Clinical Care Research Articles

Data set for the reporting of lung cancer: recommendations from the International Collaboration on Cancer Reporting (ICCR).

Lung cancer is the leading cause of cancer related deaths worldwide, although some patients with early-stage disease can be cured with surgical resection. Standardised reporting of all clinically relevant pathological parameters is essential for best patient care and is also important for ongoing data collection and refinement of important pathological features that impact patient prognosis, staging and clinical care. Using the established International Collaboration on Cancer Reporting (ICCR) procedure, a representative international expert panel of nine lung pathologists as well as an oncologist was convened. Essential core elements and suggested non-core elements were identified for inclusion in the resected lung cancer pathology data set based on predetermined levels of evidence as well as consensus expert opinion. A lung cancer histopathology reporting guide was developed that includes relevant clinical, macroscopic, microscopic and ancillary testing. Critical review and discussion of current evidence was incorporated into the new data set including changes from the 2021 World Health Organisation (WHO) Classification of Thoracic Tumours, fifth edition, new requirements for grading invasive non-mucinous adenocarcinomas, assessment of response to neoadjuvant therapy and requirements for molecular testing in early-stage resected lung carcinomas. This ICCR data set represents incorporation of all relevant parameters for histology reporting of lung cancer resection specimens. Routine use of this data set is recommended for all pathology reporting of resected lung cancer and it is freely available worldwide on the ICCR website (https://www.iccr-cancer.org/datasets/published-datasets/). Widespread implementation will help to ensure consistent and comprehensive pathology reporting and data collection essential for lung cancer patient care, clinical trials and other research.

Caregiver Experiences, Healthcare Provider Perspectives and Child Outcomes with Virtual Care in a Neonatal Neurodevelopmental Follow-Up Clinic: A Mixed-Methods Study

Background: Caregiver and healthcare provider perspectives of virtual care have not been explored in depth in the literature for neonatal follow-up clinics. Our objective was to evaluate caregivers’ and healthcare providers’ perspectives and compare neurodevelopmental outcomes of preterm neonates before and after implementing virtual care during the SARS-CoV-2 pandemic. Methods: Semi-structured interviews were conducted with families and healthcare providers, designed and analyzed using phenomenological qualitative methods. A retrospective cohort study was conducted to evaluate and compare neurodevelopmental characteristics of two preterm cohorts, one before (“in-person”) and after (“virtual”) virtual care. Results: Three themes were identified: increased confidence in in-person assessments, adequate delivery of information using virtual platforms and a preference for specialized care through the neonatal follow-up clinic. A total of 252 infants born preterm, 104 infants in the in-person group and 148 infants in the virtual group, were included in the study. The adjusted odds ratio (aOR) of cerebral palsy was lower when virtual care was used compared to in-person assessments (aOR = 0.11, 95% CI 0.01–0.98) while the adjusted odds of cognitive delay measured by in-person standardized testing were higher (aOR = 2.78, 95% CI 1.25–6.19). Conclusions: Caregivers and healthcare providers prefer in-person assessments for comprehensive developmental support. It may be more challenging to detect subtle cognitive differences using caregiver-reported measures. Cerebral palsy may be missed when assessments are completed virtually.

Changing Landscape of Randomized Clinical Trials in Stroke: Explaining Contemporary Trial Designs and Methods.

Evidence generated from randomized clinical trials (RCTs) plays an indispensable role in advancing clinical stroke care. Although the number of stroke-related RCTs published every year has grown exponentially over the past 25 years, the execution and completion of RCTs, particularly those conducted in a hyperacute setting, have grown more complicated and challenging over the years. In addition to the practical challenges associated with conducting a clinical trial, like obtaining human subjects approval, identifying clinical sites, training trial personnel, and enrolling the target number of patients within the available funding and timeline, the complexity of contemporary RCT designs and analyses has become much more exacting. It is no longer sufficient to have a decent understanding of the 2-arm, placebo-controlled RCT, combined with a rudimentary grasp of the P value; things are now much more complicated. Innovations in trial design and analysis, including adaptive, Bayesian, platform, and noninferiority designs, have occurred to address the problems of poor trial efficiency. However, these advances require the end user to have a much greater level of understanding regarding the rationale, conduct, analysis, and interpretation of each design. While these newer designs seek greater efficiency, there are inevitably tradeoffs that need to be understood. In this month's edition of Stroke, we introduce a new series designed to help fill in these knowledge gaps. Over the next few months, 4 papers will be published that address major design innovations (adaptive, Bayesian, platform, and noninferiority) with the aim of illustrating how these approaches can make trials more efficient (where efficiency is defined as getting to the right answer, sooner, with a potentially lower sample size). In addition to introducing this series, this current article also reviews traditional hypothesis testing and the common misinterpretations of the P value; fortunately, new philosophical schools of inference are beginning to vanquish the overreliance on the P value. We are excited about the opportunity to educate the Stroke readership about these new trial designs and the profound implications that they bring.

Contribution of an Artificial Intelligence Tool in the Detection of Incidental Pulmonary Embolism on Oncology Assessment Scans

Introduction: The incidence of venous thromboembolism is estimated to be around 3% of cancer patients. However, a majority of incidental pulmonary embolism (iPE) can be overlooked by radiologists in asymptomatic patients, performing CT scans for disease surveillance, which may significantly impact the patient’s health and management. Routine imaging in oncology is usually reviewed with delayed hours after the acquisition of images. Nevertheless, the advent of AI in radiology could reduce the risk of the diagnostic delay of iPE by an optimal triage immediately at the acquisition console. This study aimed to determine the accuracy rate of an AI algorithm (CINA-iPE) in detecting iPE and the duration until the management of cancer patients in our center, in addition to describing the characteristics of patients with a confirmed pulmonary embolism (PE). Materials and Methods: This is a retrospective analysis of the role of Avicenna’s CE-certified and FDA-cleared CINA-iPE algorithm in oncology patients treated at Gustave Roussy Cancer Campus. The results obtained from the AI algorithm were compared with the attending radiologist’s report and were analyzed by both a radiology resident and a senior radiologist. In case of any discordant results, the reason for this discrepancy was further investigated. The duration between the exact time of the CT scan and analysis was assessed, as well as the duration from the result’s report and the start of active management. Results: Out of 3047 patients, 104 alerts were detected for iPE (prevalence of 1.3%), while 2942 had negative findings. In total, 36 of the 104 patients had confirmed PE, while 68 alerts were false positives. Only one patient reported as negative by the AI tool was deemed to have a PE by the radiologist. The sensitivity and specificity of the AI model were 97.3% and 97.74%, while the PPV and NPV were 34.62% and 99.97%, respectively. Most causes of FP were artifacts (22 cases, 32.3%) and lymph nodes (11 cases, 16.2%). Seven patients experienced delayed diagnosis, requiring them to return to the ER for treatment after being sent home following their scan. The remaining patients received prompt care immediately after their testing, with a mean delay time of 8.13 h. Conclusions: The addition of an AI system for the detection of unsuspected PEs on chest CT scans in routine oncology care demonstrated a promising efficacy in comparison to human performance. Despite a low prevalence, the sensitivity and specificity of the AI tool reached 97.3% and 97.7%, respectively, with detection of all the reported clinical PEs, except one single case. This study describes the potential synergy between AI and radiologists for an optimal diagnosis of iPE in routine clinical cancer care. Clinical relevance statement: In the oncology field, iPEs are common, with an increased risk of morbidity when missed with a delayed diagnosis. With the assistance of a reliable AI tool, the radiologist can focus on the challenging analysis of oncology results while dealing with urgent diagnosis such as PE by sending the patient straight to the ER (Emergency Room) for prompt treatment.

Understanding Tinnitus Clinical Care in the Veterans Health Administration and Department of Defense: Overview of Survey Results.

In 2021, the Veterans Health Administration (VHA) and Department of Defense (DOD) Tinnitus Working Group conducted a survey of DOD and VHA clinicians to evaluate clinical services provided for tinnitus. The online survey included a mix of multiple-choice and open-ended questions. Respondents included VHA and DOD health care providers in audiology, otolaryngology, mental health, and primary care, as well as DOD hearing conservation technicians. Quantitative and qualitative methods were used to analyze the data. A total of 669 providers responded to this combined survey. Results indicated that compared to DOD and VHA providers in other fields, audiologists tended to be more confident and more aware of their role in tinnitus management. In terms of confidence and scope of practice, DOD mental health care providers were the group least familiar with tinnitus care. Other results explored herein include barriers to tinnitus care, facilitators for progressive tinnitus management programs, interventions and patient materials offered, new patient materials wanted, and respondents' preferred information sources and training methods. Survey results indicated that more directed education and support are needed to increase DOD and VHA clinicians' awareness of the need for tinnitus services and their roles in providing that care. https://doi.org/10.23641/asha.27229215.

Improving the nursing quality of non-pharmacological interventions for elderly constipation patients in the hospital: a best practice implementation project.

Non-pharmacological interventions are the preferred treatment for constipation; however, health care professionals in clinical settings tend to focus more on pharmacological treatments. This best practice implementation project aimed to integrate the best evidence on non-pharmacological interventions for elderly patients with constipation in clinical care practice and to promote the use of non-pharmacological interventions for such patients in the hospital setting. This project is based on the JBI Evidence Implementation Framework, which follows three stages. The first stage involved a baseline audit using two audit criteria derived from the best available evidence. This audit evaluated current clinical scenarios, guided by the i-PARIHS framework. The second stage involved analyzing the results of the baseline audit, identifying barriers to compliance, and developing and implementing strategies to overcome those barriers. Strategies included nursing education, development of constipation information booklets for nurses and patients, establishment of a nursing workflow, and modification of the department environment. In the third stage, a follow-up audit was conducted to evaluate the implementation, using the same data collection indicators and methods as in the baseline audit. Sixty patients participated in the project. Compliance for Criterion 1 (patient education) increased from 0% to 60% (P < 0.001), while compliance for Criterion 2 (monitoring patients' bowel health) increased from 0% to 100% (p < 0.001). The results indicate that this evidence-based implementation project facilitated the application of non-pharmacological interventions for elderly patients with constipation. Nurses played a significant role in developing regular defecation habits in patients and monitoring their defecation. http://links.lww.com/IJEBH/A284.

Emergent resistance-associated mutations at first- or second-line HIV-1 virologic failure with second-generation InSTIs in two- and three-drug regimens: the Virostar-1 study.

Second-generation integrase strand transfer inhibitors (InSTIs) have a high barrier to resistance and potent antiretroviral activity. They are recommended as first- or second-line (FL and SL) options in two- and three-drug regimens (2DR and 3DR) in international treatment guidelines. However, there are limited real-world data on emerging resistance at the time of virological failure (VF) with these regimens. The Virostar-1 study objective is to analyse the emergence of resistance-associated mutations (RAMs) over 3 years with DTG-based 2DRs and DTG- or bictegravir (BIC)-based 3DRs in people living with HIV (PLWH) experiencing a VF (FL or SL). Retrospective analysis of genotypic resistance detected at the time of a FL or SL VF with BIC/FTC/TAF, DTG/ABC/3TC, DTG/3TC and DTG/RPV between 2019 and 2022 was conducted from a French multicentre database. VF was defined as two consecutive HIV-1 plasma viral loads > 50 c/mL. Sanger assays were performed at VF within standard clinical care. Resistance mutations were reported using the ANRS algorithm. Selection biases prevent group comparisons. During the period, N = 5986 PLWH were followed either in FL or SL. The VF rate was overall low: BIC/FTC/TAF, 6.8%; DTG/ABC/3TC, 7.5%; DTG/3TC, 5.1%; and DTG/RPV, 2.1%. Some emergent InSTI or NRTI RAMs were detected with BIC/FTC/TAF 4%, DTG/ABC/3TC 8.5%, DTG/3TC 18% and 39% emergent NNRTI RAMs with DTG/RPV. However, a complete absence of dual resistance against NRTIs and InSTIs was observed. We detected rare emergent InSTI RAMs and few emergent NRTI RAMs in PLWH failing DTG- or BIC-based regimens in FL or SL. The observed rates of emergent RAMs at VF were 4% with BIC/FTC/TAF, 8.5% with DTG/ABC/3TC, 18% with DTG/3TC and 39% with DTG/RPV.

A comprehensive overview of neuropsychiatric symptoms in adolescents with 22q11.2 deletion syndrome.

The 22q11.2 deletion syndrome (22q11DS) is associated with a variety of neuropsychiatric outcomes that vary across deletion carriers. We adopted a dimensional approach to provide a comprehensive overview of neuropsychiatric symptom expression in adolescents with 22q11DS and further our understanding of the observed phenotypical heterogeneity. Participants were 208 adolescents with 22q11DS between 10 and 19years old. Semi-structured clinical interviews and IQ tests were used to quantify symptom expression on multiple symptom dimensions, some reflecting DSM-IV diagnostic domains. We investigated symptom expression in those with and without a formal DSM-IV classification and examined between and within symptom dimensions. We used correlation analyses to explore associations between different symptom dimensions. We demonstrated inter-individual differences in symptom expression, both between and within neuropsychiatric symptom dimensions. On most symptom dimensions, more than 50% of adolescents expressed at least one clinically relevant symptom. In addition, a significant proportion of youth without a formal DSM-IV diagnosis reported clinically relevant symptoms (e.g. >85% of those without an ADHD diagnosis reported ADHD symptoms). The exploratory correlation analysis indicated mostly positive correlations between symptom dimensions. The finding that most adolescents with 22q11DS express neuropsychiatric symptoms, even in the absence of a DSM-IV classification, has substantial ramifications for guiding adequate support. Findings may spur further research into the dimensional structure of neuropsychiatric symptoms in 22q11DS and aid in uncovering mechanisms that contribute to symptom expression. Ultimately, this provides leads to improve clinical care for 22q11DS and to understand phenotypical variation in other high-risk genetic variants.

A validated NICU database: recounting 50 years of clinical growth, quality improvement and research.

The importance of a Neonatal Intensive Care Unit (NICU) database lies in its critical role in improving the quality of care for very preterm neonates and other high-risk newborns. These databases contain extensive information regarding maternal exposures, pregnancy complications, and neonatal care. They support quality improvement (QI) initiatives, facilitate clinical research, and track health outcomes in order to identify best practices and improve clinical guidelines. The Parkland Memorial Hospital NICU database was originally part of the Maternal and Neonatal Data Acquisition, Transmission and Evaluation project funded by the Robert Wood Johnson Foundation to assess perinatal-neonatal care in Dallas County Texas, 1977-1982. Clinical data points were defined, transcribed and validated in 1977; revalidation has occurred multiple times. Data are prospectively extracted from health records of high-risk neonates among >11,000 births annually. The database contains clinical information on >50,000 neonates, including all initially admitted to the NICU regardless of gestational age or birthweight and since 10/03/2011, all neonates admitted for observation and transferred to the term newborn nursery. The database has provided the basis for QI studies and research designed to assess and improve neonatal care. We discuss the history, evolution, administration, impact on neonatal outcomes, and future directions of our database. IMPACT: A single neonatal intensive care unit (NICU) database was designed for prospective data collection, validated and maintained for 46yrs. This database has supported quality improvement assessment, original clinical research, education and administrative requirements and impacted clinical neonatal care.

Development of an Expert-Based Scoring System for Early Identification of Patients with Inborn Errors of Immunity in Primary Care Settings - the PIDCAP Project.

Early diagnosis of inborn errors of immunity (IEIs) has been shown to reduce mortality, morbidity, and healthcare costs. The need for early diagnosis has led to the development of computational tools that trigger earlier clinical suspicion by physicians. Primary care professionals serve as the first line for improving early diagnosis. To this end, a computer-based tool (based on extended Jeffrey Modell Foundation (JMF) Warning Signs) was developed to assist physicians with diagnosis decisions for IEIs in the primary care setting. Two expert-guided scoring systems (one pediatric, one adult) were developed. IEI warning signs were identified and a panel of 36 experts reached a consensus on which signs to include and how they should be weighted. The resulting scoring system was tested against a retrospective registry of patients with confirmed IEI using primary care EHRs. A pilot study to assess the feasibility of implementation in primary care was conducted. The scoring system includes 27 warning signs for pediatric patients and 24 for adults, adding additional clinically relevant criteria established by expert consensus to the JMF Warning Signs. Cytopenias, ≥ 2 systemic infections, recurrent fever and bronchiectasis were the leading warning signs in children, as bronchiectasis, autoimmune diseases, cytopenias, and > 3 pneumonias were in adults. The PIDCAP (Primary Immune Deficiency "Centre d'Atenció Primària" that stands for Primary Care Center in Catalan) tool was implemented in the primary care workstation in a pilot area. The expert-based approach has the potential to lessen under-reporting and minimize diagnostic delays of IEIs. It can be seamlessly integrated into clinical primary care workstations.

Modified Rules for Classification of Variants Associated With Disorders of Somatic Mosaicism.

Disorders of somatic mosaicism (DoSMs) are rare genetic disorders arising from postzygotic alteration leading to segmental/nonsegmental disease. Current professional guidelines for standardized variant interpretation focus on germline and cancer variants, making them suboptimal for DoSM variant interpretation. The Brain Malformations Variant Curation Expert Panel (BMVCEP) modified existing guidelines to account for brain-specific disorders of somatic mosaicism, but applicability to other DoSM presentations is limited. At Washington University in St. Louis School of Medicine, we have adopted the BMVCEP interpretation framework but suggested alterations that make it more suitable for generalized DoSM variant classification. These modifications include (1) expanding applicability beyond genes associated with brain malformations, (2) introduction of a criterion to interpret truncating variants at the C-terminus of gain of function genes, (3) establishment of a variant allele fraction (VAF) cutoff for applying de novo criteria, and (4) demonstration that in silico prediction tools are relevant to interpretation of gain of function missense variants. Furthermore, modifications to BMVCEP guidelines reduce the number of variants classified as uncertain. The variant classification considerations that we propose have the potential to improve the accuracy of somatic variant classification, better inform clinical care, and may benefit clinical laboratories also conducting DoSM testing.

Optimizing revision arthroplasty: the role of customized articulating spacers

Introduction The advancement of surgery is set against a backdrop of continuous development and surgical innovations have transformed the way clinical care is delivered. Revision surgery might be required to address complications of primary arthroplasty. The first stage of revision arthroplasty would involve removal of an implant and placement of an antibiotic-impregnated cement spacer to maintain the joint space and stability, prevent soft tissue retraction, provide local antibiotic release and preserve bone tissue for revision implantation at the final stage of revision. Custom-made articulating spacers are a promising tool for optimizing the first stage of revision arthroplasty.The objective was to summarize the current data and present comprehensive information about spacers used in two-stage revision arthroplasty including manufacturing techniques, physical and chemical properties, clinical applications, the possibility of customization within the first stage of revision arthroplasty, current and promising directions for research.Material and methods The original literature search was conducted on key resources including Scientific Electronic Library (www.elibrary.ru), the National Library of Medicine (www.pubmed.org), the Cochraine Library (www.cochranelibrary.com) between 2018 and 2023 using search words and phrases: total arthroplasty, complications, revision arthroplasty, articulating spacer, periprosthetic joint infection, additive manufacturing, 3D printing.Results A comparative analysis of factory supplied, home-made, dynamic and static spacer models showed that the choice of articulating spacers for revision arthroplasty of major joints is of great relevance. Advantages of factory-made spacers include standardized range of sizes, the reliability and availability for medical institutions. They are characterized by limited use in repair of severe bone defects.Discussion Custom-made articulating spacers enable specific tailoring to accommodate individual defects. Despite high expectations from custom-made spacers, development of optimal technologies for rapid prototyping is essential. Investments in research and development in this area have the potential to create innovative solutions that can significantly improve the results of revision arthroplasty.Conclusion The paper explores the importance of systemization of knowledge about spacers and the role of new research in improving the design and functionality. Progress in the field of materials science, additive technologies and a personalized approach to spacer manufacturing can expand possibilities of revision arthroplasty and the effectiveness. Personalized approaches and improved methods of local drug delivery that provide controlled release of antibiotics can improve the results of treatment of periprosthetic joint infections.

Facilitating Efficient and Ethical Trials at the Intersection of Research and Clinical Care

Facilitating Efficient and Ethical Trials at the Intersection of Research and Clinical Care

The role of platelets and megakaryocytes in sepsis and ARDS.

Since the global COVID-19 pandemic, there has been a renewed focus on lung injury during infection. Systemic inflammatory responses such as acute respiratory distress syndrome (ARDS) and sepsis are a leading cause of morbidity and mortality for both adults and children. Improvements in clinical care have improved outcomes but mortality remains ∼40% and significant morbidity persists for those patients with severe disease. Mechanistic studies of the underlying biological processes remain essential to identifying therapeutic targets. Furthermore, methods for identifying the underlying drivers of organ failure are key to treating and preventing tissue injury. In this review, we discuss the contribution of megakaryocytes (MKs) and platelets to the pathogenesis of systemic inflammatory syndromes. We explore the role of MKs and the new identification of extramedullary MKs during sepsis. We describe the alterations in the platelet transcriptome during sepsis. Lastly, we explore platelet function as defined by aggregation, activation and the formation of heterotypic aggregates. Much more work is necessary to explore the contribution of platelets to these heterogenous syndromes, but the foundation of platelets as key contributors to inflammation has been laid.

Development of a risk predication model for critical care needs in patients with intracerebral hemorrhage: a retrospective cohort.

It is very important to provide the correct nursing care for patients with intracerebral hemorrhage (ICH), but the level of critical care needs in patients with intracerebral hemorrhage is not clear. The purpose of this study is to establish a risk model based on the epidemiological and clinical characteristics of ICH patients, to help identify the critical care needs of ICH patients. The clinical data of ICH patients from January 2018 to September 2023 were analyzed retrospectively. The full cohort was used to derive the clinical prediction model and the model was internally validated with bootstrapping. Discrimination and calibration were assessed using the area under curve (AUC) and the Hosmer-Lemeshow tests, respectively. 611 patients with ICH were included for model development. 61.21% (374/611) ICH patients had received critical care interventions. The influencing factors included in the model were Glasgow Coma Scale (GCS) score, intraventricular hemorrhage, past blood pressure control, systolic blood pressure on admission and bleeding volume. The model's goodness-of-fit was evaluated, which yielded a high area under the curve (AUC) value of 0.943, indicating a good fit. For the purpose of model validation, a cohort of 260 patients with ICH was utilized. The model demonstrated a Youden's index of 0.750, with a sensitivity of 90.56% and a specificity of 78.22%. GCS, systolic blood pressure, intraventricular hemorrhage, bleeding volume and past blood pressure control are the main factors affecting the critical care needs of patients with ICH. This study has deduced a clinical predictive model with good discrimination and calibration to provide scoring criteria for clinical health care providers to accurately evaluate and identify the critical care needs of ICH patients, to improve the rational integration and allocation of medical resources.

Nursing Care and Ethical Challenges in the COVID-19 Pandemic: A Review

The COVID-19 pandemic has placed unprecedented pressures on healthcare systems across the globe, with nurses playing a pivotal role in managing patient care during this crisis. As front-line caregivers, nurses were not only responsible for delivering essential medical care but also found themselves navigating a series of ethical challenges that were often fraught with complexity. This review delves into the multifaceted role of nursing during the pandemic, focusing on both the clinical care provided and the significant ethical dilemmas faced by nurses. One of the most pressing ethical challenges was the allocation of scarce medical resources. The surge in COVID-19 cases led to critical shortages of ventilators, ICU beds, personal protective equipment (PPE), and other medical supplies. Nurses, often collaborating with multidisciplinary teams, were forced to make difficult decisions regarding which patients would receive these limited resources, raising profound ethical concerns about fairness and equity in healthcare. The review highlights the need for transparent, consistent decision-making frameworks that prioritize justice and equity. Such frameworks help ensure that resource allocation is guided by ethical principles rather than subjective judgments, thus fostering a fairer and more consistent approach to patient care. Another significant ethical issue addressed in this review is the balance between personal safety and professional duty. Nurses were often placed in situations where they had to weigh their commitment to patient care against the risks posed to their own health, particularly when faced with shortages of adequate PPE. This balancing act between personal safety and professional obligation introduced ethical dilemmas, such as the extent to which nurses were adequately informed of the risks they faced and whether healthcare institutions fulfilled their responsibility to provide a safe working environment. The review underscores the importance of developing robust infection control measures and ensuring the continuous supply of PPE to safeguard the health and well-being of healthcare workers. Patient autonomy and consent were also critical concerns during the pandemic. The urgency of care for critically ill COVID-19 patients, combined with isolation protocols that restricted family involvement, made it challenging to uphold patients' decision-making rights. The review explores how informed consent processes were affected by the rapid progression of illness and the necessity for immediate medical interventions, often with limited patient or family input. This issue further underscores the need for ethical guidelines that protect patient rights while ensuring timely and effective care. The psychological impact of the pandemic on nurses is another key focus of this review. Nurses faced not only physical exhaustion from long hours of work but also significant emotional strain from witnessing high mortality rates and making difficult ethical decisions. The review emphasizes the need for mental health resources, such as counseling and support groups, to help nurses cope with the emotional toll of their work. Addressing issues such as moral injury, compassion fatigue, and burnout is essential to maintaining a resilient nursing workforce. In conclusion, this review provides a comprehensive examination of the ethical challenges faced by nurses during the COVID-19 pandemic. It highlights the critical need for clear ethical guidelines, transparent resource allocation frameworks, protective measures, and mental health support systems. The lessons learned from this pandemic are invaluable for shaping future responses to global health crises, ensuring that nurses and other healthcare professionals are better equipped to navigate the ethical complexities of emergency care.

Pheochromocytoma-Paraganglioma Syndrome: A Multiform Disease with Different Genotype and Phenotype Features.

Pheochromocytoma and paraganglioma (PPGL) are rare tumors derived from the adrenal medulla and extra-adrenal chromaffin cells. Diagnosis is often challenging due to the great variability in clinical presentation; the complexity of management due to the dangerous effects of catecholamine excess and the potentially malignant behavior require in-depth knowledge of the pathology and multidisciplinary management. Nowadays, diagnostic ability has certainly improved and guidelines and consensus documents for treatment and follow-up are available. A major impulse to the development of this knowledge has come from the new findings on the genetic and molecular characteristics of PPGLs. Germline mutation in susceptibility genes is detected in 40% of subjects, with a mutation frequency of 10-12% also in patients with sporadic presentation and genetic testing should be incorporated within clinical care. PPGL susceptibility genes include "old genes" associated with Neurofibromatosis type 1 (NF1 gene), Von Hippel Lindau syndrome (VHL gene) and Multiple Endocrine Neoplasia type 2 syndrome (RET gene), the family of SDHx genes (SDHA, SDHB, SDHC, SDHD, SDHAF2), and genes less frequently involved such as TMEM, MAX, and FH. Each gene has a different risk of relapse, malignancy, and other organ involvement; for mutation carriers, affected or asymptomatic, it is possible to define a tailored long-life surveillance program according to the gene involved. In addition, molecular characterization of the tumor has allowed the identification of somatic mutations in other driver genes, bringing to 70% the PPGLs for which we know the mechanisms of tumorigenesis. This has expanded the catalog of tumor driver genes, which are identifiable in up to 70% of patients Integrated genomic and transcriptomic data over the last 10 years have revealed three distinct major molecular signatures, triggered by pathogenic variants in susceptibility genes and characterized by the activation of a specific oncogenic signaling: the pseudo hypoxic, the kinase, and the Wnt signaling pathways. These molecular clusters show a different biochemical phenotype and clinical behavior; they may also represent the prerequisite for implementing customized therapy and follow-up.

Using a Patient-Reported Outcome Measure to Assess Physical, Psychosocial, and Existential Issues in COPD.

Background: Chronic obstructive pulmonary disease (COPD) is marked by severe physical symptoms, impaired quality of life, and high psychological distress. Despite its impact, the identification of not only physical but also psychosocial and existential issues in the clinic lags behind that of other patient groups. Methods: This study aimed to assess physical, psychosocial, and existential issues among patients with COPD using a patient-reported outcome measure for general palliative care (the 'PRO-Pall') in a Danish outpatient clinic. We included 115 adults with COPD who completed the PRO-Pall either electronically or in the clinic. Sociodemographic and illness-related data were retrieved from their electronic health records. Results: We found that shortness of breath, tiredness, and difficulty walking were predominant physical issues. Worry about change in social roles was the most frequently reported psychosocial issue, while existential issues were reported by approximately one in ten patients. Most patients (44.5%) felt able to share their feelings with family or friends, and a majority (62.2%) felt their illness-related issues were addressed satisfactorily. Females expressed a greater need for rest and males more frequently reported intimacy issues. Higher COPD-impact on life measured by the COPD Assessment Test was associated with lower ratings on the quality-of-life item of the PRO-Pall independent of age, gender, lung function, and smoking status. Conclusions: Patients reported issues in physical, psychosocial, and existential dimensions of the PRO-Pall. The PRO-Pall shows potential as a broader alternative to measures that focus mainly on physical issues.

Multiple Pediatric Extracorporeal Membrane Oxygenation Runs and Futility. What Are the Limits?

Despite high mortality rates, pediatric extracorporeal membrane oxygenation (ECMO) redeployments are frequently discussed in everyday clinical care. We aim to investigate predictors of mortality in those patients. Clinical data from a single pediatric center were retrospectively analyzed. Patients with multiple ECMO runs between 2010 and 2023 were included. A total of 70 (13%) patients required multiple ECMO runs. Of those, 56 (80%) died before discharge; late mortality was 89% at a median of 1.6 (1.0-3.9) years. A total of 47 (67%) patients had neurologic findings. Only one (1%) survivor had a normal neurodevelopmental follow-up. Duration of the first ECMO run (odds ratio [OR]: 2.63, 1.08-7.96), total duration on ECMO (OR: 4.72, 1.29-23.54), neurologic findings at any time (OR: 7.94, 1.46-43.24), need for renal replacement therapy (OR: 4.79, 1.06-25.58), and lactate values correlated with late mortality. All 19 (27%) patients with neurologic findings before the second run died. The frequency of multiple-run ECMOs increased within the study period. Outcomes in pediatric patients with multiple ECMO runs are disheartening. Given all patients in our cohort with neurological findings before the second ECMO run died, neurological findings should be taken into consideration when determining the utility of further ECMO support.

Promise and Peril of a Genotype-First Approach to Mendelian Cardiovascular Disease.

Precision medicine, which among other aspects includes an individual's genomic data in diagnosis and management, has become the standard-of-care for Mendelian cardiovascular disease (CVD). However, early identification and management of asymptomatic patients with potentially lethal and manageable Mendelian CVD through screening, which is the promise of precision health, remains an unsolved challenge. The reduced costs of genomic sequencing have enabled the creation of biobanks containing in-depth genetic and health information, which have facilitated the understanding of genetic variation, penetrance, and expressivity, moving us closer to the genotype-first screening of asymptomatic individuals for Mendelian CVD. This approach could transform health care by diagnostic refinement and facilitating prevention or therapeutic interventions. Yet, potential benefits must be weighed against the potential risks, which include evolving variant pathogenicity assertion or identification of variants with low disease penetrance; costly, stressful, and inappropriate diagnostic evaluations; negative psychological impact; disqualification for employment or of competitive sports; and denial of insurance. Furthermore, the natural history of Mendelian CVD is often unpredictable, making identification of those who will benefit from preventive measures a priority. Currently, there is insufficient evidence that population-based genetic screening for Mendelian CVD can reduce adverse outcomes at a reasonable cost to an extent that outweighs the harms of true-positive and false-positive results. Besides technical, clinical, and financial burdens, ethical and legal aspects pose unprecedented challenges. This review highlights key developments in the field of genotype-first approaches to Mendelian CVD and summarizes challenges with potential solutions that can pave the way for implementing this approach for clinical care.