Five-day Course Research Articles

A Blended Learning Approach to Emergency Airway Training in a Low Resource Environment

Introduction:Global Emergency Care Skills (GECS) is a charity which delivers medical training to health care professionals in low and middle income countries. Teaching airway management both didactically and through simulation training is a key component of the GECS Emergencies and Trauma Course. In 2022, a team of doctors delivered an intensive, five-day teaching course with a strong emphasis on airway management and airway emergencies at St. Joseph’s Nyabondo Mission Hospital in rural Kenya. This course was delivered to a group of doctors, nurses and clinical officers. At the conclusion of this course we collected qualitative feedback from course participants. The aim of this study was to assess airway knowledge and skills acquisition, as well as real-world application and potential for ongoing teaching of acquired airway skills.Method:A questionnaire was distributed to course participants to ascertain their experience of didactic airway teaching, airway skills stations, and airway simulation. Each question offered a binary response. To continue to enhance course content, we invited participants to submit qualitative feedback at the end of the questionnaire.Results:Questionnaires were returned by 19 of a total 24 participants. 53% were registered nurses, 21% were clinical officers, 5% were medical officers and 21% did not respond to this question. Median post graduate clinical experience was four years (2.75-5.25). 37% indicated that they had not heard of simulation training for medical education before undertaking this course. 58% had no previous airway training although 63% had prior exposure to clinical situations which required emergency airway management. 100% reported feeling more confident in their airway skills and potential for training colleagues following this course.Conclusion:The results indicate that participants gained knowledge, skills, and confidence when approaching airway emergencies. Furthermore, results showed increased perceived competence by participants at providing airway training to colleagues.

Chorea as the Initial Manifestation of Antiphospholipid Syndrome (P9-5.020)

<h3>Objective:</h3> To discuss a rare case of chorea presenting as the initial manifestation of autoimmune disease. <h3>Background:</h3> Autoimmune chorea, including paraneoplastic, post-infectious, and idiopathic etiologies, is one of the leading causes of adult-onset chorea behind Huntington’s and vascular diseases.¹ In particular, in primary antiphospholipid syndrome (APS) and systemic lupus erythematosus, chorea is the initial manifestation of disease in 0.9 to 2% of cases.^1,2 <h3>Design/Methods:</h3> Verbal and written consent were obtained from the patient. <h3>Results:</h3> 73-year-old female with PMH of ITP, left MCA ischemic stroke, SDH, and DVT on anticoagulation who presented initially to ED with choreoathetoid movements starting 3 days prior to admission. History was unremarkable for triggering factor. Head imaging was unremarkable for acute intracranial process. B12, folate, TSH, electrolytes, RPR, serum copper, ANA, anti-dsDNA, SS-A, SS-B, Smith, and RNP antibodies negative. Lupus anticoagulant, β2 glycoprotein, and anti-cardiolipin antibodies positive. EEG unremarkable. Pelvic ultrasound negative. Genetic testing for Huntington’s negative. LP normal with exception of positive Coxsackie B1–B6 and A24 antibodies. After five-day course of IVIg, movements improved and she was discharged on no immunosuppression. Five weeks later, patient returned to ED with worsening of choreoathetoid movements. Repeat head CT again negative for acute pathology. Repeated spinal was unremarkable. Patient received Solumedrol 1g for four days with significant improvement in symptoms, and discharged on Prednisone 60 mg daily with recommendation to follow-up with rheumatology and neurology. On follow-up several months later, patient maintained on Prednisone 5 mg daily with no recurrence of choreoathetoid movements. <h3>Conclusions:</h3> While chorea is not the most commonly reported movement disorder in the context of autoimmune disease, it is often a delayed diagnosis, resulting in recurrent admissions and healthcare costs. Laboratory testing for autoimmune disorders should be included in the initial work-up of new-onset chorea to establish the diagnosis and properly treat as to prevent development of fulminant disease. <b>Disclosure:</b> Ms. Alayon has nothing to disclose. Mrs. Goodis has nothing to disclose. Dr. Feinberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia. Dr. Feinberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Catalyst. Dr. Feinberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for eisai. Dr. Feinberg has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Argenx. Dr. Feinberg has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Abbvie. Dr. Feinberg has stock in Amarin. Stuart N. Kieran, MD has nothing to disclose. Dr. Wirkowski has nothing to disclose.

FLAIR-hyperintense lesions in anti-MOG-associated Encephalitis with Seizures (FLAMES) mimicking new daily persistent headache. Updating the diagnostic paradigm with recommendations for timely diagnosis and management. (P13-5.024)

<h3>Objective:</h3> We present a case report of a patient with abrupt right fronto-temporal headache and neck pain that persisted for 13 days, followed by first-time generalized tonic-clonic seizures, weakness, neglect, and encephalopathy. She was ultimately diagnosed with FLAIR-hyperintense lesions in anti-MOG-associated Encephalitis with Seizures (FLAMES), which resolved with IV methylprednisolone. <h3>Background:</h3> FLAIR-hyperintense lesions in anti-MOG-associated Encephalitis with Seizures <b>(</b>FLAMES) was first described in 2017 as a distinct clinical and radiological syndrome from other anti-MOG-associated syndromes. MOG is a protein on the surface of oligodendrocytes. It helps to modulate myelin immune interactions, and its location on the outermost part of the myelin sheath serves as an immunogenic agent. Main presenting symptoms are seizures (85%) and headaches (70%). <h3>Design/Methods:</h3> History, physical exam, review of literature <h3>Results:</h3> We discuss a case of a 25-year-old previously healthy Asian woman, not on home medications, who experienced abrupt onset of right fronto-temporal headache and neck pain, which persisted for 13 days. She saw her primary care doctor four days prior to admission who recommended continuing ibuprofen. Brain imaging was not obtained at that time. She subsequently developed generalized tonic-clonic seizures with acute left sided weakness, neglect, and encephalopathy, which prompted presentation to the hospital. Video EEG showed right sided lateralized rhythmic delta activity (LRDA), as well as diffuse slowing. Lumbar puncture was performed: OP of 22 mm H20, W108 (35% PMNs, 55% lymphocyte), R 20, P 63.4, G 58.7, CSF culture was negative. CSF MOG antibody was positive at 1:100 and serum MOG antibody was positive at 1:320. Antivirals and antibiotics were stopped when infectious workup returned negative, and she began a five-day course of IV methylprednisolone with dramatic improvement. <h3>Conclusions:</h3> FLAIR-hyperintense lesions in anti-MOG-associated Encephalitis with Seizures (FLAMES) should be included in the differential diagnosis of new, sudden-onset, severe, and persistent headache. Recommendations include early imaging and treatment with corticosteroids. <b>Disclosure:</b> Dr. Michaelson has nothing to disclose. Dr. Langan has nothing to disclose. Dr. Kaunzner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Kaunzner has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Medlearning.

Posterior Spinal Cord Infarct: To Make the Diagnosis, Think of the Unthinkable! (P12-5.004)

<h3>Objective:</h3> We report a case of posterior spinal artery (PSA) infarct initially misdiagnosed as transverse myelitis (TM) and highlight some of the differentiating features of this exceedingly rare entity. <h3>Background:</h3> Spinal cord infarcts (SCIs) represent 1% of strokes and 5–8% of acute myelopathy. In a systematic review of 133 cases of SCI collected over two decades, PSAs presented 11% of the total pool. Redundancy in the vascular supply of the posterior portion of the spinal cord accounts for PSA rarity. <h3>Design/Methods:</h3> A single case report. <h3>Results:</h3> A 62-year-old woman with a history of recurrent nephrolithiasis, vitamin B12 deficiency, hypertension, and hyperlipidemia presented painless and rapidly progressive severe numbness and weakness of the legs. Sphincter symptoms were absent. Enhanced Magnetic Resonance Imaging (MRI) of the brain and spinal cord were unremarkable. Cerebral spinal fluid (CSF) was unremarkable. She was diagnosed with TM, given a five-day course of intravenous (IV) steroids, and discharged to a rehabilitation facility with a protracted and incomplete recovery. She presented two years later with fluctuating sensory and motor symptoms in the context of ureteral stent removal. Repeat CSF was unremarkable. However, on repeat thoracic spine MRI, there was interval development of a T2 hyperintensity along the dorsal columns and myelomalacia from T3–T4 disc to T12. She received IV steroids with minimal improvement. She had recurrent myelopathy pseudoexacerbations in the context of concurrent illnesses subsequently. Spinal magnetic resonance angiography, computerized chest, abdomen, pelvis tomography, positron emission tomography scan, and cardiovascular investigations were unremarkable. <h3>Conclusions:</h3> Given its scarcity, PSA infarct can often go misdiagnosed. A high index of suspicion for PSA should be kept in mind, particularly in the case of 1) acute, severe, and rapidly progressive myelopathic symptoms, 2) an extensively normal CSF analysis, and 3) an initially normal MRI of the spinal cord that eventually shows some T2 hyperintensity and cord atrophy. <b>Disclosure:</b> Dr. Solis has nothing to disclose. Dr. Zabad has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer. Dr. Zabad has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Zabad has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Zabad has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene/BMS. Dr. Zabad has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme. Dr. Zabad has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck Serono. Dr. Zabad has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva Neurosciences. Dr. Zabad has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Zabad has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Teva. Dr. Zabad has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Zabad has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genentech. Dr. Zabad has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BMS. The institution of Dr. Zabad has received research support from Adamas. The institution of Dr. Zabad has received research support from Biogen. The institution of Dr. Zabad has received research support from Novartis. The institution of Dr. Zabad has received research support from Sun Pharma. The institution of Dr. Zabad has received research support from Parexel &amp; MedDay Pharmaceuticals.

Economic efficiency of castration of boars using different methods on the background of immunocorrection under the conditions of industrial technology

The article presents the results of determining the economic efficiency of the use of two immunocorrectors — thymogen and mikovit (ribav) during castration of boars in industrial technology.The studies were performed on 49 boars (aged 5 months), divided into seven groups — two control and five experimental ones (n=7 in each).All animals were castrated: in the 1st control, 1st, 2nd, 3rd and 4th experimental groups — using open method; in the 2nd control and the 5th experimental groups — using closed method. Preoperative support was carried out according to the methodology used to the farm.The boars of the experimental groups were additionally treated with immunomodulators: in the first one — with thymogen (five-day course before surgery), in the second one — with mycovit (ribav), according to the scheme of the first group with local application after surgery, in the third — according to the scheme of the first group, but after the surgery; in the 4th and 5th — only with the working solution of mikovit (ribav) according to the method of the 2nd experimental group.The economic effect of the developed schemes was defined as the difference between the damage prevented as a result of veterinary measures and veterinary costs, taking into account the additional cost obtained by increasing the quantity of manufactured products and improving their quality. As an additional method, the total index of the effectiveness of veterinary measures was used, which was calculated by multiplying the economic damage by veterinary costs (per animal in each group) and then dividing the resulting number by their minimum multiplication.It was shown that the inclusion of thymogen at a dose of 100 μg/cm3 into the basic regimen of intramuscular injections with a five-day course after surgery using an open castration method or irrigation of the wound surface according to the above scheme with the solution of mycovit (ribav) can significantly increase the economic effect of veterinary measures. In the conditions of industrial pig breeding (taking into account the higher manufacturability of the application), preference should be given to thymogen.

An Assessment of the Training Program on Mental Health for Community Health Workers in Kashmir, India.

In recent years mental health has emerged as a major health threat in low income countries like India. In response, mental health care has been integrated into primary health care, in turn creating a rising demand for trained and skillful mental health professionals. This study was conducted in district Budgam (J&K), India with the aim of providing training to community health workers (CHWs) and measuring the change using pre- and post-training evaluations. The pre and post tests were undertaken, assessing changes in mental health literacy at three different points of time: pre-training, post-training, and three month follow-up. Mental health literacy was assessed using the interviewer-administered Mental Health Literacy Survey. The training intervention was a five-day course based on a facilitator's manual developed specifically for community health workers in India. A total of 25 community health workers from rural areas of Budgam District (mostly Integrated Child Development Service supervisors), Health Educators and Anganwadi Workers, were engaged for the study. Findings demonstrate that the training course improved participants' ability to recognize any mental health disorders. There was a clear distinction between the level of awareness pre- and post- training. The results were statistically significant on various domains Ability to recognize disorders (Pre-post P= 0.001), Knowledge of the professional help available (Pre-post p= 0.000), Attitudes that promote the recognition or appropriate help-seeking behavior (Pre-post p= 0.000) (p<0.05). Further follow up after three months was done. The mixed findings from this study, suggesting the training course has potential to improve some aspects of mental health literacy among the CHWs, including their understanding of various mental health problems.

The First Known Documented Case of Ewingella Americana Urinary Tract Infection

We present a 73-year-old male with a history of end-stage renal disease (ESRD) on dialysis, type 2 diabetes mellitus, coronary artery disease status post stents, prostate carcinoma status post radiation, and prostatectomy, with recurrent bladder neck contracture requiring suprapubic catheter, left urethral stricture with nephrostomy tube placement, penile implant, and recurrent urinary tract infections, who presented to the emergency room complaining of constant bilateral groin pain for one day. Physical exam was significant for suprapubic tenderness and a chronic suprapubic catheter and left-sided nephrostomy tube. An initial examination of the patient's urine revealed turbid, yellow-colored fluid, positive for white blood cells, leukocyte esterase, and bacteria. A urine culture was obtained, which returned positive for E. americana, with>100,000colony-forming units (CFUs)as well as Enterococcus faecalis (E. faecalis) demonstrating low colony counts.The patient was treated with a seven-day course of meropenem 1 gm twice daily, whichimproved of his symptoms, and then completed a 10-day course of ertapenem 500 mg daily. The patient received a five-day course of vancomycin 1 gm on dialysis days for additional coverage of E. faecalis, despite low colony counts. This is the first documented case of a urinary tract infection caused by E. americana.The organism is primarily found in immunocompromised individuals, and a debate is still ongoing as to whether it is a true pathogen or exists primarily as an opportunistic infection.We suggest further inquiry and study of this resistant organism are paramount in establishing its role in both immunocompromised as well as immunocompetent individuals.E. americana is a multidrug-resistant organism, which to date has sparse documentation regarding its prevalence and potential for morbidity, especially in compromised individuals.In the era of increasing antibiotic resistance, we suggest that more research is needed to understand the pathogenicity of E. americana.

Evaluation of the effectiveness of migraine therapy using functional resting MRI with course rhythmic transcranial magnetic stimulation

Introduction. In the context of the search for new migraine therapy options, strict control of their eff ectiveness by means of objective examination methods is required.Objective. Objective assessment of the eff ectiveness of TMS in patients with migraine on the basis of functional magnetic resonance imaging (fMRI) data.Material and methods. Resting-state fMRI before and after a fi ve-day course of TMS of the junction of the inferior frontal and temporal lobes bilaterally was performed in 19 patients with migraine. Changes in functional connectivity (FC) of the main neuronal networks of the brain, as well as clinical parameters of pain and quality of life of the patients were assessed before and after the course of TMS.Results. A decrease in pain intensity and anxiety scores, as well as a decrease in the number of acute pain medications taken, was observed against the background of the therapy. Changes in FC aff ected three main networks: the default mode network, the salience and visual networks. At the same time, decreased effi cacy of therapy was noted in patients with higher severity of depressive symptoms and presence of neuroimaging criteria of depression.Conclusion. The study suggests the effi cacy of TMS in patients with migraine based on neuroimaging criteria. It is worth paying special attention to the presence of depressive symptoms in migraine patients.

Efficacy and safety of ivermectin in patients with mild and moderate COVID-19: A randomized controlled trial

Objective: To evaluate the effectiveness and safety of ivermectin in patients with mild and moderate COVID-19. Methods: This study was a single-center, randomized, open-label, controlled trial with a 2-arm parallel-group design on 68 patients with COVID-19. According to the 1:1 ratio between the study groups (ivermectin group and standard treatment group), patients were randomly admitted to each intervention arm. Results: The mean age of the participants in the ivermectin group was (48.37±13.32) years. Eighteen of them were males (54.5%) and the participants in the control group had a mean age of (46.28±14.47) years, with nineteen of them being males (59.4%). As a primary outcome, after 5 days of randomization, there was no significant difference between the ivermectin group and the control group in the length of stay in the hospital (P=0.168). ICU admission (P=0.764), length of stay in ICU (P=0.622), in-hospital mortality (P=0.427), adverse drug reactions, and changes in the mean difference of laboratory data had not any significant difference between the two groups (except for urea change). In addition, the radiologic findings of the two groups of patients were not significantly different. Linear regression analysis showed that for every 10 years increase of age, 0.6 day of hospitalization duration was increased. There was no statistically significant association between other variables and clinical outcomes. Conclusions: Among adult hospitalized patients with moderate to severe COVID-19, there was no significant relationship between the administration of ivermectin single dose in a five-day course and clinical improvement, and mortality of the participants.

Blue toe syndrome secondary to multiple spontaneous aortic thrombi following pneumonia

A 65-year-old man presented with bilateral ischaemic toes 11 days following hospital discharge for pneumonia. His initial admission was complicated by atrial fibrillation requiring rivaroxaban on discharge. A thromboembolic cause of his toe ischaemia was suspected. An echocardiogram demonstrated only moderate atherosclerosis. However, repeat echocardiogram revealed five thrombi within the descending aorta. Medical management included therapeutic enoxaparin, aspirin, atorvastatin and a five-day course of iloprost. Subsequent right 5th toe amputation was required for osteomyelitis, but otherwise the patient made a full recovery and was asymptomatic at 12 months.

Education on Vaccination Competence: an Intensive Course for Skillful Health Science Students.

Vaccination is one of the most successful and cost-effective interventions for public health. Studies have shown that health professionals who have good knowledge and positive attitudes towards vaccination are more likely to provide effective vaccination protection to people, including themselves. Therefore, health science students must acquire evidence-based knowledge during their education to meet the challenges of healthcare. The aim of this study was to investigate the knowledge, attitudes and feedback of health science students who participated in the Educating Vaccination Competence (EDUVAC) Intensive Course. A five-day Intensive Course was implemented for health science students, which included a pre-assignment. The EDUVAC Intensive Course used different teaching methods (lectures, workshops, interactive games, discussions), group work, study visits, and cultural programs to encourage students' motivation. For the purpose of the study, students filled out an online questionnaire after giving informed consent. Sample consisted of 31 health science students from five European Higher Institutions. They had very good knowledge on most knowledge questions. In the post measurement it was significantly greater and equal to 81%, p<0.001. Almost all students (93.5%) totally agreed that "It is important for adults to receive all recommended vaccines according to national guidelines". The statement "I have had an active attitude and participation in the Intensive Course" received 80.6% total agreement. Over 90.3% rated the Intensive Course as "excellent" or "above average". After completing the EDUVAC Intensive Course, students felt confident in their vaccination knowledge and skills, which benefited their professional development.

Teaching eco-translation

Abstract The coronavirus pandemic has kept us individually as well as publicly in a state of preoccupation that prohibited us from staying with the trouble of an ecologically damaged planet. The authors of this contribution are sharing their experience and reflections upon teaching, as an active intervention to this absent presence in everyday Covid-19 lives, an eco-translation course. For this we will first offer a short discussion of our scholarly backgrounds and biases. Second, we will describe our efforts in translating these biases into concrete teaching. The course that serves here as a case study was taught in a project format in the 2021 winter term 2 at the Faculty for Translation Studies, Linguistics and Cultural Studies at Mainz University. It was a five-day course which blended localisation and nature writing framed by a holistic approach to scholarship and teaching. Third, we will discuss the teaching experience in terms of the presences and absences it made apparent.

925. Remdesperate for Stewardship: Impact of a Remdesivir Stewardship Strategy on the Care of Patients with COVID-19 Admitted to a Community Teaching Hospital

Abstract Background The use of remdesivir (RDV) in patients hospitalized with COVID-19 has resulted in a significantly shorter time to recovery, especially in patients receiving low flow oxygen. Despite the shortened time to recovery, concerns have been raised regarding the $3,120 cost of a five-day course. This price was originally justified by the suggestion that RDV would save hospitals approximately $12,000 per patient by shortening hospital length of stay (LOS) by four days, however, this has not been consistently demonstrated in clinical practice. A preliminary review of RDV orders at our facility revealed hospital discharges were being delayed to complete a five-day course of treatment in patients otherwise medically ready to discharge. Methods This single-center, retrospective, comparative study was conducted at AdventHealth Orlando, a 1,368-bed community teaching hospital in central Florida. In January 2021, the campus stewardship committee devised a RDV stewardship strategy including targeted education and escalation of orders not meeting institutional criteria at time of order verification. This study compared pre-intervention patients who received RDV from December 1, 2020, to January 7, 2021, to post-intervention patients who received RDV from January 8, 2021, to February 28, 2022. The primary objective of this study was to assess the impact of a pharmacist-driven RDV stewardship initiative on the duration of therapy in hospitalized patients with COVID-19. Results A total of 2104 remdesivir orders were included in the study (209 pre-intervention and 1895 post-intervention). Overall, patients had a median age of 59 years and 49% were male. Majority of patients in both groups required low flow supplemental oxygen at the time of RDV initiation. Significantly more orders in the intervention group aligned with institutional criteria at the time of order entry (47% vs 84%, p&amp;lt; .001). Patients completing the full 5-day course of remdesivir therapy decreased from 79 to 53% (p&amp;lt; .001). A decreased duration of therapy and length of stay were observed in the intervention group. Conclusion Pharmacist-driven RDV stewardship increased adherence to the institutional algorithm and reduced duration of therapy. Disclosures Amy L. Carr, PharmD, BCIDP, Shionogi: Advisory Board.

4-Year Multiple Sclerosis Disease Remission After a Single Cycle of Alemtuzumab: a case report

Introduction. Alemtuzumab is a humanized monoclonal antibody against the CD52 antigen. It is a highly efficacious drug for the treatment of relapsing remitting multiple sclerosis (MS). The treatment protocol consists in 2 treatment cycles: 12mg/day i.v. infusions for 5 consecutive days and after one-year 12mg/day infusions for 3 days. To our knowledge, there is a single case series in the literature detailing MS remission after a single cycle of Alemtuzumab. Here, we report a similar experience. Case report. A 48-year-old woman with fluctuating right leg weakness for three years and burning pain in the right foot was diagnosed with MS. She was started on Betaferon©. Her condition progressed and in less than one year, she was switched to glatiramer and after new MS relapses to fingolimod. Disease progressed to Expanded Disability Status Scale (EDSS) of 7.0. She was started on Alemtuzumab (five-day course of 12mg i.v. on 6/2018). A second Alemtuzumab cycle was not given since she failed to follow monitoring guidelines. She had no signs of disease activity after four years. Conclusions. It is possible that MS remission may be achieved with a single cycle of Alemtuzumab.

Treatment-Refractory Autoimmune Glial Fibrillary Acidic Protein Meningoencephalomyelitis in a Young Adult Female

Objective To describe a case of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy refractory to immunotherapy without evidence of malignancy or coexisting autoimmunity. Background Autoimmune GFAP astrocytopathy is an autoimmune disease of the central nervous system associated with the presence of GFAP-IgG in the CSF. Patients may present with acute or subacute onset of headache, encephalopathy, seizures, abnormal vision, weakness or numbness, postural tremor and cerebellar ataxia. GFAP astrocytopathy is usually corticocorticosteroid-responsive in the acute setting but may rarely require maintenance immunotherapy to prevent relapse. Treatment refractory cases should trigger work up for coexisting autoimmunity or malignancy. Design/Methods A 35-year-old female patient presented with subacute meningoencephalomyelitis with prodromal symptoms. Results Her cerebrospinal fluid revealed lymphocytic pleocytosis and elevated protein. Brain magnetic resonance imaging (MRI) with and without contrast showed perivascular radial enhancement and periventricular T2 FLAIR hyperintensity. Spinal MRI with and without contrast demonstrated longitudinal T2 FLAIR hyperintensity from T1-T2 to T7-T8. Despite high dose steroid treatment, her disease progressed with an enlarging periventricular lesion and worsening visual acuity. Biopsy of the enhancing periventricular lesion showed perivascular inflammation. After five cycles of plasma exchange along with a five-day course of intravenous methylprednisolone 1 gram daily, her symptoms stabilized. The CSF autoimmune encephalopathy panel (Mayo Clinic Laboratories) came back positive for GFAP-IgG antibody on tissue immunofluorescence assay, and was confirmed positive by GFAP cell-based assay. No neoplastic disease was identified using high resolution PET/CT scans. Based on the aggressiveness of her disease, she received one cycle of cyclophosphamide, and was discharged home on an oral corticosteroid taper. Even one year after addition of both mycophenolate mofetil and rituximab, MRI imaging continued to reveal new enhancing lesions. Conclusions Autoimmune GFAP astrocytopathy may sometimes require long-term immunosuppression even without presence of malignancy or other coexisting autoimmune disease.

Проект краткого курса «Избранные вопросы инженерии»

It is proposed to supplement the existing university courses "Introduction to Engineering" with a brief overview of the author's project-based learning course "Selected engineering issues". As an example, a five-day course plan is given. The course is intended for a general understanding of the specifics, structure and problems of engineering activities, and, according to the plan, should improve the mastering of the material of the Introduction to Engineering courses. The course has the format of a collective educational and project process, which is implemented in the cognitive infrastruc- ture of the situation center on the resources available to the organizers. Such a center can be set up outside the class- room using participants' smartphones. The cognitive environment is ensured by the presence of a support team consist- ing of a coordinator, a methodologist, a tablet keeper and a game technician. The functions of the support team can be performed by one specially trained teacher capable of reflexive perception of the learning situation. A constructor of course options is proposed, which includes various types of implementation processes. A variant of a metaphorical cog- nitive engineering map as a set of pictures and comments to them is proposed. The need for separate consideration of the setting tasks stages, working on bugs and opportunities for students to quickly access network resources and team- work technologies is noted. The author's "4C" approach (collective, cognitive, configurative, convergent) is used in combination with a cross-technology system that provides multidisciplinarity. The concept of mutual adjustment of students' cognitive profiles and teaching formats of academic subjects (visual, audio, kinesthetic, tactile) is also used. The use of the listed author's tools ensures the originality of the proposed solutions.

Hydrocortisone or Placebo to Reduce Dexamethasone-Induced Neurobehavioral Side Effects: Results of a Phase 3 National, Double-Blind, Placebo-Controlled Randomized Trial with Crossover Design

Background The introduction of dexamethasone for the treatment of pediatric acute lymphoblastic leukemia (ALL) significantly contributed to the current overall survival rate of more than 90% in high-income countries. The downside however, is that dexamethasone can induce serious side effects, of which neurobehavioral side effects are experienced as detrimental with respect to health-related quality of life (HRQoL) by both patients and parents. Our previous study suggests that children who suffer most from neurobehavioral side effects might benefit from physiological hydrocortisone addition to dexamethasone treatment. We aimed to validate this finding in a prospective large cohort of pediatric ALL patients. Methods Our phase 3, double-blind, randomized controlled trial with crossover design included ALL patients (3-18 years) during medium risk maintenance therapy in a national tertiary hospital between May 17, 2018 and August 5, 2020. A baseline measurement before and after one five-day dexamethasone course was performed to identify patients with clinically relevant dexamethasone-induced neurobehavioral problems, defined as a rise of ≥5 points on the Strengths and Difficulties Questionnaire (SDQ) Total Difficulties score. These patients were subsequently randomized to receive an intervention during the following four five-day dexamethasone courses. The intervention consisted of two courses hydrocortisone (physiological dose of 10mg/m2/day in a circadian rhythm), followed by two courses placebo, or vice versa. Neurobehavioral problems were assessed before and after each course using the parent-reported SDQ as primary endpoint. Secondary endpoints were sleep problems, HRQoL, hunger feeling, and parental stress, measured with separate questionnaires and actigraphy. A generalized mixed model was estimated to study the intervention effect. Findings Of 79 included patients, 52 (66%) experienced clinically relevant dexamethasone-induced neurobehavioral problems. Both hydrocortisone and placebo significantly and relevantly decreased dexamethasone-induced neurobehavioral problems measured with the SDQ (estimated effect hydrocortisone: -8.19 (95%-confidence interval (CI) -12.35 to -4.04), estimated effect placebo: -6.75 (95%-CI -10.95 to -2.56) (table 1 and figure 1). This indicates that, when adding hydrocortisone or placebo to dexamethasone treatment, the SDQ Total Difficulties score is estimated to be 8.19 or 6.75 points lower than without the addition of hydrocortisone or placebo. Since one SD of SDQ norm values is between 4 and 6 points, the decrease on the SDQ after hydrocortisone or placebo addition is more than 1 SD, and therefore clinically significant. The strength of the effect was similar in both interventions. There was no benefit from hydrocortisone or placebo in reducing sleep problems, hunger, parental stress or improving HRQoL. Interpretation Clinically relevant dexamethasone-induced neurobehavioral problems decreased equally and significantly after both hydrocortisone and placebo addition. Using the placebo effect in clinical practice could be a powerful and innovative way to diminish neurobehavioral problems in children who experience clinically relevant dexamethasone-induced side effects. Moreover, the high proportion of patients who experience clinically relevant dexamethasone-induced neurobehavioral problems might be caused by a nocebo effect of dexamethasone. By offering both interventions (hydrocortisone and open-label placebo) in clinical practice and by diminishing the nocebo effect of dexamethasone, we hope to improve dexamethasone-induced side effects in those patients who suffer most. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Chemical induction of gut β-like-cells by combined FoxO1/Notch inhibition as a glucose-lowering treatment for diabetes

ObjectiveLifelong insulin replacement remains the mainstay of type 1 diabetes treatment. Genetic FoxO1 ablation promotes enteroendocrine cell (EECs) conversion into glucose-responsive β-like cells. Here, we tested whether chemical FoxO1 inhibitors can generate β-like gut cells. MethodsWe used Ngn3-or Villin-driven FoxO1 ablation to capture the distinctive developmental effects of FoxO1 on EEC pool. We combined FoxO1 ablation with Notch inhibition to enhance the expansion of EEC pool. We tested the ability of an orally available small molecule of FoxO1 inhibitor, Cpd10, to phenocopy genetic ablation of FoxO1. We evaluated the therapeutic impact of genetic ablation or chemical inhibition of FoxO1 on insulin-deficient diabetes in Ins2Akita/+ mice. ResultsPan-intestinal epithelial FoxO1 ablation expanded the EEC pool, induced β-like cells, and improved glucose tolerance in Ins2Akita/+ mice. This genetic effect was phenocopied by Cpd10. Cpd10 induced β-like cells that released insulin in response to glucose in gut organoids, and this effect was enhanced by the Notch inhibitor, DBZ. In Ins2Akita/+ mice, a five-day course of either Cpd10 or DBZ induced intestinal insulin-immunoreactive β-like cells, lowered glycemia, and increased plasma insulin levels without apparent adverse effects. ConclusionThese results provide proof of principle of gut cell conversion into β-like cells by a small molecule FoxO1 inhibitor, paving the way for clinical applications.

INFLUENCE OF THYMOGEN IN DISEASES OF HOOVES IN MOOSES ON HEMATOLOGICAL INDICATORS

The article presents data reflecting hematological parameters in domesticated moose with standard treatment, as well as in combination with thymogen in case of damage to the hooves.Experiments were performed on three groups of moose cows 2 months before calving: control (n=10, healthy) and two experimental groups (n=3 in each): d - with a more severe one and with the additional inclusion in the treatment regimen of a five-day course of thymogen, at a dose of 300 μg / animal, intramuscularly.Blood was taken before, on the 14th and 30th days of the experiment. Visually, the number of erythrocytes, leukocytes, leukogram, ESR were taken into account.It has been established that hoof injuries in sick moose cows are accompanied by changes in the hematological profile. They register a higher level of erythrocytes, leukocytes, lymphocytes, absolute and relative - stab and segmented neutrophils, against the background of lower levels of basophils, eosinophils, monocytes.It was shown that the direction of the dynamics of hematological parameters in the animals of the control and the 1st experimental groups had differences in 12 out of 14 indicators, and compared with the 2nd experimental group, only in six. The highest degree of coincidence between the control and the 1st experimental group was noted on the 14th day in seven cases (50%), on the 30th - in four (28.6%), compared with 2 th, moose cow additionally treated with thymogen in 11 (78%) and seven (50%) cases, in the complex on the 14th-30th in two (14.3%) and seven (50%) cases, respectively.This assessment of the coincidence of the direction of the dynamics of hematological parameters of the experimental groups in comparison with the control group indicates that complex therapy supplemented with thymogen allows to normalize the dynamics of hematological parameters.

INFLUENCE OF THYMOGEN IN DISEASES OF HOOVES IN MOOSES ON INDICATORS OF MINERAL, PIGMENT AND LIPID METABOLISM

Data are presented that reflect the indicators of mineral, pigment and lipid metabolism in domesticated elks with hoof damage in standard treatment, as well as in combination with thymogen.The study was performed on three groups of breeding stock 2 months before calving: control - healthy animals (n = 10) and two experimental animals (n = 3 in each): group 1 - with mild damage to the hooves (basic treatment regimen ), 2nd - with more severe and with additional inclusion in the treatment regimen of a five-day course of thymogen at a dose of 300 μg/head, intramuscularly.Blood for the study was taken before, on the 14th and 30th day of the experiment. Serum-ku was obtained by the conventional method.It was shown that a mild degree of damage to the hooves was accompanied by an increase in the level of calcium, sodium, magnesium, cholesterol, triglycerides, calcium-phosphorus ratio, a decrease in chlorine, phosphorus, potassium, total and direct bilirubin, osmolarity, and in more severe cases, an increase phosphorus, sodium, triglycerides against the background of a decrease in other components.The additional inclusion of thymogen in the scheme of therapeutic treatments in animals with a severe degree of damage contributed to a greater extent to the normalization of mineral metabolism, as evidenced by the indicators at the final stage of the experiments, which are closer to those of healthy animals than in the 1st experimental group. . The use of an immunocorrector minimized disturbances in pigment and lipid metabolism.