Current and future trends in multiple sclerosis management: Near East perspective.

BACKGROUND: Multiple sclerosis (MS) prevalence is rising in the Middle East. Most MS medications are available in the region, but not all, possibly affecting neurologists' prescribing habits. OBJECTIVES: To provide an overview of the current practices of Near East (NE) healthcare practitioners by probing their prescribing decisions, to report the COVID-19 impacts on neurologists' prescribing habits, and to explore the future relevance of current medication used in MS management among other newcomers. METHODS: A cross-sectional study was carried out using an online survey from April 27, 2022, to July 5, 2022. The questionnaire was designed with the input of five neurologists representing five NE countries (Iran, Iraq, Lebanon, Jordan & Palestine). They identified several factors that play a crucial role in the optimal care of MS patients. The link was shared among neurologists using snowball sampling. RESULTS: The survey included 98 neurologists. Effectiveness and safety balance was the most important factor considered when selecting the MS treatment. Among patients with MS, the most challenging factor for the patients was thought to be related to family planning, followed by affordability and tolerability of side effects. In the treatment of mild to moderate relapsing remitting multiple sclerosis (RRMS) in men, Interferon beta 1a SC, Fingolimod, and Glatiramer acetate were the most commonly recommended treatments. Dimethyl fumarate substituted fingolimod in female patients. Interferon beta 1a SC was the safest treatment for mild to moderate RRMS. Interferon beta 1a SC was preferred over other treatments for patients with mild to moderate MS and planning for pregnancy (56.6%) or breastfeeding (60.2%). Fingolimod was not a choice for these patients. Neurologists seemed to discuss the top three treatments of Natalizumab, Ocrelizumab, and Cladribine with patients with highly active MS. When asked to position future disease-modifying therapies five years from today, more than 45% of physicians expressed a lack of information on Bruton's tyrosine kinase (BTK) inhibitors. CONCLUSIONS: Most neurologists in the NE region followed Middle East North Africa Committee for Treatment and Research in Multiple Sclerosis (MENACTRIMS) recommendations for prescribing treatment. The treatment choice also depended on the availability of disease-modifying therapies (DMTs) in the region. Regarding the use of upcoming DMTs, there is a clear need for real-world data, long-term extension studies, and comparative studies to support their efficacy and safety profiles in treating patients with MS.

Progress in understanding of association between metabolic associated fatty liver disease and viral infectious diseases.

Metabolic associated fatty liver disease (MAFLD) is a chronic liver disease with the highest incidence in the world, which affects 1/4-1/3 of the world population and has a serious effect on people's health. As is a multi-systemic disease, MAFLD is closely related to the occurrence and prognosis of many diseases. Studies have shown that MAFLD is associated with viral infectious diseases, and their interaction affects the prognosis of the disease. This paper reviews the research progress in this field in recent years.Copyright © The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.

Antiviral Potential of the Genus Panax: An updated review on their effects and underlying mechanism of action.

Viral infections are known as one of the major factors causing death. Ginseng is a medicinal plant that demonstrated a wide range of antiviral potential, and saponins are the major bioactive ingredients in the genus Panax with vast therapeutic potential. Studies focusing on the antiviral activity of the genus Panax plant-derived agents (extracts and saponins) and their mechanisms were identified and summarized, including contributions mainly from January 2016 until January 2022. P. ginseng, P. notoginseng, and P. quinquefolius were included in the review as valuable medicinal herbs against infections with 14 types of viruses. Reports from 9 extracts and 12 bioactive saponins were included, with 6 types of protopanaxadiol (PPD) ginsenosides and 6 types of protopanaxatriol (PPT) ginsenosides. The mechanisms mainly involved the inhibition of viral attachment and replication, the modulation of immune response by regulating signaling pathways, including the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway, phosphoinositide-dependent kinase-1 (PDK1)/ protein kinase B (Akt) signaling pathway, c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) pathway, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. This review includes detailed information about the mentioned antiviral effects of the genus Panax extracts and saponins in vitro and in vivo, and in human clinical trials, which provides a scientific basis for ginseng as an adjunctive therapeutic drug or nutraceutical.

Can plant-derived anti-HIV compounds be used in COVID-19 cases?

People living with HIV are more exposed to the adverse health effects of the worldwide COVID-19 pandemic. The pandemic's health and social repercussions may promote drug abuse and inadequate HIV management among this demographic. The coronavirus pandemic of 2019 (COVID-19) has caused unprecedented disruption worldwide in people's lives and health care. When the COVID-19 epidemic was identified, people with HIV faced significant obstacles and hurdles to achieving optimal care results. The viral spike protein (S-Protein) and the cognate host cell receptor angiotensin-converting enzyme 2 (ACE2) are both realistic and appropriate intervention targets. Calanolides A, Holy Basil, Kuwanon-L, and Patentiflorin have anti-HIV effects. Our computational biology study investigated that these compounds all had interaction binding scores related to S protein of coronavirus of -9.0 kcal /mol, -7.1 kcal /mol, -9.1 kcal /mol, and -10.3 kcal/mol/mol, respectively. A combination of plant-derived anti-HIV compounds like protease inhibitors and nucleoside analogs, which are commonly used to treat HIV infection, might be explored in clinical trials for the treatment of COVID-19.

Experiences to date with the logistical management of long-acting cabotegravir and rilpivirine.

The logistical management of an injectable therapy for the treatment of HIV can be expensive, time consuming, frustrating and riddled with barriers. In this Commentary, we describe our experiences to date with acquiring, storing, handling, administering and billing for long-acting cabotegravir and rilpivirine through four scenarios, each of which have presented their own unique obstacles and learning curves. At the time of writing, we have successfully transitioned four patients from the CUSTOMIZE trial to long-acting cabotegravir and rilpivirine. In doing so, we encountered a variety of barriers to acquiring, handling and administering the medication for both insured and uninsured patients; it is expensive, on a limited number of insurance formularies, and often requires a prior authorization from the provider. Cold-chain handling of the injectable therapy, along with individual patient characteristics, present barriers to management and administration of this therapy. Whilst a seemingly very attractive option for the treatment of HIV-1 infection in adults, long-acting cabotegravir and rilpivirine present a variety of challenges to pharmacists, providers and clinic staff on how to obtain it for and administer it to the patient. We plan to continue documenting our experiences, progress and successes, or lack thereof, in order to fine-tune our process and share with others.

A CASE REPORT OF PNEUMOCYSTIS JIROVECI PNEUMONIA CAUSING ARDS IN HIV/AIDS IN THE SETTING OF COVID-19 PANDEMIC

SESSION TITLE: Critical Care in Chest Infections Case Report Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: During the COVID-19 pandemic, acute respiratory distress syndrome (ARDS) was a very common presentation. Many clinicians sought to rule out COVID-19 in those presenting with hypoxia and shortness of breath due to the importance of triage and quarantining infected individuals and those under investigation. As a result, delay in diagnosis of other viral and bacterial pathogens occurred. There is a known but rare overlapping of disease processes and sometimes even co-infections with COVID-19 and Pneumocystis jirovecii pneumonia (PJP) which made narrowing the differential challenging [1,2]. We present a case of a patient with known HIV who presented with typical features of COVID-19 and clinically worsened. Further investigation revealed PJP and AIDS. CASE PRESENTATION: A 55-year-old female with a past medical history of human immunodeficiency virus (HIV), previously controlled on highly active antiretroviral therapy (HAART), presented with shortness of breath, cough, and syncope. She required sedation and mechanical ventilation following significant hypoxia on admission. Chest radiograph and computed tomography (CT) were concerning for acute respiratory distress syndrome (ARDS) with diffuse bilateral ground glass opacities (Figure 1 and Figure 2) and she was found to be in septic shock requiring vasopressors. She presented during the COVID-19 pandemic and it was initially thought to be the cause of her condition, however she repeatedly tested negative via polymerase chain reaction (PCR). Through further investigation, it was found that her total cluster of differentiation 4 (CD4) cell count was 184/??L, posing a risk for opportunistic infections. Prior records indicated her last CD4 count was greater than 250/??L. Bronchoscopy showed progressively darker-tinged aliquots significant for diffuse alveolar hemorrhage that stained positive for Pneumocystis jirovecii pneumonia (PJP). She was treated with appropriate antimicrobial therapy, eventually weaned from ventilation, and transferred to the floor despite her high risk of morbidity and mortality [3]. DISCUSSION: This clinical case demonstrates PJP infection in an individual with features on imaging nearly identical to those of COVID-19 during the pandemic. There is a strong role in verifying CD4 count and HIV viral level in those affected with HIV with reported medication adherence who present with critical illness. There should be a low threshold to perform bronchoscopy in patients with ARDS and negative COVID-19 if no known source is identified. CONCLUSIONS: It is important to consider all causes of ARDS in patients who are immunocompromised with a low threshold to test for and treat uncommon causes, such as opportunistic infections, because the treatment should be directed at the underlying cause. Reference #1: Coleman, H., Snell, L., Simons, R., Douthwaite, S. and Lee, M., 2020. Coronavirus disease 2019 and Pneumocystis jirovecii pneumonia: a diagnostic dilemma in HIV. AIDS, 34(8), pp.1258-1260. Reference #2: Menon, A., Berg, D., Brea, E., Deutsch, A., Kidia, K., Thurber, E., Polsky, S., Yeh, T., Duskin, J., Holliday, A., Gay, E. and Fredenburgh, L., 2020. A Case of COVID-19 and Pneumocystis jirovecii Coinfection. American Journal of Respiratory and Critical Care Medicine, 202(1), pp.136-138. Reference #3: Dworkin, M., Hanson, D. and Navin, T., 2001. Survival of Patients with AIDS, after Diagnosis of Pneumocystis carinii Pneumonia, in the United States. The Journal of Infectious Diseases, 183(9), pp.1409-1412. DISCLOSURES: No relevant relationships by salah alandary No relevant relationships by Joella Lambert No relevant relationships by Joshua Lung

Improving ART initiation among men who use HIV self-testing in Malawi: a qualitative study.

INTRODUCTION: HIV self-testing (HIVST) increases HIV testing uptake among men; however, the linkage to antiretroviral therapy (ART) among HIVST users is low. Innovative strategies for ART initiation are needed, yet little is known about the unique barriers to care experienced by male HIVST users, and what ART-related interventions men desire. METHODS: We conducted semi-structured in-depth interviews with cisgender men (≥15 years) in Malawi who tested HIV positive using HIVST between 2018 and 2020, as well as interviews with their female partners (≥15 years) who distributed the HIVST kits. Medical records from seven facilities were used to identify respondents. We included men who received HIVST from a health facility (primary distribution) and from sexual partners (secondary distribution). Interview guides focused on unique barriers to ART initiation following HIVST and desired interventions to improve linkage and initiation. Interviews were audio recorded, translated and transcribed to English, and analysed using constant comparison methods in Atlas.ti v.8.4. Themes were compared by HIVST distribution strategy. Data were collected between 2019 and 2020. RESULTS: Twenty-seven respondents were interviewed: eight male/female dyads (16 respondents), eight men without a female partner and three women who represented men who did not participate in the study. Among the 19 men represented (16 men interviewed in person, three represented by secondary report from female partners), seven received HIVST through primary distribution, 12 through secondary distribution. Six men never initiated ART (all secondary HIVST distribution). Barriers to ART initiation centred on the absence of healthcare workers at the time of diagnosis and included lack of external motivation for linkage to care (men had to motivate themselves) and lack of counselling before and after testing (leaving ART-related fears and misconceptions unaddressed)--the latter was especially true for secondary HIVST distribution. Desired interventions were similar across distribution strategies and included ongoing peer mentorship for normalizing treatment adherence, counselling messages tailored to men, outside-facility services for convenience and privacy, and facility navigation to help men understand how to navigate ART clinics. CONCLUSIONS: Male HIVST users face unique challenges to ART initiation, especially those receiving HIVST through secondary distribution. Male-tailored interventions are desired by men and may help overcome barriers to care.

Treatment of AIDS: Development of Medicine by Innovation with Special Emphasis on Protease Inhibitors

In the light of the recent events in the world concerning COVID-19 virus, it is important to review the challenges faced by the world by another pandemic, AIDS. The painstaking research by the scientists, the pharmaceutical companies, the medical professionals have led to this day when AIDS patients are living their whole life span. Though we do not have any vaccine for AIDS but by intelligent use of medication, we have been able to combat the disease to a large extent. HIV is a RNA virus, whose treatment is mainly done by finding the structure and function of the proteins that are vital to its life cycle. Designing a drug/inhibitor to make those proteins ineffective constitutes the next step. WHO has recognized AIDS as a pandemic almost 40 years back but the world is yet to find a cure or a vaccine. The current treatment method is called HAART, Highly Active Anti Retroviral Therapy, where different types of inhibitors,eg. Reverse Transcriptase inhibitors, Protease inhibitors;each arresting a different important protein are given in combination. The virus replicates very fast and forms mutations which render it ineffective to the inhibitors thus resistance to the inhibitors develop. Hence development of new types of inhibitors is crucial to the problem. There are certain similarities between AIDS and COVID-19, both in terms of the attacking virus and effective medication, which make it more important than ever that the research on HIV is revisited and knowledge we gain from it is used to battle the new pandemic.

[Effective therapy in highly active pediatric multiple sclerosis]. / Magas aktivitású sclerosis multiplex hatásos kezelése gyermekkorban.

Multiple sclerosis (MS) is typically a disease of young adults. Childhood MS can be defined in patients under 18 years of age, although some authors set the limit un-der the age of 16 formerly known as "early-onset multiple sclerosis" or "juvenile multiple sclerosis", seen in 3-5% of all MS patients. Nowadays, owing to ever-evolving, better diagnostic tools and well-traced, strictly defined diagnostic criteria, childhood MS is showing an increasing incidence worldwide (0.05-2.85/100 000). MS is characterized by recurrent episodes of the central nervous system with demyelination separated in space and time. In childhood almost exclusively the relapsing-remitting (RR) type of MS occurs. Based on experience in adults, the goal in the pediatric population is also the early diagnosis, to initiate adequate DMT as soon as possible and to achieve symptom relief and good quality of life. Based on efficacy and safety studies in the adult population, inter-feron ß-1a and glatiramer acetate were first approved by the FDA and EMA for the treatment of childhood MS also. The increased relapse rate and rapid progression of childhood MS and unfavorable therapeutic response to nearly 45% of the first DMT necessitated the testing of more effective and second-line drugs in the population under 18 years of age (PARADIGMS, CONNECT). Although natalizumab was reported to be effective and well-tolerated in highly active RRMS in childhood, evidence based studies were not yet available when our patients' treatment started. In this article, we report on the successful treatment of three active RRMS patients with individually authorized off-label use of natalizumab.

DIAGNOSING KAPOSI'S SARCOMA IN ABSENCE OF CUTANEOUS LESIONS IN THE HAART ERA

TYPE: Case Report TOPIC: Chest Infections INTRODUCTION: Kaposi sarcoma (KS) is very commonly associated with Human Immunodeficiency Virus (HIV) infection. The clinical course of HIV associated KS could be indolent with muco-cutaneous or aggressive with visceral organ system involvement. It is extremely uncommon for the visceral involvement to occur in the absence of mucocutaneous manifestations. CASE PRESENTATION: A 45-year male with HIV, presented with fatigue, exertional dyspnea, cough. Vital signs showed low grade fever and hypoxia. On physical exam the pertinent positive finding was diffuse inspiratory crackles. The CT chest showed multiple irregular nodular infiltrates in the lungs. Blood and sputum cultures were collected, and the patient was started on empiric antibiotics and fluconazole. The viral load and the absolute CD4 count were 64,360 and 17, respectively. The transesophageal echocardiogram was negative for vegetations. SARS-COVID19, blood culture and three sputum acid fast bacilli were negative. The patient continued to worsen. The bronchoscopy showed a friable mass in the left lower trachea. The immunohistochemistry analysis of the lesions was positive for CD34, CD31, HHV-8, FLI-1 which was diagnostic of KS. The patient was started on Highly Active Antiretroviral Therapy (HAART) and was discharged on HAART with a scheduled follow up. DISCUSSION: The introduction of HAART has decreased the incidence of KS to 0.03 per 1000 patient years in the HAART era. 15.5 % of patients have pulmonary KS in the absence of mucocutaneous lesions. These rates of pulmonary KS in autopsy findings were noted in the pre-HAART era. CONCLUSIONS: To establish a diagnosis of pulmonary KS in the absence of the characteristic cutaneous lesions is challenging. DISCLOSURE: Nothing to declare. KEYWORD: Kaposi Sarcoma

Cough and Dyspnea in 2021: A Case of Asthma, COVID-19, or.?

Background: COVID-19 has changed the perspective through which medical staff look at dyspnea and hypoxemia cases. Epidemiological links are frequently missing, and clinical and imagological findings are often unspecific, overlapping substantially with other respiratory infections. Case summary: We report the case of an 11-year-old girl with a known history of asthma who had recently moved from Guinea-Bissau with her mother. Although the mother reported being Ag HBs positive, no serologic studies had ever been performed on the child. The patient was admitted to the Emergency Room after 4 days of cough and the feeling of thoracic oppression, without fever. No contact with suspected or confirmed individuals infected with SARS-CoV-2 or other respiratory viruses was reported. She presented with peripheral oxygen saturation of 90%, costal retractions and a prolonged expiratory phase. After an unsuccessful course of bronchodilators and prednisolone, she was admitted to the Pediatric Intermediate Care Unit because of a sustained need for oxygen therapy. Polymerase chain reaction analysis for SARS CoV-2 came back negative. A chest radiograph displayed a bilateral reticular infiltrate, and therapy with azithromycin was started. Due to a deterioration of the dyspnea, a chest tomography was eventually performed, revealing an exuberant and bilateral ground glass-like densification suggestive of alveolar injury. Echocardiogram and e electrocardiogram were both normal. After a positive serologic result for HIV, the patient was transferred to a Level III hospital, and Pneumocystis jirovecii was identified in bronchoalveolar lavage. T cell count was 12/mm3. Highly active antiretroviral therapy and cotrimoxazole were started, prompting clinical and analytical recovery. Discussion: Pneumocystis jirovecii can cause fatal pneumonia in immunocompromised children. Even though an asthma exacerbation and atypical bacterial or viral infections, namely COVID-19, present as more usual causes of dyspnea, a low suspicion index is warranted in children coming from HIV-endemic countries, particularly those who are unresponsive to conventional bronchodilator and antibiotic therapy.

[Monoclonal antibody therapies for rapidly progressive and highly active multiple sclerosis in the era of the COVID-19 pandemic]. / Terapiya monoklonal'nymi antitelami bystroprogressiruyushchego i vysokoaktivnogo rasseyannogo skleroza v epokhu pandemii COVID-19.

As the COVID-19 pandemic continues, reducing the risk of infection for immunocompromised patients remains an important issue. Patients with aggressive multiple sclerosis (MS) require immunosuppressive therapy in order to control the overactive autoimmune response. Preliminary international and national trials demonstrate that older age, higher disability status and progressive MS are generally associated with a more severe clinical course of COVID-19. However, uncertainty remains about the effect of disease-modifying therapies on the COVID-19 clinical presentation. In this article, we pay special attention to monoclonal antibodies used for immune reconstitution therapy, which results in significant changes to the T-cell and/or B-cell repertoire. Based on the published data from registries in different countries, we attempted to estimate the benefits and risks of these therapies in a complicated epidemiological setting.