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Liver transplantation (LT) from donors-with-HIV to recipients-with-HIV (HIV D+/R+) is permitted under the HOPE Act. There are only three international single-case reports of HIV D+/R+ LT, each with limited follow-up. We performed a prospective multicenter pilot study comparing HIV D+/R+ to donors-without-HIV to recipients-with-HIV (HIV D-/R+) LT. We quantified patient survival, graft survival, rejection, serious adverse events (SAEs), human immunodeficiency virus (HIV) breakthrough, infections, and malignancies, using Cox and negative binomial regression with inverse probability of treatment weighting. Between March 2016-July 2019, there were 45 LTs (8 simultaneous liver-kidney) at 9 centers: 24 HIV D+/R+, 21 HIV D-/R+ (10 D- were false-positive). The median follow-up time was 23 months. Median recipient CD4 was 287 cells/µL with 100% on antiretroviral therapy; 56% were hepatitis C virus (HCV)-seropositive, 13% HCV-viremic. Weighted 1-year survival was 83.3% versus 100.0% in D+ versus D- groups (p = .04). There were no differences in one-year graft survival (96.0% vs. 100.0%), rejection (10.8% vs. 18.2%), HIV breakthrough (8% vs. 10%), or SAEs (all p .05). HIV D+/R+ had more opportunistic infections, infectious hospitalizations, and cancer. In this multicenter pilot study of HIV D+/R+ LT, patient and graft survival were better than historical cohorts, however, a potential increase in infections and cancer merits further investigation.

Background The use of Renin-Angiotensin system inhibitors (RASi) in patients with coronavirus disease 2019 (COVID-19) has been questioned because both share a target receptor site. Methods HOPE-COVID-19 (NCT04334291) is an international investigator-initiated registry. Patients are eligible when discharged after an in-hospital stay with COVID-19, dead or alive. Here, we analyze the impact of previous and continued in-hospital treatment with RASi in all-cause mortality and the development of in-stay complications. Results We included 6503 patients, over 18 years, from Spain and Italy with data on their RASi status. Of those, 36.8% were receiving any RASi before admission. RASi patients were older, more frequently male, with more comorbidities and frailer. Their probability of death and ICU admission was higher. However, after adjustment, these differences disappeared. Regarding RASi in-hospital use, those who continued the treatment were younger, with balanced comorbidities but with less severe COVID19. Raw mortality and secondary events were less frequent in RASi. After adjustment, patients receiving RASi still presented significantly better outcomes, with less mortality, ICU admissions, respiratory insufficiency, need for mechanical ventilation or prone, sepsis, SIRS and renal failure (p

Many digital service providers have adopted gamification to promote customer engagement. Critical questions, however, remain about the most effective way to enhance customer engagement and increase sales by applying gamification. With a research design that combines qualitative and quantitative methods, including the use of objective sales data from a large field study and replication of the findings across different contexts, this study explores how gamification fosters customer engagement. Both field study results and a simulation study reveal gamification principles (i.e., social interaction, sense of control, goals, progress tracking, rewards, and prompts) that promote hope and consequently increase customer engagement and digital sales. Furthermore, we find that hope is more strongly associated with customer engagement than the psychological condition of compulsion, which even exerts a negative impact. This research thus explores how gamification creates value for customers and provides actionable insights for managers to foster hope through gamification as opposed to get customers hooked.

Purpose: This study investigated the effects of Mandala art therapy on subjective well-being, resilience, and hope among psychiatric inpatients. Methods: Recruited 36 people who had been treated as inpatients in a psychiatric ward at a university hospital in Seoul, South Korea, and divided them evenly into experimental and control groups. The experimental group was required to attend a total of 8 sessions of Mandala art therapy, twice per week, between August 11 and October 30, 2015; measures of the three main variables were administered at pre-test and post-test in both groups. Results: Hope significantly increased in both groups, but the overall increase was greater in the experimental group (mean score of 9.5 and 15.3 at pre- and post-test, respectively) than in the control group (10.9 and 11.9). Conclusion: These results suggest that Mandala art therapy can have a positive effect on the hope of psychiatric inpatients. However, further research concerning its effects on subjective well-being and resilience, as well as other psychological constructs, is warranted to better understand the effects of Mandala art therapy on psychiatric inpatients.

Context Supporting patients' spiritual needs is central to palliative care. Adolescents and young adults (AYAs) may be developing their spiritual identities; it is unclear how to navigate conversations concerning their spiritual needs. Objectives To 1) describe spiritual narratives among AYAs based on their self-identification as religious, spiritual, both, or neither and 2) identify language to support AYAs' spiritual needs in keeping with their self-identities. Methods In this mixed-methods, prospective, longitudinal cohort study, AYAs (14–25 years old) with newly diagnosed cancer self-reported their "religiousness" and "spirituality." One-on-one, semistructured interviews were conducted at three time points (within 60 days of diagnosis, six to 12 months, and 12–18 months later) and included queries about spirituality, God/prayer, meaning from illness, and evolving self-identity. Post hoc directed content analysis informed a framework for approaching religious/spiritual discussions. Results Seventeen AYAs (mean age 17.1 years, SD = 2.7, 47% male) participated in 44 interviews. Of n = 16 with concurrent survey responses, five (31%) self-identified as both "religious and spiritual," five (31%) as "spiritual, not religious," one (6%) as "religious, not spiritual," and five (31%) as neither. Those who endorsed religiousness tended to cite faith as a source of strength, whereas many who declined this self-identity explicitly questioned their preexisting beliefs. Regardless of self-identified "religiousness" or "spirituality," most participants endorsed quests for meaning, purpose, and/or legacy, and all included constructs of hope in their narratives. Conclusion AYA self-identities evolve during the illness experience. When words such as "religion" and "spirituality" do not fit, explicitly exploring hopes, worries, meaning, and changing life perspectives may be a promising alternative.

Hope can carry considerable allure for people facing imminent mortality and for those who care for them. Yet, how hope is variously and relationally (re)produced within end-of-life care settings, remains under-researched. In this study, we aimed to better understand hope as it circulates within palliative care, drawing on video recorded family meetings and pre- and post-meeting qualitative interviews, within two hospitals in Queensland, Australia. Our findings highlight family meetings as an important site for articulations of hope and hopefulness. The results illustrate how hope is recalibrated within the transition to and through palliative care, the tensions between hope and futility, and the work of hope in discussions of goals and expectations. Through our analysis we argue that hopefulness within family meetings, and in palliative care more broadly, is collectively produced and opens up discourses of hope to the lived experience of terminality. Attending to the nuances of hope, including moving beyond the determinative (hope for more life/hope for a quick death), can elucidate the possibilities and problems of the collective negotiation of hope at the end of life, including how hope can be drawn on to express support and solidarity.\ud \ud

Summary Emerging infectious diseases are an important public health threat and infections with pandemic potential are a major global risk. Although much has been learned from previous events the evidence for mitigating actions is not definitive and pandemic preparedness remains a political and scientific challenge. A need exists to develop trust and effective meaningful collaboration between countries to help with rapid detection of potential pandemic infections and initiate public health actions. This collaboration should be within the framework of the International Health Regulations. Collaboration between countries should be encouraged in a way that acknowledges the benefits that derive from sharing biological material and establishing equitable collaborative research partnerships. The focus of pandemic preparedness should include upstream prevention through better collaboration between human and animal health sciences to enhance capacity to identify potential pathogens before they become serious human threats, and to prevent their emergence where possible. The one-health approach provides a means to develop this and could potentially enhance alignment of global health and trade priorities.

Objective Genomics is increasingly used for diagnostic testing in children. This study describes the expectations of parents whose child received genomic testing and whether or not they were met. Methods A diverse stratified, purposive sample of parents of 22 children in New York City was interviewed using a semi-structured guide. Genomic test results were positive, negative, or uncertain. Results Parents expressed their expectations in narrative and numeric fashion. Parents expected that their child’s test would have a direct effect on their child’s diagnosis. Some believed that results would be definitive, while others recognized testing limitations. Expectations reflected parents’ hope to find a diagnosis and led to disappointment when results were uninformative or did not impact clinical management. Conclusion Results suggest pre-test genetic counseling emphasize the low likelihood of actionable results; however, parents’ expectations of genomics’ diagnostic capabilities are strongly rooted in their need to end the diagnostic odyssey and may be difficult to manage. Practice Implications Parents’ hope for a resolution and effective treatment for their child is a powerful context in which genetic counseling is heard. Clinicians who provide genomic testing should continue to acknowledge parents’ preconceptions. Additional research in other settings will help understand how to best address and manage parent expectations of genomic medicine.

This study investigates the antecedents and effects of hospitality students' coping mechanisms during the COVID-19 pandemic. The relationship between career adaptability, hope, resilience, and life satisfaction are explored to unveil students' adaptability during times of crisis. The findings confirmed that hope is an important driver of resilience and life satisfaction. Despite all the negativity and uncertainty about jobs and careers during the COVID-19 pandemic, resilience has a double acting effect on the students' life satisfaction via individual and community resilience. Critical implications for academic institutions and the hospitality industry are presented. As the industry recovers from the pandemic and moves toward normality, the potential impact of career adaptability, hope, resilience, and life satisfaction on future job pursuit and career magnetism towards particular industry or organizations should be considered.

For decades, patients with sickle cell disease have had only a limited number of therapies available. In 2019, voxelotor (1500 mg), an oral once-daily sickle haemoglobin polymerisation inhibitor, was approved in the USA for the treatment of sickle cell disease in patients aged 12 years and older on the basis of HOPE trial data. To further describe the applicability of voxelotor as a treatment for this chronic illness, we report the long-term efficacy and safety of this drug at 72 weeks of treatment; the conclusion of the placebo-controlled HOPE trial.HOPE is an international, randomised, double-blind, placebo-controlled, phase 3 trial done at 60 clinical sites in Canada, Egypt, France, Italy, Jamaica, Kenya, Lebanon, Netherlands, Oman, Turkey, the USA, and the UK. Patients (aged 12-65 years) with confirmed sickle cell disease, a haemoglobin concentration of 5·5-10·5 g/dL at enrolment, and who had between one and ten vaso-occlusive crisis events in the previous 12 months were enrolled. Patients receiving regularly scheduled transfusion therapy, who had received a transfusion in the previous 60 days, or who had been admitted to hospital for a vaso-occlusive crisis in the previous 14 days were excluded. Patients were randomly assigned (1:1:1) to receive either once-daily oral voxelotor 1500 mg, voxelotor 900 mg, or placebo for 72 weeks. Randomisation was done centrally by use of an interactive web response system, stratified by baseline hydroxyurea use (yes vs no), age group (adolescents [12 to18 years] vs adults [18 to 65 years]), and geographic region (North America vs Europe vs other). The primary endpoint (already reported) was the proportion of patients who achieved a haemoglobin response at week 24. In this final analysis, we report prespecified long-term efficacy assessments by intention to treat, including changes in haemoglobin concentrations from baseline to week 72, changes in the concentration of haemolysis markers (absolute and percentage reticulocytes, indirect bilirubin concentrations, and lactate dehydrogenase concentrations) from baseline to week 72, the annualised incidence of vaso-occlusive crises, and patient functioning, as assessed with the Clinical Global Impression of Change (CGI-C) scale. Safety was assessed in patients who received at least one dose of treatment (modified intention-to-treat population). This trial is registered with ClinicalTrials.gov, NCT03036813.Between Dec 5, 2016, and May 3, 2018, 449 patients were screened, of whom 274 were randomly assigned to the voxelotor 1500 mg group (n=90), the voxelotor 900 mg group (n=92), or the placebo group (n=92). At week 72, the adjusted mean change in haemoglobin concentration from baseline was 1·0 g/dL (95% CI 0·7 to -1·3) in the voxelotor 1500 mg group, 0·5 g/dL (0·3 to -0·8) in the voxelotor 900 mg group, and 0·0 g/dL (-0·3 to 0·3) in the placebo group, with a significant difference observed between the voxelotor 1500 mg group and the placebo group (p0·0001), and between the voxelotor 900 mg group and the placebo group (p=0·014). Significant improvements in markers of haemolysis, as assessed by the difference in adjusted mean percentage change from baseline at week 72 versus placebo, were observed in the voxelotor 1500 mg group in indirect bilirubin concentrations (-26·6% [95% CI -40·2 to -12·9]) and percentage of reticulocytes (-18·6% [-33·9 to -3·3]). The proportion of patients in the voxelotor 1500 mg group who were rated as "moderately improved" or "very much improved" at week 72 with the CGI-C was significantly greater than in the placebo group (39 [74%] of 53 vs 24 [47%] of 51; p=0·0057). Serious adverse events unrelated to sickle cell disease were reported in 25 (28%) of 88 patients in the voxelotor 1500 mg group, 20 (22%) of 92 patients in the voxelotor 900 mg group, and 23 (25%) of 91 patients in the placebo group. Grade 3 or 4 adverse events were infrequent (ie, occurred in10% of patients); anaemia occurred in five or more patients (two [2%] patients in the voxelotor 1500 mg group, seven [8%] patients in the voxelotor 900 mg group, and three [3%] patients in the placebo group). Of all 274 patients, six (2%) deaths occurred during the study (two deaths in each treatment group), all of which were judged as unrelated to treatment.Voxelotor 1500 mg resulted in rapid and durable improvements in haemoglobin concentrations maintained over 72 weeks and has potential to address the substantial morbidity associated with haemolytic anaemia in sickle cell disease.Global Blood Therapeutics.

Although recent scientific studies suggest that artificial intelligence (AI) could provide value in many radiology applications, much of the hard engineering work required to consistently realize this value in practice remains to be done. In this article, we summarize the various ways in which AI can benefit radiology practice, identify key challenges that must be overcome for those benefits to be delivered, and discuss promising avenues by which these challenges can be addressed.

Minibus taxi public transport is a seemingly chaotic phenomenon in the developing cities of the Global South with unique mobility and operational characteristics. Eventually this ubiquitous fleet of minibus taxis is expected to transition to electric vehicles, which will result in an additional energy burden on Africa's already fragile electrical grids. This paper examines the electrical energy demands of this possible evolution, and presents a generic simulation environment to assess the grid impact and charging opportunities. We used GPS tracking and spatio-temporal data to assess the energy requirements of nine electric minibus taxis as well as the informal and formal stops at which the taxis can recharge. Given the region's abundant sunshine, we modelled a grid-connected solar photovoltaic charging system to determine how effectively PV may be used to offset the additional burden on the electrical grid. The mean energy demand of the taxis was 213kWh/d, resulting in an average efficiency of 0.93kWh/km. The stopping time across taxis, a proxy for charging opportunity, ranged from 7.7 h/d to 10.6 h/d. The energy supplied per surface area of PV to offset the charging load of a taxi while stopping, ranged from 0.38 to 0.90kWh/m2 per day. Our simulator, which is publicly available, and the results will allow traffic planners and grid operators to assess and plan for looming electric vehicle roll-outs.

Rural communities in the inland areas of Northern Sweden have long suffered from a steady population decline as young people, particularly women, have moved to the growing urban areas for education/employment. However, in recent years, alongside strategies for survival relating to tourism/hospitality industry, refugee reception has emerged as a strategy for survival whereby these rural municipalities seek to staunch the downward spiral of decline by accepting refugees in the hope that this will provide not only job opportunities but also support for local services. Using thematic analysis, we focus on media representations of rural refugee reception in small municipalities Northern Sweden and aim to contribute to an understanding of how spatial and social relations are reproduced through these representations; to understand in how ‘the rural’ is constructed in relation to power relations such as race and gender and how these interact with a more explicit spatial power dimension. We are interested in understanding rural refugee reception as a contested hope for the future – a strategy for survival. Our analysis shows that the media highlight the stories of how the municipalities set their hopes on refugee reception to ‘save’ the place not only by bringing in new, younger inhabitants, but also employment opportunities. However, it also shows that refugee reception may become merely a short-term, temporary solution and not something that challenges or changes the more general migratory patterns in Sweden.

This 2020 Presidential Address was given at the American Pediatric Surgical Association 2021 Virtual Annual Meeting, May 20–22, 2021.

BACKGROUND: Chromosome 15q11-q13 duplication syndrome (Dup15q) is a neurogenetic disorder caused by duplications of the maternal copy of this region. In addition to hypotonia, motor deficits, and language impairments, Dup15q patients commonly meet the criteria for autism spectrum disorder (ASD) and have a high prevalence of seizures. It is known from mouse models that synaptic impairments are a strong component of Dup15q pathophysiology, however, cellular phenotypes that relate to seizures are less clear. The development of patient-derived induced pluripotent stem cells (iPSCs) provides a unique opportunity to study human neurons with the exact genetic disruptions that cause Dup15q. METHODS: Here, we explored electrophysiological phenotypes in iPSC-derived neurons from four Dup15q patients compared to six unaffected controls, one patient with a 15q11-q13 paternal duplication, and three Angelman syndrome patients. RESULTS: We identified several properties of Dup15q neurons that could contribute to neuronal hyperexcitability and seizure susceptibility. Compared to controls, Dup15q neurons had increased excitatory synaptic event frequency and amplitude and increased density of dendritic protrusions, along with increased action potential firing and decreased inhibitory synaptic transmission. Dup15q neurons also showed impairments in activity-dependent synaptic plasticity and homeostatic synaptic scaling. Finally, Dup15q neurons showed an increased frequency of spontaneous action potential firing compared to control neurons, in part due to disruption of KCNQ2 potassium channels. CONCLUSIONS: Together these data point to multiple electrophysiological mechanisms of hyperexcitability that may provide new targets for the treatment of seizures and other phenotypes associated with Dup15q.

This research explored the impact of self-threat on two types of hope, distinguished by regulatory focus: prevention hope versus promotion hope. Two experimental studies were conducted. The results of Study 1 indicated that individuals are more likely to focus on prevention hope when their self-view is threatened. Additionally, the findings in Study 1 were extended in the next experiment using an advertising context. Study 2 revealed that prevention hope-focused advertising messages were more persuasive (namely, advertising trust and the attitude toward both advertising and the brand) and inspired consumers' behavioral intention (or purchase intention) more than promotion hope-focused advertising messages when self-threat occurred. The implications of the study's findings and suggestions for future research are also discussed.

As the world faces the current SARS-CoV-2 pandemic, extensive efforts have been applied to identify effective therapeutic agents. Convalescent plasma collected from recovered patients has been a therapeutic modality employed for over a hundred years for various infectious pathogens. Specifically, it has been used in the treatment of many viral infections with varying degrees of clinical efficacy. As we consider the use of convalescent plasma in the battle against this new strain of coronavirus, it is prudent to review what is known from past experiences. Accordingly, the aim of this review is to examine in detail studies of convalescent plasma used during previous viral outbreaks and pandemics with particular focus on hemorrhagic fevers, influenza, and other coronaviruses. The concluding sections of this review address the potential use of convalescent plasma during the present-day SARS-CoV-2 pandemic, not only insofar as its clinical benefit but also the steps required to make convalescent plasma treatments readily available for an exponentially growing patient population. By the end, the authors hope to address the extent to which convalescent plasma represents a realistic therapeutic approach, or a distraction from other potentially useful treatments.

This article reviews the hope level of chronic non-malignant diseases patients and its influencing factors. We also introduced to the concept of hope level, related theory of hope, measuring tools and the basic strategy of improving the hope level of chronic non-malignant diseases patients. We proposed that we should better understand and apply the theory of hope to make targeted nursing intervention measures for different patients.

BACKGROUND Data are lacking on the relationship between hope and other variables in non-advanced cancer patients. The study explored the relationship between hope, symptoms, needs, and spirituality/religiosity in patients treated in a supportive care unit (SCU). PATIENTS AND METHODS From September 2013 to March 2014, the consecutive patients who accepted to complete: (i) Needs Evaluation Questionnaire (NEQ), (ii) the Edmonton Symptom Assessment System (ESAS), (iii) Hope Herth Index (HHI), and (iv) the System of Belief Inventory (SBI) were enrolled. Moreover, clinical/demographic data were collected and the findings were analyzed. RESULTS A total of 276 patients who completed the HHI questionnaire (participation rate 276/300 = 92%) were included; 131 reported HHI total score >37 (median value). The majority of patients had a Karnofsky performance status >80; 71% were on cancer therapies, and only 29 patients had metastases or relapse. Patients with higher HHI scores were less educated (P = 0.012), reported lower ESAS total score (15.4 versus 22.6, P < 0.001), and had less often been referred to a psychologist previously to the study (P = 0.002); patients with a higher HHI score also reported higher spirituality (P < 0.001). Some NEQ items resulted significantly associated with HHI score after adjustment for other variables: the need to have sincere clinicians (β = -2.7), better dialogue (β = -2.1), and more reassurance from the clinicians (β = -2.5); better attention (β = -4.4) and respect for intimacy (β = -3.3) from nurses; to speak with people who have the same illness experience (β = -2.5), to be more reassured by relatives (β = -3.3) and to feel less abandoned (β = -4.3). Higher SBI scores were independently associated with higher HHI scores (β = 1.7 for 10 points increase). CONCLUSIONS In cancer patients, hope can be encouraged by clinicians through dialogue, sincerity, and reassurance, as well as assessing and considering the patients' needs (above all the psycho-emotional), symptoms, psychological frailty, and their spiritual/religious resources.

Therapeutic drug monitoring (TDM) plays a vital role in implementing precision medicine in inflammatory bowel disease (IBD), and may contribute to increased effectiveness, lower rates of drug toxicity and cost savings. While expert panels advocate the use of reactive TDM for anti-tumor necrosis factor (anti-TNF) agents, TDM is not yet widely recommended for non-anti TNF biologicals. We provide an overview of the observational evidence of the value of TDM in case of vedolizumab and ustekinumab. We also shed light on obstacles that need to be addressed before establishing wide acceptance of TDM in the field of IBD. In this respect, new analytical techniques and modelling approaches are being developed to further optimize efficacy of TDM and to facilitate general acceptance of this tool in personalizing IBD management.

Are the candidate vaccines in late-stage human trials really everything the world has been waiting for, asks Graham Lawton

Acute myocardial infarction (MI) is a major cause of death worldwide. Although timely and successful reperfusion could reduce myocardial ischemia injury, limit infarct size, and improve ventricular dysfunction and reduce acute mortality, restoring blood flow might also lead to unwanted myocardial ischemic-reperfusion (I/R) injury. Pre-clinical studies have demonstrated that multiple approaches are capable of attenuating the myocardial I/R injury. However, there is still no effective therapy for preventing myocardial I/R injury for the clinical setting. It is known that myocardial I/R injury could induce cardiac autonomic imbalance with over-activated sympathetic tone and reduced vagal activity, in turn, contributing to pathogenesis of myocardial I/R injury. Cumulative evidence shows that the enhancement of vagal activity, so called vagus nerve stimulation (VNS), is able to reduce injury and promote recovery of injured myocardium. Therefore, VNS might be a potentially novel strategy choice for preventing/attenuating myocardial I/R injury. In this review, we describe the protective role of VNS in myocardial I/R injury and related potential mechanisms. Then, we discuss the challenge and the opportunity of VNS in the treatment of acute myocardial I/R injury.

Post-myocardial infarction ventricular septal defect (VSD) is a life-threatening complication following ST Elevation myocardial infarction (STEMI). Current guidelines recommend the urgent VSD closure for his significant mortality. Despite VSD has been generally treated by surgical repair, often surgeons refrain from early surgery due to extremely poor results. We report the case of a 76-year-old female admitted to our hospital for a subacute myocardial infarction complicated by acute heart failure with VSD and apical thrombosis. The patient has undergone an urgent surgical repair of VSD with a bovine pericardium patch and concomitant double saphenous vein graft for the left anterior descending and the first diagonal branch. After two days a rescue percutaneous closure of a new shunt formation due to an early surgical patch dehiscence was necessary. Considering the particular morphology of the new shunt following the unnatural anatomy of the septum generating by dehiscence, we have planned to close the defect using a device undedicated for ventricular rupture, as 30/30 mm Amplatzer ASD-MF occluder, obtaining an optimal final result. At one-year follow up the patient was alive, with a NYHA class II-III without significant residual shunt.

Highlights • Radiomics studies in NSCLC suffer from a number of limitations. • No single radiomic signature has been translated into clinical use. • Identification of limitations can help future studies to expedite biomarker translation., Radiomics has become a popular image analysis method in the last few years. Its key hypothesis is that medical images harbor biological, prognostic and predictive information that is not revealed upon visual inspection. In contrast to previous work with a priori defined imaging biomarkers, radiomics instead calculates image features at scale and uses statistical methods to identify those most strongly associated to outcome. This builds on years of research into computer aided diagnosis and pattern recognition. While the potential of radiomics to aid personalized medicine is widely recognized, several technical limitations exist which hinder biomarker translation. Aspects of the radiomic workflow lack repeatability or reproducibility under particular circumstances, which is a key requirement for the translation of imaging biomarkers into clinical practice. One of the most commonly studied uses of radiomics is for personalized medicine applications in Non-Small Cell Lung Cancer (NSCLC). In this review, we summarize reported methodological limitations in CT based radiomic analyses together with suggested solutions. We then evaluate the current NSCLC radiomics literature to assess the risk associated with accepting the published conclusions with respect to these limitations. We review different complementary scoring systems and initiatives that can be used to critically appraise data from radiomics studies. Wider awareness should improve the quality of ongoing and future radiomics studies and advance their potential as clinically relevant biomarkers for personalized medicine in patients with NSCLC.

Allocation of statin therapy for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) in borderline- and intermediate-risk patients has traditionally been based on population-based global risk assessment and other clinical and laboratory characteristics. Patient-specific treatment decisions are needed to provide maximal benefit and avoid unnecessary treatment. Guideline-based lipid management proposes that coronary artery calcium scoring is reasonable to implement in patients with a 10-year risk of 5.0% to 19.9% (borderline to intermediate risk) by using the pooled cohort equations when the decision about whether to initiate statin therapy is uncertain. We report data from both observational studies and a large primary prevention randomized controlled trial that support the position that this decision is, in fact, uncertain in about half of such patients because of risk misclassification. Such misclassification can be largely avoided by more widespread implementation of coronary calcium scoring, which helps to identify those with coronary artery calcium scores of 0, a finding associated with a less than 5.0% 10-year probability of an ASCVD event. Deferral of statin therapy in such patients, in the absence of smoking, diabetes, or a family history of premature ASCVD, provides more individualized and appropriate care and avoids the expense and potential adverse effects of statin therapy in those with low potential for absolute risk reduction. A rationale is also provided for the importance of coronary artery calcium scoring in women 50 years and older, possibly in place of 1 screening mammogram in women at least 55 years of age to avoid incremental radiation exposure, on the basis of the substantially higher lifetime risk of morbidity and mortality from ASCVD than from breast cancer. In patients with borderline or intermediate ASCVD risk, coronary artery calcium scoring should be used, whenever possible, as an aid to rational statin allocation for the primary prevention of ASCVD.

Joint Bone Spine - In Press.Proof corrected by the author Available online since dimanche 22 decembre 2019

Radiation therapy benefits the majority of patients across the spectrum of cancer types. However, both local and distant tumor recurrences limit its clinical success. While departing from the established tenet of fractionation in clinical radiotherapy, ablative-intensity hypo-fractionated radiotherapy, especially stereotactic radiosurgery (SRS) and stereotactic ablative radiotherapy (SABR), has emerged as an alternative paradigm achieving unprecedented rates of local tumor control. Direct tumor cell killing has been assumed to be the primary therapeutic mode of action of such ablative radiation. But with increasing recognition that tumor responses also depend on the immunostimulatory or immunosuppressive status of the tumor microenvironment, the immunologic effect of ablative radiotherapy is emerging as a key contributor to anti-tumor response. More recently, novel radiation modalities, such as spatially fractionated radiotherapy (SFRT) and ultra-high dose rate FLASH irradiation, that venture even further from conventional paradigms have shown promise of increasing the therapeutic index of radiation therapy with the potential of immunomodulation. Here, we review the immunomodulatory impact of novel radiation therapy paradigms, heretofore considered radiobiological heresies, a deeper understanding of which is imperative to realizing fully their potential for more curative cancer therapy.

Acute basilar artery occlusion (BAO) is associated with major morbidities and a high mortality rate. The prevalence of acute BAO is 10.4% among patients treated with thrombectomy for acute large vessel occlusion. Vertebral artery stump syndrome (VASS) reportedly causes ischemic stroke with tandem occlusions as vertebral artery (VA) origin occlusion and BAO. The pathogenesis of ischemic stroke due to VASS can be attributed to thrombi or emboli. Acute embolic BAO due to VASS accounted for 2 of 25 cases (8.0%) of BAO treated using thrombectomy between April 2014 and May 2019 in our registry. VASS must be considered as one cause of BAO. With the initial Magnetic resonance angiography on arrival, it is difficult to distinguish between BAO due to simple cardiogenic embolus and due to embolus caused by VASS rapidly. In patients suffering from acute embolic BAO due to VASS, the presence of VA origin occlusion makes endovascular therapy (EVT) difficult to perform. Here, we report consecutive cases of thrombectomy for acute embolic BAO due to VASS, showing markedly different outcomes. VA origin occlusion severely limits the technical options for EVT. Visualization or conjecture of the origin of both or dominant VAs conceivably offers the possibility of successful EVT and may allow good outcomes.

How can surgeons deliver compassionate, holistic care to patients who are beyond cure? Interacting emotionally and understanding hope, fear, and spiritual suffering is key. Responsibly reframing hope to underlying meanings, and away from specific outcomes, is critical. Facilitating moves from cure to comfort to a peaceful dying process requires some retooling of the surgical toolbox. Surgeons possess a unique set of skills, including imagination and an undying sense of hope. Surgeons who have the courage to delve into their emotions and sustain realistic hope for their patients, all the way to the end, will reap deep personal and professional rewards.

AIMS The HOPE score, based on covariates available at hospital admission, predicts the probability of in-hospital survival after extracorporeal life support (ECLS) rewarming of a given hypothermic cardiac arrest patient with accidental hypothermia. Our goal was to externally validate the HOPE score. METHODS We included consecutive hypothermic arrested patients who underwent rewarming with ECLS. The sample comprised 122 patients. The six independent predictors of survival included in the HOPE score were collected for each patient: age, sex, mechanism of hypothermia, core temperature at admission, serum potassium level at admission and duration of CPR. The primary outcome parameter was survival to hospital discharge. RESULTS Overall, 51 of the 122 included patients survived, resulting in an empirical (global) probability of survival of 42% (95% CI = [33-51%]). This was close to the average HOPE survival probability of 38% calculated for patients from the validation cohort, while the Hosmer-Lemeshow test comparing empirical and HOPE (i.e. estimated) probabilities of survival was not significant (p = 0.08), suggesting good calibration. The corresponding area under the receiver operating characteristic curve was 0.825 (95% CI = [0.753-0.897]), confirming the excellent discrimination of the model. The negative predictive value of a HOPE score cut-off of

In this article, I discuss the significance of understanding within the context of the campaign for affordable and accessible HIV/AIDS treatments in South Africa, the transformational effects of the interplay between political rationality and affect for HIV-positive subjectivities. The article focuses on the policy tactics, in 2001, of the lobbying for a policy to prevent mother-to-child-transmission of HIV. A close reading of the lobby groups' rationalization of healthcare as a fundamental human right reveals a strategic attempt to recast a sense of helplessness into self-responsibilization, which concurrently involved nourishing hope in the preferred future for women with HIV to be afforded the right to individual choice associated with self-determination. Therefore, the struggle for a policy to prevent mother-to-child-transmission of HIV - an exemplary initiative to reconstitute HIV-positive subjectivity - maneuvered within both rationalizing and emotive spaces. Ongoing engagement of the broader campaign's contribution to redefining being HIV-positive thus also necessitates accounting for the effects of the convergence of political rationality and emotion in its tactically emancipatory project.

Hypertension is the leading cause of cardiovascular disease globally. Despite proven benefits, hypertension control is poor. We hypothesised that a comprehensive approach to lowering blood pressure and other risk factors, informed by detailed analysis of local barriers, would be superior to usual care in individuals with poorly controlled or newly diagnosed hypertension. We tested whether a model of care involving non-physician health workers (NPHWs), primary care physicians, family, and the provision of effective medications, could substantially reduce cardiovascular disease risk.HOPE 4 was an open, community-based, cluster-randomised controlled trial involving 1371 individuals with new or poorly controlled hypertension from 30 communities (defined as townships) in Colombia and Malaysia. 16 communities were randomly assigned to control (usual care, n=727), and 14 (n=644) to the intervention. After community screening, the intervention included treatment of cardiovascular disease risk factors by NPHWs using tablet computer-based simplified management algorithms and counselling programmes; free antihypertensive and statin medications recommended by NPHWs but supervised by physicians; and support from a family member or friend (treatment supporter) to improve adherence to medications and healthy behaviours. The primary outcome was the change in Framingham Risk Score 10-year cardiovascular disease risk estimate at 12 months between intervention and control participants. The HOPE 4 trial is registered at ClinicalTrials.gov, NCT01826019.All communities completed 12-month follow-up (data on 97% of living participants, n=1299). The reduction in Framingham Risk Score for 10-year cardiovascular disease risk was -6·40% (95% CI 8·00 to -4·80) in the control group and -11·17% (-12·88 to -9·47) in the intervention group, with a difference of change of -4·78% (95% CI -7·11 to -2·44, p0·0001). There was an absolute 11·45 mm Hg (95% CI -14·94 to -7·97) greater reduction in systolic blood pressure, and a 0·41 mmol/L (95% CI -0·60 to -0·23) reduction in LDL with the intervention group (both p0·0001). Change in blood pressure control status (140 mm Hg) was 69% in the intervention group versus 30% in the control group (p0·0001). There were no safety concerns with the intervention.A comprehensive model of care led by NPHWs, involving primary care physicians and family that was informed by local context, substantially improved blood pressure control and cardiovascular disease risk. This strategy is effective, pragmatic, and has the potential to substantially reduce cardiovascular disease compared with current strategies that are typically physician based.Canadian Institutes of Health Research; Grand Challenges Canada; Ontario SPOR Support Unit and the Ontario Ministry of Health and Long-Term Care; Boehringer Ingelheim; Department of Management of Non-Communicable Diseases, WHO; and Population Health Research Institute. VIDEO ABSTRACT.

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Introduction Although renal replacement therapy can lead to improved health, it also can cause emotional disturbances in patients. It is believed that the success of renal replacement therapy hinges not only on medical parameters, but also on psychosocial factors, which is why modern medicine provides an ever-increasing role in the improvement of patients' quality of life. Purpose The purpose of this study was to compare the level of life satisfaction, purpose in life, and basic hope in patients who had received renal replacement due to chronic kidney disease. We also tested whether the specific type of renal replacement therapy and kidney function parameters were influential factors on the above variables. Patients and methods Sixty-one adult patients treated via renal replacement for chronic kidney disease took part in the study. Patients were divided into two groups: 31 hemodialysis patients (15 women and 16 men, ages 23–77 years, mean 51.19 years, SD 14.53 years) and 30 patients who had undergone kidney transplantation (14 women and 16 men, ages 22–69 years, mean 48.40 years, SD 12.64 years). The following research tools were used for analysis: Satisfaction With Life Scale (SWLS), Purpose in Life Test (PIL), and Basic Hope Inventory (BHI-12). Results There were no statistical differences in the level of satisfaction with life between hemodialysis patients and postkidney transplant patients. The results for the SWLS obtained from both groups fell within the normal range. The average SWLS for hemodialysis patients remained 20.61, SD = 5.79; for postkidney transplant patients, it was 22.57, SD = 5.16. The PIL level in the group of hemodialysis patients (101.5, SD = 15.64) was significantly lower than in the group of postkidney transplant patients (109.7, SD = 15.54). The average BHI-12 level was similar in both groups. The average BHI-12 result for hemodialysis patients was 29.00 (SD = 5.06), and for postkidney transplant patients 29.93 (SD = 3.55). The correlations between the psychological variables and selected biochemical parameters are worthy of particular attention. Among hemodialysis patients, there was an additional correlation between SWLS and hematocrit; whereas for postkidney transplant patients, there was an additional correlation of PIL and eGFR. Conclusions Our data show that satisfaction with life and basic hope do not increase in patients after renal replacement therapy. The form of renal replacement therapy (hemodialysis or kidney transplantation) does not change the above variables. Patients treated via renal replacement require specialized psychological support to improve the efficacy of renal replacement therapy.

Objective threatened miscarriage is a common complication of early pregnancy, which increases the risk of miscarriage or pregnancy complications such as premature birth. Currently there is limited evidence to recommend beneficial medical treatments or lifestyle changes, resulting in a ‘watchful waiting' approach. The aim of this study was to describe women's experiences of threatened miscarriage through examining postings to Internet discussion forums. Design a Goggle alert for threatened miscarriage was created with emails containing hyperlinks sent to the first author and collected over a seven month period (April to November 2011). Data was analysed using thematic analysis. Findings one hundred and twenty one discussion threads were collected. The overarching theme that emerged was one of ‘a search for hope and understanding'. Within this there were four sub themes that illustrated this search. ‘A reason for hope: stories and real life experiences' illustrated how women sought hope for a viable pregnancy through others. ‘Becoming the expert,' captures how women gave advice from their own experiences. ‘A safe place to share' and ‘connecting to empathic support' illustrates how women used this medium for long distance support. Key conclusion internet discussion forums were used by women to seek hope and support they were not receiving from their health professionals. Women urged each other to remain hopeful despite a negative medical prognosis. There was an acceptance of a lay expertise within the forums that was valid enough to challenge medical expertise. Implications for practice health practitioners may need education that helps them balance their delivery of medical information with hope in order to increase feelings of trust. With women seeing the Internet as a useful form of support, it may be relevant for practitioners to consider recommending relevant Internet sites and discuss this with women.