ANTI-TNF TREATMENT MODIFIES PAIN MODULATION DESCENDING PATHWAYS. A PROSPECTIVE, 6 MONTHS STUDY IN ACTIVE CHRONIC INFLAMMATORY RHEUMATISM PATIENTS' NAÏVE OF BDMARD

BackgroundIn rheumatoid arthritis (RA) and spondyloarthritis (Spa), persistent pain remains challenging. In active disease, diffuse noxious inhibitory controls (assessed through conditioned pain modulation (CPM)) are impaired [1]. Little is known regarding impairment of pain pathways in patients under bMDARD.ObjectivesThe main objective of the RAPID (Rheumatism Pain Inhibitory Descending pathways) study, was to assess descending pain modulation (through CPM paradigm) in patients with active RA or Spa, after introduction of first bDMARD with anti-TNF.MethodsWe included 50 RA and 50 Spa patients with active disease, naïve of bDMARD. We assessed clinical disease variables for patients, together with responses to various psychological questionnaires. All participants underwent QST with the determination of heat and cold pain thresholds (HPT-CPT) on dominant forearm and CPM. CPM paradigm require a conditioning stimulus, here applied to the non-dominant foot (cold circulating bath at 8°C during 1min). Descending pain control was assessed as the change in HPT (in °C) following the conditioning stimulus: the higher the CPM effect, the more efficient the inhibitory control. Patients were followed at 3 and 6 months after TNF inhibitor initiation. At both follow-up visits, clinical monitoring of the rheumatism and repeated thermal QST and CPM.ResultsOne hundred patients were included, 59 women, mean age 45.8 (± 14.6) and mean disease duration 7.93 (± 7.96) years. Due to COVID surge 87 patients initiated an anti-TNF, 74 patients completed the follow-up. At 6 months, 40 patients achieved a good therapeutic response (good EULAR response or ASDAS major improvement), 19 patients had a moderate therapeutic response (moderate EULAR response or clinically important improvement) and 15 patients had no therapeutic response. At the end of follow-up, 51 patients were in remission or low disease activity and 47 patients had a pain intensity <4/10. Thermal pain thresholds did not significantly change during follow-up. Mean HPT was at beaseline 42.35°C (+/- 3.68) and at 6 months 42.17°C (+/- 3.67). Mean CPT was at baseline 13.11°C (+/- 10.04) and at 6 months 12.86°C (+/- 9.45). Conditioned pain modulation was significantly changed during follow-up. Mean CPM effect was at baseline 0.25°C (±2.57), 2.64°C (±2.12) at 3 months and 2.96°C (±2.50) at 6 months. At the end of the 6 months follow-up, mean CPM effect was significantly higher in patients with residual mean pain intensity <4/10 compared to patients with persisting pain ≥ 4/10: 3,25°C (± 2,68) vs 2,47 (± 2,11) (p=0.04).ConclusionAfter TNF inhibitor initiation in active RA or SpA, impaired diffuse noxious inhibitory controls are significantly improved. Apart from their articular efficacy, TNF inhibitor have an action on the central nervous system and pain modulation pathways. In patients with persisting pain under bDMARD, diffuse noxious inhibitory controls are not as efficient as patient without residual pain.Reference[1]Trouvin AP, Simunek A, Coste J, Medkour T, Carvès S, Bouhassira D, Perrot S. Mechanisms of chronic pain in inflammatory rheumatism: the role of descending modulation. Pain. 2022 Aug 3. doi: 10.1097/j.pain.0000000000002745.Figure 1.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Deviation from standard cancer treatment during the first wave of the COVID-19 pandemic in India: A cross-sectional study

Background: During the coronavirus disease 2019 (COVID-19) pandemic, established best practices in cancer care were modified to diminish the risk of COVID-19 infection among patients and health-care workers. Objective(s): We aimed to study the modifications in cancer-directed therapy during the first wave of the COVID-19 pandemic. Material(s) and Method(s): A cross-sectional study of patients with cancers of the head and neck, thoracic, urologic, and central nervous systems who visited the medical oncology department of the Tata Memorial Hospital, Mumbai, India, between April 22, 2020 and June 01, 2020, was conducted. Data were prospectively collected in an online pro forma and supplemented from the electronic medical records. Result(s): Of a total of 514 patients, 363 (71%) were men. The most common malignancy was lung cancer in 234 patients (46%). Cancer-directed therapy was modified in 83 patients (16%). Deviations consisted of modification of the chemotherapy regimen (48%), temporary discontinuation of chemotherapy in 37%, and interim chemotherapy to delay surgery in 5%. Changes in the chemotherapy regimen included a shift to a less intensive regimen in 45%, changing from intravenous to oral in 40%, and less frequent dosing of immunotherapy in 7%. Considering missed appointments as a deviation from planned cancer therapy, 68% of patients had a deviation in the standard planned cancer care. Conclusion(s): Almost two-thirds of the patients could not reach the hospital during the COVID-19 pandemic lockdown in India. Of those who could reach the hospital, one of out every six patients with cancer had a change in their cancer-directed treatment, half of which consisted of a modification in the standard chemotherapy regimens. The effects of these therapy deviations are likely to be long-lasting. (Clinical Trials Registry-India, CTRI/2020/07/026533).Copyright © 2023 Neurology India, Neurological Society of India Published by Wolters Kluwer - Medknow.

Six consecutive cases of primary intracranial sarcoma in children in two private institutions from Lima during COVID-19 pandemic.

Objective: The article describes the clinical and neuroimaging characteristics of six children with the diagnosis of brain tumor attended in two private institutions from Lima, during the COVID-19 pandemic. Material(s) and Method(s): Descriptive study of cases of brain tumor in patients aged 18 and younger, followed at two private institutions in in Lima, from March 2020 to December 2021. Result(s): Six consecutive cases of intracranial tumors were detected during a large part of the COVID-19 pandemic's first year (October 2020 to March 2021), all of them with diagnosis of primary intracranial sarcoma. Before the pandemic, the last primary intracranial sarcoma in children, operated in the mentioned institutions, occurred in June 2018 and was the only case that year. Conclusion(s): During the COVID-19 pandemic, an unusual frequency of primary intracranial sarcoma in children was found in two private institutions from Lima.Copyright © 2023 Authors. All rights reserved.

A Case Report on Heart Rate Variability Biofeedback and Postconcussion Syndrome: Healing the Autonomic Nervous System

Postconcussion syndrome is a devastating condition of the mind, body, and even personality. Mounting research demonstrates that heart rate variability biofeedback can help the concussed individual in three critical ways: (a) eliciting high amplitude oscillations in cardiovascular functions and thereby strengthening self-regulatory control mechanisms;(b) restoring autonomic balance;and (c) increasing the afferent impulse stream from the baroreceptors to restore balance between inhibitory and excitatory processes in the brain.

To the tumor and beyond: Tales of a holistic miRNA delivery vehicle

Like the challenges and skepticism that faced the antibody therapeutics field over a decade ago, RNA therapeutics is facing the same. And, like the antibody therapeutics field, we are beginning to realize the clinical impact of RNA therapeutics amiss these challenges. This is most clearly highlighted with the recent approval of mRNA vaccines to prevent against SARS-CoV-2 and the first FDA approved RNAi drugs targeted to the liver. Unfortunately, RNA-based drugs targeted to cancer cells is lagging behind, even with countless years of work that has revealed the power of using RNAi for treating oncological diseases. Lack of success in this space is attributed to inability to deliver RNAi safely and effectively. A successful delivery agent requires multiple features. First, the agent must deliver the RNA specifically to the intended cells. Second, the agent must have a large therapeutic window, meaning that toxicity, if observed, should occur at doses that are orders of magnitude higher than the therapeutic dose. Third, if delivery of the RNA is by way of a specific ligand and receptor pair, as is the case herein, the RNA must successfully escape the endosome. Simply swelling the endosome is not enough if noncovalent interactions between the ligand and the receptor cannot be disrupted. Fourth, the RNA should include appropriate stabilizing modifications to increase intracellular half-life that will reduce dosing and cost. Through hard work and dedication in this space, we have come up with an inclusive, easily synthesized, intramolecular molecule that achieves all of these essential features. Moreover, the ligand used to achieve successful delivery is also being evaluated for imaging tumors localized in the central nervous system. Here, the challenges we face, the hurdles we have overcome, and the barriers that still remain to achieve success in revealing the clinical potential of miRNA as anti-cancer therapeutics will be presented.

Pericytes may facilitate SARS-CoV-2 entry into the nervous system

Objective: Although the neurological and olfactory symptoms of coronavirus disease 2019 have been identified, the neurotropic properties of the causative virus, severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2), remain unknown. We sought to identify the susceptible cell types and potential routes of SARS-CoV-2 entry into the central nervous system, olfactory system, and respiratory system. Method(s): We collected single-cell RNA data from normal brain and nasal epithelium specimens, along with bronchial, tracheal, and lung specimens in public datasets. The susceptible cell types that express SARS-CoV-2 entry genes were identified using single-cell RNA sequencing and the expression of the key genes at protein levels was verified by immunohistochemistry. We compared the coexpression patterns of the entry receptor angiotensin-converting enzyme 2 (ACE2) and the spike protein priming enzyme transmembrane serine protease (TMPRSS)/cathepsin L among the specimens. Result(s): The SARS-CoV-2 entry receptor ACE2 and the spike protein priming enzyme TMPRSS/cathepsin L were coexpressed by pericytes in brain tissue;this coexpression was confirmed by immunohistochemistry. In the nasal epithelium, ciliated cells and sustentacular cells exhibited strong coexpression of ACE2 and TMPRSS. Neurons and glia in the brain and nasal epithelium did not exhibit coexpression of ACE2 and TMPRSS. However, coexpression was present in ciliated cells, vascular smooth muscle cells, and fibroblasts in tracheal tissue;ciliated cells and goblet cells in bronchial tissue;and alveolar epithelium type 1 cells, AT2 cells, and ciliated cells in lung tissue. Conclusion(s): Neurological symptoms in patients with coronavirus disease 2019 could be associated with SARS-CoV-2 invasion across the blood-brain barrier via pericytes. Additionally, SARS-CoV-2-induced olfactory disorders could be the result of localized cell damage in the nasal epithelium.Copyright © Wolters Kluwer Health, Inc. All rights reserved.

Relationship between neurological manifestations and severity of COVID-19. San Vicente de Paul Hospital. Ecuador 2021.

Introduction: SARS-CoV-2 mainly affects the respiratory system, but the damage caused by this virus also extends to other systems, including the nervous system, and the mechanisms of neurological infection can be direct or indirect. Objective(s): To determine the relationship between neurological manifestations and disease severity in symptomatic COVID-19 positive patients at San Vicente de Paul Hospital in 2021. Material(s) and Method(s): A cross-sectional observational study was conducted using medical records of patients hospitalized with COVID-19 and neurological manifestations, which were classified into manifestations of the central nervous system and manifestations of the peripheral nervous system. Result(s): The results show that 74,1 % of patients presented neurological manifestations;the highest percentage was concentrated in patients who developed severe disease (15 [60 %], CNS;91 [77,1 %], PNS;125 [65,4 %], CNS and PNS). The joint presence of central and peripheral neurological manifestations was significantly associated with critical COVID-19 (P value= 0,011;OR: 2,005). The mortality rate reached 2,69 %. Conclusion(s): Neurological manifestations in hospitalized COVID-19 patients are very common, and critical COVID-19 is more likely to have neurological manifestations.Copyright © 2022 Universidad de Ciencias Medicas de La Hab. All rights reserved.

ID: 215433 The History of Spinal Cord Stimulation to Treat Painful Diabetic Peripheral Neuropathy

Introduction: Diabetic peripheral neuropathy (DPN) is the most common neuropathic syndrome seen in patients with diabetes. Roughly 30% of the diabetes patient population1 experience painful DPN symptoms including bilateral stabbing or burning pain in addition to numbness in the feet and lower legs. Traditionally painful DPN symptoms have been treated with conventional medical management (CMM) including glycemic control, general risk factor management, as well as pharmaceutical agents. These treatment approaches are often unsuccessful in the long-term1. Spinal cord stimulation (SCS) has been demonstrated as an effective treatment for painful DPN of the lower extremities with multiple publications dating back to 1996 showing benefits of SCS for pain relief and improved Quality of Life (QoL) in DPN patients (Figure 1)2-18. Method(s): A systematic literature review of the robust body of evidence for SCS in the treatment of painful DPN was conducted. Publications were selected for inclusion by two independent reviewers using defined selection criteria. Additional relevant publications from outside the search dates were included. Result(s): SCS was first documented as an effective treatment for DPN in three single-arm studies published between 1996 and 20122,4,5, one of which was followed-up to thirty-six months18, and another to seven-years3. These studies paved the way for two RCTs published in 20146,7, one of which was followed-up to five-years in two publications8,10, and another7 was followed-up with analyses on QoL9 and an evaluation of the effects of burst SCS17. Two meta-analyses were published in 2020 and 202111,12. A post-hoc analysis of a multi-center single-arm study on high frequency (10kHz) SCS to treat DPN was published in 202013 and followed by an RCT published in 202114 with additional 1-year follow-up15,16. Collectively these studies demonstrate that SCS is an effective therapy for patients with painful DPN by reducing pain and increasing QoL for DPN patients (Figure 1). Conclusion(s): This review of a large body of evidence shows a decades-long history of the effectiveness of SCS for symptom relief in patients suffering from painful DPN. Future research on the effectiveness of new waveforms and novel methods of energy delivery to the spinal cord are needed. The study of outcomes in addition to pain relief is also needed, which may better illustrate the breadth of effects of SCS therapy on the underlying disease factors. Increasing awareness of the current evidence is essential to increasing therapy adoption by expanding payer support and influencing referring health care provider behavior. Disclosure: Eric Grigsby, MD: AE Mann Foundation: Consulting Fee: Self, Bioness Inc.: Consulting Fee: Self, Medallion Therapeutics: Consulting Fee: Self, Medtronic: Consulting Fee: Self, SPR Therapeutics: Consultant: Self, Tenex Health: Consultant: Self, Voyager Therapeutics: Consultant: Self, Xalud: Consulting Fee: Self, AE Mann Foundation: Consulting Fee: Self, Medallion Therapeutics: Consulting Fee: Self, Bioness Inc.: N/A: Self, Medallion Therapeutics: N/A: Self, SPR Therapeutics: N/A: Self, Abbott / St. Jude Medical: N/A: Self, Tenex: N/A: Self, Vertos: N/A: Self, Xalud: N/A: Self, AE Mann Foundation: Consulting Fee: Self, Bioness Inc.: Consulting Fee: Self, Medtronic, Inc.: N/A: Self, Collegium Pharmaceutical, Inc.: Trustee: Self, Flowonix Medical: Served on speakers' bureau: Self, Jazz Pharmaceuticals: Served on speakers' bureau: Self, Jazz Pharmaceuticals: Trustee: Self, Spinal Restoration, Inc.: Trustee: Self, Jazz Pharmaceuticals: N/A: Self, Alfred Mann Foundation: N/A: Self, Boston Scientific: N/A: Self, CNS Therapeutics: N/A: Self, Collegium Pharmaceutical, Inc.: N/A: Self, Flowonix Medical: N/A: Self, Jazz Pharmaceuticals: N/A: Self, Medtronic, Inc.: N/A: Self, Myoscience: N/A: Self, NeurAxon Inc.: N/A: Self, Spinal Restoration, Inc.: N/A: Self, St. Jude Medical, Inc.: N/A: Self, Abbott Laboratories: Consultant: Self, Alfred Mann Foundation: Consulting Fee: Self, Cervel Neurotech, Inc.: Consultant: Self, CNS Therapeutics: Consultant: Self, Covidien: Consultant: Self, Cumberland Pharmaceuticals, Inc.: Consultant: Self, Flowonix Medical: Consultant: Self, Jazz Pharmaceuticals: Consultant: Self, Mainstay Medical: Consultant: Self, Medtronic, Inc.: Consultant: Self, Myoscience: Consultant: Self, NeuroPhage Pharmaceuticals: Consultant: Self, Nevro Corp: Consultant: Self, Palyon: Consultant: Self, Spinal Modulation: Consultant: Self, SPR Therapeutics: Consultant: Self, St. Jude Medical, Inc.: Consultant: Self, Tenex Health, Inc.: Consultant: Self, VertiFlex Inc.: Consultant: Self, Vertos Medical, Inc.: Consultant: Self, Xalud Therapeutics, Inc.: Contracted Research: Self, Medtronic, Inc.: Served on speakers' bureau: Self, Flowonix Medical: Served on advisory board: Self, Medtronic, Inc.: N/A: Self, Jazz Pharmaceuticals: N/A: Self, Medtronic, Inc.: Ownership Interest: Own Stock, Stock Options, Future Stock Options: Self, Nevro Corp: Ownership Interest: Own Stock, Stock Options, Future Stock Options: Self, Rachel Slangen, PhD: None, Lisa Johanek, PhD: Medtronic: Salary/Employee: Self, Maddie LaRue, PHD: Medtronic: Employee:, Cecile de Vos, PhD: None, Melissa Murphy: Medtronic: Consulting Fee:, Relievant: Consulting Fee:Copyright © 2023

LIVED EDUCATIONAL EXPERIENCE OF YOUNG ADULTS WITH CHILDHOOD- AND ADULT-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS: A MULTI-CENTER CANADIAN QUALITATIVE STUDY

BackgroundEducation and employment established in young adulthood predict future lifetime socioeconomic achievements. Young adults with Systemic Lupus Erythematosus (SLE) have physical, cognitive and mental health issues and other comorbidities that may impact employment.ObjectivesTo understand the lived experiences of young adults with SLE (YASLE), as students, and to assess their perceived barriers from SLE.MethodsYASLE were recruited from two Lupus clinics in Toronto and Winnipeg. Semi-structured qualitative interviews were conducted individually via secure video conferencing. As this study was conducted during the coronavirus pandemic, participants were also asked about the pandemic impacts on their education experiences. All interviews were transcribed verbatim, double-coded and analysed using a reflexive thematic approach.ResultsTwelve participants (2 males), 9 of childhood- and 3 adult-onset SLE (cSLE, aSLE) were interviewed. Nine participants (82%) were <25 years old. Five also worked while studying. Five were Asians, 5 were White, 2 of other ethnicities. Half have severe disease (central nervous system or renal involvement). Median duration of disease was 4.0 (25th-75th percentile, 1.8- 5.3) years. The impacts of SLE on their education experience emerged in 5 themes:1) Challenges imposed by SLE: Difficulties adjusting to the diagnosis, physical and cognitive symptoms of SLE. While most participants disclosed their diagnosis to their schools, some expressed hesitation.2) Changes in aspirations: Education/career goals were modified by reducing course load or shifting to more sedentary or less cognitively demanding careers.3) Coping and acceptance: More adaptive than maladaptive coping strategies were used to manage their SLE, including self-acceptance, pacing, planning and avoidance. All strived to do well in their studies despite SLE and were hopeful for their futures.4) Facilitating factors for education success: Family and friends' social support, individualized accommodations from school and parental financial support were identified.5) Pandemic impacts: Virtual learning and flexible schedules enabled participants to adapt their schedules according to their physical conditions (e.g. pain, fatigue). However, fewer opportunities to interact in-person were viewed as challenges. Participants want hybrid options to continue even after the pandemic.ConclusionSLE affected students' performance through physical symptoms, fatigue and cognitive dysfunction. Ongoing social and school supports help to support them. Maintaining the remote learning options may increase accessibility for them. These results identified opportunities for developing future supportive interventions for YASLE patients in their schooling which then better prepare them for future employment.References[1]Jetha A, Badley E, Beaton D, Fortin PR, Shiff NJ, Gignac MA. Unpacking early work experiences of young adults with rheumatic disease: an examination of absenteeism, job disruptions, and productivity loss. Arthritis care & research. 2015;67:1246-54.[2]E. F Lawson, A. O. Hersh, L. Trupin, E. von Scheven, M. J. Okumura, J. Yazdany, et al. Educational and vocational outcomes of adults with childhood and adult onset systemic lupus erythematosus: nine years of follow-up. Arthritis Care Res 2014;66: 717-24.Acknowledgements:NIL.Disclosure of InterestsMike Golding: None declared, Fareha Nishat: None declared, Kaitlyn Merrill: None declared, Ramandeep Kaur: None declared, Jennifer Stinson: None declared, Jennifer Protudjer Speakers bureau: Nutricia (Food allergy university, Nov 2022), Consultant of: Novartis 2021, allergy products, Roberta Woodgate: None declared, Christine Peschken: None declared, Diane Lacaille: None declared, Umut Oguzoglo: None declared, Zahi Touma: None declared, Lily Lim Speakers bureau: Pfizer Feb 2023. Not drug related and not related to this .

Patient Centricity: Design and Conduct of Clinical Trials in Orphan Diseases: Third of Three Sets of Expanded Proceedings from the 2020 ISCTM Autumn Conference on Pediatric Drug Development

This article expands on a session, titled "Patient Centricity: Design and Conduct of Clinical Trials in Orphan Diseases," that was presented as part of a two-day meeting on Pediatric Drug Development at the International Society for Central Nervous System (CNS) Clinical Trials and Methodology (ISCTM) Autumn Conference in Boston, Massachusetts, in October 2020. Speakers from various areas of pediatric drug development addressed a variety of implications of including children in drug development programs, including implications for rare/orphan diseases. The speakers have written summaries of their talks. The session's lead Chair was Dr. Joan Busner, who wrote introductory and closing comments. Dr. Simon Day, regulatory consultant, outlined some of the past mistakes that have plagued trials that did not consult with patient groups in the early design phase. Dr. Atul Mahableshwarkar provided an industry perspective of a recent trial that benefited from the inclusion of patient input. Drs. Lucas Kempf and Maria Sheean provided regulatory input from the perspectives of the United States (US) Food and Drug Administration (FDA) and European Medicines Agency (EMA), respectively. Dr. Judith Dunn outlined a novel approach for assessing and rank ordering patient and clinician clinical meaningfulness and the disconnect that may occur. Dr. Busner provided closing comments, tied together the presented issues, and provided a synopsis of the lively discussion that followed the session. In addition to the speakers above, the discussion included two representatives from patient advocacy groups, as well as an additional speaker who described the challenges of conducting a pediatric trial in the US and European Union (EU), given the often competing regulatory requirements. This article should serve as an expert-informed reference to those interested and involved in CNS drug development programs that are aimed at children and rare diseases and seek to ensure a patient-centric approach.Copyright © 2023, Matrix Medical Communications. All rights reserved.

RELATION BETWEEN COVID-19 AND ANCA VASCULITIS. STUDY IN A SINGLE UNIVERSITY HOSPITAL

BackgroundAnti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) is a small vessel vasculitis. Hallmarked by the presence of antibodies against antigens in cytoplasmic granules of neutrophils. Different microbiological agents and vaccines can trigger an AAV, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection and Coronavirus disease 2019 (COVID-19) vaccine.ObjectivesTo compare: a) proportion of positive ANCA (+ANCA) test in 2019 (COVID-19 pre-pandemic) vs 2021 (COVID-19 pandemic), b) clinical features and c) vasculitis activity between vasculitis related to COVID 19 vaccination vs non-related.MethodsAll ANCA tests performed in 2019 and 2021 in a referral hospital were reviewed. Additionally, we studied 18 +ANCA patients diagnosed in 2021 and accepted to participate in present study. The patients were divided in two groups: a) +ANCA after SARS-CoV-2 mRNA vaccine (COVID-related) and +ANCA before COVID-19 vaccine (COVID-nonrelated). Diagnosis of underlying AAV was based on ACR/EULAR 2022 criteria. Disease activity was assessed with Birmingham Vasculitis Activity Score (BVAS). ANCA testing was done by chemiluminescence assay using IO-FLASH (Inova, San Diego, CA) according to the instructions of the manufacturer.ResultsANCA tests were positive in 14 of 1287 cases (1.1%) and in 32 of 1434 (2.2%) cases in 2019 and 2021, respectively (figure 1, the differences were statistically significant (p=0.020). The main features of 18 ANCA+ patients diagnosed in 2021 are summarized in table 1. COVID-19 related patients showed a median of 7 points on BVAS score compared of the median of 5 points on BVAS score on not related patients.ConclusionThere seems to be an increase of +ANCA at the expense of anti-PR3 antibodies following the COVID-19 vaccine. In patients with +ANCA following vaccination there seems to be an increased disease activity according to BVAS score without reaching statistical significance.References[1]Damoiseaux, J., et al Autoimmunity Reviews.2021. PMID 34896650.[2]Irure-Ventura, et al. IScience.2022. PMID 35937087.Table 1.Main general features of 18 patients with ANCA+ test diagnosed in 2021.FEATURESAll cases n= 18Related n= 13Non-related n= 5p*Age (years), mean±SD62±1767±15.352±16.50.167Male/ Female n, (% male)10/8 (55.6)9/4 (69.2%)1/4(20)0.067ANCA-test specificity, n (%)MPO-ANCA9 (50)7 (53.8)2(40)0.609PR3-ANCA8 (44.4)5 (38.5)3(60)0.423Both1 (5.6)1 (7.7)0-CRP (mg/dL), median [IQR]2,4 [0.4-10.7]3.8 [0.4-10.1]1 [0.4-10.9]0.802ESR, mm/1st hours, median [IQR]50 [25-104]47 [25.3-71.8]50 [25-120]0.634BVAS, median [IQR]6.5 [4.2-8]7 [4-8]5 [5-8]0.842FFS, n (%)03 (16.7)2 (15.4)1 (20)0.819≥115 (83.3)11 (84.6)4 (80)0.819ENT involvement, n (%)12(66.7)10 (76.9)2 (40)0.148MSK involvement, n (%)11(61.1)7(53.8)4 (80)0.322CNS/PNS involvement, n (%)10 (55.6)7 (53.8)3 (60)0.819Lung involvement, n (%)9 (50)6 (46.2)3 (60)0.609Kidney involvement, n (%)8 (44.4)7 (53.8)1 (40)0.208Ocular involvement, n (%)2 (11.1)2 (15.4)00.366Cutaneous involvement, n (%)2 (11.1)02 (40)0.019*p values according to Man Whitney test.Abbreviations (in alphabetical order):AAV: anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis;ACR: American college of Rheumatology;ANCA: Antineutrophil cytoplasmic antibody;BVAS: Birmingham Vasculitis Activity Score;CNS: central nervous system;CRP: C-Reactive protein;dL: deciliter;ENT: ear, nose, throat;ESR: erythrocyte sedimentation rate;FFS: Five-Factors Score;g;IQR: Interquartile range;mg: milligram;MSK: musculoskeletal;MPO-ANCA= ANCA specific for myeloperoxidase;n=Number;PNS: peripheral nervous system;PR3-ANCA= ANCA specific for proteinase 3;SD: Standard DeviationFigure 1.Comparison of ANCA test in 2019 and 2021.[Figure omitted. See PDF]Acknowledgements:NIL.Disclosure of InterestsFabricio Benavides-Villanueva: None declared, Vanesa Calvo-Río Speakers bureau: Dra V. Calvo had participation in company-sponsored speaker´s bureau from Roche, Novartis, Galápagos, UCB Pharma, MSD, Celgene, and Grünenthal and received support for attending m etings and/or travel from Janssen, Abbvie, Roche, Novartis, MSD, UCB Pharma, Celgene, Lilly, Pfizer, Galápagos., J. Loricera Speakers bureau: Dr. J. Loricera had participation in company-sponsored speaker´s bureau from Roche, Novartis, Galápagos, UCB Pharma, MSD, Celgene, and Grünenthal., Consultant of: Dr. J. Loricera had consultation fees in company-sponsored speaker´s bureau from Roche, Novartis, Galápagos, UCB Pharma, MSD, Celgene, and Grünenthal and received support for attending meetings and/or travel from Janssen, Abbvie, Roche, Novartis, MSD, UCB Pharma, Celgene, Lilly, Pfizer, Galápagos., Juan Irure-Ventura: None declared, Marcos Lopez-Hoyos: None declared, Ricardo Blanco Speakers bureau: Dr. R. Blanco had participation in company sponsored speaker´s bureau from Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD., Consultant of: Dr. R. Blanco had consultation from Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD., Grant/research support from: Dr. R. Blanco received grants/research supports from Abbvie, MSD and Roche.

Big data approach on the impact of COVID-19 lockdown on pediatric neurosurgery

Objective: COVID-19 lockdowns in 2020 limited activities of daily life. Data on the impact on healthcare systems is ambiguous. So far no data has been published for pediatric neurosurgery in Germany. We present the results of a big data approach. Method(s): We obtained anonymous data from the nationwide database of hospital statistics (German Federal Statistical Office, www. desta tis. de) in August 2022. For the age group <18 years in 2016- 2020, the following diagnoses (ICD-10 code) were analysed: Intracranial injury (S06), malignant (C71), benign (D33) and unspecified (D43) neoplasia, abuse (T74), violent attack (Y09) and, for comparison, forearm fracture (S52). The following operations (OPS code) were chosen: Operation of the central nervous system (CNS, 5-01- 05), excision of intracranial lesion (5-015), shunt insertion (5-023), shunt revision (5-024), plastic operations of the spinal cord (5-036) and, for comparison, overall number of operations (OPS-5), spondylodesis (5-836) and functional neurosurgery (5-028) at all ages. Result(s): The number of operations declined from 17.23 million in 2019 to 15.82 million in 2020 (8.2%). CNS operations declined by 5%. Shunt insertion declined by 8.1%, revision by 5.1% and spinal cord operations by 6.6%, whereas excisions of intracranial lesions increased by 1.7%. Spondylodesis and functional operations both decreased by 11.9%. The hospitalisations for intracranial neoplasia declined by 8.8% compared to previous years. The number of inpatients with intracranial injury declined by 16%. Violent attack was also documented less often (-13.2%), but child abuse increased by 3.3%. Forearm fractures declined by 5.6%. Conclusion(s): The COVID-19 lockdown in 2020 lead to reduction of operations. Neuro-oncological operations were not affected. Intracranial injury even declined by 16%, reflecting limited activities and mobility. An increase in documented child abuse by 3.3% compared to the average of previous years was observed. These results help understand the impact of pandemics and political decisions and guide future decision-making.

The influence of post-COVID syndrome on cognitive functions of students

A survey of senior students of the Faculty of General Medicine of the NAO MUK who had recovered from Covid-19 was conducted. The disease in all respondents proceeded in a mild form or moderate severity. Post-covid syndrome developed in students who had a coronavirus infection in the form of moderate severity. The most frequent complications were loss of smell and taste, cough and shortness of breath, as well as cognitive dysfunction in the form of impaired attention, memory and thinking. The decline in performance is associated with the above violations of the central nervous system.

Coronavirus in patient with positive PCR test in cerebrospinal fluid led to generalized tonic-clonic seizure without brain lesion: a case report

SARS-CoV-2 which first was observed in Wuhan region, China in December 2019 is affected many organs, such as central nervous system. We describe a case of a 57-year-old male patient, in hospital with the loss of consciousness, in the form of lack of verbal and visual communication. He got a seizure attack for about 3 minutes in the form of generalized tonic-clonic seizure (GTS) and admitted to the neurological department and was intubated. Since, the patient was not aware, awake, did not obey, corneal reflexes test was positive and his pupils were isochoric and reactive therefore, the primary diagnosis was cerebrovascular accident (CVA). On the second day after admission, although the brain computed tomography (CT) did not show brain lesion, but chest X-ray (CXR) revealed lung involvement. In addition, on third day the RT-PCR test for coronavirus RNA in and the cerebrospinal fluid and nasopharyngeal swap done and the result was positive for both of them. Therefore, treatment for the covid-19 was started. Result(s): Since, the treatment for the covid-19 was started with Atazanavir, Clindamycin and ceftriaxone, ten days after hospitalization, the lung involvement and general condition of patient got better and after two weeks he was released from the hospital. Conclusion(s): GTS should be considered as a neurological outcome of COVID-19 and medications against the coronavirus, such as Atazanavir, Clindamycin and ceftriaxone can recover the neurological deficits in these patients.Copyright© 2020, TMU Press.

Update on Viral Infections Involving the Central Nervous System in Pediatric Patients.

Infections of the central nervous system (CNS) are mainly caused by viruses, and these infections can be life-threatening in pediatric patients. Although the prognosis of CNS infections is often favorable, mortality and long-term sequelae can occur. The aims of this narrative review were to describe the specific microbiological and clinical features of the most frequent pathogens and to provide an update on the diagnostic approaches and treatment strategies for viral CNS infections in children. A literature analysis showed that the most common pathogens worldwide are enteroviruses, arboviruses, parechoviruses, and herpesviruses, with variable prevalence rates in different countries. Lumbar puncture (LP) should be performed as soon as possible when CNS infection is suspected, and cerebrospinal fluid (CSF) samples should always be sent for polymerase chain reaction (PCR) analysis. Due to the lack of specific therapies, the management of viral CNS infections is mainly based on supportive care, and empiric treatment against herpes simplex virus (HSV) infection should be started as soon as possible. Some researchers have questioned the role of acyclovir as an empiric antiviral in older children due to the low incidence of HSV infection in this population and observed that HSV encephalitis may be clinically recognizable beyond neonatal age. However, the real benefit-risk ratio of selective approaches is unclear, and further studies are needed to define appropriate indications for empiric acyclovir. Research is needed to find specific therapies for emerging pathogens. Moreover, the appropriate timing of monitoring neurological development, performing neuroimaging evaluations and investigating the effectiveness of rehabilitation during follow-up should be evaluated with long-term studies.

The functional and structural changes in the hippocampus of COVID-19 patients.

Since the hippocampus is predominantly susceptible to injuries caused by COVID-19, there are increasing data indicating the likelihood of post-infection memory loss and quickening neurodegenerative disorders, such as Alzheimer's disease. This is due to the fact that the hippocampus has imperative functions in spatial and episodic memory as well as learning. COVID-19 activates microglia in the hippocampus and induces a CNS cytokine storm, leading to loss of hippocampal neurogenesis. The functional and structural changes in the hippocampus of COVID-19 patients can explain neuronal degeneration and reduced neurogenesis in the human hippocampus. This will open a window to explain memory and cognitive dysfunctions in "long COVID" through the resultant loss of hippocampal neurogenesis.

Causal associations and genetic overlap between COVID-19 and intelligence.

OBJECTIVE: COVID-19 might cause neuroinflammation in the brain, which could decrease neurocognitive function. We aimed to evaluate the causal associations and genetic overlap between COVID-19 and intelligence. METHODS: We performed Mendelian randomization (MR) analyses to assess potential associations between three COVID-19 outcomes and intelligence (N = 269,867). The COVID phenotypes included SARS-CoV-2 infection (N = 2,501,486), hospitalized COVID-19 (N = 1,965,329), and critical COVID-19 (N = 743,167). Genome-wide risk genes were compared between the genome-wide association study (GWAS) datasets on hospitalized COVID-19 and intelligence. In addition, functional pathways were constructed to explore molecular connections between COVID-19 and intelligence. RESULTS: The MR analyses indicated that genetic liabilities to SARS-CoV-2 infection (OR: 0.965, 95% CI: 0.939-0.993) and critical COVID-19 (OR: 0.989, 95% CI: 0.979-0.999) confer causal effects on intelligence. There was suggestive evidence supporting the causal effect of hospitalized COVID-19 on intelligence (OR: 0.988, 95% CI: 0.972-1.003). Hospitalized COVID-19 and intelligence share ten risk genes within two genomic loci, including MAPT and WNT3. Enrichment analysis showed that these genes are functionally connected within distinct subnetworks of 30 phenotypes linked to cognitive decline. The functional pathway revealed that COVID-19-driven pathological changes within the brain and multiple peripheral systems may lead to cognitive impairment. CONCLUSIONS: Our study suggests that COVID-19 may exert a detrimental effect on intelligence. The tau protein and Wnt signaling may mediate the influence of COVID-19 on intelligence.

Medical Rehabilitation and Infectious Diseases in Children

Today, medical rehabilitation is undergoing significant transformation. The new system built around the biopsychosocial model includes assessment of physical constraints and rehabilitation diagnosis, determination of rehabilitation potential, formulation of goals and objectives of individual interventions, development of rehabilitation plans, and progress evaluation. All of these rehabilitation components can be implemented using a personalized, problem-oriented, multidisciplinary approach, which is now being actively introduced into clinical practice. The current pandemic of the novel coronavirus infection has demonstrated that medical rehabilitation is crucial for convalescents. However, its principles and techniques have not been fully elaborated yet. This review describes the current state of medical rehabilitation of children with or after infectious diseases and identifies its avenues and prospects.Copyright © 2022 Obstetrics, Gynecology and Reproduction. All rights reserved.