICI), programmed cell death 1 (PD-1, Nivolumab) and cytotoxic T-lymphocyte 4 (CTLA-4, Ipilimumab), has provided a significant improvement in overall survival for malignant mesothelioma (MM). Despite this major breakthrough, the median overall survival of patients treated with the two ICIs only reached 18.1 months vs. 14 months in standard chemotherapy. With an objective response rate of 40%, only a subset of patients benefits from immunotherapy. A critical step in the success of immunotherapy is the presentation of tumor-derived peptides by the major histocompatibility complex I (MHC-I) of tumor cells. These neoantigens are potentially immunogenic and trigger immune responses orchestrated by cytotoxic cells. In MM, tumor development is nevertheless characterized by a low mutation rate despite major structural chromosomal rearrangements driving oncogenesis (BAP1, NF2, CDKN2AB). In this opinion, we propose to investigate an approach based on the mechanisms of the DNA damage tolerance (DDT) pathways to increase the frequency of non-synonymous mutations. The idea is to transiently activate the error-prone DDT in order to generate neoantigens while preserving a fully competent antitumor immune response. [ABSTRACT FROM AUTHOR]

Oncology and hematology physicians aim during the COVID-19 pandemic to protect their patients from COVID-19 infection without impairing the prognosis of the disease. We describe how at-home treatment was used in our department to maintain multiple myeloma treatment while protecting the patient. [Extracted from the article]

Endothelial cells are the first non-self-barrier encountered by the recipient's immune system after allograft transplantation and thus are involved early during alloimmune response. Our goal was to study processes of endothelial cell injury/activation in a mouse model of lung transplantation. Mouse orthotopic left lung transplantation was performed in isografts (C57BL/6 to C57BL/6) and allografts (Balbc to C57BL/6), both received daily immunosuppression (10 mg/kg cyclosporin A and 1.6 mg/kg methylprednisolone) and were serially sacrificed at day 1, 7 and 35 post-transplant (n=6/timepoint/group). Left transplanted lungs were made into single cell suspension and absolute cell numbers were quantified by flow cytometry for CD31+ endothelial cells, CD45+ leukocytes and MHCI/II, VCAM-1 and ICAM-1 for cell activation. One additional allograft and isograft were scanned with high resolution (HR) ex vivo microCT (µCT) to visualize airways and blood vessels at day 70 post transplantation. Endothelial cell numbers decreased from day 1 until day 7 (p=0.03) in allografts and recovered slightly at day 35. While in isografts, endothelial cells seemed to increase non-significantly over time. In contrast, leukocytes significantly increased at day 7 in allografts versus day 1 (p=0.036) and isografts at day 7 (p=0.003). Leukocytes remained stable in isografts over time (p=0.3). Mean fluorescence intensity (MFI) was increased for MHC I/II and VCAM-1 (p=0.003; p<0.0001; p=0.04) on endothelial cells, the MFI of MHC I/II and ICAM-1 on leukocytes was increased in allografts versus isografts (p=0.0002; p=0.006; p=0.002). HR µCT showed normal airway morphology while lumen of arteries and veins was narrowed in allograft compared to isograft. Arterioles and venules were occluded in allograft. Destruction of endothelial cells may represent the very first onset of alloimmune response post lung transplantation and warrant further investigations towards diagnostic and therapeutic approaches. [ABSTRACT FROM AUTHOR]

Simple Summary: Therapies for squamous cell carcinomas of the head and neck (SCCHN) have been rapidly evolving, initially with the inclusion of immunotherapy, but more recently with the consideration of anti-angiogenic therapies. Recent preclinical and clinical data reveal a strong correlation between vascular endothelial growth factor (VEGF) and the progression of SCCHN, with nearly 90% of these malignancies expressing VEGF. Our review article not only elaborates on the utility of anti-VEGF therapies on SCCHN but also its interaction with the immune environment. Furthermore, we detailed the current data on immunotherapies targeting SCCHN and how this could be coupled with anti-angiogenics therapies. Despite the lack of approved anti-angiogenic therapies in squamous cell carcinoma of the head and neck (SCCHN), preclinical and more recent clinical evidence support the role of targeting the vascular endothelial growth factor (VEGF) in this disease. Targeting VEGF has gained even greater interest following the recent evidence supporting the role of immunotherapy in the management of advanced SCCHN. Preclinical evidence strongly suggests that VEGF plays a role in promoting the growth and progression of SCCHN, and clinical evidence exists as to the value of combining this strategy with immunotherapeutic agents. Close to 90% of SCCHNs express VEGF, which has been correlated with a worse clinical prognosis and an increased resistance to chemotherapeutic agents. As immunotherapy is currently at the forefront of the management of advanced SCCHN, revisiting the rationale for targeting angiogenesis in this disease has become an even more attractive proposition. [ABSTRACT FROM AUTHOR]

Falls risk is elevated in chronic obstructive pulmonary disease (COPD). However, there is a lack of evidence regarding the contributing factors. Here, we examined the feasibility of, and initial responses to, large walking perturbations in COPD, as well as the adaptation potential of people with COPD to repeated walking perturbations that might indicate potential for perturbation-based balance training in COPD. 12 participants with COPD undergoing inpatient pulmonary rehabilitation and 12 age-gender-matched healthy control participants walked on an instrumented treadmill and experienced repeated treadmill-belt acceleration perturbations (leading to a forward balance loss). Three-dimensional motion capture was used to quantify the stability of participants body position during perturbed walking. Feasibility, stability following the initial perturbations and adaptation to repeated perturbations were assessed. Using perturbations in this manner was feasible in this population (no harness assists and participants completed the minimum number of perturbations). No clear, specific deficit in reactive walking stability in COPD was found (no significant effects of participant group on stability or recovery step outcomes). There were mixed results for the adaptability outcomes which overall indicated some adaptability to repeated perturbations, but not to the same extent as the healthy control participants. Treadmill-based perturbations during walking are feasible in COPD. COPD does not appear to result in significant deficits in stability following sudden perturbations and patients do demonstrate some adaptability to repeated perturbations. Perturbation-based balance training may be considered for fall prevention in research and practice in people with COPD. • Treadmill-based gait perturbations are feasible in people with COPD. • People with COPD do not show large deficits in reactive gait stability. • People with COPD demonstrate some but reduced adaptability to perturbations. • Perturbation-based balance training may be considered for people with COPD. [ABSTRACT FROM AUTHOR]

Simple Summary: Nasopharyngeal cancer (NPC) is a malignant epithelial tumor endemic to parts of Asia and associated with infection by the Epstein–Barr virus (EBV) in these regions. The cancer is often detected at a late stage which is associated with poor outcomes (63% 5-year survival). Advances for the management of this disease have remained largely stagnant and treatment relies primarily on radiotherapy and chemotherapy, as well as surgery when indicated. Nevertheless, our understanding of its underlying biology has grown rapidly in the past two decades, laying the foundation for the development of improved therapeutics which have the potential to improve outcomes. This review offers a comprehensive, up-to-date summary of this disease, with a focus on the role of somatostatin receptor 2 (SSTR2) in NPC and how this increased knowledge may lead to improved diagnosis and management of this disease. Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor, most commonly located in the pharyngeal recess and endemic to parts of Asia. It is often detected at a late stage which is associated with poor prognosis (5-year survival rate of 63%). Treatment for this malignancy relies predominantly on radiotherapy and/or systemic chemotherapy, which can be associated with significant morbidity and impaired quality of life. In endemic regions NPC is associated with infection by Epstein–Barr virus (EBV) which was shown to upregulate the somatostatin receptor 2 (SSTR2) cell surface receptor. With recent advances in molecular techniques allowing for an improved understanding of the molecular aetiology of this disease and its relation to SSTR2 expression, we provide a comprehensive and up-to-date overview of this disease and highlight the emergence of SSTR2 as a key tumor biomarker and promising target for imaging and therapy. [ABSTRACT FROM AUTHOR]