History of scurvy and use of vitamin C in critical illness: A narrative review.

In 1747, an important milestone in the history of clinical research was set, as the Scottish surgeon James Lind conducted the first randomized controlled trial. Lind was interested in scurvy, a severe vitamin C deficiency which caused the death of thousands of British seamen. He found that a dietary intervention with oranges and lemons, which are rich in vitamin C by nature, was effective to recover from scurvy. Because of its antioxidative properties and involvement in many biochemical processes, the essential micronutrient vitamin C plays a key role in the human biology. Moreover, the use of vitamin C in critical illness-a condition also resulting in death of thousands in the 21st century-has gained increasing interest, as it may restore vascular responsiveness to vasoactive agents, ameliorate microcirculatory blood flow, preserve endothelial barriers, augment bacterial defense, and prevent apoptosis. Because of its redox potential and powerful antioxidant capacity, vitamin C represents an inexpensive and safe antioxidant, with the potential to modify the inflammatory cascade and improve clinical outcomes of critically ill patients. This narrative review aims to update and provide an overview on the role of vitamin C in the human biology and in critically ill patients, and to summarize current evidence on the use of vitamin C in diverse populations of critically ill patients, in specific focusing on patients with sepsis and coronavirus disease 2019.

Oncological emergencies

The incidence of cancer continues to rise, with an estimated 1 in 2 of the UK population born after 1960 diagnosed with malignancy at some point during their lifetime. This is in the context of an ageing population with increasing multimorbidity and polypharmacy. Cancer patients are frequent users of emergency care services and have a high rate of ambulance conveyance and hospital admission after review in emergency departments. Presentations can be a consequence of the cancer, its treatment or coexistent morbidity. Given the expanding armamentarium of cancer therapies, acute and general physicians are faced with a myriad of complex issues and require a knowledge of the broad principles of initial assessment, initial management and timely access to the wider multi-professional cancer team. © 2022

MAINTAINING AN ACTIVE RESEARCH CAREER DURING COVID-19 LOCKDOWNS

Maintaining an active medical research career is a multifaceted undertaking, and many challenges arise, even under normal circumstances. Therefore, the Australian government mandated COVID19 lockdowns and worksite restrictions from 2020 2021 inflicted an additional layer of complexity to an already complicated career for most researchers. A critical issue I faced during these COVID19 lockdowns was to establish whether our research focus was considered an essential service during a period of time when the public health advice was to restrict the movement of research staff and students by enacting new laws to ensure they stay at home. My research team members were also rightfully worried about contracting COVID19 during a period when a viable vaccine was not available. In this presentation, I will be covering some of the adaptive changes I implemented during the COVID19 lockdowns to ensure the continuity of our research program, which includes: 1) Proactive engagement with our medical institute and university COVID-19 taskforces to formulate a joint vision of which research areas should be prioritised during these lockdowns in pursuit of both treatments and vaccines;2) Continuous communication with my research team to encourage, motivate and energise staff and students to allow them to contribute to the research program meaningfully;3) Provide flexible working hours for research team members to work within the confinements of a reduced worksite footprint with an appreciation for social distancing;and 4) Contingency planning to ensure if one research team member contracts COVID-19, there are others with the cross-functional skillset to take over their responsibilities. Taking such steps ensured the rapid development of a new treatment regime that was showing impressive results in reversing multi-organ dysfunction in another clinically challenging area in intensive care units (sepsis). Following the preclinical assessment of safety and efficacy of this new treatment regime, we were able to compassionately treat a critically ill COVID19 patient receiving intensive care at Austin Health. In a short period of time, we saw improved regulation of blood pressure, arterial blood oxygen levels and kidney function. The patient was able to be taken off machine ventilation 12 days after starting sodium ascorbate treatment and discharged from hospital without any complications 22 days later. This research has now informed the design and commencement of multi-centre randomised controlled clinical trials at four hospital intensive care units in Australia.

Coagulation System Abnormalities in Patients with COVID-19 Infection

COVID-19 infection caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) in China led to a pandemic all over the world. Although mortality rate between 4.3% to 14.6%, studies have shown that coagulation dysfunction is a major cause of death in patients with severe COVID-19 infection. The majority of the severely ill patients have underlying disease (i.e. diabetes, cardiovascular disease, hypertension) and initially present with respiratory insufficiency but some of them progress to systemic disease causing multiple organ dysfunction. This manuscript reviews coagulation system abnormalities in patients with COVID-19 infection.

Hepcidin and ferritin levels as markers of immune cell activation during septic shock, severe COVID-19 and sterile inflammation.

Introduction: Major clinically relevant inflammatory events such as septic shock and severe COVID-19 trigger dynamic changes in the host immune system, presenting promising candidates for new biomarkers to improve precision diagnostics and patient stratification. Hepcidin, a master regulator of iron metabolism, has been intensively studied in many pathologies associated with immune system activation, however these data have never been compared to other clinical settings. Thus, we aimed to reveal the dynamics of iron regulation in various clinical settings and to determine the suitability of hepcidin and/or ferritin levels as biomarkers of inflammatory disease severity. Cohorts: To investigate the overall predictive ability of hepcidin and ferritin, we enrolled the patients suffering with three different diagnoses - in detail 40 patients with COVID-19, 29 patients in septic shock and eight orthopedic patients who were compared to nine healthy donors and all cohorts to each other. Results: We showed that increased hepcidin levels reflect overall immune cell activation driven by intrinsic stimuli, without requiring direct involvement of infection vectors. Contrary to hepcidin, ferritin levels were more strongly boosted by pathogen-induced inflammation - in septic shock more than four-fold and in COVID-19 six-fold in comparison to sterile inflammation. We also defined the predictive capacity of hepcidin-to-ferritin ratio with AUC=0.79 and P = 0.03. Discussion: Our findings confirm that hepcidin is a potent marker of septic shock and other acute inflammation-associated pathologies and demonstrate the utility of the hepcidin-to-ferritin ratio as a predictor of mortality in septic shock, but not in COVID-19.

Peripheral Blood Genes Crosstalk between COVID-19 and Sepsis.

Severe coronavirus disease 2019 (COVID-19) has led to a rapid increase in death rates all over the world. Sepsis is a life-threatening disease associated with a dysregulated host immune response. It has been shown that COVID-19 shares many similarities with sepsis in many aspects. However, the molecular mechanisms underlying sepsis and COVID-19 are not well understood. The aim of this study was to identify common transcriptional signatures, regulators, and pathways between COVID-19 and sepsis, which may provide a new direction for the treatment of COVID-19 and sepsis. First, COVID-19 blood gene expression profile (GSE179850) data and sepsis blood expression profile (GSE134347) data were obtained from GEO. Then, we intersected the differentially expressed genes (DEG) from these two datasets to obtain common DEGs. Finally, the common DEGs were used for functional enrichment analysis, transcription factor and miRNA prediction, pathway analysis, and candidate drug analysis. A total of 307 common DEGs were identified between the sepsis and COVID-19 datasets. Protein-protein interactions (PPIs) were constructed using the STRING database. Subsequently, hub genes were identified based on PPI networks. In addition, we performed GO functional analysis and KEGG pathway analysis of common DEGs, and found a common association between sepsis and COVID-19. Finally, we identified transcription factor-gene interaction, DEGs-miRNA co-regulatory networks, and protein-drug interaction, respectively. Through ROC analysis, we identified 10 central hub genes as potential biomarkers. In this study, we identified SARS-CoV-2 infection as a high risk factor for sepsis. Our study may provide a potential therapeutic direction for the treatment of COVID-19 patients suffering from sepsis.

Monocyte Distribution Width (MDW) as a biomarker of sepsis: An evidenced-based laboratory medicine approach.

Monocyte Distribution Width (MDW) is a new generation cell blood count parameter providing a measure of monocyte anisocytosis. In the last decades, it has emerged as a reliable biomarker of sepsis in the acute setting, especially emergency department, and intensive care unit. MDW has several advantages over commonly used sepsis biomarkers, including low-cost, ease and speed of measurement. The clinical usefulness of MDW has been established in several studies and some clinical laboratory medicines have already implemented it in their routine. In this article, we describe the analytical and clinical features of MDW to guide its appropriate use in clinical practice by integrating the research evidence with real-world laboratory experience. The proper use of a biomarker is critical for improving patients' care and outcome as well as ensuring healthcare quality.

Rapidly Progressive Emphysematous Pancreatitis With Massive Hemorrhage and Multi-Organ Failure: A Severe Sequela of COVID-19.

The COVID-19 global pandemic continues to wreak havoc on a number of affected patients and poses a significant burden on the healthcare system. Even though it has been over two years since the pandemic emerged, clinical presentations in affected patients continue to appall clinicians. Emphysematous pancreatitis is a rare, fatal complication of acute necrotizing pancreatitis presenting with a high mortality rate. This rare entity stems from superinfection of acute necrotizing pancreatitis with gram-negative bacteria, most commonly from Escherichia coli (E. coli), among others. Herein, we present a rare case of acute necrotizing pancreatitis complicated by emphysematous necrosis with hemorrhagic conversion and E. coli septicemia in a 60-year-old morbidly obese male patient without any underlying risk factors. He presented with respiratory failure in the setting of COVID-19 and was subsequently diagnosed with acute necrotizing pancreatitis complicated by emphysematous necrosis. To our knowledge, emphysematous pancreatitis in the setting of COVID-19 with no other attributable causes for pancreatitis was not previously reported in the literature. This article aims to report an unusual association between COVID-19 infection and acute emphysematous pancreatitis with evidence of hemorrhagic conversion. Furthermore, given the neoteric nature of this viral infection, we hope to promote sensitivity toward capturing additional clinical features associated with active COVID-19 infection, with the goal to keep clinicians abreast with its many possible sequelae.

Continuous diagnosis and prognosis by controlling the update process of deep neural networks.

Continuous diagnosis and prognosis are essential for critical patients. They can provide more opportunities for timely treatment and rational allocation. Although deep-learning techniques have demonstrated superiority in many medical tasks, they frequently forget, overfit, and produce results too late when performing continuous diagnosis and prognosis. In this work, we summarize the four requirements; propose a concept, continuous classification of time series (CCTS); and design a training method for deep learning, restricted update strategy (RU). The RU outperforms all baselines and achieves average accuracies of 90%, 97%, and 85% on continuous sepsis prognosis, COVID-19 mortality prediction, and eight disease classifications, respectively. The RU can also endow deep learning with interpretability, exploring disease mechanisms through staging and biomarker discovery. We find four sepsis stages, three COVID-19 stages, and their respective biomarkers. Further, our approach is data and model agnostic. It can be applied to other diseases and even in other fields.

Extracellular Vesicles: New Players in the Mechanisms of Sepsis- and COVID-19-Related Thromboinflammation.

Sepsis and COVID-19 patients often manifest an imbalance in inflammation and coagulation, a complex pathological mechanism also named thromboinflammation, which strongly affects patient prognosis. Extracellular vesicles (EVs) are nanoparticles released by cells into extracellular space that have a relevant role in cell-to-cell communication. Recently, EVs have been shown to act as important players in a variety of pathologies, including cancer and cardiovascular disease. The biological properties of EVs in the mechanisms of thromboinflammation during sepsis and COVID-19 are still only partially known. Herein, we summarize the current experimental evidence on the role of EVs in thromboinflammation, both in bacterial sepsis and in COVID-19. A better understanding of EV involvement in these processes could be useful in describing novel diagnostic and therapeutic applications of EVs in these diseases.

Patients with SARS-CoV-2-Induced Viral Sepsis Simultaneously Show Immune Activation, Impaired Immune Function and a Procoagulatory Disease State.

BACKGROUND: It is widely accepted that SARS-CoV-2 causes a dysregulation of immune and coagulation processes. In severely affected patients, viral sepsis may result in life endangering multiple organ dysfunction. Furthermore, most therapies for COVID-19 patients target either the immune system or coagulation processes. As the exact mechanism causing SARS-CoV-2-induced morbidity and mortality was unknown, we started an in-depth analysis of immunologic and coagulation processes. METHODS: 127 COVID-19 patients were treated at the University Hospital Essen, Germany, between May 2020 and February 2022. Patients were divided according to their maximum COVID-19 WHO ordinal severity score (WHO 0-10) into hospitalized patients with a non-severe course of disease (WHO 4-5, n = 52) and those with a severe course of disease (WHO 6-10, n = 75). Non-infected individuals served as healthy controls (WHO 0, n = 42). Blood was analyzed with respect to cell numbers, clotting factors, as well as pro- and anti-inflammatory mediators in plasma. As functional parameters, phagocytosis and inflammatory responses to LPS and antigen-specific stimulation were determined in monocytes, granulocytes, and T cells using flow cytometry. FINDINGS: In the present study, immune and coagulation systems were analyzed simultaneously. Interestingly, many severe COVID-19 patients showed an upregulation of pro-inflammatory mediators and at the same time clear signs of immunosuppression. Furthermore, severe COVID-19 patients not only exhibited a disturbed immune system, but in addition showed a pronounced pro-coagulation phenotype with impaired fibrinolysis. Therefore, our study adds another puzzle piece to the already complex picture of COVID-19 pathology implying that therapies in COVID-19 must be individualized. CONCLUSION: Despite years of research, COVID-19 has not been understood completely and still no therapies exist, fitting all requirements and phases of COVID-19 disease. This observation is highly reminiscent to sepsis. Research in sepsis has been going on for decades, while the disease is still not completely understood and therapies fitting all patients are lacking as well. In both septic and COVID-19 patients, immune activation can be accompanied by immune paralysis, complicating therapeutic intervention. Accordingly, therapies that lower immune activation may cause detrimental effects in patients, who are immune paralyzed by viral infections or sepsis. We therefore suggest individualizing therapies and to broaden the spectrum of immunological parameters analyzed before therapy. Only if the immune status of a patient is understood, can a therapeutic intervention be successful.

Circadian orchestration of host and gut microbiota in infection.

Circadian rhythms are present in almost every organism and regulate multiple aspects of biological and physiological processes (e.g. metabolism, immune responses, and microbial exposure). There exists a bidirectional circadian interaction between the host and its gut microbiota, and potential circadian orchestration of both host and gut microbiota in response to invading pathogens. In this review, we summarize what is known about these intestinal microbial oscillations and the relationships between host circadian clocks and various infectious agents (bacteria, fungi, parasites, and viruses), and discuss how host circadian clocks prime the immune system to fight pathogen infections as well as the direct effects of circadian clocks on viral activity (e.g. SARS-CoV-2 entry and replication). Finally, we consider strategies employed to realign normal circadian rhythmicity for host health, such as chronotherapy, dietary intervention, good sleep hygiene, and gut microbiota-targeted therapy. We propose that targeting circadian rhythmicity may provide therapeutic opportunities for the treatment of infectious diseases.

Not all shortness of breath and throat pain is COVID

Case Report: A previously, healthy 18-year-old female presents to a Pediatric Emergency Medicine Department with shortness of breath, fever, and worsening throat and abdominal pain for 3 days. She had a sick contact, a teacher that tested positive for COVID-19 2 weeks prior to presentation. She denies runny/stuffy nose, cough, loss of taste/smell, or rashes/lesions. She denies any significant past medical history including allergies, as well as any history of smoking or any illicit drug use. Upon arrival to the ED, the patient was noted to be tachycardic, hypotensive and febrile. There were no desaturations. Initial physical examination revealed a generally uncomfortable female that was alert and oriented, with noted tenderness over the right anterior neck region, diffuse cervical lymphadenopathy, and painful neck range of motion. Her pharynx was noted to be erythematous without exudates or any unilateral tonsillar swelling. In the ED patient received IV fluid resuscitation and was started on norepinephrine drip, broad spectrum antibiotics. Initial lab workup revealed an anion gap metabolic acidosis, likely secondary to uremia or lactic acidosis from poor perfusion in setting of sepsis and hypovolemia. BUN and creatinine were elevated, likely due to an acute kidney injury (AKI) secondary to hypovolemia. The patient was also found to have an elevated LDH, fibrinogen, and mild elevation of AST. D-Dimer was elevated at 29 000. Covid PCR, Rapid Strep, and respiratory PCR panel were negative. Her chest X-ray (CXR) was negative and ECG showed sinus tachycardia. Given the patient's history of throat and neck pain with shortness of breath, in the setting of a septic picture, a CT scan of neck, chest, abdomen was ordered prior to transferring the patient to the PICU. CT scan of the chest revealed small patches of consolidation with ground glass opacities in the right lung apex, as well as an nearly occlusive, acute thrombosis of the anterior right facial vein. The patient's initial blood cultures grew gram negative bacilli which later were revealed to be Fusobacterium necrophorum. These findings are consistent with Lemierre's syndrome. The patient was treated in the PICU on vasopressors, heparin anticoagulation, and antibiotics for 6 days and discharged with a course of Augmentin. Lemierre's syndrome is an infectious thrombophlebitis of the internal jugular vein. First described by Andre Lemierre in 1936, it begins as a bacterial pharyngitis, generally developing into a peritonsillar abscess or other deep space neck infection with progressive erosion into the internal jugular vein. Diagnostic criteria for Lemierre's syndrome includes radiographically evidence of thrombophlebitis of the internal vein and positive blood cultures. CT and MRI can help make the diagnosis, but are not always required. Treatment is prompt intravenous antibiotics with beta-lactamase penicillins, metronidazole, clindamycin, and third generation cephalosporins. [Figure presented] Copyright © 2023 Southern Society for Clinical Investigation.

Risk factors for moderate to severe COVID-19 infection in systemic lupus erythematosus

Background: People with systemic lupus erythematosus (SLE) are at greater risk of developing infections, including COVID-19. This study describes the characteristics and outcomes of COVID-19 infection among patients with SLE seen in a tertiary hospital in Manila, Philippines. Method(s): This cross-sectional study included patients with diagnosed SLE seen over 24 months from March 2020 to February 2022, who were confirmed with COVID-19 infection. We collected data from patients' electronic records and clinic charts and analyzed underlying SLE characteristics including disease activity and medications, COVID-19 involvement, vaccination status and outcomes including hospitalization and mortality. Result(s): Of the 507 patients with SLE, 53 patients reported positive for COVID-19. Cough, fever, dyspnea, diarrhea, anosmia, ageusia, and sore throat were the common presenting complaints. Three were asymptomatic, 41 had mild symptoms, 2 had moderate, and 7 had severe COVID-19 infection. Sixteen patients (30%) were hospitalized, and 37 (70%) were confined at home or an isolation facility. More than half of patients were unvaccinated during the time of COVID-19 infection (28, 54%), 3 (6%) were partially vaccinated and 21 (40%) were fully vaccinated. Use of methotrexate, mycophenolate mofetil, prednisone <10 mg/day, and hydroxychloroquine did not affect the risk for moderate to severe COVID-19 infection. Patients in low disease activity or remission tended to have asymptomatic to mild COVID-19 infection. Two (4%) died with severe COVID 19 infection: a lupus nephritis patient with end-stage renal disease on hemodialysis and a lupus nephritis patient with concomitant double gynecologic malignancy (vulval and cervical) who underwent 35 cycles of radiotherapy prior to COVID-19 infection. Conclusion(s): This study on SLE patients with COVID-19 infection showed that patients with high disease activity, co-morbidity especially ESRD and the use of high dose glucocorticoid had higher risk for moderate to severe COVID-19 infection and hospitalization. Use of immunosuppressants and prednisone <10 mg/day did not appear to contribute to increased severity of COVID-19 infection, hospitalization and mortality.

Acute renal infarction presenting as hypertensive urgency

Case Report: A 46-year-old lady with medical history of hypertension, diabetes mellitus, and peripheral neuropathy was admitted to the hospital with the diagnosis of sepsis without septic shock secondary to a right foot pressure ulcer. Her presentation was non-specific as she was complaining of fatigue, myalgia, fever, and chills. Routine COVID-19 test was done on admission and it came back positive despite her denying having any respiratory symptoms. She was being treated with fluids and antibiotics until her third night of admission. According to the patient, she got up to use the restroom when she suddenly noticed weakness in her lower extremities. She thought it may be due to a muscle spasm;hence, she did not notify the medical team. Later, her nurse was routinely checking the patient's blood pressure when she noted a blood pressure of 220/105 mmHg. She then received a total of 3 doses of intravenous labetalol over three hours;however, her blood pressure continued to be elevated. Patient did endorse right flank pain but it was responding to intravenous fentanyl. The on-call physician then proceeded to perform a full physical examination and noted paleness, weakness, and absent pulses in bilateral lower extremities. A STAT computed tomography (CT) angiogram of the abdominal aorta and iliofemoral arteries was performed and it revealed low-density defects in the right kidney compatible with infarcts, occlusive thrombus in the infrarenal abdominal aorta and extensive bilateral arterial thrombosis. Vascular surgery was immediately consulted and they kept the patient on heparin drip and took her to the operation room within few hours for thrombectomies. Her blood pressure improved following the removal of the thrombus and there were no other documented occurrence of uncontrolled hypertension during her hospitalization. Discussion(s): Acute renal infarction is an arterial vascular event that leads to sudden disruption of blood flow in the renal artery. It can often be diagnosed late due to its rare incidence. In addition, it has a nonspecific clinical presentation that can mimic many common causes. The most common causes of renal infarction include atrial fibrillation, endocarditis, ischemic heart disease, hypercoagulable disorders, and spontaneous renal artery dissection. A case report published by Bourgault M, et al. on renal infarction suggested that around 97% had abdominal/flank pain and 48% of patients had marked uncontrolled hypertension at initial presentation of renal infarction. Our patient did not have any of the afore mentioned risk factors except for a possible hypercoagulable state from her COVID-19 infection and she did present with the two most common presentations. In conclusion, clinicians should have a low threshold for the suspicion of renal ischemia in patients with severe hypertension and flank pain. Copyright © 2023 Southern Society for Clinical Investigation.

Dermatomyositis following SARS-CoV- 2 2 vaccination

Purpose: To report a case of a 51-year- old male who developed dermatomyositis following the second dose of coronavirus disease (COVID-19) vaccine. Method(s): Case report Result: Case: We report a case of 51-year- old male who developed erythematous maculopapular rash on the upper anterior chest and upper back along with symmetric proximal muscle weakness two months after receiving his second dose of CoronaVac vaccine. His symptoms were followed by edema in the periorbital area which later involved the upper and lower extremities. He had dysphagia and weight loss. He had no known family history of autoimmune diseases. Physical examination revealed macular erythema over the lower anterior neck and upper back. Heliotrope rash and hyperkeratotic pink scaly papules on bilateral lateral second digits (mechanic's hands) were seen. Symmetric proximal muscle weakness in the upper and lower extremities was objectified. Blood tests showed elevated muscle enzymes (total CK: 3899 U/L, CK MB mass: 15.4 ng/mL, LDH: 683, AST: 232 U/L, ALT: 66 IU/L) elevated ESR (36) and normal CRP. Anti Jo 1 and anti U1 RNP were negative. Work up for systemic infection, thyroid function and malignancy were unremarkable. Diagnosis: Diagnosis of dermatomyositis was made based on clinical history and physical exam findings of symmetric proximal weakness, presence of heliotrope rash, V sign and shawl sign. Laboratory tests revealed elevated total CK, CK MB mass, LDH, AST, ALT and ESR consistent with an inflammatory myositis. Intervention(s): Hydrocortisone 1 mg/kg/day was started. Azathioprine was commenced on the 3rd hospital day. Ethical consideration: Informed consent for both written and photographic content was secured and patient confidentiality was observed. Conclusion(s): This case highlights the possible association between COVID 19 vaccine and this rare autoimmune disease. We hypothesize that among patients with genetic predisposition, the possibility of vaccines triggering and unmasking an autoimmune event is possible. (Figure Presented).

A Case of SARS-CoV-19-Associated Encephalitis in a Neonate

Objective: To describe a case of SARS-CoV-19-associated encephalitis in a neonate. Method(s): Case report. Report: A 9-day-old term neonate presented with two focal motor seizures (right upper limb jerking and facial twitching). He had a 1-day history of coryzal illness with reduced feeding, but was afebrile. Antenatal course was uneventful. He was born at term via vaginal delivery. He did not require resuscitation or admission to SCBU. Maternal history was notable for symptomatic SARS-CoV-19 infection at time of delivery. Two siblings subsequently tested positive for SARS-CoV-19. He had further seizures in the emergency department and was loaded with phenobarbitone. The infant was stabilised locally and transferred to a tertiary paediatric hospital for the management of neonatal sepsis. He never required respiratory support. However, he was diffusely hypotonic with poor suck, necessitating nasogastric feeding. Nasopharyngeal PCR was positive for SARS-CoV-19. Lumbar puncture microscopy was negative (WCC 6). All CSF bacterial and viral investigations were negative. CSF testing of SARS-CoV-19 was not available. Brain MRI revealed bilateral asymmetric areas of reduced diffusivity involving the subcortical white matter, medulla and the corpus callosum with frontal lobe predominance. He made a full neurologic recovery with supportive therapies and was discharged following a 9-day admission. He had no further clinical seizures and phenobarbitone was successfully weaned pre-discharge. Conclusion(s): In the absence of another aetiology or antenatal risk factor, SARS-CoV-19 infection was presumed causative in this case of focal seizures and white matter changes in this term neonate. White matter abnormalities on MRI imaging are reported in neonates with seizures in the context of other viral infections. Single case reports have been published of SARS-CoV-19 infection with associated abnormal MRI brain findings, particularly diffusion abnormalities of the corpus callosum, as seen in our case.

Case report: Covid-19 and disseminated tuberculosis coinfection unveiling catastrophic antiphospholipid antibody syndrome: An association or de novo phenomenon

Background: Disseminated infections such as tuberculosis are known to result in a systemic inflammatory response leading to thrombosis, with increasing reported cases of thrombotic event being observed in patients infected with covid-19. This is the first reported case on co-infection with COVID-19 pneumonia and disseminated tuberculosis causing catastrophic antiphospholipid syndrome (CAPS). Method(s): The report highlighted the challenges in the diagnosis and management which include the use of corticosteroid in setting of systemic infections. Another diagnostic dilemma was to explain the cause of myositis by tuberculous or autoimmune. Case Presentation: We report a 26-year- old man with HbE trait thalassemia who reported unintentional weight loss, night sweats for 1 month prior to the diagnosis of covid-19 infection on 10th March 2022. Seven days later, he was hospitalized for suspected perforated appendix. Computed tomography (CT) abdomen revealed hepatosplenomegaly, prostatitis, seminal vesiculitis. Multiple matted abdominal lymph nodes were not amenable for biopsy. Soon, he appeared toxic, dyspneic required non-invasive ventilation with bilateral parotitis. He had raised erythrocyte sedimentation (ESR) 52 mm/hour, C-reactive protein (CRP) 221 mg/dl, lactate dehydrogenase (LDH) 730U/L. Direct Coomb's antibody was positive but did not have any form of haemolysis. Complement 3 (0.45 g/L) and complement 4 (0.1 g/L) levels were low. Serum IgG4, procalcitonin, anti-nuclear antibody, cultures and virology were negative. Sputum for acid fast bacilli (AFB) was positive on Auramine O stain but the Ziehl-Nelson (ZN) stain and tuberculous PCR (GeneXpert) were negative. Diagnosis of disseminated tuberculosis was made but his abdominal pain persisted despite being on anti-tuberculous therapy (ATT), and he had new evidence of splenic infarct. CT angiogram also revealed celiac trunk and superior mesenteric artery thrombosis. Antiphospholipid (aPL) test was positive for lupus anticoagulant, beta 2 glycoprotein 1 and anti-cardiolipin antibodies. Therapeutic anticoagulation and plasma exchange were initiated for probable CAPS followed by intravenous immunoglobulin and corticosteroid. Thereafter, the patient developed severe bilateral pelvic girdle pain with evidence of myositis on the MRI (Figure 2). Serum creatine kinase was never elevated. Anti-PL- 7 and anti Ro-52 were borderline elevated. He recovered well and ambulant before discharged home. Conclusion(s): Our case highlight the complexicity of presentation of CAPS who manifested as multiple arterial thrombosis. The diagnosis of disseminated tuberculosis relied strongly on microbiological, imaging and clinical presentation as histopathological evidence was not feasible. Management challenges were deciding on corticosteroid in disseminated infection and the need for confirmation of persistent positive aPL test and to monitor myositis symptom to help guide decision making. (Figure Presented).

Use of Intravenous Vitamin C in Critically Ill Patients With COVID-19 Infection.

INTRODUCTION: The pathophysiology for Coronavirus Disease 2019 (COVID-19) infection is characterized by cytokine oxidative stress and endothelial dysfunction. Intravenous (IV) vitamin C has been utilized as adjuvant therapy in critically ill patients with sepsis for its protective effects against reactive oxygen species and immunomodulatory effects. The primary objective of this study was to evaluate the effects of IV vitamin C in critically ill patients with COVID-19 infection. METHODS: Retrospective observational cohort study with propensity score matching of intensive care unit (ICU) patients who received 1.5 grams IV vitamin C every 6 hours for up to 4 days for COVID-19 infection. The primary study outcome was in-hospital mortality. Secondary outcomes included vasopressor requirements in norepinephrine equivalents, ICU length of stay, and change in Sequential Organ Failure Assessment (SOFA) score. RESULTS: Eight patients received IV vitamin C and were matched to 24 patients. Patients in the IV vitamin C group had higher rates of hospital mortality [7 (88%) vs. 19 (79%), P = 0.049]. There was no difference in the daily vasopressor requirement in the treatment group or between the 2 groups. The mean SOFA scores post-treatment was higher in the IV vitamin C group (12.4 ± 2.8 vs. 8.1 ± 3.5, P < 0.005). There was no difference in ICU length of stay between the treatment and control groups. CONCLUSION: Adjunctive IV vitamin C for the management of COVID-19 infection in critically ill patients may not decrease the incidence of mortality, vasopressor requirements, SOFA scores, or ventilator settings.