bluuebunny/crossref_metadata_2025 huggingface dataset:
Suddenly not the same
Authors: Vahia Ipsit V.
Published: May 2022

Delirium is a common condition in older adults, especially those with multiple medical comorbidities, and manifests as an acute confusional state with accompanying behavioral symptoms. Delirium is especially common among older adults with medical comorbidities, and requires a thorough clinical assessment with collateral history from reliable informants, detailed physical examination, monitoring vital signs, and lab assessments to identify underlying organic etiology. The occurrence of delirium is much higher among older adults who are hospitalized or who live in nursing homes or long-term care facilities and among those taking multiple medications. Management of delirium depends primarily on nonpharmacologic approaches including supportive care, eliminating triggers, and careful management of sleep, nutrition, and hydration. Psychotropic medications may be considered for acute agitated behavioral symptoms but should generally be minimized.
It’s just a nightcap
Authors: Luca Luminita , Crocco Elizabeth A.
Published: May 2022

Substance use disorders (SUDs) pose unique risks to older individuals due to the effects of aging on metabolism and the brain. Alcohol use disorder is the most common SUD in late life. Signs and symptoms of SUDs are important to recognize as they present in physical, psychiatric, and social dimensions, and sometimes can be masked by other comorbid conditions. Comorbid anxiety, depression, and sleep disorders are commonly associated with SUDs and should be treated promptly, using both therapeutic approaches and standard antidepressants or other targeted medications while avoiding use of benzodiazepines. Treatment should address acute withdrawal states as well as maintenance approaches using medications as well as psychotherapy and support groups such as Alcoholics Anonymous (AA) and or Narcotics Anonymous (NA).
Disaster Preparedness and Response
Authors: Rega Paul P.
Published: May 2022

This book introduces the field of disaster medicine and disaster management at its most basic and practical level by presenting a series of scenarios and discussing the optimal responses. Throughout, emphasis is placed on the critical importance of advance planning for disasters, including conducting hazard vulnerability analyses, maintaining staff and hospital readiness, and communicating and cooperating with other community, state, and federal agencies. Chapters address the history of emergency medicine as a specialty, triage systems, crisis leadership and organization, modern training methods, and how to respond to natural disasters, acts of terrorism, mass casualty incidents, vehicular accidents, HAZMAT accidents, radiological emergencies, active shooter situations, pandemics, and more. In each chapter suggestions are made for further reading, and three appendices list accidental and intentional hazardous agents; bioterror agents, and major disasters in history.
Hydrofluoric acid: One of the worst HAZMAT agents you never heard of
Authors: Rega Paul P.
Published: May 2022

This chapter explores a HAZMAT situation involving an attack on a group of glass-factory workers that involves an unusual agent, hydrofluoric acid. The first steps are to sound the alarm, provide critical interventional advice to EMS, alert your staff, reach out to other hospital departments, and don PPE. As victims arrive in the ED, acute management consists of airway, breathing, circulation, decontamination, antidotes, and pain control. Victims of hydrofluoric acid exposures die early because they have absorbed enough of the chemical that they develop life-threatening hypocalcemia, not to mention hyperkalemia. Details are given about antidotes that can be used in hydrofluoric acid exposures, including management of the associated burns.
“We’re evacuating the hospital . . . now!”
Authors: Rega Paul P.
Published: May 2022

In the case examined in this chapter, an accidental detonation of an illegal fireworks factory has forced the emergency evacuation of a nearby hospital. The building’s integrity has been compromised, thereby necessitating an evacuation of all patients in the emergency department as well as the rest of the hospital, along with the staff. The “reverse triage” technique is applied, in which ambulatory patients are evacuated first. Different techniques for evacuation are discussed, including the “mattress and bedsheet” technique in which patients are wrapped in their own bedsheets and evacuated down stairwells using a mattress slide. The importance of planning and drilling for an emergency evacuation is stressed.
The classical causes of heart failure
Authors: Jackson Colette E. , Gardner Roy S.
Published: May 2022

This chapter discusses the ‘classical causes’ of heart failure. Heart failure is the common endpoint of a diverse range of cardiovascular and non-cardiovascular conditions. The list of potential causes of this syndrome continues to expand as the knowledge of the pathophysiology of heart failure increases. In western societies, coronary heart disease and hypertension are the commonest causes of heart failure. However, valvular heart disease, arrhythmias, and alcohol are also frequently implicated. The prevalence of heart failure secondary to coronary heart disease has increased in recent years, due in part to improved survival following acute myocardial infarction. The chapter then highlights the importance of establishing an aetiology of heart failure. Establishing the aetiology of heart failure is important, but it is often challenging for the clinician. Several causes of heart failure frequently coexist and determining the primary aetiology can be difficult: one cause may obviously dominate, but frequently patients may have multiple contributing aetiologies.
Amyloidosis
Authors: Whelan Carol J.
Published: May 2022

The heart is frequently involved in systemic amyloidosis. More than 30 precursor proteins have been identified that can form amyloid fibrils in vivo, and determination of the fibril type by immunohistochemistry, proteomics and genetic sequencing is crucial as this guides therapy. Most cases of cardiac amyloidosis are either transthyretin (TTR) type, which can be acquired, especially in men at a later age (wild type) or hereditarily at a younger age, or monoclonal immunoglobulin light chain (AL) type amyloidosis, which is acquired and most often occurs in middle age. Cardiac involvement occurs in about 50% of patients with AL amyloidosis and is the major determinant of prognosis in that condition. There are now several imaging modalities available to allow accurate evaluation of cardiac amyloidosis. The variable organ involvement often leads to delays in diagnosis. Improving awareness of amyloidosis is essential if patients are to be diagnosed early to impact on survival and quality of life.
Takotsubo syndrome
Authors: Lyon Alexander R.
Published: May 2022

Takotsubo syndrome (TTS) is an acute, reversible heart failure syndrome typically but not exclusively observed in postmenopausal women who have experienced an extremely stressful triggering event. Patients with TTS present with acute chest pain, dyspnoea, palpitations, increased serum troponin, and acute ECG changes including ST elevation and/or T-wave inversion. The most common apical variant is associated with hypo- or akinesia of the apical and mid-left ventricular myocardium with basal hypercontractility, resembling the Japanese fisherman’s octopus pot, the ‘takotsubo’. Other anatomical patterns exist including the basal and mid-ventricular variants. TTS appears to reflect the cardiovascular response to a sudden surge in adrenaline levels, and may be a form of acute catecholaminergic stunning. TTS may also be secondary to stressful acute medical and surgical conditions, and also may be triggered by various drugs. Acute inpatient mortality is high (4–5%), and risk stratification is important following diagnosis. Access to modern cardiac imaging is important to confirm the diagnosis, screen for complications, and confirm recovery at follow-up. TTS cases with evidence of heart failure may require a short course of β‎-blockers and/or angiotensin converting enzyme inhibitors. If cardiogenic shock occurs, mechanical support with a left ventricle assist device or extracorporeal membrane oxygenation may be required as a ‘bridge to recovery’. Mechanistic studies suggest that TTS may be a cardioprotective response to severe stress.
Cardiopulmonary exercise testing in chronic heart failure
Authors: Ferguson Carrie , Witte Klaus K.
Published: May 2022

In patients presenting with heart failure, assessment of underlying aetiology is critical for optimal management. To differentiate between ischaemic and non-ischaemic cardiomyopathy, invasive coronary angiography is frequently performed. This technique is currently considered the reference standard for the detection of coronary artery disease (CAD). In patients with intermediate–high probability of CAD or in patients with documented ischemia on non-invasive stress testing, this method is recommended, especially since the technique also provides the opportunity for direct intervention. However, in patients with low–intermediate risk of CAD and no chest pain symptoms, anatomical imaging with coronary computed tomography (CT) angiography may be more appropriate. With this technology, high-resolution images of the coronary arteries are obtained. In addition, detailed information on cardiac structures, myocardial function, and to some extent also myocardial scar can be derived from cardiac CT. The aim of the current chapter is to review the various applications of cardiac CT that may be relevant in the setting of heart failure.
Ventilatory support
Authors: Armstrong Christopher , Gray Alasdair
Published: May 2022

Heart failure is a leading cause of hospitalization across the world, accounting for around 2% of health expenditure in western countries. Acute pulmonary oedema, caused by decompensated heart failure, is a common emergency presentation. This accumulation of interstitial fluid, caused by increasing pulmonary capillary pressure secondary to increased left atrial pressure, causes increased work of breathing and decreased oxygenation and ventilation, so further worsening cardiac function. In those patients with acute respiratory distress or failure, non-invasive ventilation (NIV) (continuous positive airway pressure (CPAP) or biphasic positive airway pressure (BiPAP)) improves lung compliance, tidal volumes, and gas exchange, and decreases work of breathing. It also decreases cardiac preload and afterload, including transmural pressure so improving cardiac output in the failing heart. It can be delivered through a variety of patient interfaces according to patient preference and has been shown to be safe and viable both in the pre-hospital setting and in emergency departments and intensive care units. CPAP has been shown to reduce dyspnoea and improve clinical parameters such as respiratory rate and oxygen saturations and may reduce the need for intubation and mortality. NIV should be employed in the setting of acute heart failure with pulmonary oedema as part of a clinical pathway incorporating pharmacological therapies and a multidisciplinary team.
Angiotensin converting enzyme inhibitors and vasodilators
Authors: Squire Iain , Clark Andrew L.
Published: May 2022

This chapter details how, during the 1980s and 1990s, evidence mounted for the central role to the pathophysiology of chronic heart failure of activation of the renin–angiotensin–aldosterone system (RAAS) and adrenergic nervous system. Over those years and into the early part of the twenty-first century, large randomized, controlled trials provided physicians with enormous amounts of evidence for the benefits to patients with heart failure of angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor antagonists, mineralocorticoid receptor antagonists, and β‎-receptor blockers, in addition to diuretics and digoxin. The chapter then reviews the development and pharmacology of ACE inhibitors and their physiological actions. It also discusses the side-effect profile of ACE inhibitors and the place of vasodilators which do not block the RAAS as potential alternatives to ACE inhibition. Moreover, the chapter looks at the huge clinical impact of ACE inhibitors in the treatment of heart failure.
β‎-Adrenoreceptor antagonists
Authors: Beggs Simon A. S. , Gardner Roy S. , McDonagh Theresa A.
Published: May 2022

This chapter explores the use of β‎-adrenoreceptor (AR) antagonists, commonly referred to in clinical practice as β‎-blockers, in heart failure. The idea that β‎-blockers might be of value in heart failure was consistent with the developing ‘neuroendocrine hypothesis’ of heart failure. It was suggested that several neurohormonal systems, principally the renin–angiotensin–aldosterone system (RAAS) and the sympathetic nervous system, could be responsible for the apparently inexorable deterioration of cardiac function and high mortality in heart failure. Thereafter, inhibition of this neuroendocrine response by angiotensin converting enzyme (ACE) inhibitors, selective inhibition of angiotensin II receptors by angiotensin receptor blockers (ARBs), and angiotensin receptor–neprilysin inhibitors (ARNIs), and of aldosterone receptors, together with β‎-blockers has become the standard evidence-based approach to the medical treatment of heart failure. This combination of treatments markedly improves survival by reducing both sudden cardiac death and death due to worsening heart failure. It also leads to improved ventricular function due to amelioration of ventricular remodelling consequent upon myocardial cell loss from myocardial infarction or other heart muscle disorders.
Problems with polypharmacy, alternative therapies and medication adherence
Authors: Forsyth Paul , McGlynn Steve
Published: May 2022

Heart failure rarely exists in isolation: patients frequently have other diagnoses which require treatment. Many commonly used medicines have adverse effects on cardiovascular health, particularly so in patients with heart failure. The mechanisms of these effects are varied, and, whereas some are common and predictable, others are less so. Prescribers should be aware of these effects when treating co-morbidities. Patients and prescribers, however, may not be aware of the effects of over-the-counter or complementary medicines. The adverse effects and safety of complementary medicines are less well studied and often unclear. Adherence to prescribed medication regimens is also frequently suboptimal resulting in poorer outcomes. Medication adherence is, however, influenced by a number of complex interwoven factors, making it difficult to improve. This chapter reviews the potentially detrimental effects of both conventional and complementary medicines and discusses the challenges in ensuring optimal medication.
Cardiac rehabilitation and chronic heart failure
Authors: Piepoli Massimo F. , Clark Andrew L.
Published: May 2022

This chapter reviews the use of a multifactorial cardiac rehabilitation approach for patients with established chronic heart failure (CHF). Cardiac rehabilitation is the ideal comprehensive structured disease intervention since it best addresses the complex interplay of medical, psychological, and behavioural factors facing patients with CHF. It is a coordinated multidimensional intervention designed to stabilize or slow disease progression, alleviate symptoms, improve exercise tolerance, and enhance quality of life, thereby reducing morbidity and mortality. In populations of patients with CHF, such a programme has been shown to improve functional capacity, recovery, and emotional well-being and to reduce hospital admission. Exercise training as a key component in a cardiac rehabilitation programme may improve survival and reduce hospitalization in stable heart failure patients. However, despite the virtues of cardiac rehabilitation, only a small percentage of eligible heart failure patients ever get referred, due to barriers such as lack of physician and patient-family awareness of its benefits, and logistical or financial constraints.
Non-pharmacological management
Authors: Blue Lynda
Published: May 2022

This chapter discusses the non-pharmacological management of heart failure. Providing effective non-pharmacological advice is an important component of heart failure care. The consequences of failing to address this issue adequately can be both considerable and wide-ranging for patients and their caregivers, as well as incurring significant economic costs on the health care system generally. Heart failure patients need continuous, long-term support in the community and should ideally be seen as soon as possible following hospital discharge. A community-based healthcare professional can provide advice and support that complements the information given on hospital discharge. Moreover, a comprehensive assessment of both patients’ and caregivers’ needs and knowledge base is essential to inform future education and care requirements. As heart failure management continues to evolve, the requirement for effective and responsive strategies increases. Key areas for further research and development will include the use of digital technology in supporting healthcare professionals, patients, and their caregivers to implement self-care behaviours effectively.
Introduction
Authors: Abel Julian , Kellehear Allan
Published: May 2022

This is a book about the public health approach within palliative care. Often when we think about ‘public health’ it is more usual to think about palliative care as part of the public health system – similar to the hospitals, nursing homes, and community clinics – but also the broader supports for population health such as sewerage and water purification systems or workplace health and safety. In universities, we often think of public health in terms of the surveillance sciences – epidemiology, health services research, computer modeling, or the bench sciences devoted to understanding disease. But in this volume, we are specifically addressing a newer and less recognized aspect of public health – public health practice methods such as education, health policy, community development, or social ecology. We are also specifically examining the role of the ‘new’ public health, sometimes also known as health promotion. Health promotion is a major departure from the emphases on surveillance, disease, and health services by placing its gaze and efforts on practice solutions, health and wellbeing, and community and civic involvement in healthcare – in this case, palliative care. The Oxford Textbook of Public health Palliative Care is an introduction to this dimension of practice. This chapter provides an overview of what public health palliative care is and outlines the themes and topics that will be covered in each section.
The ‘new’ public health
Authors: Spreckley Mark , Kellehear Allan
Published: May 2022

Public health palliative care draws its main ideas and methods from the wider field of the new public health. This chapter outlines the key ideas of the new public health and identifies the main reasons this approach has emerged from earlier historical ideas about public health and healthcare. Three non-palliative care examples (the long-term management of an ageing population living with HIV, new public mental health management, and ear and hearing health) are described to illustrate how these ideas infuse other healthcare specialisms before examining how some of these ideas persist or have changed for public health palliative approaches.
Health and well-being
Authors: Abel Julian
Published: May 2022

Concepts of health and well-being are used as part of the language of public health palliative care, particularly in health-promoting palliative care. However, these terms remain unexplored in the research literature on palliative care. Consequently, assumptions are made about what living well with terminal illnesses means for patients and families. This not only makes it difficult to know whether palliative care service provision is doing what matters most to the people they look after, it is also symptomatic of a deficit model of care. In this model, areas of need are highlighted and these needs are met by service provision. The major assumption of this is that if needs are met, then quality of life and health and well-being are good. However, this is not the case. Evidence of what health and well-being means outside of palliative care is clear. The primary factors can be found in the social ecology of care, in which the people we know and love in the places we know and love are of primary importance. Relationships are key. The evidence for this is drawn from the literature on the mortality and morbidity of loneliness and the positive impact of good social relationships. In the palliative setting, paying attention to the circles of care, the inner, outer, and community networks of relationships, provides a theoretical model which alters the priorities of how services can help and, as a consequence, provides what is most meaningful to people who are undergoing the experiences of death, dying, loss, and caregiving.
Participatory relations
Authors: Noonan Kerrie
Published: May 2022

Public health initiatives depend on participation. Whether it be a grassroots programme led by citizens or a palliative care service delivered to citizens by health professionals, participation—and the way we relate to each other while participating—is important. Relationships and connections between institutions, professionals, and citizens need to be negotiated and nurtured. This chapter considers these questions and explores the concept of participatory relations in public health palliative care and some of the practice models of participation and invites the reader to reflect on their own experiences as a practitioner.
Community development
Authors: Patel Manjula , Noonan Kerrie
Published: May 2022

Compassionate communities as a public health approach adopts many of the principles of community development. Community development is organic, multifaceted, and not easily defined but some of the principles involve engagement, participation, and empowerment, working alongside individuals building relationships. Similarly, there is no single way of describing compassionate communities but it involves the interactions of social networks around the dying individuals and their families. Hence, a compassionate communities approach includes both formal and informal care to support those dying at home and their carers. The development of compassionate communities can be found around the world and they provide different perspectives. This chapter provides an overview of compassionate communities initiatives across the globe and considers the emerging research data. The literature to date has found that many of the compassionate communities initiatives are initiated by formal health services with a top-down model. Although a bottom-up approach is the most preferred model, there are very few examples of communities taking the ownership of providing informal care. Reflecting on the benefits and challenges of developing compassionate communities, the chapter outlines key questions to consider for community empowerment when thinking about initiating the development of compassionate communities.
Complexities and challenges in public health palliative care research
Authors: Vanderstichelen Steven , Deliens Luc
Published: May 2022

This chapter explores the challenges and complexities of public health palliative care research. The rapid development of public health palliative care research over the last decades foretells a whole new domain of research and policy in end of life care. This chapter reviews what the public health approach to palliative care entails and suggests appropriate research designs that can be used to develop and evaluate public health palliative care studies. Furthermore, it provides an overview of how observational, experimental, and change-oriented designs have been used in public health palliative care research. Finally, it explores what complexity means in public health palliative care research and what particular sources of complexity one may encounter in the research experience.
Economic perspectives on public health approaches to palliative care
Authors: Normand Charles
Published: May 2022

This chapter discusses how an economic perspective can be useful in understanding issues and the challenges in making choices in public health approaches to palliative care. Adopting an economic viewpoint does not solve all difficult problems, but it provides useful insight and understanding. The chapter starts with a brief summary of the history of health economics and economics of public health and some key features of an economic perspective. It then considers how economics has been applied in palliative care. It acknowledges the particular challenges in applying conventional economic tools in this context, and discusses how they are not fully fit for purpose. However, using some examples of challenges in setting priorities in palliative care it suggests ways in which the economic perspective can be useful. While the needs and responses are complex, choices must be made and economics can help in making better choices.
Pedagogical approaches for professional learning
Authors: Hodgson Mary , Richardson Heather
Published: May 2022

This chapter describes some of the pedagogical principles that might be adopted for a public health palliative care approach to learning and teaching for the professions. It commences with curriculum considerations of audience and relevance as well as the importance of including certain essential content areas such as community development, social ecology, power and social justice, and participatory storytelling. The second half of the chapter explores and describes the value of learning approaches that consider the role of learning relationships and environments, and the importance of learning continuously and for change.
Public health palliative care education
Authors: Paul Sally
Published: May 2022

Public health palliative care recognizes the impact of wider social systems in shaping how children experience illness, caregiving, and bereavement. As such, public health palliative care education identifies the significance of meaningful support for children that moves beyond individual experiences to the role and capacity of educational communities to proactively prepare its members to care for themselves and others at these times. As such, this chapter highlights the role of school communities in public health, focusing on the relevance of health-promoting schools and, in turn, health-promoting palliative care schools. Indicators for health-promoting palliative care schools are provided along with examples of public health palliative care education and the associated challenges and opportunities for developing related work.
Internal oligo(dT) priming introduces systematic bias in bulk and single-cell RNA sequencing count data
Authors: Svoboda Marek , Frost H Robert , Bosco Giovanni
Published: May 2022

Significant advances in RNA sequencing have been recently made possible by using oligo(dT) primers for simultaneous mRNA enrichment and reverse transcription priming. The associated increase in efficiency has enabled more economical bulk RNA sequencing methods and the advent of high-throughput single-cell RNA sequencing, already one of the most widely adopted methods in transcriptomics. However, the effects of off-target oligo(dT) priming on gene expression quantification have not been appreciated. In the present study, we describe the extent, the possible causes, and the consequences of internal oligo(dT) priming across multiple public datasets obtained from various bulk and single-cell RNA sequencing platforms. To explore and address this issue, we developed a computational algorithm for RNA counting methods, which identifies the sequencing read alignments that likely resulted from internal oligo(dT) priming and removes them from the data. Directly comparing filtered datasets to those obtained by an alternative method reveals significant improvements in gene expression measurement. Finally, we infer a list of human genes whose expression quantification is most likely to be affected by internal oligo(dT) priming and predict that when measured using these methods, the expression of most genes may be inflated by at least 10% whereby some genes are affected more than others.
Quantifying postpartum blood loss
Authors: Smith Jennifer , Breda Karen Lucas , Karl Cherry A.
Published: May 2022

What are the recommendations to identify postpartum hemorrhage? Use this step-by-step process to minimize barriers and build confidence to efficiently quantify excessive blood loss postpartum.
Sedation Practices in the PICU: An Unexpected Casualty of COVID-19
Authors: Pumphrey Katherine , Bouzaher Alisha , Achuff Barbara-Jo , Traube Chani
Published: May 2022

Pediatric intensivists often use an “analgosedation” approach in mechanically ventilated children. By prioritizing analgesia and minimizing sedation, patients experience less delirium. However, when COVID-19 surged, our pediatric intensive care unit providers were tasked with caring for adults with severe acute hypoxemic respiratory failure (AHRF). As documented in the literature, adults with COVID-19-AHRF received significantly higher doses of sedatives than matched cohorts with non-COVID-19 AHRF. Surprisingly, when the pediatric intensive care unit returned to caring for children, a quality review showed that we were unintentionally using far more sedatives than that prior to COVID-19. This experience is not unique to our institution, or to COVID-19. Lingering effects of crisis care can persist beyond the event itself. We seek to share our experience in order to extend the conversation regarding the unexpected effects of crises on best practices and to stress the need for high-quality research on interventions to support mental health and resilience in frontline healthcare providers.
Identification of a Germline Pyrin Variant in a Metastatic Melanoma Patient With Multiple Spontaneous Regressions and Immune-related Adverse Events
Authors: Oswalt Cameron J. , Al-Rohil Rami N. , Theivanthiran Bala , Haykal Tarek , Salama April K.S. , DeVito Nicholas C. , Holtzhausen Alisha , Ko Dennis C. , Hanks Brent A.
Published: May 2022

The mechanisms underlying tumor immunosurveillance and their association with the immune-related adverse events (irAEs) associated with checkpoint inhibitor immunotherapies remain poorly understood. We describe a metastatic melanoma patient exhibiting multiple episodes of spontaneous disease regression followed by the development of several irAEs during the course of anti–programmed cell death protein 1 antibody immunotherapy. Whole-exome next-generation sequencing studies revealed this patient to harbor a pyrin inflammasome variant previously described to be associated with an atypical presentation of familial Mediterranean fever. This work highlights a potential role for inflammasomes in the regulation of tumor immunosurveillance and the pathogenesis of irAEs.
Pinocembrin ameliorates depressive-like behaviors by regulating P2X7/TRL4 receptors expression in mouse hippocampus
Authors: Li Jia-Mei , Hu Ting , Jiang Chun-Lei , Wang Wei
Published: May 2022

Mounting evidence indicates that immune dysfunction may contribute to the neurobiology of major depressive disorder (MDD). Toll-like receptor 4 (TLR4) and P2X7 receptor (P2X7R) were recently reckoned pivotally to regulate NOD-like receptor protein 3 (NLRP3) in microglia. Pinocembrin, one of the primary flavonoids from Pinus heartwood and Eucalyptus, has been studied in various animal models of human disease with anti-inflammatory and antioxidant activities. Herein, we investigated the potential antineuroinflammatory effects of pinocembrin on chronic unpredictable mild stress (CUMS)-induced depressive-like behavior. Male C57BL/6J mice were subjected to CUMS for 4 weeks, treatment group was injected with pinocembrin at a dose of 20 mg/kg. After the stress procedure, behavioral tests, including sucrose preference tests (SPTs) and tail suspension tests (TSTs) were performed to evaluate depressive-like phenotype. Subsequently, the expression of cytokines and microglia-related inflammatory biomarkers were assessed. In the study, we found that pinocembrin significantly blocked the declination of SPT percentage and the extension of TST immobility durations in the depression mouse model. Also, we observed that pinocembrin significantly suppressed microglial activation in the hippocampus. Additionally, pinocembrin downregulated hippocampal NLRP3 through P2X7/TLR4 pathway, and also regulated the CUMS-induced imbalance of pro-inflammatory cytokines, including interleukin-1beta, tumor necrosis factor-alpha and interleukin-6. In conclusion, pinocembrin ameliorates CUMS-induced depressive-like behaviors possibly through downregulating P2X7/TLR4 pathway, providing the mechanism of antidepressant treatment.
An Approach to the Treatment of Children With COVID-19
Authors: Boast Alison , Curtis Nigel , Holschier Johanna , Purcell Rachael , Bannister Samantha , Plover Christine , Chinnapan Maidhili , Burgner David , Boyce Suzanne L. , McNab Sarah , Gwee Amanda ,   on behalf of the RCH COVID-19 Treatment Working Group
Published: May 2022

There are limited data to guide treatment recommendations for children with acute, symptomatic coronavirus disease 2019 (COVID-19). This review outlines a proposed management approach for children based on the published evidence to date and the approval of medications through drug regulatory agencies, as well as the known safety profile of the recommended drugs in this age group.
Effectiveness and safety of warm needling therapy combined with electroacupuncture for patients with plantar heel pain syndrome
Authors: Wu Juecan , Lu Jinghua , Jiang Chengyang
Published: May 2022

Background:

Several studies have reported positive therapeutic effects of electroacupuncture, warm needling, or a combination of the 2 for heel pain; however, the quality of the evidence is limited by methodological limitations. Given that there are no high-quality meta-analyses or reviews incorporating the available evidence, the aim of this study was to systematically review the level I evidence in the literature to determine whether a combination of electroacupuncture and warm needling therapy is more beneficial than acupuncture alone in patients with plantar heel pain syndrome.

Methods:

From the inception to May 2022, the Wanfang, CNKI, EMBASE, PubMed, Web of Science, and Cochrane Library electronic databases will be searched using the key phrases “acupuncture”, “warm needling”, “electroacupuncture”, “heel pain”, “plantar pain”, and “prospective” for all relevant studies. The outcomes include pain, physical disability, plantar fascia thickness, and foot functional status. Quality assessment of all studies included in this review will be independently assessed by 2 reviewers using the Cochrane Collaborations tool. We consider significant heterogeneity between trials if I
2 > 50%, and severe heterogeneity if I
2 > 75%. When significant heterogeneity is indicated, we will find the source of heterogeneity by subgroup or sensitivity analysis.

Results:

The results of our review will be reported strictly following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines and the recommendations of the Cochrane Collaboration.

Conclusions:

We initially hypothesized that combination therapy would lead to better treatment outcomes.

Registration number: 10.17605/OSF.IO/VWBYJ.
IFNL4, ACE1, PKR, IFNG, MBL2 genetic polymorphisms and severe COVID-19
Authors: Tu Hengjia , Bao Junrong
Published: May 2022

Background:

Corona virus disease 2019 (COVID-19) is caused by SARS-CoV-2, the pathogenic process of SARS-Cov-2 is related to the angiotensin-2 converting enzyme (ACE-2) on host cells. The genetic polymorphisms among different populations may influence the progression of COVID-19. However, the effects of IFNL4, ACE1, PKR, IFNG, and MBL2 in severe COVID-19 have not been systematically assessed.

Methods:

We will include all relevant English and Chinese studies by searching the following electronic databases: PubMed, MEDLINE, Embase, Web of Science, Scopus, the Cochrane Library, and Google Scholar before March 31, 2022. Two researchers will independently screen and extract the literature. The methodological quality of the included studies will be evaluated by the Cochrane Handbook for Systematic Reviews of Interventions.

Result:

This systematic review and meta-analysis will summarize the association of IFNL4, ACE1, PKR, IFNG, MBL2 genetic polymorphisms, and severe COVID-19. The results will be submitted to a peer-reviewed journal once completed.

Conclusion:

The conclusion of our study will provide evidence for the early prevention of severe COVID-19.

PROSPERO registration number:

CRD42022301735.
Metronidazole-induced hepatotoxicity in a patient with xeroderma pigmentosum
Authors: Vanoli Jennifer , Nava Miriam , Invernizzi Chiara , Panizzuti Fabio , Grassi Guido
Published: May 2022

Rationale:

Whereas metronidazole-induced hepatotoxicity is quite rare in the general population, in individuals carrying a nucleotide excision repair disorder, namely Cockayne syndrome, there is a high risk of developing this complication.

Patient concerns:

We report the case of a 44-year-old man, affected by xeroderma pigmentosum, who was admitted to the hospital presenting aspiration pneumoniae caused by worsening dysphagia and with severe hepatotoxicity during the hospitalization.

Diagnoses:

Acute hepatitis, which was leading to acute liver failure, occurred during antibiotic treatment with metronidazole and ceftazidime with an elevation of liver enzymes consistent with hepatocellular damage pattern.

Interventions:

Hydration with glucose 5% solution, pantoprazole and vitamin K were administered, meanwhile other causes of hepatitis were ruled out and the ongoing antibiotic treatment was stopped suspecting a drug-induced liver injury.

Outcomes:

Liver function nearly completely recovered 1 month later with a first rapid improvement, within few days, of aminotransferases and coagulation studies, and slower of cholestatic enzymes.

Lessons:

We describe the first case available in the literature of hepatotoxicity associated with metronidazole treatment in a xeroderma pigmentosum patient. Clinicians therefore, based on this report and according to the possible underlying mechanism shared by other genetic diseases characterized by alterations in the pathway of DNA-repair, should consider such adverse event also in patients affected by this rare disease.
Epidural abscess formation after chemoradiation therapy for esophageal cancer
Authors: Shin Kyung Eun
Published: May 2022

Rationale:

Esophageal cancer is one of the leading causes of death worldwide; the treatments vary according to the stage at diagnosis. Advanced esophageal cancer is usually treated by concurrent chemoradiation which is associated with complications including esophagitis, esophageal stricture or perforation, radiation pneumonitis, and/or cardiac toxicity. Herein, we describe epidural abscess, which is a very rare but severe complication that can occur after concurrent chemoradiation therapy for advanced esophageal cancer.

Patient concerns:

A 75-year-old man developed a fever during concurrent chemoradiation therapy for advanced esophageal cancer, which progressed to neurological deficit and paraplegia. Enhanced chest computed tomography and C-spine magnetic resonance imaging were performed.

Diagnosis:

Chest computed tomography revealed a poorly enhanced necrotic change in the cervical esophageal cancer, with mottled dirty material and fluid collection. C-spine magnetic resonance imaging revealed a prevertebral abscess with pyogenic spondylitis at the C6–T2 level. In addition, an anterior epidural abscess at the C6–7 level compressed the spinal cord.

Interventions:

The patient underwent emergency anterior cervical discectomy and decompression corpectomy.

Outcomes

: After surgery, the neurological symptoms gradually improved.

Lessons:

Pyogenic spondylitis with an epidural abscess is a rare but life-threatening complication that can develop after concurrent chemoradiation therapy for advanced esophageal cancer. Rapid, accurate diagnosis and prompt surgical treatment are important to ensure a favorable long-term prognosis and a good quality of life.
Advances in neuroRehabilitation of TREM2-related dementia
Authors: De Luca Rosaria , Marra Angela , Pollicino Patrizia , Buda Marella , Mucari Maria , Bonanno Mirjam , Torregrossa William , Caminiti Angelo , Rifici Carmela , Calabrò Rocco Salvatore
Published: May 2022

Rationable:

The aim of this study is to investigate the effects of an advanced neuroRehabilitation protocol using virtual reality in the treatment of a patient with fronto- temporal dementia due to TREM2 mutation.

Patient's concern:

A 41-year-old caucasian male, affected by Nasu-Hakola Disease (NHD), presented a 1-year history of change in behavioral and cognitive functioning, before our observation. The onset of the disease was characterized by severe pain in the lower limbs and knees with limitations in the performance of daily life activities.

Diagnosis:

Motor and cognitive deficits in NHD.

Interventions:

As the patient was in a chronic phase, to manage his cognitive and motor status, we decided to treat him by using a specific rehabilitation protocol, including 2 different types of training: conventional cognitive and motor treatment and a combined advanced approach using the virtual reality rehabilitation system (VRRS). The two protocols were separated by 4 weeks of rest, to avoid/reduce a cumulative effect. The patient's cognitive and motor profile was assessed three times: that is before (at T0) and after (at T1) the conventional training as well as at the beginning (T2) and at the end of the combined experimental approach (T3).

Outcomes:

After the combined therapeutic approach with the virtual reality rehabilitation system, we observed a significant reduction in anxiety, apathy, indifference and depressive symptoms with a more evident motor improvement involving the head and the trunk control.

Lessons:

Virtual reality can be considered a promising tool for the motor and cognitive rehabilitation of rare neurodegenerative disorders, including patients with NHD.
Is there a correlation between preoperative neutrophil-to-lymphocyte, platelet-to-lymphocyte, and lymphocyte-to-monocyte ratios and postoperative pain in video-assisted thoracoscopic surgery?
Authors: Ülger Gülay , Baldemir Ramazan , Zengin Musa , Sazak Hilal , Alagöz Ali
Published: May 2022

Many thoracic surgery procedures are now performed with video-assisted thoracoscopic surgery (VATS). Postoperative pain is a common condition in patients undergoing VATS. In this study, we aimed to investigate whether neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) are effective in evaluating postoperative pain in patients undergoing VATS.

This prospective observational study was performed between March 2021 and September 2021 at a tertiary thoracic surgery center. The study included patients who had undergone elective VATS. Preoperative and postoperative NLR, PLR, LMR, hemogram values and postoperative visual analog scale (VAS) were recorded.

A total of 105 patients were analyzed. A positive correlation was observed between postoperative monocyte, neutrophils and VAS resting and VAS cough levels in the early postoperative period. No significant correlation was found between preoperative and postoperative NLR, PLR, and LMR values and VAS rest and VAS cough values. When compared to the preoperative period, a negative correlation was found between the change in the postoperative LMR value and the VAS rest and VAS cough values in the early postoperative period.

When compared to the preoperative period, the change in postoperative neutrophil, postoperative monocytes, and postoperative LMR values in patients undergoing VATS in thoracic surgery can be used as a guide in the objective evaluation of postoperative acute pain. It is the belief of the researchers that comprehensive new studies on this subject will contribute significantly to the determination of objective criteria in postoperative pain evaluation.
Supportive management of patients with pheochromocytoma/paraganglioma undergoing noninvasive treatment
Authors: Talvacchio Sara , Nazari Matthew A. , Pacak Karel
Published: May 2022

Purpose of review

Many publications review perioperative management of pheochromocytomas/paragangliomas (PPGLs); however, a large population, including 10–20% of metastatic PPGL patients, have inoperable disease. This has necessitated the development of noninvasive treatments (e.g., radio/chemotherapy), which, in affording disease-modification, have led to an ever-growing population of surviving patients with inoperable PPGL. These patients experience debilitating symptoms arising from discomforts related to the masses themselves (e.g., pain from osseous metastasis) and symptoms from tumoral catecholamine production and release. Unfortunately, management of these conditions is not yet well-defined. Adding further insult-to-injury, these noninvasive treatments can trigger catecholamine release, worsening catecholamine-induced symptoms. Herein, we detail these ailments and their management, especially while patients receive these noninvasive treatments.

Recent findings

Improved diagnostic evaluations have allowed for earlier detection of PPGL, prolonging survival in patients with inoperable PPGLs. Accordingly, noninvasive treatment strategies have rapidly evolved alongside state-of- the-art theranostics and genetic testing, which inform ongoing management and therapeutic response.

While treatments afford improved survival, there must be a corresponding attention to quality-of-life. This is ensured by employing supportive management, which mitigates debilitating symptoms. This is best accomplished with a multidisciplinary approach and familiarity with genetic and biochemical determinants which guide patient education and management.
The uncommon forms of congenital adrenal hyperplasia
Authors: Auchus Richard J.
Published: May 2022

Purpose of review

Clinicians recognize 21-hydroxylase deficiency as the most common form of congenital adrenal hyperplasia (CAH), and many papers have been published on this condition. In contrast, much less awareness has been addressed to the other, rare forms of CAH.

Recent findings

The second most common form of CAH varies with country and ethnic background. In Brazil, 17-hydroxylase/17,20-lyase deficiency is the second most common, whereas 11-hydroxylase deficiency is most common in the Middle East. In Japan and Korea, both congenital lipoid adrenal hyperplasia and P450-oxidoreductase deficiency are more common than in the rest of the world. Finally, 3β-hydroxysteroid dehydrogenase/isomerase deficiency is rare worldwide, but pockets of affected populations, such as the Amish in Lancaster County, Pennsylvania are found. The treatment of each form varies by both the nature of steroids produced in excess above the enzymatic block and the deficiencies of steroids other than cortisol past these blocks.

This article summarizes the pathophysiology, diagnosis, and management of rare forms of CAH.