bluuebunny/crossref_metadata_2025 huggingface dataset:
Pancreatic tumours
Authors: Bowden David , Ajithkumar Thankamma
Published: February 2022

Approximately 90% of primary pancreatic tumours are ductal adenocarcinomas, which usually occur in the head and neck of the pancreas. This chapter discusses the role of different imaging modalities in the staging, assessment of operability, and therapeutic response assessment of pancreatic ductal adenocarcinoma (PDAC). Current role of radiotherapy for PDAC is summarized. Most guidelines recommend consideration for radical chemo-radiotherapy or stereotactic ablative body radiotherapy (SABR) if there is at least stable localized disease after 3–4 months of chemotherapy. Palliative radiotherapy is given for pain relief or bleeding into the duodenum. The role of different imaging modalities in the planning for conventional radiotherapy and SABR techniques is highlighted. Pancreatic neuroendocrine tumours are uncommon and are discussed in in Chapter 19.
Gynaecological cancers
Authors: Lankester Kate , Vitta Lavanya
Published: February 2022

Chapter 15 covers gynaecological cancers, including, uterine, cervical, and vaginal and vulval cancers. Ovarian cancer has not been included, as radiotherapy has only a limited role in its management. MRI is the preferred imaging modality for local staging and follow-up of uterine, cervical, and vaginal cancers due to its superior tissue contrast and delineation of anatomy and pathology. The use of intravenous gadolinium and diffusion weighted imaging provides more accurate characterization of the tumour. Contrast enhanced CT is used for assessment of distant metastasis and FDG PET/CT has a role in selected cases. Most vulval cancers are treated surgically with initial clinical assessment of the primary tumour, but for more advanced cases, MRI can help assess tumour extent and involvement of regional nodes.
Ethnic and cultural aspects of palliative and end of life care
Authors: Koffman Jonathan , Calanzani Natalia
Published: February 2022

Historic migration and the ever-increasing current migration into Western countries have greatly changed the ethnic and cultural patterns of patient populations, and their families, across the life course. This chapter attempts to identify ‘differences that make a difference’ when individuals living with, and dying from, advanced diseases who are from black, Asian, and minority ethnic groups negotiate institutions and practices for palliative and end of life care. The World Health Organization’s definition of palliative care specifies two goals: improving quality of life of patients and families and preventing and relieving suffering. It identifies three ‘colour-blind’ strategies for meeting those goals: early identification, impeccable assessment, and (appropriate) treatment. Lastly, the definition addresses four domains of care: (1) problems related to pain, (2) physical conditions, (3) the psychosocial, and (4) the spiritual. This chapter specifically addresses these goals, strategies, and domains in relation to delivering quality palliative care in cross- or multicultural settings.
Communication with the patient and family
Authors: LeBlanc Thomas W. , Tulsky James
Published: February 2022

High-quality palliative medicine depends upon communication that is patient-centred, clear, and attends to the central role of emotion in the medical encounter. Good communication leads to a number of improved outcomes including greater adherence to therapy, higher patient satisfaction, decreased anxiety and depression, and care that is more consistent with patients’ goals. Unfortunately, in practice, communication frequently does not meet these standards and opportunities are lost to meet patients’ most basic needs. That said, good communication can be deconstructed and conceptualized as a series of discrete behaviours and skills including assessing patient understanding before entering into difficult conversations, asking permission to discuss tough topics, delivering information in small manageable chunks while checking for understanding, responding to patients’ emotions, eliciting patients’ values, and aligning treatment preferences to their goals. Specific techniques and cognitive roadmaps exist to help navigate these conversations and ought to be in the toolbox of every palliative care clinician.
Acute cancer pain syndromes
Authors: Cherny Nathan I.
Published: February 2022

Cancer-related acute pain syndromes are most commonly due to diagnostic or therapeutic interventions and generally pose little diagnostic difficulty. Although some tumour-related pains have an acute onset (such as pain from a pathological fracture), most of these will persist unless effective treatment for the underlying lesion is provided. It is important to be familiar with these syndromes for several reasons: (1) when acute pain is anticipated, patients must be forewarned and steps undertaken to reduce the likelihood of distress, and if pain occurs, it requires an established therapeutic response. (2) Acute pain syndromes have variable natural histories which may influence management. This may be important in terms of pain prognosis (i.e. the anticipated time course of this problem). (3) Many of these syndromes have adverse effects and may be associated with a risk of substantial morbidity. It is important therefore to understand the significance of pain assessment and whether the pain may represent a substantial risk of harm or not. Finally, (4) there is often an important differential diagnosis with chronic pain syndromes associated with the underlying cancer.
Interventional approaches for chronic pain
Authors: Swarm Robert A. , Karanikolas Menelaos , Rao Lesley K. , Shah Rajiv K.
Published: February 2022

Severe, uncontrolled pain remains common in populations with serious or life-threatening illness. Despite the availability of oral opioid therapy in most developed countries, over 50% of persons with advanced, metastatic, or terminal cancer continue to have moderate to severe pain. Published guidelines endorse the view that these patients should be considered for procedural, or so-called interventional, pain therapies. Generally accepted indications for interventional pain therapies include (a) uncontrolled pain despite systemic analgesics and (b) unacceptable systemic analgesic adverse effects. This chapter describes these therapies and discusses how they are best used within a multimodal strategy for symptom management. Interventional pain therapies are now incorporated into best practices for cancer pain management. These therapies, especially spinal analgesics, neurolytic coeliac plexus block, and vertebroplasty, have become essential components of palliative care, in order to control pain that cannot be safely and effectively managed with systemic analgesics.
Neurostimulation in pain management
Authors: Knotkova Helena
Published: February 2022

Pain management may be challenging in those with advanced illness and/or multiple chronic conditions. Despite advances in pharmacological treatments, non-pharmacological treatment strategies are needed to optimize analgesic outcomes. Neurostimulation is a promising approach that includes an array of invasive and non-invasive methods suitable for stimulation of selected functional targets at various levels of the neuraxis, from peripheral nerves to the brain. Findings from neuroimaging and neurophysiological studies have facilitated insight into mechanisms that underlie neurostimulation-induced analgesic effects, and propelled advances in neurostimulation technology. The pool of evidence on efficacy of neurostimulation for pain management has greatly increased in the past two decades, and the interest of scientists, medical professionals, and patients in this promising non-pharmacological approach is growing.
Dysuria, frequency, and bladder spasm
Authors: Rothschild Jennifer G. , Canvasser Noah E. , Meyers Frederick J. , Evans Christopher P.
Published: February 2022

Although lower urinary tract symptoms such as dysuria, frequency, and bladder spasms may not be life-threatening, these symptoms can have a large impact on a patient’s quality of life as well as the lives of the patient’s family and caregivers in the palliative care setting. A range of medical problems can contribute to common causes of irritative voiding symptoms; the goal is to identify these potential problems and address them, taking into account the palliative care patient’s severity of symptoms, frailty, and life expectancy. In the evaluation and treatment of the patient’s symptoms, a methodical approach is best offered with the treatment options ranging from the least conservative to the more invasive. Clinicians should begin with a history and physical examination, urine analysis and/or culture to rule out urinary tract infection, and obtain post-void residual to rule out urinary retention. Patient education regarding normal urinary tract function should be reviewed and then treatment goals solidified. Conservative options include behavioural and dietary modification. If treatment goals are not yet achieved, then additional pharmacological or procedural options can be considered. The potential risks and benefits for each treatment option should be specifically tailored to the palliative care setting and the unique clinical situations presented. The goal being to decrease the most physical distress while not confounding the palliative care situation with potential complications.
Assessment and management of bleeding complications in the medically ill
Authors: Hulme Bill , Wilcox Sarah , Ashwood Paul , Deacon Laura , Gilkes Hazel , Montgomery Victoria
Published: February 2022

Haemorrhage can be a distressing symptom encountered as a presenting feature of illness, or in extreme cases as a terminal event. Bleeding can occur locally at the site of disease, as a complication of its treatment, or as part of a systemic bleeding disorder. Initial management includes control of blood loss, fluid resuscitation, and identification and reversal of potential causes. Careful consideration and discussion with the patient is needed to clarify preferences for life-prolonging treatment versus symptom control alone, and preferred place of care. Acute care settings can provide additional therapeutic options such as surgery, interventional radiology, and radiotherapy for cancers. Site-specific measures are included in this chapter along with general interventions for control of bleeding.
The role of general surgery in the palliative care of patients with cancer
Authors: Krouse Robert , Badgwell Brian
Published: February 2022

Palliative surgery is defined as surgical intervention in patients with incurable malignancy for symptoms attributable to their cancer. A considerable percentage of consultations at major cancer centres are palliative in nature, resulting in 13–21% of all operations meeting the criteria for palliative surgery. Common symptom groups for evaluation include gastrointestinal obstruction, wound problems/infections, gastrointestinal bleeding, and obstructive jaundice. This chapter outlines the indications, treatment options, and outcomes for these diagnoses, along with a few less common indications for surgical consultation. Clinical trials are infrequent in this population and there is a paucity of prospective studies with quality of life outcomes measures. Most studies focus on morbidity and mortality as palliative surgery has long been recognized as having increased risk for complications. The benefits of palliative surgery should focus on quality of life, symptom control, and symptom prevention. Future studies will be needed to better assess success, including patient-reported outcomes assessment.
Malignant bowel obstruction
Authors: Boland Jason W. , Boland Elaine G.
Published: February 2022

Malignant bowel obstruction is the clinical presentation of patients with symptoms, signs, or radiographic evidence of obstruction to the transit of gastrointestinal contents caused by cancer, or the consequences of anticancer therapy including surgery, chemotherapy, and radiotherapy. Malignant bowel obstruction is often encountered in oncology, surgery, and hospice/palliative care practice. It causes symptoms including nausea, vomiting, abdominal distension, colic, and continuous abdominal pain and constipation. Careful clinical assessment and an understanding of the goals of care, patient’s disease trajectory, prognosis, and treatment preferences with discussion in a multidisciplinary team are crucial in managing malignant bowel obstruction. In patients with a single-level obstruction and good functional status, surgical opinion/stenting should be offered. Patients with multilevel obstruction generally have a poor prognosis, are rarely surgical candidates, and management is with pharmacological therapy, sometimes combined with parenteral hydration, nasogastric tube drainage, or venting gastrostomy.
Palliative care issues in populations with haematological malignancies
Authors: LeBlanc Thomas W. , El-Jawahri Areej
Published: February 2022

Haematological malignancies (HM) are a heterogeneous group of diseases, both in terms of commonly used treatments and associated outcomes. Compared to patients with solid tumours, those with HM have similar or greater palliative care needs, including marked symptom burden, quality of life impairment, and psychological distress. HM patients also struggle with poor illness understanding, may face very difficult treatment decisions, and receive more intense care at the end of life compared to solid tumour patients, including terminal hospitalizations, receipt of chemotherapy in the last 2 weeks of life, and a failure to use hospice care services. There are several barriers to integrated palliative care in HM, including illness-specific, clinician-related, and systems-based factors. However, recent evidence demonstrates the feasibility and efficacy of integrated palliative care in HM settings. More research is needed to heighten the understanding of unmet palliative care needs in HM patients, and to inform the development of novel interventions to improve the experience of patients, their families, and the clinicians who treat these diseases.
Truth telling and consent
Authors: Emanuel Linda , Johnson Rebecca , Boyken Lara
Published: February 2022

The ways in which people ascertain reality and cope with unwanted truths is deep and complex. Truth telling and informed consent are established legal and ethical norms in end of life healthcare. This chapter provides an exploratory guide to the evolution of both norms, highlighting some benefits, problems, and issues associated with both terms. It presents a selection of stepwise protocols and practices, which Western medicine has developed to deliver patient-centred palliative care. In addition, it discusses the impact that constant adjustment to loss can have on patient psychology and decision-making in end of life care scenarios and the value of framing that experience as continuous reintegration. Finally, the chapter discusses what can be learned from the contested place of family within healthcare systems where decision-making depends on truth telling and informed consent, and lessons from familism across the globe.
Informatics and literature search
Authors: Tieman Jennifer , Currow David C.
Published: February 2022

Health information technology is changing how health professionals engage with and use knowledge and how health systems organize care. Tools and resources can facilitate access to evidence and enable its application in practice, improving outcomes for the individual patient and for the healthcare system. However, the quality of these applications relies on the quality and currency of the domain knowledge that is embedded within them and distributed through them. Therefore, being able to identify and retrieve palliative care’s evidence base is more critical than ever. Given the complexity of timely, efficient, and effective retrieval of needed knowledge, new approaches are needed to manage the expanding and diffuse knowledge base for palliative care. Such strategies include developing online repositories of clinical knowledge to ensure immediate access and creating search solutions that shortcut access to literature and evidence to support practice, research, and education.
Validated assessment tools for psychological, spiritual, and family issues
Authors: Li Madeline , Balboni Tracy A. , Nissim Rinat , Rodin Gary
Published: February 2022

Palliative care encompasses psychological, spiritual, and family domains along with physical concerns. Validated measures of relevant outcomes are increasingly available and can contribute to improving the quality of care by enhancing the assessment of disturbances, allowing for greater confidence in what is being measured, improving specificity in subsequent assessments or interventions, and increasing comparability and generalizability of research findings across different settings. This chapter provides an overview of validated tools that can be used to assess well-being, distress, and impairment in psychological, spiritual, and family domains of palliative care. Optimal clinical use of the measurement tools is discussed and the quality of research evidence is evaluated. Recommendations for integration of these measures into clinical practice and future directions for research are made.
Nurses
Authors: Kurita Geana Paula , Larkin Philip J.
Published: February 2022

The values, knowledge, and skills of nursing practice are applicable across all clinical settings and notably in common with palliative care principles. Nurses possibly hold the highest level of engagement and interaction with patients, relatives, and caregivers and play a central role in the care of patients at the end of life, offering a unique opportunity to foster and integrate principles and practice of palliative care into their daily work. Efforts to build nursing education in this area have been realized over the last two decades and a core principle is that all nurses must be educated to develop competencies and implement palliative care in their practice, whether generalist or specialist. This chapter describes the principles of palliative care nursing and educational recommendations to build knowledge and to advance the specialty. There is a special focus on nursing roles and levels of education, besides examples of major educational activities and curriculum content. Furthermore, challenges and future directions in the provision of optimal patient and family care are discussed, recognizing the significant nursing contribution.
It is not just the category: behavioral effects of fMRI-guided electrical microstimulation result from a complex interplay of factors
Authors: Kumar Satwant , Mergan Eline , Vogels Rufin
Published: February 2022

Functional imaging and electrophysiological studies in primates revealed the existence of patches selective for visual categories in the inferior temporal cortex. Understanding the contribution of these patches to perception requires causal techniques that assess the effect of neural activity manipulations on perception. We used electrical microstimulation (EM) to determine the role of body patch activity in visual categorization in macaques. We tested the hypothesis that EM in a body patch would affect the categorization of bodies versus objects but not of other visual categories. We employed low-current EM of an anterior body patch (ASB) in the superior temporal sulcus, which was defined by functional magnetic resonance imaging and verified with electrophysiological recordings in each session. EM of ASB affected body categorization, but the EM effects were more complex than the expected increase of body-related choices: EM affected the categorization of both body and inanimate images and showed interaction with the choice target location, but its effect was location-specific (tested in 1 subject) on a millimeter scale. Our findings suggest that the behavioral effects of EM in a category-selective patch are not merely a manifestation of the category selectivity of the underlying neuronal population but reflect a complex interplay of multiple factors.
Inattentive and hyperactive traits differentially associate with interindividual functional synchrony during video viewing in young children without ADHD
Authors: Tansey Ryann , Graff Kirk , Rohr Christiane S , Dimond Dennis , Ip Amanda , Dewey Deborah , Bray Signe
Published: February 2022

Inattention and hyperactivity present on a spectrum and may influence the way children perceive and interact with the world. We investigated whether normative variation in inattentive and hyperactive traits was associated with differences in brain function, while children watched clips from an age-appropriate television program. Functional magnetic resonance imaging (fMRI) data and parent reports of inattention and hyperactivity traits were collected from 81 children 4–7 years of age with no parent-reported diagnoses. Data were analyzed using intersubject correlations (ISCs) in mixed effects models to determine if inattentive and hyperactive traits were associated with idiosyncrasy of fMRI response to the video. We hypothesized that pairs of children with higher average inattention and hyperactivity scores would show less interindividual brain synchrony to one another than pairs with lower average scores on these traits. Video watching engaged widespread visual, auditory, default mode and dorsal prefrontal regions. Inattention and hyperactivity were separably associated with ISC in many of these regions. Our findings suggest that the spectrum of inattention and hyperactivity traits in children without ADHD are differentially associated with neural processing of naturalistic video stimuli, which may have implications for understanding how children with different levels of these traits process audiovisual information in unconstrained conditions.
Anticoagulation Monitoring in the Intensive Care Unit
Authors: Gilbert Brian W. , Reeder Jacob A. , Reynolds Tessa R. , Tabaka Caitlynn A. , Rech Megan A.
Published: February 2022

Patients with critical illness often display variable hypo- and hypercoagulable sequalae requiring intense monitoring and anticoagulation pharmacotherapy to prevent or treat inappropriate clot formation. It is imperative to understand the various stages of the clotting cascade and where each pharmacotherapy agent exerts its therapeutic effect. Common coagulation tests are utilized to monitor the areas of the clotting cascade and the effects that anticoagulant pharmacotherapy exhibits. Many novel coagulation tests are also in development. The purpose of this narrative review is to evaluate commonly utilized coagulation tests that monitor anticoagulation while in the intensive care unit.
Use of Prothrombin Complex Concentrate in Oral Anticoagulant-Associated Major Bleeding
Authors: Lukas Jack G. , Reichert Michael J. , Jones G. Morgan
Published: February 2022

Severe bleeding remains the most significant adverse effect associated with both warfarin and the direct oral anticoagulant agents. Due to the life-threatening nature of these bleeds, knowledge and understanding of agents that are able to rapidly overcome the anticoagulation effects of these medications is paramount to their use. Worldwide, the most commonly used agent for this indication is prothrombin complex concentrate (PCC). This review summarizes the evidence on the use of PCC in this population and provides practical information regarding patient-specific administration considerations.
Use of the Three-dimensional Viewing System and Microscope Tilting to Extend the Peripheral Retinal View
Authors: Sandali Otman , Tahiri Joutei Hassani Rachid , Dulière Cedric , El Sanharawi Mohamed , Borderie Vincent , Williams George A.
Published: February 2022

Purpose:

To describe and evaluate the effectiveness of the microscope and lens tilting technique associated with the three-dimensional viewing system for improving the peripheral retinal view in noncontact lens vitreoretinal surgeries.

Methods:

Prospective, single-center, single-surgeon, consecutive case series of 25 patients undergoing vitrectomy for macular surgeries with three-dimensional visualization system. At the end of each surgery, the microscope and the noncontact lens were rotated by 20° in a direction opposite to the rotation of the eye to extend the peripheral visual field.

Results:

Microscope and lens tilting technique extended the edge of the peripheral viewing field relative to its position with the microscope untilted, by 1.72 mm (±0.37) for the superior retina and 1.93 mm (±0.42) for the inferior retina (P < 0.0001). The ora serrata was visualized in 33% and 0% of cases for the superior retina and 91% and 36% of cases for the inferior retina, in tilted and nontilted microscope positions, respectively (P < 0.01).

Conclusion:

Microscope and lens tilting could be useful to extend the peripheral visual field of view in retinal surgery. The three-dimensional system allowed to maintain surgeon comfort and posture during surgery.
Stripping of the Posterior Hyaloid for the Treatment of Vitreomacular Traction
Authors: Rizzo Stanislao , Scampoli Alessandra , Gambini Gloria , D'Amico Guglielmo , Governatori Lorenzo , Baldascino Antonio , Carlà Matteo Mario , Caporossi Tomaso
Published: February 2022

Purpose:

To describe and evaluate the effectiveness of stripping the posterior hyaloid as vitreomacular traction treatment.

Methods:

This prospective, consecutive, interventional study examined 10 eyes of 10 patients who underwent vitrectomy for vitreomacular traction.

Results:

The best-corrected visual acuity improved from 20/63 (0.5 ± 0.18 logMAR) preoperatively to 20/36 (0.25 ± 0.15 logMAR) 3 months after the surgeries. Optical coherence tomography analysis showed a reduction of the mean foveal thickness from 462 ± 82 µ to 372 ± 28 µ at 3-month follow-up in all the eyes. No postoperative complications were reported.

Conclusion:

Stripping of the posterior hyaloid for the treatment of vitreomacular traction could improve the symptoms and visual acuity of patients, alleviating the traction on the macula and avoiding secondary retinal damage as macular hole formation.
Perceptions on Screening for Developmental Disabilities and Autism in Childcare Settings
Authors: Uzonyi Thelma E. , Page Jessica M. , DuBay Michaela , Crais Elizabeth R.
Published: February 2022

This qualitative study explored the knowledge and perceptions about early screening for developmental disabilities and autism spectrum disorder (ASD) in childcare settings using semistructured interviews with directors, teachers, and parents at 12 childcare centers. Results indicated that most of the directors and teachers, who were interviewed, were cautiously open to implementing screening programs but wanted additional training in recognizing early signs of ASD and other developmental disabilities, as well as communicating with families about concerns. All interviewed parents reported wanting childcare professionals to communicate with them if they had developmental concerns for their child, and all but one parent was open to the idea of universal screening at their child's center.
Vestibular Nerve Section via Middle Cranial Fossa Approach
Authors: Vesole Adam S. , Shapiro Scott B. , Samy Ravi N.
Published: February 2022

Vestibular nerve section (VNS) is a surgical intervention with hearing preservation used for the treatment of Menière's disease after conservative medical therapy has failed (1,2). With the recent rise in less invasive treatments such as intratympanic gentamicin, VNS has been performed less frequently (3). The middle cranial fossa (MCF) approach for VNS is an uncommon approach due to its technical difficulty. However, it can provide the best distinction of internal auditory canal contents compared with retrosigmoid and retrolabyrinthine approaches. Several advancements in the MCF approach have been described, including the use of intraoperative facial nerve monitoring with electromyography, early removal of the temporal lobe retractor, and the use of an ultrasonic bone aspirator for internal auditory canal decompression (4–6). We demonstrate a case study with a step-by-step approach to successfully sectioning the superior and inferior vestibular nerves while utilizing these advancements and avoiding facial and cochlear nerve injury via the MCF (7).

SDC video link: http://links.lww.com/MAO/B409.
A Possible Mechanism for Flecainide Induced Dizziness
Authors: Garaycochea Octavio , Riesgo Álvaro , Manrique-Huarte Raquel , Pérez-Fernández Nicolás
Published: February 2022

Objective:

Flecainide is an oral class IC antiarrhythmic drug whose most common extracardiac adverse reactions are “dizziness” and “visual disturbances.” We describe a case of flecainide associated- bilateral vestibulopathy and a literature review of this drug's effect on the vestibular system.

Patient:

Sixty-nine-year-old man with a 3-month history of unsteadiness and dizziness after an increase in the dose of flecainide.

Interventions:

Otologic examination, video head-impulse test, vestibular evoked myogenic potentials, pure tone audiometry and high-resolution magnetic resonance imaging.

Results:

Otologic examination, including the head-impulse test, and vestibular testing revealed bilateral vestibulopathy.

Conclusions:

Dizziness is a common extracardiac adverse reaction of Flecainide. Based on the clinical case that we present and the literature review carried out, we hypothesized that a possible mechanism by which flecainide might cause dizziness and visual disturbances is bilateral vestibulopathy.
Late Bleeding Episodes Following Intestinal Transplantation: It Is Not Always Rejection or Infection
Authors: Singh Harveen , Selvarajan Lakshmi , Ong Sik-Yong , Ali Sajeed , Sharif Khalid , Mirza Darius , Gupte Girish
Published: February 2022

Ectopic varices have been reported in 5% of children presenting with variceal bleeding and are defined as portosystemic venous collaterals occurring anywhere in the abdomen except in the cardioesophageal region. The liver-intestinal transplant or isolated liver-intestinal transplant patient presenting several years post-transplant with ectopic variceal bleeding as a consequence of portal hypertension is a seldom reported complication. Etiologies such as rejection or infection are a more common source of bleeding, and only after excluding these can differentials such as portal hypertension secondary to a blocked portacaval shunt or native liver disease be considered.
Chronic Diarrhea in an Infant With Malrotation: A Diagnostic Dilemma
Authors: Josyabhatla Rohit , Tatevian Nina , Tchakarov Amanda S. , Cox Charles S. , Van Arsdall Melissa R.
Published: February 2022

In children, diarrhea has a global incidence of 2.7 episodes per child-year and contributes to significant disease burden and mortality in children under 5 years of age. Chronic diarrhea, defined as diarrhea lasting for more than 2 weeks, may be particularly challenging to evaluate and manage in children under 2 years of age. While most have infectious enteritis or cow milk protein intolerance, others have conditions such as malnutrition, anatomic abnormalities, or congenital enteropathies that can be challenging to diagnose and treat. We present here a complex case of chronic diarrhea in an infant and highlight such diagnostic and therapeutic challenges.
Esophageal Squamous Papilloma in the Pediatric Population
Authors: Malhotra Neha , Lendner Nuphar , Gagliardo Christina , Pittman Meredith , Breglio Keith , Mor Niv , Wetzler Graciela
Published: February 2022

Esophageal squamous papillomas (ESP) are rare benign tumors of the esophagus, which occur mostly in the adult population. Few cases have been reported in children and due to the low incidence, the pathogenesis of ESP is not entirely understood and the management is not standardized. It is thought that mucosal irritation from underlying inflammation, perhaps from GERD, trauma or human papilloma viruses can play a role in the formation of ESP. This report describes 4 cases of pediatric ESP from a single center and discusses the management of these lesions, including the use of antacids and the human papilloma viruses vaccine as treatment modalities. Given the limited data on ESP in the pediatric population, this report aims to describe the management of this condition in 1 center.
Does Wait Time During Acute Care for Transfer to Rehabilitation Admission Impact the Outcomes After a Traumatic Spinal Cord Injury?
Authors: Richard-Denis Andréane , Dionne Antoine , Bourassa-Moreau Étienne , Khoueir Paul J. , Maurais Gilles , Mac-Thiong Jean-Marc
Published: February 2022

Background

The objective of this study was to determine the impact of wait time in acute care for inpatient functional rehabilitation admission on the inpatient functional rehabilitation length of stay and functional outcome after a traumatic spinal cord injury.

Methods

A retrospective cohort including 277 patients admitted to a single level 1 spinal cord injury acute care center was completed. Partial correlations were used between wait time (in days) for transfer to inpatient functional rehabilitation, the inpatient functional rehabilitation length of stay, and the Spinal Cord Independence Measure total score in the chronic period, adjusting for confounding variables. Stratified analyses were carried out based on the age group and severity of the injury.

Results

Patients had to wait a mean of 7.3 ± 6.4 days (median = 6 days, interquartile range = 2–10 days, max = 29 days) for inpatient functional rehabilitation admission after rehabilitation readiness, which was not associated with the outcomes when adjusted (P > 0.05). However, individuals 65 yrs or older with a motor-complete injury showed a lower functional status when exposed to wait time for transfer (r = −0.87, P = 0.02).

Conclusions

Wait time up to 29 days may have no impact on the inpatient functional rehabilitation length of stay nor functional outcome after traumatic spinal cord injury. However, additional resources and/or prioritization should be considered for vulnerable subgroups.
Paratriathlon Race Performance in High-Level Athletes With Visual Impairments
Authors: Lima Gabriel Benedito , Kons Rafael Lima , Detanico Daniele , Fischer Gabriela
Published: February 2022

Objective

The aim of this study was to compare time-trial performances in elite paratriathlon athletes, according to visual classes, sex, and medal distribution.

Design

The data were acquired from official books on Para Triathlon World Cups (2018–2020). The sample included 150 athletes with visual impairment, in classes: PTVI1, PTVI2, and PTVI3. One-way analysis of variance, the Student t test, and χ2 were used to compare the performance variables and association between visual impairment classes and distribution of medals within different visual impairment classes.

Results

Sex comparisons demonstrated better performance for male athletes compared with female athletes (P < 0.05). In the sex-specific analysis, only cycling velocity was higher for female, being lower for PTVI1 compared with PTVI3 (P = 0.012). In visual impairment class results, the first transition time was higher for PTVI1 compared with PTVI2 (P = 0.050) and PTVI3 (P = 0.027) and, in the second transition, higher for PTVI1 compared with PTVI2 (P = 0.001). The χ2 test showed a higher percentage of gold medals for PTVI3 athletes considering the whole group (P = 0.050).

Conclusions

These results indicate that male athletes have better performance than female athletes. PTVI1 female athletes showed lower cycling velocity compared with PTVI3. Considering both male and female groups, blind athletes presented higher transition times and a lower percentage of medals.
Using molecular epidemiology to trace the history of the injection-related HIV epidemic in New York City, 1985–2019
Authors: Torian Lucia V. , Forgione Lisa , Wertheim Joel O.
Published: February 2022

Objective:

Unintentional drug poisoning and overdose deaths in New York City (NYC) increased 175% between 2010 and 2017, partly due to the transition from noninjectable opioids to heroin injection. This transition has led to concern of a resurgent HIV epidemic among persons who inject drugs (PWID) in NYC. Thus, we sought to characterize HIV transmission dynamics in PWID.

Design:

Genetic network analysis of HIV-1 public health surveillance data.

Methods:

We analyzed HIV diagnoses reported to public health surveillance to determine the trajectory of the HIV epidemic among PWID in NYC, from 1985 through 2019. Genetic distance-based clustering was performed using HIV-TRACE to reconstruct transmission patterns among PWID.

Results:

The majority of the genetic links to PWID diagnosed in the 1980s and 1990s are to other PWID. However, since 2011, there has been a continued decline in new diagnoses among PWID, and genetic links between PWID have become increasingly rare, although links to noninjecting MSM and other people reporting sexual transmission risk have become increasingly common. However, we also find evidence suggestive of a resurgence of genetic links among PWID in 2018–2019. PWID who reported male-male sexual contact were not preferentially genetically linked to PWID over the surveillance period, emphasizing their distinct risk profile from other PWID.

Conclusion:

These trends suggest a transition from parenteral to sexual transmission among PWID in NYC, suggesting that harm reduction, syringe exchange programs, and legalization of over-the-counter syringe sales in pharmacies have mitigated HIV risk by facilitating well tolerated injection among new PWID.
High Cellular Uptake Gene Delivery Platform with Chitosan and L-arginine Complex for Cancer Treatment
Authors: Wang Maidou , Zhang Hongqian , Yang Chuanxu
Published: February 2022

Gene therapy outperforms chemotherapy in limiting the harm to human body. A major impediment to the progress of gene therapy is a lack of proper carriers. Chitosan, derived from shellfish, is a desirable candidate for nucleic acid delivery because of its outstanding biodegradability and biocompatibility. However, previous works show that chitosan has poor cell membrane permeability. In this study, we synthesize a complex delivery system for gene therapy by compounding chitosan with L-arginine, and test the encapsulation, uptake, and cancer cell treatment power. Encapsulation efficiency of the chitosan/L-arginine complex (CA) can reach more than 90% in weight. Flow cytometry reveal that siRNA delivered by the complex can be taken in by cells 10 times better than free siRNA and 2 times better than chitosan alone. Confocal imaging confirmed the high cellular uptake, and siRNA tests in HeLa cells indicate the successful silencing of the target gene (RRM2). The complex serves as a gene delivery system that is capable of loading and delivering a variety of genetic materials in which the specific nucleic acid molecule to be delivered could be altered at will.
Risk of Long Covid in people infected with SARS-CoV-2 after two doses of a COVID-19 vaccine: community-based, matched cohort study
Authors: Ayoubkhani Daniel , Bosworth Matthew L. , King Sasha , Pouwels Koen B. , Glickman Myer , Nafilyan Vahé , Zaccardi Francesco , Khunti Kamlesh , Alwan Nisreen A. , Walker A. Sarah
Published: February 2022

Background

It is unclear whether receiving two COVID-19 vaccinations before SARS-CoV-2 infection reduces the risk of developing Long Covid symptoms. We examined whether the likelihood of symptoms 12 weeks after infection differed by vaccination status.

Methods

We included COVID-19 Infection Survey participants aged 18-69 years who tested positive for SARS-CoV-2 between 26 April 2020 and 30 November 2021; we excluded participants who, before their first test-confirmed infection, had suspected COVID-19 or Long Covid symptoms, or were single-vaccinated. Participants who were double-vaccinated ≥14 days before infection were 1:1 propensity-score matched, based on socio-demographic characteristics and time from infection to follow-up for Long Covid, to those unvaccinated at time of infection. We estimated adjusted odds ratios (aOR) of Long Covid symptoms ≥12 weeks post-infection, comparing double-vaccinated with unvaccinated (reference group) participants.

Results

The study sample comprised 3,090 double-vaccinated participants (mean age 49 years, 54% female, 92% white, median follow-up from infection 96 days) and matched control participants. Long Covid symptoms were reported by 294 double-vaccinated participants (prevalence 9.5%) compared with 452 unvaccinated participants (14.6%), corresponding to an aOR for Long Covid symptoms of 0.59 (95% CI: 0.50 to 0.69). There was no evidence of heterogeneity by adenovirus vector versus messenger ribonucleic acid vaccines (p=0.25).

Conclusions

COVID-19 vaccination is associated with reduced risk of Long Covid, emphasising the need for public health initiatives to increase population-level vaccine uptake. Longer follow-up is needed, as is the assessment of further vaccine doses and the Omicron variant.
COVID-19 mortality in the United States: It’s been two Americas from the start
Authors: Stoto Michael A. , Schlageter Samantha , Kraemer John
Published: February 2022

During the summer of 2021, a narrative of “two Americas” emerged: one with high demand for the COVID-19 vaccine and the second with widespread vaccine hesitancy and opposition to masks and vaccines.

We analyzed “excess mortality” rates (the difference between total deaths and what would have been expected based on earlier time periods) prepared by the CDC for the United States from January 3, 2020 to September 26, 2021.

Between Jan. 3, 2020 and Sept. 26, 2021, there were 895,693 excess deaths associated with COVID-19, 26% more than reported as such. The proportion of deaths estimated by the excess mortality method that were reported as COVID-19 was highest in Northeast (92%) and lowest in the West (72%) and South (76%).

Of the estimated deaths, 43% occurred between Oct. 4, 2020 and Feb. 27, 2021. Before May 31, 2020, approximately 56% of deaths were in the Northeast, where 17% of the population resides. Subsequently, 48% of deaths were in the South, which makes up 38% of the population. Since May 31, 2020, the South experienced COVID-19 mortality 26% higher than the national rate, whereas the Northeast’s rate was 42% lower.

If each region had the same mortality rate as the Northeast, more than 316,234 COVID-19 deaths between May 31, 2020 and Sept. 26, 2021 were “avoidable.” More than half (63%) of the avoidable deaths occurred between May 31, 2020 and February, 2021, and more than half (60%) were in the South.

Regional differences in COVID-19 mortality have been strong throughout the pandemic. The South has had higher mortality rates than the rest of the U.S. since May 31, 2020, and experienced 62% of the avoidable deaths. A comprehensive COVID-19 policy, including population-based restrictions as well as vaccines, is needed to control the pandemic.
In vitroevolution ofListeria monocytogenesreveals selective pressure for loss of SigB and AgrA function at different incubation temperatures
Authors: Guerreiro Duarte N. , Wu Jialun , McDermott Emma , Garmyn Dominique , Dockery Peter , Boyd Aoife , Piveteau Pascal , O’Byrne Conor P.
Published: February 2022

The alternative sigma factor B (σB) contributes to the stress tolerance of the foodborne pathogenListeria monocytogenesby upregulating the General Stress Response. We previously showed that σBloss-of-function mutations arise frequently in strains ofL. monocytogenes, and suggested that mild stresses might favour the selection of such mutations. In this study, we performedin vitroevolution experiments (IVEE) whereL. monocytogeneswas allowed to evolve over 30 days at elevated (42°C) or lower (30°C) incubation temperatures. Isolates purified throughout the IVEE revealed the emergence ofsigBoperon mutations at 42°C. However, at 30°C independent alleles in theagrlocus arose, resulting in the inactivation of the Agr quorum sensing. Colonies of bothsigB−andagr−strains exhibited a greyer colouration on 7-days-old agar plates compared with the parental strain. Scanning electron microscopy revealed a more complex colony architecture in the wild type than in the mutant strains.sigB−strains outcompeted the parental strain at 42°C, but not at 30°C, whilstagr−strains showed a small increase in competitive fitness at 30°C. Analysis of 40,080L. monocytogenespublicly available genome sequences revealed a high occurrence rate of premature stop codons in both thesigBandagrCAloci. An analysis of a localL. monocytogenesstrain collection revealed 5 out of 168 strains carryingagrCAalleles. Our results suggest that the loss of σBor Agr confer an increased competitive fitness in some specific conditions and this likely contributes to the emergence of these alleles in strains ofL. monocytogenes.

Importance

To withstand environmental aggressionsL. monocytogenesupregulates a large regulon through the action of the alternative sigma factor B (σB). However, σBbecomes detrimental forL. monocytogenesgrowth under mild stresses, which confer a competitive advantage to σBloss-of-function alleles. Temperatures of 42°C, a mild stress, are often employed in mutagenesis protocols ofL. monocytogenesand promote the emergence of σBloss-of-function alleles in thesigBoperon. In contrast, lower temperatures of 30°C promote the emergence of Agr loss-of-function alleles, a cell-cell communication mechanism inL. monocytogenes. Our findings demonstrate that loss-of-function alleles emerge spontaneously in laboratory-grown strains. These alleles rise in the population as a consequence of the trade-off between growth and survival imposed by the activation of σBinL. monocytogenes. Additionally, our results demonstrate the importance of identifying unwanted hitchhiker mutations in newly constructed mutant strains.
The ankyrin repeat protein RARP-1 is a periplasmic factor that supportsRickettsia parkerigrowth and host cell invasion
Authors: Sanderlin Allen G. , Hanna Ruth E. , Lamason Rebecca L.
Published: February 2022

Rickettsiaspp. are obligate intracellular bacterial pathogens that have evolved a variety of strategies to exploit their host cell niche. However, the bacterial factors that contribute to this intracellular lifestyle are poorly understood. Here, we show that the conserved ankyrin repeat protein RARP-1 supportsRickettsia parkeriinfection. Specifically, RARP-1 promotes efficient host cell entry and growth within the host cytoplasm, but it is not necessary for cell-to-cell spread or evasion of host autophagy. We further demonstrate that RARP-1 is not secreted into the host cytoplasm byR. parkeri. Instead, RARP-1 resides in the periplasm, and we identify several binding partners that are predicted to work in concert with RARP-1 during infection. Altogether, our data reveal that RARP-1 plays a critical role in the rickettsial life cycle.

Importance

Rickettsiaspp. are obligate intracellular bacterial pathogens that pose a growing threat to human health. Nevertheless, their strict reliance on a host cell niche has hindered investigation of the molecular mechanisms driving rickettsial infection. This study yields much needed insight into theRickettsiaankyrin repeat protein RARP-1, which is conserved across the genus but has not yet been functionally characterized. Earlier work had suggested that RARP-1 is secreted into the host cytoplasm. However, the results from this work demonstrate thatR. parkeriRARP-1 resides in the periplasm and is important both for invasion of host cells and for growth in the host cell cytoplasm. These results reveal RARP-1 as a novel regulator of the rickettsial life cycle.