LANGERHANS CELL HISTIOCYTOSIS IN A CHILD WITH MULTISYSTEMIC LESIONS ASSOCIATED WITH INFECTED POLIOMYELITIS AND SARS-COV-2, FEATURES OF DIAGNOSTICS. CLINICAL CASE.

Langerhans cell histiocytosis (LCH) is an abnormal clonal proliferation of Langerhans cells. The prognosis varies depending on the form of the disease and organ damage. Any organs and systems can be involved in the pathological process in various combinations. A poor response to standard therapy and an unfavorable prognosis are characteristic of patients with a multisystem form of LCH and involvement of organs at risk. Skin lesions are a classic sign of LCH. Purpose - to describe the complexity and duration of diagnosis of LCH with multisystem damage in a boy aged 2 years and 2 months, infected with poliomyelitis and coronavirus. Clinical case. The first clinical manifestations of LCH in the child debuted with an eczematous-seborrheic rash on the scalp with spread to the limbs and trunk. The child was treated for toxicoderma, hemorrhagic vasculitis at the place of residence for 6 months. The boy lost 1.5 kg of body weight in 1 month. At the time of hospitalization, seborrheic-eczematous rashes on the skin with a hemorrhagic component, trophic-inflammatory changes in the nails of the hands, signs of protein-energy deficiency, stomatitis, gingivitis, hepatosplenomegaly, polyserositis, diabetes insipidus, osteolytic foci of the frontal bones were found. Results of the tests: anemia, thrombocytopenia, hypoproteinemia and hypoalbuminemia, coagulation disorders. The patient had the onset of lower flaccid paraparesis, muscle hypotonia. The boy was diagnosed with a number of infectious complications, including poliomyelitis (a derivative of vaccine poliovirus type 2), COVID-19. The child received LCH-III cytostatic therapy with a positive effect. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies.Copyright © 2023 Institute of Physics of the Russian Academy of Sciences. All rights reserved.

Initiating Home Parenteral Nutrition Therapy in a Patient at High Risk of Refeeding Syndrome After COVID-19 Infection

Background: An emerging finding about COVID-19 is its effect on nutrition and weight loss. The COVID-19 symptoms of fatigue, altered taste or smell, and lack of appetite are well known. But COVID-19 may have a more profound effect on clinical nutrition status. Two recent studies have identified that approximately one-third of ambulatory COVID-19 patients are at risk of experiencing weight loss >= 5% (Anker, et al;di Filippo, et al). The case study presented here discusses home start total parenteral nutrition (TPN) in a patient recently diagnosed with COVID-19 at high risk for refeeding syndrome. Method(s): N/A Results: Case Study: A 92-year-old patient was diagnosed with COVID-19 on June 8, 2022. Over the next week, she was hospitalized twice to manage symptoms of acute mental status changes, lethargy, aphasia, hypotension, and loss of appetite. The patient received nirmatrelvir/ritonavir, remdesivir, and bebtelovimab to treat COVID-19 at different times between June 9, 2022, and June 18, 2022. She remained COVID positive and continued to deteriorate clinically. On June 20, 2022, the patient began receiving 24/7 homecare, including intravenous (IV) fluids of dextrose 5% in normal saline (D5NS) 1000 mL daily for three days. She continued to experience loss of appetite and had no bowel movement for 3 days. On June 23, 2022, she was referred to this specialty infusion provider to initiate TPN therapy in the home setting. The patient's BMI was 18.2 kg/m2. Lab results revealed potassium 3.0 mmol/L, phosphate 1.6 mg/dL, and magnesium 1.6 mg/dL. High risk of refeeding syndrome was identified by the level of hypophosphatemia and hypokalemia. The specialty infusion provider's registered dietitian recommended to discontinue D5NS and begin NS with added potassium, phosphate, and magnesium. Thiamine 200mg daily was added to prevent Wernicke's encephalopathy. The patient's clinical status and lab values were monitored closely each day until her electrolyte levels stabilized (Table 1). Home TPN therapy was initiated on June 28, 2022, with <10% dextrose and 50% calorie requirement with 85% protein and 1.0 g/kg lipids. Three-day calorie count and nutrition education were performed four days post TPN initiation. Oral intake met only 25% of estimated needs. Over several days, theTPN formula was gradually increased to goal calories and the infusion cycle was slowly decreased. The following week, the patient's oral intake improved to 60%-75% of estimated needs. Her constipation resolved, and she showed improvement in functional status and mobility. Her appetite drastically improved when the TPN was cycled. Another three-day calorie count was performed when TPN calories reached goals. Oral intake demonstrated 100% estimated calorie and protein needs. TPN therapy was ultimately discontinued on July 14, 2022. As of September 30, 2022, the patient has stabilized at her pre-COVID weight of 45 kg with full recovery of appetite, function, and cognition. Discussion(s): The ASPEN Consensus Recommendations for Refeeding Syndrome (da Silva, et al) describe the repletion of electrolyte levels before introducing calories to prevent end-organ damage associated with refeeding syndrome (respiratory muscle dysfunction, decreased cardiac contractility, cardiac arrhythmias, and encephalopathy). Conclusion(s): This case study highlights the successful initiation of home TPN therapy in a patient at high risk of refeeding syndrome post COVID-19 infection. Although home start TPN and the risk of refeeding syndrome are not new concepts, they must be considered in the setting of COVID-19. Given the effects COVID-19 has on taste, smell, and appetite and the recent finding that one-third of patients with COVID infection may experience weight loss of >= 5%, nutrition support and patient education are vital components of overall patient care. (Figure Presented).

Cyclic [68Ga] and [18F]AlF-labeled peptides for specific detection of human angiotensin-converting enzyme 2

Objectives: In this study, we developed angiotensin-converting enzyme 2 (ACE2)-specific, peptide-derived 68Ga- and 18F-labeled radiotracers, motivated by the hypotheses that ACE2 is an important determinant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility and that modulation of ACE2 in coronavirus disease 2019 (COVID-19) drives severe organ injury. Our current efforts are focusing on broader dissemination of ACE2-targeted PET radiotracers based on chelation of [18F]AlF enabling advanced murine and potentially human studies. Method(s): A series of NOTA-conjugated peptides derived from the known ACE2 inhibitor DX600 were synthesized, with variable linker identity. Since DX600 bears 2 cystine residues, both linear and cyclic peptides were studied. An ACE2 inhibition assay was used to identify lead compounds, which were labeled with 68Ga and 18F-AlF to generate the corresponding peptide radiotracers (68Ga-NOTA-PEP). The most potent 68Ga and 18F-AlF DX600 derivatives were subsequently studied in a humanized ACE2 (hACE2) transgenic model. Result(s): Cyclic DX-600-derived peptides had markedly lower half-maximal inhibitory concentrations than their linear counterparts. The 3 cyclic peptides with triglycine, aminocaproate, and polyethylene glycol linkers had calculated half-maximal inhibitory concentrations similar to or lower than the parent DX600 molecule. Peptides were readily labeled with 68Ga and 18F-AlF, and the biodistribution of both tracers was determined in an hACE2 transgenic murine cohort. Pharmacologic concentrations of coadministered NOTA-PEP (blocking) showed a significant reduction of 68Ga-NOTA-PEP4 signals in the heart, liver, lungs, and small intestine. Ex vivo hACE2 activity in these organs was confirmed as a correlate to in vivo results. The biodistribution of both tracers was similar, with apparent blocking observed in the lungs using the 18F-AlF peptide that needs to be verified via additional experiments. Conclusion(s): NOTA-conjugated cyclic peptides derived from the known ACE2 inhibitor DX600 retain their activity when N-conjugated for 68Ga or 18F-AlF chelation. In vivo studies in a transgenic hACE2 murine model using the lead tracer, 68Ga-NOTA-PEP4, showed specific binding in the heart, liver, lungs and intestine-organs known to be affected in SARS-CoV-2 infection. Blocking studies using the 18F-AlF labeled correlate showed modulation of PET signals in the normal lungs. These results suggest that 68Ga-NOTA-PEP4 or the 18F-AlF correlate could be used to detect organ-specific suppression of ACE2 in SARS-CoV-2-infected murine models and COVID-19 patients.Copyright © 2023 Southern Society for Clinical Investigation.

Inflammation and Organ Injury the Role of Substance P and Its Receptors.

Tightly controlled inflammation is an indispensable mechanism in the maintenance of cellular and organismal homeostasis in living organisms. However, aberrant inflammation is detrimental and has been suggested as a key contributor to organ injury with different etiologies. Substance P (SP) is a neuropeptide with a robust effect on inflammation. The proinflammatory effects of SP are achieved by activating its functional receptors, namely the neurokinin 1 receptor (NK1R) receptor and mas-related G protein-coupled receptors X member 2 (MRGPRX2) and its murine homolog MRGPRB2. Upon activation, the receptors further signal to several cellular signaling pathways involved in the onset, development, and progression of inflammation. Therefore, excessive SP-NK1R or SP-MRGPRX2/B2 signals have been implicated in the pathogenesis of inflammation-associated organ injury. In this review, we summarize our current knowledge of SP and its receptors and the emerging roles of the SP-NK1R system and the SP-MRGPRX2/B2 system in inflammation and injury in multiple organs resulting from different pathologies. We also briefly discuss the prospect of developing a therapeutic strategy for inflammatory organ injury by disrupting the proinflammatory actions of SP via pharmacological intervention.

Respiratory manifestations of long COVID

As we near the third year of the COVID-19 pandemic, greater attention is now being paid to the potential long-term consequences of SARS-CoV-2 in the hundreds of millions of people infected globally. A syndrome termed "long COVID" has emerged, which predominantly manifests as persistent fatigue, dyspnea, chest pain, and cognitive dysfunction following acute infection. The incidence of long COVID is in the range of 15% based on current best evidence, and symptoms are likely a result of several different pathophysiological mechanisms including multi-organ injury from acute infection, systemic viral persistence, immune dysregulation, and/or autoimmunity. Pulmonary symptoms represent a significant component of long COVID, and there is a growing body of research describing the epidemiology, risk factors, physiology, and radiology of the respiratory manifestations of long COVID. In this clinical review, we examine the most recent evidence relating to "respiratory long COVID," discuss how innovative technologies such as Xenon-129 gas transfer magnetic resonance imaging (MRI) and respiratory oscillometry are helping to elucidate its unique pathophysiology, and consider the role of preventative strategies and possible treatments such as adapted pulmonary rehabilitation. The burden of respiratory long COVID is likely to continue to grow, and all healthcare professionals who care for patients with respiratory disease must prepare for this emerging chronic condition. This will require increased resources from healthcare decision makers, inventive approaches to healthcare delivery, further research, and the same spirit of collaboration that has enabled the many success stories to date in the global effort against COVID-19.Copyright © 2023 Canadian Thoracic Society.

Diagnostic features of multiple organic system disorders associated with COVID-19 in a child of primary school age.

The advent of the COVID-19, specialists are increasingly encountering previously unknown pathological conditions in their practice. For some time, we have believed, that COVID-19 in children is most often mild and asymptomatic. However, with the passage of time and. the accumulation, of the experience, it became obvious that the new infectious disease it will be quite severe in children. Differential diagnosis of multiple organ disorders in children during the COVID-19 pandemic should, be primary carried out with the Multisystem. Inflammatory Syndrome in Children, associated, with COVID-19 (MIS-C), as well as Long-COVID-19. According to published, data, the manifestations of these conditions are due to frequent lesions of the gastrointestinal tract (60-100%), cardiovascular (80%), nervous (29-58%) and respiratory (21-65%) systems. At present, there is no exact idea of these pathological conditions, the criteria for their diagnosis and. the tactics of managing children, not only at the stage of diagnosis, but also at the stage of observation. The authors present a diagnostically complex clinical case describing the development of multiple organ damage in a 7-year-old. child, after contact with a mother who was sick with COVID-19. The data on the course features, the results of the examination and. the difficulties of differential diagnosis of this case with other diseases with a similar clinic are summarized.Copyright © 2022 Authors. All rights reserved.

Diagnostic features of multiple organic system disorders associated with COVID-19 in a child of primary school age.

The advent of the COVID-19, specialists are increasingly encountering previously unknown pathological conditions in their practice. For some time, we have believed, that COVID-19 in children is most often mild and asymptomatic. However, with the passage of time and. the accumulation, of the experience, it became obvious that the new infectious disease it will be quite severe in children. Differential diagnosis of multiple organ disorders in children during the COVID-19 pandemic should, be primary carried out with the Multisystem. Inflammatory Syndrome in Children, associated, with COVID-19 (MIS-C), as well as Long-COVID-19. According to published, data, the manifestations of these conditions are due to frequent lesions of the gastrointestinal tract (60-100%), cardiovascular (80%), nervous (29-58%) and respiratory (21-65%) systems. At present, there is no exact idea of these pathological conditions, the criteria for their diagnosis and. the tactics of managing children, not only at the stage of diagnosis, but also at the stage of observation. The authors present a diagnostically complex clinical case describing the development of multiple organ damage in a 7-year-old. child, after contact with a mother who was sick with COVID-19. The data on the course features, the results of the examination and. the difficulties of differential diagnosis of this case with other diseases with a similar clinic are summarized.Copyright © 2022 Authors. All rights reserved.

From 2020 Home BP Consensus to 2022 TSOC/THS Hypertension Guideline

Background: Hypertension is the most important modifiable cause of cardiovascular (CV) disease and all-cause mortality worldwide. Numerous epidemiological studies and pharmacological intervention trials have demonstrated that lower and lowering blood pressures (BP) are associated with fewer CV events and lower mortality. Despite the positive correlations between BP levels and later CV events are continuous since BP levels as low as 90/60 mmHg in almost all large-scale epidemiological studies, the diagnostic criteria of hypertension and BP thresholds and targets of antihypertensive therapy have largely remained at the level of 140/90 mmHg in the past 30 years (since the release of the Fifth Report of the Joint National Committee [JNC 5] on high BP in 1993). The publication of both the SPRINT and the STEP trials (comprising >8,500 Caucasian/African and Chinese participants, respectively) provides enough evidence to shake this 140/90 mmHg dogma. In both trials, lowering systolic BP (SBP) to <130 mmHg, compared to the traditional SBP target of <140 (130-139) mmHg, was consistently associated with a 25-30% relative risk reduction in CV events. Another dogma regarding hypertension management is "office (or clinic) BP measurements" Although standardized office BP measurement has been widely recommended, the practice of office BP measurements is hard to be or has never been ideal in real-world practice. Further, the debate regarding the numerical equivalence between automated office BP (AOBP) measurements adopted in the SPRINT trial and office BP measurements has never been settled. The variations of office BP readings and the differences between office BP and home BP readings bewilder not only patients, but also healthcare professionals. On the other hand, out-of-office BP monitoring receives growing attention in contemporary hypertension guidelines. Home BP monitoring (HBPM) and ambulatory BP monitoring (ABPM) are two recognized approaches to obtaining out-of-office BP. HBPM is easy-to-use, more likely to be free of environmental and/or emotional stress (such as white-coat effect), feasible to document long-term BP variations, of good reproducibility and reliability, and more correlated with hypertension-mediated organ damage (HMOD) and CV events. Methods/Results: The Taiwan Hypertension Society (THS) and the Taiwan Society of Cardiology (TSOC) jointly issued the Consensus Statement on HBPM in 2020. The "722" protocol to standardize HBPM has been advocated by both Societies and widely accepted by healthcare professionals. In the 2022 Taiwan Hypertension Guidelines, we break the dogma of "office BP-based management strategy" and further expand the role of HBPM to the whole hypertension management process, from diagnosis to long-term follow-up. The Task Force considers that, to improve the quality of long-term management of all chronic diseases including hypertension, patients themselves should take an active role and HBPM is the right tool to achieve this goal, regardless of many other advantages of HBPM. This approach is of particularly importance in the post-COVID era and can bridge the management with artificial intelligence technologies. Conclusion(s): To facilitate implementation of the guidelines, a series of flowcharts to encompass assessment, adjustment, and HBPM-guided hypertension management are provided.

Is There Any Role of IL-6 Inhibition in COVID-19?

An emergent coronavirus, now named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was declared a pandemic on the 22nd March 2020. It has since caused unprece-dented pressures on the healthcare systems worldwide, leading to over five million cases and over three hundred thousand deaths. This has resulted in a global struggle to fight this disease, without any known cure or any definite treatment and with no vaccine. This challenge is exemplified by many with COVID-19 (Coronavirus Disease 2019) rapidly deteriorating to critical illness, developing respiratory failure, multi-organ dysfunction or failure, and septic shock. This rapid deteriora-tion is thought to be due to the activation of the cytokine storm. The cytokine storm is characterised by mass cytokine and chemokine release, leading to wide-spread multi-organ damage. One of these such cytokines that plays a role in the cytokine storm is Interleukin (IL-) 6. Raised levels of IL-6 in many diseases have been observed to both correlate with disease severity and predict poor outcomes. Early studies began to show high levels of IL-6 in those with severe and critical COVID-19, and there is ongoing research into immune modulators to block IL-6, in the hope of halting disease progression and improving the chance of recovery. This article will explore the role that IL-6 plays in COVID-19 and whether an IL-6 blockade can prevent poor outcomes and reduce mortality.Copyright © 2021 Bentham Science Publishers.

Microbiome in the Framework of Predictive, Preventive and Personalised Medicine

The human body is inhabited by trillions of diverse microorganisms collectively called "microbiome" or "microbiota". Microbiota consists of bacteria, viruses, fungi, protozoa, and archaea. Microbiome demonstrates multi-faceted effects on human physical and mental health. Per evidence there is a multi-functional interplay between the whole-body microbiome composition on the epithelial surfaces including skin, nasal and oral cavities, airway, gastro-intestinal and urogenital tracts on one hand and on the other hand, the individual health status. Microbiota composition as well as an option to modulate it - together create a highly attractive operation area for the translational bio/medical research with multi-professional expertise and healthcare-relevant output in the framework of predictive, preventive and personalised medicine (PPPM/3 PM). Advanced PPPM strategies implemented in the microbiome area are expected to significantly improve individual outcomes and overall cost-efficacy of healthcare. According to the accumulated research data, corresponding diagnostic and treatment approaches are applicable to primary care (health risk assessment in individuals with sub-optimal health conditions and prevention of a disease development), secondary care (personalised treatment of clinically manifested disorders preventing a disease progression) and tertiary care (making palliation to an optimal management of non-curable diseases). In the current book, we do highlight the implementation potential of the microbiome-relevant research in the framework of predictive diagnostics, targeted prevention and treatments tailored to the individualised patient profile.Copyright © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Longitudinal analysis of electrolyte prolife in intensive care COVID-19 patients

Introduction: According to a substantial body of research, electrolyte abnormalities are a common manifestation in coronavirus disease 2019 (COVID-19) patients and are associated with adverse outcomes. This study aimed to investigate electrolyte imbalances in COVID-19 patients and assess their relation to mortality. Method(s): Adult COVID-19 patients hospitalized in the Security Forces Hospital in Saudi Arabia from June 8th till August 18th, 2020 were enrolled in this retrospective observational study. We examined baseline characteristics, comorbidities, acute organ injuries, medications, and electrolyte levels including sodium, potassium, chloride, calcium, bicarbonate, phosphate, and magnesium on ICU admission, as well as every following day of ICU stay, until death or discharge. Patients were stratified according to survival, and differences in variables between groups were compared using Mann-Whitney's U test or Fisher's exact test. Longitudinal electrolyte profiles were modeled using random intercept linear regression models. Result(s): A total of 60 COVID-19 patients were enrolled. Compared to survivors, non-survivors had significantly higher sodium and phosphate on admission and death, higher potassium and magnesium at death, and significantly lower calcium at death. Abnormalities in admission levels of chloride and bicarbonate were also more frequently observed in non-survivors. Furthermore, in the deceased group, we observed a daily increase in potassium and phosphate levels, and a daily decrease in sodium and chloride. Finally, calcium increased in non-survivors over time, however, not as significantly as in the survivor group. Conclusion(s): Admission levels of electrolytes and changes over the course of ICU stay appear to be associated with mortality in COVID-19 patients.Copyright © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

CLINICAL RESEARCH IN LATIN AMERICA: FROM SPONSORED TO INVESTIGATOR INITIATED RESEARCH

Latin American clinical researchers had participated in many controlled clinical trials in the 80 s and 90 s sponsored initiated that confirmed the place of calcium channel blockers and RAS blockade in hypertension treatment. Later, non-inferiority or superiority trials like ONTARGET, Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial and VALUE, Valsartan Antihypertensive Long-term Use Evaluation were performed worldwide including Latin-American countries. In the last decade, the absence of new drugs in the pipeline and sponsors portfolios at one side, and the recommendation of fixeddose combination as initial treatment tool at the other could be supposed as main causes of a dramatic reduction in sponsored hypertension research. At the same time, a huge increase in investigator initiated research was observed. Scientific national and regional societies in many cases fueled this increase. In this scenario, the Cardiovascular Risk Factor Multiple Evaluation in Latin America, CARMELA study was the first large-scale population-based study that assessed cardiovascular risk factor prevalence in 7 Latin American cities and its relationship to hypertension mediated organ damage. CARMELA is an example of an epidemiological study investigator initiated supported by a sponsor in Latin America The FOCUS study, Fixed-Dose Combination Drug for Secondary Cardiovascular Prevention was another example of an investigator initiated research supported by a private company. FOCUS was funded by the 7th Framework Programme European Commission Consortium with the participation of the Centro Nacional De Investigaciones Cardiovasculares CNIC Madrid, Spain, World Heart Federation, Federación Argentina De Cardiología, and some European research organizations, supported by FERRER Internacional. FOCUS help to understand the reasons of treatment non-adherence in Latin American countries and also to recognize the potential benefits of fixed-dose combinations in secondary prevention. More recently, the Interamerican Society of Cardiology SIAC developed the CorCOVID Latam study which aim was to study changes in lifestyle habits, treatment adherence, and mental health status in patients with cardiometabolic disease, but no clinical evidence of COVID-19 during the pandemic. This study is a good example of the feasibility of non-sponsored research in Latam supported by a regional scientific society structure and members. Five publications related to gender differences in the impact of the pandemic in Latam, Influenza and Pneumococcal vaccination during the pandemic, and the psychological impact in more than 4 thousand patients were the fruit of this society research initiative.

POSTAL MEDICINE DELIVERY FOR STAGE-2 HYPERTENSIVE PATIENTS IN COVID-19 SITUATION: TURNING CRISIS TO OPPORTUNITY

Introduction: The COVID-19 pandemic has influenced healthcare systems, particularly in the areas of non-communicable diseases, such as hypertension, where the majority of patients require medication therapy and frequent visits. The postal medicine delivery (PMD) approach was an innovative solution to keep antihypertensive drugs accessible under the social distance regulation. Objective: We aimed to investigate the effectiveness of the PMD in terms of blood pressure (BP) control (< 140/90 mmHg), and target organ damage (TOD) including myocardial infarction, heart failure, acute stroke, and progression of chronic kidney disease) during the use of PMD. Design and method: This was a cross-sectional study in a university hospital, conducted between 11th March to 27th May 2020 when the hospital policy stated that outpatient departments' service would be reduced, and physicians were encouraged to use PMD. Patients without a history of TOD and who had a history of well BP control (< 140/90 mmHg) for the last 2 weeks, were enrolled. All of the patients used smartphones and LINE® applications for contacting the nurse coordinator every 3 months to report their home BP. After 6 months of PMD, patients were assigned to have a follow-up visit at the hospital for office BP measurement and having metabolic panel checked. Results: Thirty-eight patients met the inclusion criteria, and 68% were women. Most of the patients (97.4%) had used home BP monitoring (HPBM). The rate of BP control in goal was 64.2%. There was no TOD during the PMD approach. The medication boxes were sent successfully via postal service within 5-10 days, with no loss or damage recorded. All of the patients reported that they had been taking their antihypertensive medications. More than two-thirds (68.4%) continued to follow a low-sodium diet, while 76.3 percent continued to exercise regularly. Conclusions: In the COVID-19 epidemic, the PMD method could be another effective and safe strategy to enhance medicine access, if suitable enrolment criteria and communication between healthcare practitioners and patients are maintained. (Figure Presented).

Retrospective study of risk factors for mortality in critically ill patients with COVID-19

Background: Mortality associated with COVID-19 varies in various reports, with minimal data on the factors associated with in-hospital mortality. Objective: To identify the risk factors for in-hospital death of patients with COVID-19 in an intensive care unit (ICU) in Qatar. Methods: A retrospective observational study of patients confirmed with COVID-19 and admitted to the medical-surgical ICU at The Cuban Hospital was carried out from April 12, 2020, to September 12, 2020. From patients' electronic medical records, demographic, clinical, laboratory, and radiology data was collected. Results: 275 patients with COVID-19 were admitted to the ICU, and 32 (11.6%) died. 56.1% were men, and the mean age was 52.2 years. According to the univariate analysis, patients with diabetes mellitus with end-organ damage (37.5%), cardiovascular disease (31.3%), dementia (9.4%), kidney disease (28.1%), chronic obstructive pulmonary disease (31.3%), and higher Charlson index had higher mortality. According to the multivariate analysis, an increase of mortality risk by 9% was observed for each additional year of age (Odds ratio [OR] 1.09;95% confidence interval [CI] 1.04-1.14), patients on mechanical ventilation (OR 27.33;95% CI 3.21-232.46), and those with adult respiratory distress (OR 15.85;95% CI 1.45-172.82) and elevated procalcitonin (OR 7.30;95% CI 1.25-42.58), and the PiO2/FiO2 ratio between 100 and 299 decreased the risk of death by 92% (OR 0.08;95% CI 0.02-0.39), in comparison to a PiO2/FiO2 ratio less than 100 or greater than 300. Conclusion: The study provides evidence about the risk of mortality among COVID-19 patients with a significant contribution of age, respiratory failure, and co-infections.

FUNDOSCOPIC EXAMINATION USING A SMARTPHONE CAMERA: A REVIEW OF EFFECTIVENESS AND FEASIBILITY IN DETECTING HYPERTENSIVE RETINOPATHY IN HYPERTENSIVE CRISIS PATIENTS

Introduction: In patients presented with hypertensive crises, a fundoscopic assessment is necessary because once hypertensive retinopathy is discovered, a hypertensive emergency is diagnosed, and intravenous antihypertensive medication is recommended. However, direct ophthalmoscopy is relatively underutilized, especially under the social distance regulation, which may result in delayed diagnosis and treatment. The novel method, namely, smartphone-based fundoscopy offers longer working distance and shorter doctor-patient contact time, however, there is limited data regarding its feasibility and effectiveness. Objective: We aimed to gather scientific evidence on the smartphone-based fundoscopy in terms of its effectiveness, accessibility, and trainability in detecting hypertensive retinopathy among hypertensive crisis patients in emergency room settings. Methods: A literature search was conducted on PubMed, Google Scholar, and the Cochrane Library for papers published from January 2010 to November 2021. Keywords including hypertensive crisis, hypertensive retinopathy, target organ damage, fundoscopic optic examination, direct ophthalmoscope, fundus images, smartphone fundoscopy, digital fundus camera, and COVID-19 were used. Full papers published in English and s of non-English publications were all reviewed. Results: Eight studies out of 34 fulfilled our search criteria. Five observational studies confirmed the effectiveness of smartphone-based fundoscopy in obtaining fundus images adequate for interpretation compared with those from commercially available fundus cameras. Also, smartphone-based fundoscopy offers time-saving properties as it allows fundus examination to be effectively completed within 74 seconds compared to 130 seconds with a traditional direct ophthalmoscope. Two studies investigated the accessibility of smartphonebased fundoscopy and discovered that fundus images can be obtained by using 20 diopter condensing lenses with the video mode of the smartphone camera, which can be easily provided even at a primary level hospital due to their low cost. Another study reviewed the trainability of the smartphone-based fundoscopy in 137 undergraduate medical students which concluded that 75% of these students can identify the optic nerve within 20-25 minutes of face-to-face demonstration. Conclusion: With a greater diagnostic capability, accessibility, and trainability of smartphone-based fundoscopy makes it a potentially game-changing technique for detecting hypertensive retinopathy in hypertensive emergency patients, especially during the current COVID-19 pandemic, in which longer working distance and shorter doctor-patient contact time are both required.

A Series of Catastrophic Events

Case report - Introduction: Catastrophic antiphospholipid syndrome (CAPS) is a rare, life-threatening disease occurring in up to 1% of antiphospholipid syndrome (APS) cases. It was first defined in 1992 and remains a difficult to treat entity with a mortality rate of 37%. We describe a patient with systemic lupus erythematosus (SLE) and CAPS presenting with simultaneous multi-organ injuries who was successfully managed with 'triple' therapy including cyclophosphamide. Case report - Case description: A 42-year-old female presented to her local hospital with chest pain and worsening vision. She had a background of SLE, triple antibody-positive APS (previous DVT, pregnancy loss and strokes), hypertension, a metallic mitral valve, a previous myocardial infarction and pre-existing visual impairment due to a prior intra-cerebral bleed related to anticoagulation. Examination revealed a faint malar rash, cortical blindness and long tract neurological signs. Her ECG showed ischaemic changes and the admission troponin was significantly raised (3773ng/L). An echocardiogram showed new left ventricular dysfunction and a subsequent cardiac MRI was in keeping with coronary artery disease. Investigations showed an acute kidney injury, newly deranged liver function tests and a raised INR (>11, with no bleeding). Complement was normal with a low dsDNA titre. Urinalysis revealed proteinuria and a protein creatinine ratio measured 176mg/mmol. MRI diffusion weighted brain imaging showed acute bilateral occipital and left fronto-parietal infarcts. She had symptoms of a lupus flare with arthralgia and a butterfly facial rash. COVID-19 PCR tests were negative and she had not been recently vaccinated. She was diagnosed with CAPS and transferred to St Thomas' hospital intensive care. On arrival, she received 1mg intravenous vitamin K followed by triple therapy for CAPS: an unfractionated heparin infusion, oral prednisolone 40mg daily, 5 days of plasma exchange and, given her background of SLE, she was treated with intravenous cyclophosphamide (according to the EUROLUPUS regimen). Intravenous methylprednisolone was avoided due to a previous hypertensive encephalopathy reaction. She responded rapidly. Her troponin fell from a peak of 5054 to 294ng/ L, her creatinine settled at a new baseline (232umol/L) and her liver function normalised. She was switched back to warfarin due to her metallic valve and started on aspirin for cardiovascular secondary prevention. She required physical and occupational therapy due to her strokes but recovered well. Case report - Discussion: According to the 2003 criteria, CAPS can be classified as definite when there is evidence of: -3 organs involved, development of manifestations simultaneously or within a week, confirmation by imaging and/or histopathology of small vessel occlusion and positive antiphospholipid antibodies. Probable CAPS is when 3 out of the 4 criteria are present. In this case, three organs were confirmed to be involved with imaging showing cerebral and cardiac ischaemia. Her creatinine rose from a base of 190 to 289umol/L coupled with a high protein creatinine ratio confirming renal involvement. A Budd-Chiari syndrome was also suspected due to deranged liver function tests and INR, though imaging performed after therapy did not confirm this. A biopsy of any of these four organs was not feasible given the severity of her presentation and coagulopathy. There are no randomised controlled trials but data from the CAPS registry guides treatment and management follows a logical approach: anticoagulation to treat thrombosis, glucocorticoids for inflammation and plasma exchange (or IVIG) to remove the circulating autoantibodies. Triple therapy was associated with a reduced mortality compared to no treatment (28.6% versus 75%, respectively). Following analyses from the CAPS registry we also chose to treat with cyclophosphamide, which is associated with improved survival in patients with SLE. This decision was based on the clinical features of an SLE flare as opposed to serological grounds. There have b en reports of rituximab and eculizumab being used successfully in CAPS, though generally as a last resort. As complement activation is seen in animal models of antiphospholipid syndrome thrombosis and rituximab is often used in refractory SLE, they may prove to be promising agents for refractory CAPS. Case report - Key learning points: 1. Prompt recognition and early treatment is vital in managing CAPS 2. Triple therapy with anticoagulation, glucocorticoids and plasma exchange / IVIG is associated with better survival in CAPS 3. Cyclophosphamide is associated with better survival in patients with CAPS and concomitant SLE.

COVID-19 vaccine-associated autoimmune inflammatory rheumatic diseases

Background/Purpose: Vaccination against the most recently COVID-19 is one of the critical tools to provide herd immunity, reduce mortality, and control the pandemic worldwide. Despite the immense benefits of vaccination, an occasional association between vaccination and autoimmunity induction has been detected in human subjects. The current study presented fourteen cases of autoimmune rheumatic diseases (ARDs) following various COVID-19 vaccines. Method(s): This observational two-center study was conducted in the rheumatology clinics of the Connective Tissue Diseases Research Center at Tabriz University of Medical Sciences and Kashan University of Medical Sciences. All patients were referred to clinics with ARDs symptoms after implementing the COVID-19 vaccination program in Iran from April 2021 and were considered for enrollment in the study. Inclusion criteria were the onset of ARDs symptoms at four weeks post-vaccination, age >=16, no previous history of ARDs, meeting the classification criteria of one of the ARDs, and staying in the follow-up. Result(s): Between April 2021 and January 2022, 22 adult patients with symptoms of ARDs after COVID-19 vaccination were considered for eligibility. Eventually, 14 patients were diagnosed with ARDs based on classification criteria, and whose symptoms had started within four weeks after vaccination were included in the study. The duration of follow-up was 2-10 months. The vaccines used in these patients were Sinopharm [7 cases (50%)], AstraZeneca [6 cases (42.9%)], and COVIran Barakat [1 case (7.1%)]. It should be noted that vaccines that have been used for public vaccination in Iran until January 2022 were Sinopharm (78.9%), AstraZeneca (11.7%), and COVIran Barekat (8.1%), and Sputnik (1.3%). Crosstabulaton analysis showed that ARD was significantly more common in subjects who received AstraZenca vaccine than in subjects who received other vaccines (P < 0.001). Based on the results, the involved patients were diagnosed with RA or one of its subtypes (five cases), vasculitis (four cases), SLE (three cases), and peripheral SpA (pSpA) (two cases). In eleven cases, symptoms started two weeks after vaccination. However, diagnosis in eight patients was delayed for more than four weeks. Except for one patient with self-limitation of ARD, others required treatment with anti-inflammatory drugs and disease-modifying antirheumatic drugs, which even one of them developed irreversible neurological complications. Conclusion(s): Indeed, our data can warn physicians about the possibility of ARDs post-vaccination, lead to faster diagnosis, prevent loss of window of opportunity for treatment, and prevent irreversible organ damages.

A case of post coronavirus disease 2019 (COVID-19) multisystem inflammatory syndrome in adults (MIS-A) presenting as fever and seizures

Background/Purpose: The coronavirus disease 2019 (COVID-19) pandemic has led to the emergence of a severe associated condition, multisystem inflammatory syndrome in adults (MIS-A). Initially identified in children as MIS-C, literature regarding the clinical manifestations, illness progression, and treatment of MIS-A are limited. Method(s): This study describes a case of MIS-A presenting as fever and seizures. She was initially given steroids and IVIG, and due to recurrence of fever, she was later treated with tocilizumab. Result(s): The patient was a 55-year- old Filipino female presenting to the emergency department with five days of fever, headache, and disorientation. Lumbar tap was done, which showed elevated opening pressure, normal leukocyte count, normal glucose, slightly elevated protein, and no microorganisms. She was admitted and managed as a case of viral encephalitis. On hospital day 6, she had sudden onset of head-jerking and further decrease in sensorium, hence she was transferred to the intensive care unit. Brain MRI was unremarkable, and subsequent immune-mediated encephalitis was considered. The patient underwent methylprednisolone pulse therapy and IVIG infusion, which provided immediate improvement of sensorium and resolution of fever episodes. Her condition stabilized, and she was transferred out of intensive care. She underwent physical and occupational rehabilitation as preparation for discharge. Two weeks after infusion therapy, on hospital day 26, patient had recurrence of fever episodes and persistence of elevated inflammatory markers. The patient had reported a previous COVID-19 infection 10 weeks prior to admission and received a booster dose of Moderna (Spikevax) COVID-19 vaccine three weeks prior. She tested positive for ANA (1:640, nuclear speckled), while the rest of the autoimmune antibody tests were negative. She was diagnosed as MIS-A based on the following: documented fever (>=38 degrees centigrade) for >=24 hours prior to hospitalization;new-onset neurologic signs and symptoms including seizures and encephalopathy in a patient without prior cognitive impairment;elevated CRP, ferritin, IL-6, and ESR;and a positive SARS-CoV- 2 test for recent infection by RT-PCR. Patient was treated with a locally available monoclonal antibody, tocilizumab, which was given on hospital day 43. Following infusion, she had lysis of fever and marked decrease in CRP, ferritin, IL-6, and ESR. Patient was discharged improved and without end-stage organ damage. Conclusion(s): Immunomodulators target hyperinflammation seen in MIS-A. There may be a role for the use of tocilizumab via blockage of IL-6. MIS-A remains a topic for research, particularly its disease characteristics, management, and relation to a dysregulated immune system.

Blood-based biomarkers for diagnosis, prognosis, and severity prediction of COVID-19: Opportunities and challenges.

The reasons for high morbidity and mortality with Corona virus disease (COVID-19) disease remain unanswered with extremes of manifestation and uncertainty of modes of transmission for which biomarkers are urgently needed for early prediction of severity and prompt treatment. We have reviewed publications from PubMed (years 2019-2021) analysing the biochemical, immune-inflammatory, nucleic acid, and cellular biomarkers that predict infection, disease progression in COVID-19 with emphasis on organ-specific damage. Our analysis of 65 biomarkers assessing the impact of SCoV-2 infection on five organs (lung, liver, cardiac, kidney, and neural) reported that increased levels of CRP, TNF-α, ferritin, IL-6, D-dimer, Procalcitonin, Fibrinogen to Albumin Ratio (FAR), and decrease platelet count (PC), lymphocyte count, leukocyte count, and CD4+/CD8 + ratio shows promising association in the early diagnosis, prediction of prognosis and severity disease and also correlates with cytokine storm a cardinal feature of COVID-19 progression. In the above scenario, this review has put forth the most promising biomarkers for COVID diagnosis and prognosis based on the reported literature. In recent year's chemically synthesized antibody-like biomolecules, aptamers were also used in the diagnosis of COVID-19 which could be preferably used for diagnosis over antibodies. Biomarkers including increase in free DNA and Fibrinogen-to-Albumin Ratio, CRP, PCT, and Ferritin along with a consequential decrease of CD3+ T, CD4+ T, CD8+ T, NK cells with corresponding increase in CD4+/CD8+ ratio following SARS CoV-2 infection has been consistently correlated with disease severity. Despite the two waves of COVID-19 pandemic, currently there is no standard clinical practice guideline for evaluating the severity of the devastating pandemic of COVID-19, hence these biomarkers will have immense relevance for the third and subsequent wave of COVID-19 and related pandemic.

Prediction of Complications and Death in Covid-19 Patients with Deranged Liver Function Tests at Time of Admission and Hospitalization

COVID-19 pandemic has affected millions of individuals globally over the last three years and is spreading continuously. In view of different studies and clinical findings, patients suffering with COVID-19 frequently have deranged liver function tests (LFTs), but the clinical significance of this finding is debatable. Objective(s): The present study was aimed to estimate the prevalence, features, and clinical significance of deranged LFTs in COVID-19 infected individuals, who were hospitalized but were not critically ill. Method(s): We conducted a cross sectional from May 2021 to December 2021 at The Akbar Niazi Teaching Hospital Islamabd. A total of 250 COVID-19 patients were included in the current study. The patient's blood samples were collected to get laboratory results, which included LFTs. LFTs were performed at the time of admission and every 5 +/- 2 day throughout the stay. The outcome measure was either death or transfer of the patients to an intensive care unit. Result(s): At the time of admission, 160 patients (64%) showed deranged LFTs. Individuals with deranged LFTs experienced more severe inflammation, swelling, and organ damage than those who didn't. Patients with deranged LFTs had a greater proportion of transfer to the ICU (81 vs 17), hospital stay (17 vs 7 days), and death (17 vs 5) than those with normal LFTs. Conclusion(s): The results of the current investigation demonstrated that LFTs data might forecast the degree of illness in patients with COVID-19 infections at the time of admission and during their hospital stay. Copyright © 2022 Lahore Medical And Dental College. All rights reserved.