Polio virotherapy targets the malignant glioma myeloid infiltrate with diffuse microglia activation engulfing the CNS.

BACKGROUND: Malignant gliomas commandeer dense inflammatory infiltrates with glioma-associated macrophages and microglia (GAMM) promoting immune suppression, evasion, and tumor progression. Like all cells in the mononuclear phagocytic system, GAMM constitutively express the poliovirus receptor, CD155. Besides myeloid cells, CD155 is widely upregulated in the neoplastic compartment of malignant gliomas. Intratumor treatment with the highly attenuated rhino:poliovirus chimera, PVSRIPO, yielded long-term survival with durable radiographic responses in patients with recurrent glioblastoma (Desjardins et al. New England Journal of Medicine, 2018). This scenario raises questions about the contributions of myeloid versus neoplastic cells to polio virotherapy of malignant gliomas. METHODS: We investigated PVSRIPO immunotherapy in immunocompetent mouse brain tumor models with blinded, board-certified neuropathologist review, a range of neuropathological, immunohistochemical, and immunofluorescence analyses, and RNAseq of the tumor region. RESULTS: PVSRIPO treatment caused intense engagement of the GAMM infiltrate associated with substantial, but transient tumor regression. This was accompanied by marked microglia activation and proliferation in normal brain surrounding the tumor, in the ipsilateral hemisphere and extending into the contralateral hemisphere. There was no evidence for lytic infection of malignant cells. PVSRIPO-instigated microglia activation occurred against a backdrop of sustained innate antiviral inflammation, associated with induction of the Programmed Cell Death Ligand 1 (PD-L1) immune checkpoint on GAMM. Combining PVSRIPO with PD1/PD-L1 blockade led to durable remissions. CONCLUSIONS: Our work implicates GAMM as active drivers of PVSRIPO-induced antitumor inflammation and reveals profound and widespread neuroinflammatory activation of the brain-resident myeloid compartment by PVSRIPO.

Complex decongestive therapy in a patient with poliomyelitis, bilateral lymphoedema and a deep wound: a case study.

OBJECTIVE: The aim of this case report is to describe the results of complex decongestive therapy (CDT) in a patient with poliomyelitis and bilateral lymphoedema, and to emphasise the effect of CDT on wound healing. METHOD: A 48-year-old female patient was given CDT for bilateral grade 3 lymphoedema in the lower extremities and a deep wound on the right foot. She had been diagnosed with poliomyelitis sequela and mobilised with a wheelchair for 26 years. The lymphoedema on both legs and the wound on the right foot sole had been present for five years and eight months, respectively. Detailed wound care had been performed previously upon the green, malodorous infected wound, without healing. The patient received skin care education, manual lymphatic drainage, multilayer bandaging and exercises for 4 weeks in a total of 20 sessions. The improvement was assessed by limb volumes prior to and at the end of the treatments. RESULTS: The right and left lower limb volumes were decreased significantly at the end of treatments (3042cm³ (R) and 3165cm³ (L) before versus 2702cm3 (R) and 2401cm3 (L) afterward). The wound size decreased considerably and the green malodorous flow ceased. The patient continued self-massage and self-bandaging after hospital discharge. The control follow-up, one month later, revealed a completely healed wound with maintained volume. CONCLUSION: In conclusion CDT for a duration of 4 weeks in a female patient with poliomyelitis, bilateral lymphoedema and an infectious hard-to-heal wound, improved both the lymphoedema and wound healing.

Bracing: Upper and Lower Limb Orthoses.

The goals of bracing in polio and postpolio are to optimize joint position and support weak muscles with the goal of reducing falls, reducing deformities, and optimizing energy conservation. Orthoses are primarily used in the lower extremities to optimize gait. Less frequently, upper extremity orthoses are required. Polio survivors are at increased risk of falls and injuries. Appropriate bracing and compliance with the prescribed device can prevent falls and injuries. The best orthotic results are often achieved with patients who have significant deficits but walk regularly, are well motivated, and are willing to adapt their gait for orthotic use.

Nerve Conduction Study/Electromyography: Common Neuropathies and Considerations for Patients with Polio.

Acute poliomyelitis is now extremely rare in the United States. Worldwide there are still sporadic outbreaks, which are typically treated with acute inoculation programs. Although polio has effectively been eradicated, the full scope of the disease and its myriad manifestations both in the acute phase and in the postpolio syndrome phase, remain areas of fertile research, debate, and stimulating topics.

Neuromuscular Scoliosis: When, Who, Why and Outcomes.

Scoliosis has a very high prevalence among patients with neuromuscular disease involving the thoracic spine and truncal muscles. Physical examination and radiographs are used to screen for presence of scoliosis and monitor progression. Management includes therapy participation, optimizing equipment and orthotic use, and possible surgical intervention. Unlike idiopathic adolescent scoliosis, curves tend to progress despite orthotic use compliance. Associated pelvic obliquity creates risk for pressure sores and pain. As such, education of caregivers is a key point of optimizing management.

Palliative Care for Polio and Postpolio Syndrome.

Palliative care is a team-based approach focusing on relief of physical, psychosocial, and existential distress and communication about serious illness. Patients with poliomyelitis and postpolio syndrome are at risk for contractures and can benefit from involvement of physical and occupational therapy. Hypersialorrhea can be treated with anticholinergic medications, botox, or radiation. Patients with dyspnea may require noninvasive positive pressure ventilation ± opioids or benzodiazepines. Constipation is often due to autonomic dysfunction and decreased mobility. There is a higher burden of anxiety. Early conversations about patients' goals and values as it relates to their health may help frame future decision-making.

Medical Comorbidities and Complications Associated with Poliomyelitis and Its Sequelae.

Survivors of poliomyelitis may experience long-term sequelae that put them at increased risk for injury, pain, cardiovascular deconditioning, and functional decline. Osteoporotic fractures and entrapment neuropathies, in particular, may result in greater impairments in one's mobility and ability to perform activities of daily living. Dysphagia may necessitate the use of compensatory swallow strategies to minimize aspiration risk. Comorbid conditions, including hypertension, dyslipidemia, obesity, and stroke, are also very prevalent in this population. Risk factor modification, including diet, exercise, and medication compliance, is essential to achieve optimal health and function among survivors of poliomyelitis.

The Reign of the Ventilator: Acute Respiratory Distress Syndrome, COVID-19, and Technological Imperatives in Intensive Care.

In the early phase of the COVID-19 pandemic, a dispute arose as to whether the disease caused a typical or atypical version of acute respiratory distress syndrome (ARDS). This essay recounts the emergence of ARDS and places it in the context of the technological transformation of modern hospital care-particularly the emergence of intensive care after the 1952 Copenhagen polio epidemic. The polio epidemic seemed to show the value of manual positive-pressure ventilation, leading to the proliferation of mechanical ventilators and the expansion of intensive care units in the 1960s. This created the conditions of possibility for ARDS to be described and institutionalized within modern intensive care. Yet the centrality of the ventilator to descriptions and definitions of ARDS quickly made it difficult to conceive of the disorder outside the framework of mechanical ventilation and blood gas levels, or to acknowledge the degree to which the ventilator was a source of iatrogenic injury and complications. Moreover, the imperative to understand and treat ARDS with mechanical ventilation set the stage for the early confusion about whether patients with COVID-19 should receive mechanical ventilation. This history offers many crucial lessons about how new technologies can lead to new and valuable therapies but can also subtly shape and constrain medical thinking. Moreover, ventilators not only changed how respiratory disorders were conceived; they also brought new forms of respiratory illness into existence.

Effects of muscle strengthening and cardiovascular fitness activities for poliomyelitis survivors: A systematic review and meta-analysis.

OBJECTIVE: To evaluate and assess the effectiveness of muscle strengthening and cardiovascular interventions in improving outcomes in poliomyelitis (polio) survivors. DATA SOURCES: A systematic literature search was conducted in Medline, PubMed, CINAHL, PsychINFO, Web of Science, and Google Scholar for experimental and observational studies. Study selection and extraction: Screening, data-extraction, risk of bias and quality assessment were carried out independently by the authors. The quality appraisal and risk of bias were assessed using the Downs and Black Checklist. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was followed to increase clarity of reporting. DATA SYNTHESIS: A total of 21 studies that met all the inclusion criteria were subjected to statistical analyses according to intervention (muscle strengthening or cardiovascular fitness). A random-effects meta-analysis showed a statistically significant effect for the exercise interventions favouring improvement in outcomes according to the International Classification of Functioning, Disability and Health (ICF). CONCLUSION: This review provides further insight into the effects associated with muscle strengthening and cardiovascular interventions among polio survivors, and helps to further identify the current state of research in this area. Future research is needed, focusing on individualized approaches to exercise with polio survivors and specific exercise prescription recommendations, based on established frameworks, such as the ICF.

The experiences of using polio outbreak simulation exercises to strengthen national outbreaks preparedness and response plans in sub-Saharan Africa.

INTRODUCTION: globally, by 2020 the paralytic poliomyelitis disease burden decreased to over 99% of the reported cases in 1988 when resolution 41.8 was endorsed by the World Health Assembly (WHA) for global polio eradication. It is clearly understood that, if there is Wild Poliovirus (WPV) and circulating Vaccines Derived Poliovirus (cVDPV) in the world, no country is safe from polio outbreaks. All countries remain at high risk of re-importation depending on the level of the containment of the types vaccine withdrawn, the laboratory poliovirus isolates, and the population immunity induced by the vaccination program. In this regard, countries to have polio outbreak preparedness and response plans, and conducting the polio outbreak simulation exercises for these plans remain important. METHODS: we conducted a cross-section qualitative study to review to 8 countries conducted polio outbreak simulation exercises in the East and Southern Africa from 2016 to 2018. The findings were categorized into 5 outbreak response thematic areas analyzed qualitatively and summarized them on their strengths and weaknesses. RESULTS: we found out that, most countries have the overall technical capacities and expertise to deal with outbreaks to a certain extent. Nevertheless, we noted that the national polio outbreak preparedness and response plans were not comprehensive enough to provide proper guidance in responding to outbreaks. The guidelines were inadequately aligned with the WHO POSOPs, and IHR 2005. Additionally, most participants who participated in the simulation exercises were less familiar with their preparedness and response plans, the WHO POSOPs, and therefore reported to be sensitized. CONCLUSION: we also realized that, in all countries where the polio simulation exercise conducted, their national polio outbreak preparedness and response plan was revised to be improved in line with the WHO POSOPs and IHR 2005. we, therefore, recommend the polio outbreak simulation exercises to be done in every country with an interval of 3-5 years.

Thunberg's Barospirator, a Fully Encasing Predecessor of the Iron Lung.

Used as a ventilator for assisting victims of polio, the barospirator was described by Swedish physician-scientist Torsten Thunberg in 1924. An immediate predecessor of the iron lung of Philip Drinker, the barospirator fully encased the entire body. Cyclic air-pressure changes within the chamber achieved ventilation during equilibrations of intrapulmonary and ambient pressures. Pulmonary medicine innovator Alvan Leroy Barach used a modified barospirator for lung rest as a treatment of tuberculosis in the 1940s. Adverse effects included damage to patients' tympanic membranes. Despite its limited clinical success, the barospirator was successfully used by one of Drinker's competitors, John H. Emerson, to invalidate Drinker's US patent filings.

[HOW HEALTH SERVICES IN ISRAEL COPED WITH THE POLIO EPIDEMIC OF THE 1950'S].

INTRODUCTION: Today, the introduction of a new medicine or vaccine or the clinical trial of some new potion requires the approval of a variety of bodies in accordance with Helsinki Agreement rules, National Health Laws and Health Ministry regulations. The creation of the World Health Organization (WHO) in 1946 added another essential layer to the firm base of principles governing the conduct of clinical trials that exist today. Its main contribution was to create a new reality following The Second World War and the subsequent Nuremberg Trials. The Declaration of Helsinki was only adopted eighteen years later, in 1964. In its first years of independence the infant State of Israel was attacked by a serious outbreak of polio which claimed many victims - mostly children and youngsters. Infantile paralysis - poliomyelitis (polio) was then considered as being untreatable. The disease affected 0.1% of the population of Israel. In 1950, out of a total population of 1.2 million, 1,500 were infected by polio. The epidemic struck over three successive seasons and affected more than 3,000 victims. The mortality rate stood at 10%. Experts, charlatans and fame seekers all presented their inventions to the country - creams, medicines and research projects all designed to bring relief to the sick children. Against all these stood the newly formed Ministry of Health, determined to bring order to the chaos. The only trial conducted by the Health Ministry was unsuccessful, but it was accompanied by the most stringent controls that would not have shamed even today's researchers. The clinical trials of Zibaline were conducted in the early 60's, after the polio vaccine had been introduced and the epidemic had passed. The purpose of this paper is to examine the influence of medical ethics, norms and morals on the way that medical practice dealt with the epidemic at a time when there were no laws or rules.

University of Alberta Hospital Acute and Convalescent Polio Care and the Reintegration of Polio Patients into Albertan Communities, 1953-80.

Following Canada's largest polio epidemic in 1953, Station 67 at the University of Alberta Hospital (UAH) in Edmonton became home to patients who contracted the virus. As young as nine years old, some of these patients lived at the UAH for more than three decades. Akin to wartime services, the epidemic banded together families, patients, doctors, nurses, community members, and later respiratory, physical, and occupational therapists. The nature of the disease, the government response, and the social and economic climate dramatically affected the lived experiences of patients in Alberta's fight against polio. Drawing on archival research and oral interviews, this article argues that it was the agency and resilience of patients, the contributions of healthcare providers to rapid developments in acute and convalescent care, and the dedication of families that were primarily responsible for the recovery and reintegration of polio patients back into the community.

Whole Body Vibration Methods with Survivors of Polio.

The purpose of the original study was to examine the use of whole body vibration (WBV) on polio survivors with and without post-polio syndrome as a form of weight bearing exercise. The goal of this article is to highlight the strengths, limitations, and applications of the method used. Fifteen participants completed two intervention blocks with a wash-out period in between the blocks. Each block consisted of twice a week (four weeks) WBV interventions, progressing from 10 to 20 min per session. Low intensity (peak to peak displacement 4.53 mm, frequency 24 Hz, g force 2.21) and higher intensity (peak to peak displacement 8.82 mm, frequency 35 Hz, g force 2.76) WBV blocks were used. Pain severity significantly improved in both groups following higher intensity vibration. Walking speed significantly improved in the group who participated in higher intensity intervention first. No study-related adverse events occurred. Even though this population can be at risk of developing overuse-related muscle weakness, fatigue, or pain from excessive physical activity or exercise, the vibration intensity levels utilized did not cause significant muscle weakness, pain, fatigue, or sleep disturbances. Therefore, WBV appears to provide a safe method of weight bearing exercise for this population. Limitations included the lack of measurement of reflexes, muscular activity, or circulation, the difficulty in participant recruitment, and insufficient strength of some participants to stand in recommended position. Strengths included a standard, safe protocol with intentional monitoring of symptoms and the heterogeneity of the participants in their physical abilities. An application of the methods is the home use of WBV to reduce the barriers associated with going to a facility for weight bearing exercise for longer term interventions, and benefits for conditions such as osteoporosis, particularly for aging adults with mobility difficulties due to paralysis or weakness. Presented method may serve as a starting point in future studies.

The Terrible Summer of 1952 When Polio Struck Our Family.

This is the story of my twin brother's struggle with polio. The story reflects the thoughts and feelings of Lyle and members of his family and describes how we all coped with the event.

[Polio and post-polio syndrome, viewed by patients and health professionals in primary care]. / Polio y postpolio. Visión de pacientes y profesionales en atención primaria.

OBJECTIVE: Polio affects the quality of life of those who have suffered from it and causes health problems including the post-polio syndrome. The main goals of this work were to know the patients perspective of how they have been affected by the disease and establish the knowledge of post-polio syndrome among patients and primary health care professionals. METHODS: Interpretive qualitative research based on the Grounded Theory carried out in two health-care centers in the city of Malaga, one of them with care-rural clinics. Four focal groups were established with the participation of thirteen patients and two focus groups with twenty-six professional participants. Intentional sampling is performed until saturation. The analysis follows an inductive strategy using the Atlas Ti5.2 software. RESULTS: The people affected by polio reports their personal histories of suffering counteracted by strong family support and an active coping attitude, marked by great effort exertion, willpower and endurance. These people made a positive assessment of their lives minimising the limitations. They presented compatible symptoms with post-polio syndrome, which remain unidentified due to the lack of knowledge of it among patients and health-care professionals. The health care provided was considered deficient due to several causes as for instance lack of involvement, communication problems. CONCLUSIONS: The day-to-day polio experience is focused on personal overcoming with major roles played by family support, difficult relationships with the healthcare system and lack of knowledge of the post-polio syndrome.

OBJETIVO: La polio afecta a la calidad de vida de las personas que la han padecido y ocasiona problemas de salud entre los que se encuentra el síndrome postpolio. Los objetivos de este estudio fueron conocer la perspectiva de pacientes sobre cómo les ha afectado la enfermedad y describir el conocimiento sobre el síndrome postpolio de pacientes y profesionales de atención primaria. METODOS: Investigación cualitativa interpretativa basada en la Teoría Fundamentada, realizada en dos centros de salud de la ciudad de Málaga, uno de ellos con consultorios rurales. Se realizaron cuatro grupos focales con participación de trece pacientes y dos grupos focales con veintiséis profesionales participantes. Muestreo intencional hasta saturación. El análisis siguió una estrategia inductiva con ayuda del programa Atlas Ti 5.2. RESULTADOS: Los pacientes relataron una historia personal de sufrimiento, contrarrestada por un fuerte apoyo familiar y afrontamiento activo (categoría central), marcado por el sobreesfuerzo, la superación y una alta resiliencia. Realizaron una valoración positiva de sus vi- das, minimizando las limitaciones. Presentaron síntomas compatibles con el síndrome postpolio, no identificado por el gran desconocimiento de pacientes y profesionales. La atención sanitaria fue considerada deficitaria (falta de implicación y problemas de comunicación). CONCLUSIONES: La vivencia de la polio está centrada en la superación personal, con gran relevancia del apoyo familiar, las difíciles relaciones con el sistema sanitario y el desconocimiento del síndrome postpolio.

Clearing Vaccine-Derived Poliovirus Infection Following Hematopoietic Stem Cell Transplantation: a Case Report and Review of Literature.

The use of oral poliovirus vaccine in a worldwide scale has led to a 99.9% decrease in annual incidence of wild-type poliomyelitis and the eradication of serotype 2 poliovirus. However, the emergence of vaccine-derived polioviruses (VDPVs) is endangering the eradication program. Patients with combined immunodeficiencies are at increased risk of both vaccine-associated poliomyelitis and prolonged asymptomatic infection with immunodeficiency-associated VDPVs (iVDPVs). Herein, we present a severe combined immunodeficiency patient with prolonged and asymptomatic iVDPV infection. He continued to shed poliovirus during immunoglobulin replacement therapy and cleared the infection following successful hematopoietic stem cell transplantation (HSCT). To explain the efficiency of HSCT in clearing the infection, we reviewed the literature for all reports of HSCT in iVDPV-excreting patients and discussed novel ideas about the role of different immune mechanisms, including cell-mediated interactions, in mounting immune responses against poliovirus infections. This study could provide further insights into the immune mechanisms contributing to the clearance of enteroviral infections.