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A case of hepato-splenic-renal candidiasis will be discussed with the aim to track down the causative organism and its likely susceptibility. The role of BDG, selection of the antifungal agent, and duration of therapy will be discussed. Acase ofan HIV-infected patient withcryptococcal meningitis, pulmonaryinfection, and pulmonary IRISwillbe discussed. Acase ofCandida auris fungemiaand organ infectionin aliver transplant recipientwho developed seriallyincreasing MIC will bepresented. The relevanceof MIC, tentativebreakpoints, and selectionof antifungal agentsbased on PKPDconsiderations will be discussed. Talamycosis is usually seen in HIV-infected individuals from North East India. Here we discuss a 3-year-old girl with acute lymphoblastic leukemia from Western India who developed cavitary pneumonia and multiple brain abscesses due to talaromyces. The case posed significant management challenges pertaining to both the fungal infection and cancer. Renal mucormycosis in healthy immunocompetent hosts is an entity generally reported only from India and China. We discuss the case of a previously healthy 3-month-old infant who presented with acute renal failure and renal mucormycosis. The case is unique with respect to the source of infection and management strategy. Treatment of fungal infections involving the draining system of the kidney is challenging mainly due to limited antifungal drug penetration at the site of infection. Challenges in the treatment of amphotericin-resistant Aspergillus terreus pelvicalyceal infections will be discussed. CAPA is a well-known complication of coronavirus disease 2019 (COVID-19), but usually involves the lung alone and rarely disseminates when treated. This case illustrates a rare complication of COVID-19, namely endocarditis caused by As-pergillus. Rhinosporidiosis is a well-known disease that usually involves mucosal surfaces in the head and neck. This case illustrates a rare occurrence, namely dissemination to multiple areas and mimicking the clinical presentation of other cutaneous mycoses.
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Introduction: There are no effective treatments for non-active secondary progressive MS (SPMS), which is mediated by compartmentalized CNS inflammation, including activated microglia. We found that fully human anti-CD3 intranasal monoclonal antibody (Foralumab) suppressed disease in a chronic EAE model by dampening microglia and astrocyte inflammation. Nasal Foralumab does not enter the bloodstream or brain. A dose-finding study of nasal Foralumab in controls dosed at 10ug, 50ug and 250ug for 5 days found the drug to be safe with immune effects seen at 50ug. COVID patients dosed with 100ug of nasal Foralumab for 10 days was well-tolerated and exhibited positive effects on blood markers and lung inflammation. Objective(s): To determine if nasal Foralumab has a therapeutic effect on patients with non-active SPMS. Method(s): Two patients were identified with non-active SPMS and sustained clinical progression, despite use of approved DMT. EA1 is a 61-year-old male diagnosed for over 20 years and EA2 is a 42-year-old male diagnosed for 8 years, both last treated with ocrelizumab for 3 years. Treatment occurs in 3-week cycles with intranasal Foralumab 50ug/day administered 3x/week for 2 weeks with 1 week rest. Each cycle, clinical and neurological assessments are repeated, and imaging is repeated every 3 months. Result(s): EA1 has completed 6 months and EA2 has completed 3 months of treatment. To date, there have been no adverse reactions, local irritation, or laboratory abnormalities, and symptom progression has subsided. EA1 is feeling more stable, subjectively, and has noted improvement in lower extremity strength. EDSS, pyramidal motor score and T25FW have stabilized or improved. SDMT and 9HPT were stable during treatment. Microglial activation as measured by [F-18]PBR06 PET scan was significantly reduced 3 months after the start of nasal Foralumab, and this reduction was sustained after 7-week washout and at 6 months. Serum protein measurements of cytokines showed reduction of IFN-gamma, IL-18, IL-1s and IL-6 levels (Olink assay). Cellular immune studies showed increase in CD8 naive cells and decrease in CD8 effector cells, and alteration in gene expression as measured by single cell RNA sequencing. EA2 3-month laboratory and imaging results are pending and will be presented. Conclusion(s): Nasal Foralumab in non-active SPMS patients treated for at least 3 months reduced microglial activation, decreased levels of proinflammatory cytokines, and had positive clinical effects.
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Objective: Assess the SARS-CoV2 Spike antibody response in multiple sclerosis (MS) patients on high efficacy immunotherapies. Background: There is limited knowledge about SARS-CoV2 mRNA vaccine response in MS patients on immunotherapy. Design/Methods: Patients with MS, aged 18-65, on fingolimod, siponimod, ofatumumab, or ocrelizumab for at least 3 months prior to first mRNA SARS-CoV2 vaccine (Pfizer or Moderna) were offered enrollment. A cohort of healthy controls who received the mRNA vaccines were also enrolled. Blood samples for the SARS-CoV2 Spike antibody (Anti-SARS-CoV2 S, RocheElecsys) were collected 2-3 months after the second mRNA vaccine. The proportion who seroconverted (antibody>0.4 U/ml), and SARS-CoV2 Spike antibody levels were assessed. Results: A total of 39 MS patients (6 fingolimod, 33 ocrelizumab) and 31 controls were included in this interim analysis. 33%(13/39) of MS patients seroconverted, compared to 100%(31/31) in the control group, with an estimated risk difference of -0.67,(95% confidence interval: -0.81, -0.52;Fisher's exact test, p=9.0∗10-10 ). There was no difference in seroconversion rates between MS patients who received the Pfizer (34%, 10/29) versus the Moderna vaccine (30%, 3/10) (95% confidence interval -0.38, 0.29;Fisher's exact test=1). Seroconversion was found in 100% (31/31) of controls, 66.7% (4/6) of fingolimod-treated patients, and 27.3% (9/33) of ocrelizumab-treated patients (three group comparison, Fisher's exact test p-value =2.7∗10 -10). The median Spike antibody level was <0.4 U/ml in MS patients, and 1,663 U/ml in controls (Wilcoxon rank sum test, p-value= 1.0∗10-12 ). The median Spike antibody level in the ocrelizumab group was <0.4 U/ml, 3.45 U/ml in the fingolimod group, and 1,663 U/ml in the control group (Kruskal Wallis test, p-value=5.9∗10-12 ). Total IgG correlated with Spike antibody levels in the ocrelizumab-treated group only (Spearman correlation, p=0.025). Conclusions: MS patients on ocrelizumab and fingolimod have significantly lower rates of seroconversion, and lower median Spike antibody levels in response to the mRNA SARS-CoV2 vaccines compared to controls.
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The entire world seems shaken and disrupted since the strike of Covid-19 ever since its outbreak towards the end of 2019 and its continued perils. During this unprecedented event of the century, people's health emerged as the most vulnerable and affected area either directly or indirectly by the coronavirus and its new variants. Disrupting almost all spheres of life, patients' health and care systems required timely support from healthcare professionals to provide the needed medical advice on one hand and a prescriptive mechanism to avoid another impending casualty. Similarly, a proactive approach became desirable from the health ministry, pharmaceutical firms, medical insurance companies, and other stakeholders in fine-tuning their offerings to the patients as per the recommender systems. The devices to measure the vitals of a person, became more efficient and ergonomically sound with the advent of wearable gadgets. These devices monitored the physical activities of the user and transferred the vital signals wirelessly to any base computing device and cloud-based repositories. This mechanism, however, was reported to fail in addressing the issues with non-communicating or stand-alone devices that were used by the masses in developing countries including India. If the real-time data could be used from these devices, the healthcare diagnosis and analysis of a patient's medical condition could have taken a progressive dimension with the addition of missing data points. This research thus aims to fill the information gap and proposes a transforming approach towards existing non-communicating devices used to measure the vitals like blood pressure, oxygen level, blood sugar, etc. The proposed MIST-based Cyber-Physical System shall create extensive scalability towards the retrieval of the vital details from the devices which were otherwise captured offline previously and were unused at multiple critical points of healthcare processes. © 2022 IEEE.
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The main aim of this chapter is to build a smart security device to cater to the security problems that have arisen in the recent times, in the healthcare facilities, with the onset of the covid19 pandemic. With more and more people occupied with providing emergency services, the special restricted mode in our designed smart security system will help in flexible surveillance of hospital wards as per requirement. The demand within the global market for healthcare security systems has been rising on account of the need to ensure optimal security and productivity across all hospitals and healthcare facilities. A smart security system with IoT and cloud connectivity, along with multiple smart modes to cater to the needs of the user is the need of the hour. With the onset of the pandemic situation, things have become more intense, with minimal efforts given towards surveillance. This is where our smart security system finds its application along with other restricted zones. With its seamless connection with AWS for 24 × 7 connectivity with the user, one can expect constant updates as per requirement. With the integration of raspberry pi, other security features are also achieved like a fire alarm, motion detection, gas sensing, temperature detection, footfall tracking and noise detection with stable conditions. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.
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This proposal addresses the Biology and Measurement of MS symptoms focus area of FY18 MSRP Exploration Hypothesis Development Award. The overarching aim of this proposal is to assess the role of microglial activation and norepinephrine transporter binding in pathogenesis of MS-related fatigue, using novel Positron Emission Tomography (PET) radiotracers. [F-18]PBR06 and [C-11]MRB. The major developments in the progress of this project have been the following: 1. We received permission to resume recruitment of subjects on July 15, 2020. 2. We are pleased to report that we have recruited and obtained informed consent from 10 eligible subjects already (greater than 80 percent of the target sample size). 3 of these subjects have completed all the study related procedures (25 percent of the target sample size). Based on our preliminary data about the role of neuroinflammation in pathogenesis of MS-related fatigue, we had a manuscript published in the journal Neurology: Neuroimmunology and Neuroinflammation in September, 2020. The title of the manuscript is T Singhal, S Cicero, H Pan, K Carter, S Dubey, R Chu, B Glanz, S Hurwitz, S Tauhid, Mi-Ae Park, M Kijewski, E Stern, R Bakshi, D Silbersweig, and HL Weiner. Regional Microglial Activation in Substantia Nigra is linked with Fatigue in Multiple Sclerosis. (PMID 32769103)
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Keywords: Prehabilitation, Cancer, Colorectal Purpose: Prehabilitation (Prehab) refers to a mulitmodal preoperative strategy aiming to enhance patients’ funcitonal capacity. A stepwise implementation of a pilot prehab program was undertaken and led by a Specialist Physiotherapist and Dietitian for all patients referred for colorectal surgery in Princess Royal University Hospital funded by South East London Cancer Alliance. The objective was to design and evaluate a pilot service that could be replicated in other NHS Trust/cancer centres. Methods: Prehab was offered to a cohort of all newly diagnosed colorectal cancer patients planned for curative treatment. Patient Demographics, oncological characteristics, anthropometric data, frailty scores and patient-reported global health assessment were recorded at baseline and during follow up after intervention and treatment (surgery). Clinical outcomes included hospital length of stay (LOS), morbidity, mortality, readmission rates. The intervention was delivered via telephone for dietetics and a multi-modal telephone, video and/or face to face physiotherapy intervention from July 2020 to December 2020. Personalised prehabilitation programmes were created for each patient including resistance and aerobic training. All patients were stratified into universal, targeted or specialist prehab input (based on Macmillan 2019 guidance) for physiotherapy and dietetics respectively. Results: 39 patients were treated ‘straight to surgery’. Time available for prehab for Physiotherapy was 10 days (range 1-31) and Dietetics was a median 14 days (range 2-62). One third of patients had experienced significant weight loss pre-operatievely. Dietary prehab impeded further decline: there was no difference in median Body Mass Index (BMI) between baseline and 6 weeks post-op. Physiotherapy observed an improvement in physical activity levels (measured with the GODIN leisure time questionnaire) and self-reported general health quality of life scores. The Median EQ5D5L score at follow up was 90%(range 70-99%), improved from a medial baseline pre-surgery score of 75% (range 50-83%). As the pilot reaches its conclusion favourable clinical outcomes were recorded with no mortality and reduced readmission from 15% in 2019 to 5% in 2020. The total hospital LOS did not differ from historical data. Conclusion(s): Prehabilitation can impede the nutritional and functional decline post colorectal cancer surgery. Prehabilitation contributed to reduced readmission during covid helping to keep vulnerable patients out of hospital. No differences in LOS were recorded. Holistic clinical approach to prehab and tailoring interventions to individual patient can be successfully delivered through telehealth intervention with short prehabilitation time frames. Future prehabilitation services should offer multiple appointment/intervention options with a focus on readmissions and patient quality of life data to contribute to business case development. Impact: Prehabilitation can be delivered and led by a Band 7 AHP team utilising telephone and video options to reduce travel time and provide intervention for patients with a short time frame prior to surgery. This joint dietetic and physiotherapy prehab pathway can be replicated in other district general hospitals that are diagnosing and treating colorectal cancer patients. Prehabilitation is a valuable part of the personalised care cancer strategy and NHS long term plan for cancer patients. Funding acknowledgements: South East London Cancer Alliance.
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Since the start of COVID-19, there has been several relevant corpora from various sources that were released to support research in this area. While these corpora are valuable in supporting analysis for this specific pandemic, researchers will benefit from additional benchmark corpora that contain other epidemics for better generalizability and to facilitate cross-epidemic pattern recognition and trend analysis tasks. During our research, we discover little disease related corpora in the literature that are sizable and rich enough to support such cross-epidemic analysis tasks. To address this issue, we present EPIC30M, a large-scale epidemic corpus that contains more than 30 million micro-blog posts, i.e., tweets crawled from Twitter, from year 2006 to 2020. EPIC30M contains a subset of 26.2 million tweets related to three general diseases, namely Ebola, Cholera and Swine Flu, and another subset of 4.7 million tweets of six global epidemic outbreaks, including the 2009 H1N1 Swine Flu, 2010 Haiti Cholera, 2012 Middle-East Respiratory Syndrome (MERS), 2013 West African Ebola, 2016 Yemen Cholera and 2018 Kivu Ebola. Furthermore, we explore and discuss the properties of this corpus with statistics of key terms and hashtags and trends analysis for each subset. Finally, we discuss the potential value and impact that EPIC30M could generate through a discussion of multiple use cases of cross-epidemic research topics that attract growing interest in recent years. These use cases span multiple research areas, such as epidemiological modeling, pattern recognition, natural language understanding and economical modeling. The corpus is publicly available at https://www.github.com/junhua/epic.