Broadly potent spike-specific human monoclonal antibodies inhibit SARS-CoV-2 Omicron sub-lineages.

The continuous emergence of SARS-CoV-2 variants of concern has rendered many therapeutic monoclonal antibodies (mAbs) ineffective. To date, there are no clinically authorized therapeutic antibodies effective against the recently circulating Omicron sub-lineages BA.2.86 and JN.1. Here, we report the isolation of broad and potent neutralizing human mAbs (HuMabs) from a healthcare worker infected with SARS-CoV-2 early in the pandemic. These include a genetically unique HuMab, named K501SP6, which can neutralize different Omicron sub-lineages, including BQ.1, XBB.1, BA.2.86 and JN.1, by targeting a highly conserved epitope on the N terminal domain, as well as an RBD-specific HuMab (K501SP3) with high potency towards earlier circulating variants that was escaped by the more recent Omicron sub-lineages through spike F486 and E484 substitutions. Characterizing SARS-CoV-2 spike-specific HuMabs, including broadly reactive non-RBD-specific HuMabs, can give insight into the immune mechanisms involved in neutralization and immune evasion, which can be a valuable addition to already existing SARS-CoV-2 therapies.

Assessment of Nursing Workload and Complexity Associated with Oncology Clinical Trials: A Scoping Review.

OBJECTIVES: Clinical trials (CTs) play a crucial role in advancing medical knowledge and patient care but are increasingly complex and resource-intensive. This scoping review aims to explore the current approaches for evaluating workload (WL) in oncology CTs and identify tools for measuring clinical research nurses' WL. METHODS: The search was conducted through MEDLINE, Scopus, CINAHL, and COCHRANE databases and carried out through the framework developed by Arksey and O'Malley and revised by the Joanna Briggs Institute. Data extraction and synthesis were performed to analyze instruments used for WL assessment and their dimensions. RESULTS: Of the 1,005 records identified, 12 meet the inclusion criteria. The complexity and WL associated with CTs can be attributed to five main domains: (1) protocol, (2) single case, (3) data management, (4) regulatory, and (5) worker-related. These instruments varied in their approaches, scoring systems, and domains assessed. Notably, the protocol-related domain was prevalent across most instruments, highlighting its importance in WL evaluation. Furthermore, findings revealed a wide range of WL scores across different studies, emphasizing the complexity and variability in WL management within CTs. CONCLUSIONS: This scoping review underscores the importance of evaluating WL in CTs and provides insights into existing tools and approaches. Nurses, as integral members of clinical research teams, bear significant responsibilities in trial management, necessitating a balanced approach to WL allocation. Future research should focus on validating and standardizing assessment tools to optimize resource allocation and enhance research efficiency in CT centers. IMPLICATIONS FOR NURSING PRACTICE: Understanding WL dynamics in CTs is essential for nurses involved in research delivery. By utilizing validated WL assessment tools, nurses can advocate for appropriate staffing levels and promote efficient trial management, ultimately improving patient outcomes and research quality in CT settings.

Impact of Preprocessing Parameters in Medical Imaging-Based Radiomic Studies: A Systematic Review.

BACKGROUND: Lately, radiomic studies featuring the development of a signature to use in prediction models in diagnosis or prognosis outcomes have been increasingly published. While the results are shown to be promising, these studies still have many pitfalls and limitations. One of the main issues of these studies is that radiomic features depend on how the images are preprocessed before their computation. Since, in widely known and used software for radiomic features calculation, it is possible to set these preprocessing parameters before the calculation of the radiomic feature, there are ongoing studies assessing the stability and repeatability of radiomic features to find the most suitable preprocessing parameters for every used imaging modality. MATERIALS AND METHODS: We performed a comprehensive literature search using four electronic databases: PubMed, Cochrane Library, Embase, and Scopus. Mesh terms and free text were modeled in search strategies for databases. The inclusion criteria were studies where preprocessing parameters' influence on feature values and model predictions was addressed. Records lacking information on image acquisition parameters were excluded, and any eligible studies with full-text versions were included in the review process, while conference proceedings and monographs were disregarded. We used the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool to investigate the risk of bias. We synthesized our data in a table divided by the imaging modalities subgroups. RESULTS: After applying the inclusion and exclusion criteria, we selected 43 works. This review examines the impact of preprocessing parameters on the reproducibility and reliability of radiomic features extracted from multimodality imaging (CT, MRI, CBCT, and PET/CT). Standardized preprocessing is crucial for consistent radiomic feature extraction. Key preprocessing steps include voxel resampling, normalization, and discretization, which influence feature robustness and reproducibility. In total, 44% of the included works studied the effects of an isotropic voxel resampling, and most studies opted to employ a discretization strategy. From 2021, several studies started selecting the best set of preprocessing parameters based on models' best performance. As for comparison metrics, ICC was the most used in MRI studies in 58% of the screened works. CONCLUSIONS: From our work, we highlighted the need to harmonize the use of preprocessing parameters and their values, especially in light of future studies of prospective studies, which are still lacking in the current literature.

Reduction of sacsin levels in peripheral blood mononuclear cells as a diagnostic tool for spastic ataxia of Charlevoix-Saguenay.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay is a rare neurodegenerative disease caused by biallelic variants in the SACS gene encoding for sacsin. More than 200 pathogenic variants have been identified to date, most of which are missense. It is likely that the prevalence of autosomal recessive spastic ataxia of Charlevoix-Saguenay is underestimated due to the lack of an efficient diagnostic tool able to validate variants of uncertain significance. We have previously shown that sacsin is almost absent in fibroblasts of patients with autosomal recessive spastic ataxia of Charlevoix-Saguenay regardless of the type of SACS variant, because sacsin carrying missense variants is cotranslationally degraded. In this work, we aimed to establish the pathogenicity of SACS variants by quantifying sacsin protein in blood samples, with relevant implications for autosomal recessive spastic ataxia of Charlevoix-Saguenay diagnosis. We developed a protocol to assess sacsin protein levels by western blot using small amounts of peripheral blood mononuclear cells, which can be propagated in culture and cryopreserved. The study involves eight patients with autosomal recessive spastic ataxia of Charlevoix-Saguenay (including a novel case) carrying variants of different types and positions along the SACS gene and two parents who are carriers of heterozygous missense variants. We show that patients with autosomal recessive spastic ataxia of Charlevoix-Saguenay (carrying either missense or truncating variants) almost completely lacked sacsin in peripheral blood mononuclear cells. Moreover, both carriers of a SACS missense variant showed 50% reduction in sacsin protein levels compared to controls. We also describe a patient with uniparental isodisomy carrying a homozygous nonsense variant near the 3' end of the SACS gene. This resulted in a stable sacsin protein lacking the last 202 amino acids, probably due to escape of nonsense-mediated decay of mRNA. In conclusion, we have optimized a minimally invasive diagnostic tool for autosomal recessive spastic ataxia of Charlevoix-Saguenay in blood samples based on sacsin protein level assessment. Indeed, our results provide definite evidence that sacsin carrying missense pathogenic variants undergoes cotranslational degradation. The quantitative reduction in sacsin levels in the case of missense variants of uncertain significance allows defining them as pathogenic variants, something which cannot be predicted bioinformatically with high certainty.

Leveraging Immunofocusing and Virus-like Particle Display to Enhance Antibody Responses to the Malaria Blood-Stage Invasion Complex Antigen PfCyRPA.

A vaccine protecting against malaria caused by Plasmodium falciparum is urgently needed. The blood-stage invasion complex PCRCR consists of the five malarial proteins PfPTRAMP, PfCSS, PfRipr, PfCyRPA, and PfRH5. As each subcomponent represents an essential and highly conserved antigen, PCRCR is considered a promising vaccine target. Furthermore, antibodies targeting the complex can block red blood cell invasion by the malaria parasite. However, extremely high titers of neutralizing antibodies are needed for this invasion-blocking effect, and a vaccine based on soluble PfRH5 protein has proven insufficient in inducing a protective response in a clinical trial. Here, we present the results of two approaches to increase the neutralizing antibody titers: (A) immunofocusing and (B) increasing the immunogenicity of the antigen via multivalent display on capsid virus-like particles (cVLPs). The immunofocusing strategies included vaccinating with peptides capable of binding the invasion-blocking anti-PfCyRPA monoclonal antibody CyP1.9, as well as removing non-neutralizing epitopes of PfCyRPA through truncation. Vaccination with PfCyRPA coupled to the AP205 cVLP induced nearly two-fold higher IgG responses compared to vaccinating with soluble PfCyRPA protein. Immunofocusing using a linear peptide greatly increased the neutralizing capacity of the anti-PfCyRPA antibodies. However, significantly lower total anti-PfCyRPA titers were achieved using this strategy. Our results underline the potential of a cVLP-based malaria vaccine including full-length PfCyRPA, which could be combined with other leading malaria vaccine antigens presented on cVLPs.

Gastrointestinal Stromal Tumors (GISTs) Mimicking Primary Ovarian Tumors or Metastasizing to the Ovaries: A Systematic Literature Review.

Background: Gastrointestinal stromal tumors (GISTs) are a rare neoplasm, sometimes mimicking primary ovarian tumors (OTs) and/or metastasizing to the ovaries (M-OT). We performed a systematic literature review (SLR) of OTs and M-OTs, investigating differences in recurrence-free and overall survival. Methods: Our SLR was performed according to PRISMA guidelines, searching in Pubmed, Scopus, and Web of Science databases from inception until 21 April 2024. Results: Overall, 59 OTs (Group 1) and 21 M-OTs (Group 2) were retrieved. The absence of residual disease after surgery was achieved significantly in a higher percentage of patients with Group 1 GISTs (91.5%) compared with Group 2 GISTs (57.1%). Chemotherapy was more frequently administered to Group 2 patients (33% vs. 0%). Recurrence and deaths for disease were significantly more frequent in Group 2 than Group 1 cases (54.5% vs. 6.8%, and 37.5% vs. 9.8%, respectively). Conclusions: GISTs can rarely mimic primary ovarian cancers or even more rarely metastasize to the ovaries. Group 1 GISTs occurred in younger women, were not associated with elevated tumor markers, and had a better prognosis. In contrast, Group 2 GISTs occurred in older women, may exhibit elevated tumor markers, and presented a worse prognosis. However, no significant statistical difference for survival between the two studied groups was detected. Computed tomography scans can define the size of GISTs, which correlate to stage and prognostic risk classes. The gold standard treatment is complete surgical resection, which was achieved in almost all cases of Group 1 GISTs and in half of Group 2. Histopathology and immunohistochemistry are essential for the final diagnosis and guide chemotherapy treatment.

De Novo Pathogenic Variant in FBRSL1, Non OMIM Gene Paralogue AUTS2, Causes a Novel Recognizable Syndromic Manifestation with Intellectual Disability; An Additional Patient and Review of the Literature.

FBRSL1, together with FBRS and AUTS2 (Activator of Transcription and Developmental Regulator; OMIM 607270), constitutes a tripartite AUTS2 gene family. AUTS2 and FBRSL1 are evolutionarily more closely related to each other than to FBRS (Fibrosin 1; OMIM 608601). Despite its paralogous relation to AUTS2, FBRSL1's precise role remains unclear, though it likely shares functions in neurogenesis and transcriptional regulation. Herein, we report the clinical presentation with therapeutic approaches and the molecular etiology of a patient harboring a de novo truncating variant (c.371dupC) in FBRSL1, leading to a premature stop codon (p.Cys125Leufs*7). Our study extends previous knowledge by highlighting potential interactions and implications of this variant, alongside maternal and paternal duplications, for the patient's phenotype. Using sequence conservation data and in silico analysis of the truncated protein, we generated a predicted domain structure. Furthermore, our in silico analysis was extended by taking into account SNP array results. The extension of in silico analysis was performed due to the possibility that the coexistence of FBRSL1 truncating variant contemporary with maternal and paternal duplication could be a modifier of proband's phenotype and/or influence the novel syndrome clinical characteristics. FBRSL1 protein may be involved in neurodevelopment due to its homology with AUTS2, together with distinctive neuronal expression profiles, and thus should be considered as a potential modulation of clinical characteristics in a novel syndrome. Finally, considering that FBRSL1 is apparently involved in neurogenesis and in transcriptional regulatory networks that orchestrate gene expression, together with the observation that different genetic syndromes are associated with distinct genomic DNA methylation patterns, the specific episignature has been explored.

Systemic infection in aged mice causes upregulation of crystallin alpha A in the RPE/choroid.

Aging changes the responsiveness of our immune defense, and this decline in immune reactivity plays an important role in the increased susceptibility to infections that marks progressing age. Aging is also the most pronounced risk factor for development of age-related macular degeneration (AMD), a disease that is characterized by dysfunctional retinal pigment epithelial (RPE) cells and loss of central vision. We have previously shown that acute systemic viral infection has a large impact on the retina in young mice, leading to upregulation of chemokines in the RPE/choroid (RPE/c) and influx of CD8 T cells in the neuroretina. In this study, we sought to investigate the impact of systemic infection on the RPE/c in aged mice to evaluate whether infection in old age could play a role in the pathogenesis of AMD. We found that systemic infection in mice led to upregulation of genes from the crystallin family in the RPE/c from aged mice, but not in the RPE/c from young mice. Crystallin alpha A (CRYAA) was the most upregulated gene, and increased amounts of CRYAA protein were also detected in the aged RPE/c. Increased CRYAA gene and protein expression has previously been found in drusen and choroid from AMD patients, and this protein has also been linked to neovascularization. Since both drusen and neovascularization are important hallmarks of advanced AMD, it is interesting to speculate if upregulation of crystallins in response to infection in old age could be relevant for the pathogenesis of AMD.

Cancer cachexia: A scoping review on non-pharmacological interventions.

Objective: Cancer cachexia occurs in 30%-80% of patients, increasing morbidity and mortality and impacting the health-related quality of life also for caregivers. Pharmacological interventions have been studied but have shown inconsistent effects on patients' lives in terms of relative outcomes and poor adherence to pharmacological treatment. We provide an overview of the evidence on non-pharmacological interventions for cancer cachexia. Methods: We conducted a scoping review based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses-extension for scoping review (PRISMA-ScR). On September 21, 2022, plus an update on January 10, 2024, we searched MEDLINE, Embase, CINAHL, Cochrane, PsycINFO, and Scopus for 2012-2024. We excluded pharmacological interventions defined as "any substance, inorganic or organic, natural or synthetic, that can produce functional modifications, through a chemical, physicochemical or physical action." Results: The search retrieved 9308 articles, of which 17 were eligible. Non-pharmacological interventions included nutritional counseling, complementary therapies (acupuncture), rehabilitation, and psychoeducational/psychosocial support. The data showed small and heterogeneous samples and different disease localization and stages. Thirty-nine percent were multimodal interventions and aimed at patients, not families. The common primary outcomes were body weight and composition, biomarkers, quality of life, psychological suffering, and muscular strength. Only three studies focus on the patient-caregiver dyad. Conclusions: Interventions on cancer cachexia should be multimodal and multiprofessional, proposed early, and aimed at quality of life outcomes. The caregiver's involvement is essential. Nurses can play an active role in managing cancer cachexia. More well-designed studies are needed to understand the efficacy and contents of non-pharmacological interventions. Systematic review registration: The review protocol has been registered in the OSF registry (DOI: 10.17605/OSF.IO/H4A29).

Exploring therapeutic interventions for functional neurological disorders: a comprehensive scoping review.

Functional Neurological Disorders (FNDs) are characterized by the symptoms experienced by the individuals but also by how they express personal experiences and concerns related to the clinical condition. Access to care programs for functional neurological symptoms appears challenging and may entail circular, self-perpetuating healthcare pathways. Given the challenging and misleading interpretations around FND, in advocating for care pathways beyond medical therapies, we designed a scoping review to map recently suggested practices and interventions. We identified 31 relevant papers published between January 2018 and December 2022. Most of the literature was gathered from the US and UK healthcare experiences, with documented interventions provided by multi-professional teams or stand-alone psychotherapists. We found different care pathways addressing either motor or non-motor manifestations. Persons with Functional Motor Disorder are more likely to be referred to physical therapy first, while Persons suffering from Non-Epileptic Seizures are to mental health services. A narrow focus was given to minor components of multimodal approaches (e.g. social workers, and occupational therapists). High heterogeneity was found between assessment instruments as well, reflecting different perspectives in selecting treatment outcomes (e.g., reduction of non-epileptic events, psychological functioning, motor symptoms). Among healthcare professionals, neurologists and (neuro)psychiatrists are typically engaged in formulating and delivering diagnoses, while treatment is often administered by physiotherapists and/or psychologists. In the context of FNDs, the complex etiopathological nature of the condition, including comorbidities, suggests the recommendation of multidisciplinary treatments adopting a stepped care model progressing from standard to higher level individualized modules may better suit individual complexities.

Olanzapine, risperidone and ziprasidone differently affect lysosomal function and autophagy, reflecting their different metabolic risk in patients.

The metabolic effects induced by antipsychotics in vitro depend on their action on the trafficking and biosynthesis of sterols and lipids. Previous research showed that antipsychotics with different adverse effects in patients cause similar alterations in vitro, suggesting the low clinical usefulness of cellular studies. Moreover, the inhibition of peripheral AMPK was suggested as potential aetiopathogenic mechanisms of olanzapine, and different effects on autophagy were reported for several antipsychotics. We thus assessed, in clinically-relevant culture conditions, the aetiopathogenic mechanisms of olanzapine, risperidone and ziprasidone, antipsychotics with respectively high, medium, low metabolic risk in patients, finding relevant differences among them. We highlighted that: olanzapine impairs lysosomal function affecting autophagy and autophagosome clearance, and increasing intracellular lipids and sterols; ziprasidone activates AMPK increasing the autophagic flux and reducing intracellular lipids; risperidone increases lipid accumulation, while it does not affect lysosomal function. These in vitro differences align with their different impact on patients. We also provided evidence that metformin add-on improved autophagy in olanzapine-treated cells and reduced lipid accumulation induced by both risperidone and olanzapine in an AMPK-dependent way; metformin also increased the production of bile acids to eliminate cholesterol accumulations caused by olanzapine. These results have different clinical implications. We demonstrated that antipsychotics with different metabolic impacts on patients actually have different mechanisms of action, thus supporting the possibility of a personalised antipsychotic treatment. Moreover, we found that metformin can fully revert the phenotype caused by risperidone but not the one caused by olanzapine, that still activates SREBP2.

Caregivers' burden and deep brain stimulation for Parkinson disease: A systematic review of qualitative studies.

BACKGROUND AND PURPOSE: The impact of subthalamic nucleus deep brain stimulation (STN-DBS) on caregivers' burden is understudied. We perform a systematic review and meta-synthesis aggregating qualitative studies involving partners of people with Parkinson disease (PwP) to explore their experiences and unmet needs. METHODS: A systematic review for retrieving qualitative studies included six databases: MEDLINE, Embase, CINAHL, Cochrane, PsycInfo, and Scopus. Inclusion criteria were as follows: (i) studies on the experience of caregivers of PwP in the context of STN-DBS, (ii) English peer-reviewed articles, and (iii) qualitative or mixed methods studies reporting caregivers' quotations. After the appraisal of included studies, we performed meta-synthesis of qualitative findings. Descriptive themes and conceptual elements related to PwP partners' experiences and unmet needs were generated. RESULTS: A total of 1108 articles were screened, and nine articles were included. Three categories were identified: (i) dealing with Parkinson disease (PD) every day (the starting situation characterized by the impact of PD on ordinary life; the limitations to partners' socialization; partners' efforts in stepping aside for love and care activities), (ii) facing life changes with STN-DBS (the feeling of being unprepared for changes; the fear and concern due to loved ones' behavioral changes; struggling to find an explanation for those changes), and (iii) rebuilding the role of caregiver and partner after STN-DBS. CONCLUSIONS: This meta-synthesis elucidates concerns, challenges, and unmet needs of partners of PwP who underwent STN-DBS. It is important to provide them with information, education, and adequate support to face these challenges. Professionals need to involve partners in the care and decision process, because STN-DBS-related outcomes do not depend solely on the well-being of PwP but also on the well-being of individuals surrounding them.

The Effect of Diet on Breast Cancer Recurrence: The DIANA-5 Randomized Trial.

PURPOSE: The DIANA-5 randomized controlled trial assessed the effectiveness of a diet based on Mediterranean and macrobiotic traditions (macro-Mediterranean diet) in reducing breast cancer recurrence. PATIENTS AND METHODS: The DIANA-5 study involved 1,542 patients with breast cancer at high risk of recurrence because of estrogen receptor-negative cancer, or metabolic syndrome, or high plasma levels of insulin or testosterone. Women were randomly assigned to an active dietary intervention (IG) or a control group (CG). Both groups received the 2007 American Institute for Cancer Research/World Cancer Research Fund recommendations for cancer prevention. The intervention consisted of meetings with kitchen classes, community meals, and dietary recommendations. Recommended foods included whole grain cereals, legumes, soy products, vegetables, fruit, nuts, olive oil, and fish. Foods to be avoided were refined products, potatoes, sugar and desserts, red and processed meat, dairy products, and alcoholic drinks. A compliance Dietary Index was defined by the difference between recommended and discouraged foods. RESULTS: Over the 5 years of follow-up, 95 patients of the IG and 98 of the CG developed breast cancer recurrence [HR = 0.99; 95% confidence interval (CI): 0.69-1.40]. The analysis by compliance to the dietary recommendations (IG and CG together) showed that the women in the upper tertile of Dietary Index change had an HR of recurrence of 0.59 (95% CI: 0.36-0.92) compared with women in the lower tertile. CONCLUSIONS: The DIANA-5 dietary intervention trial failed to show a reduction in breast cancer recurrence, although self-reported diet at year 1 in IG and CG combined showed a protective association with the higher Dietary Index change. See related commentary by McTiernan, p. 931.

A case of a childhood onset developmental encephalopathy with a novel de novo truncating variant in the Membrane Protein Palmitoylated 5 (MPP5) gene.

BACKGROUND: Membrane Protein Palmitoylated 5 (MPP5) is a highly conserved apical complex protein, essential for cell polarity. Defects in neuronal cell polarity are associated with neurologic disorders. Only three patients with heterozygous MPP5 de novo variants have been reported so far, with global developmental delay, behavioral changes and in only one case epileptic seizures. OBJECTIVE: To describe a new patient with a novel truncating de novo mutation in MPP5 and to characterize in detail the epileptic phenotype and electroencephalographic features of the encephalopathy. METHODS: We identified a novel truncating de novo mutation in MPP5 in a 44 year old patient by exome sequencing (p.Ser498Phefs*15). We retrospectively analyzed his clinical and instrumental data along a thirty-year follow up. RESULT: Our patient presents with generalized tonic-clonic seizures, myoclonic and clonic seizures, non-epileptic myoclonus, tremor, severe intellectual disability, mild face dysmorphic traits, and psychosis. DISCUSSION AND CONCLUSION: We present a case of a childhood onset developmental encephalopathy with a likely-pathogenic variant in the MPP5 gene.. This represents the first complete description of the epileptic syndrome associated with the MPP5 gene.

Hospice Patients' End-of-Life Dreams and Visions: A Systematic Review of Qualitative Studies.

When conscious, about 50% to 60% of hospice patients report a "visitation" by someone who is not there while they dream or are awake: a phenomenon known as End-of-Life Dreams and Visions (ELDVs). Since the dying process is frequently complicated by delirium, ELDVs risk being misidentified as such by professionals and caregivers. To observe these phenomena from patients' perspectives, we conducted a systematic review to aggregate and synthesize the findings from the qualitative studies about ELDVs of patients assisted in hospices to indicate future directions for research and care. MEDLINE/PubMed, Embase, CINAHL, PsycINFO, Scopus, and Web of Science databases were searched, yielding 293 documents after duplicates were removed. Six qualitative articles reporting on five unique studies conducted in hospice settings were included in the meta-synthesis. We generated three main categories: i) typologies of ELDVs reported, ii) emotional consequences, and iii) intersubjective meaning-making. The ELDVs reported were experiences that remained intimate and unsocialized and thus preventing participants from defining a shared sense in their relationships. Training healthcare professionals to recognize ELDVs and take advantage of them in the care relationship is desirable. We also encourage the patient's family members to listen and understand ELDVs when they occur actively. For caregivers to know how to interpret these phenomena may provide them with additional strategies for supporting, reassuring, and strengthening their relationships with their loved ones. The review allowed us to inform healthcare professionals and caregivers about how to help patients share their emotional and identity-related experiences and meaning-making in end-of-life.

The meaning of dignity in care during the COVID-19 pandemic: a qualitative study in acute and intensive care.

BACKGROUND: The pandemic Era has forced palliative care professionals to use a dignity-in-care approach in different settings from the classic ones of palliative care: acute and intensive care. We explored the meanings of dignity for patients, their family members, and clinicians who have experienced COVID-19 in the acute and intensive care setting. METHODS: A qualitative, prospective study by means of semi-structured interviews with patients hospitalized for COVID-19, family members, and clinicians who care for them. FINDINGS: Between March 2021 and October 2021, we interviewed 16 participants: five physicians, three nurses, and eight patients. None of the patients interviewed consented for family members to participate: they considered it important to protect them from bringing the painful memory back to the period of their hospitalization. Several concepts and themes arose from the interviews: humanity, reciprocity, connectedness, and relationship, as confirmed by the literature. Interestingly, both healthcare professionals and patients expressed the value of informing and being informed about clinical conditions and uncertainties to protect dignity. CONCLUSIONS: Dignity should be enhanced by all healthcare professionals, not only those in palliative care or end-of-life but also in emergency departments.

Recruitment strategies and interventions to increase participation in lung cancer screening programmes: a systematic review protocol.

INTRODUCTION: Despite strong evidence for the efficacy of low-radiation dose CT (LDCT) in reducing lung cancer (LC) mortality, implementing LC screening (LCS) programmes remains a challenge. We aim to systematically review the evidence on the strategies used to recruit the adult population at risk of LC to LDCT within LCS programmes and to estimate the effectiveness of interventions identified, used to reach the potentially eligible population, increase participation and informed choice, and ensure equitable access. METHODS AND ANALYSIS: This sequential systematic literature review will consist of three steps: (1) a scoping review of existing strategies and organisational models for LCS; (2) selecting papers reporting relevant outcomes (test coverage, screening participation and informed choice) and comparing results among different models; (3) a systematic review of interventions implemented to increase participation in LCS programmes. Each step will follow the methodological guidelines provided by the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Data sources include electronic databases such as Medline (PubMed version), Embase, CINAHL (Ebsco version), Scopus and Cochrane CENTRAL. The search will be limited to studies published from January 2000 to March 2023 in English, Italian, French, Spanish, Serbian and Croatian language. Findings will be synthesised quantitatively and qualitatively as appropriate. Risk of bias assessment will be only applied to studies selected in the second and third steps. The quality of evidence will be summarised for each outcome using the Grading Recommendation Assessment, Development and Evaluation methodology. ETHICS AND DISSEMINATION: Given that this is a review of existing literature, ethics approval is not required. The results will be published in peer-reviewed scientific journals and presented at relevant conferences. The findings of this review will help guide health authorities in organising LCS programmes and developing recommendations, policies, and actions at national and regional levels. PROSPERO REGISTRATION NUMBER: CRD42023408357.