AUTOANTIBODIES RELATED TO RHEUMATIC DISEASES AFTER COVID-19 INFECTION

BackgroundSARS-CoV-2(Severe acute respiratory syndrome coronavirus 2) has been circulating worldwide for three years. It mainly causes upper respiratory tract infection, which can manifest as pulmonary infection and even respiratory distress syndrome in severe cases. Different autoantibodies can be detected in patients infected with COVID-19.ObjectivesTo explore autoantibodies related to rheumatic diseases after COVID-19 infection.MethodsNinety-eight inpatients were tested for antinuclear antibodies (ANA), antibodies to extractable nuclear antigens(ENA), anti-neutrophil cytoplasmic antibodies（ANCA), anticardiolipin antibodies,a-β2GPI (IgG/IgM). They were from a tertiary hospital in Guangzhou during the COVID-19 epidemic. Data were described statistically.ResultsNinety-eight hospitalized patients were tested for relevant antibodies. The average age was 50.64±19.54;67 (68.4%) were male, 64 (65.3%) were COVID-19 positive, 90 (90.9%) had rheumatic diseases, and 56 of them were COVID-19 positive patients with rheumatic diseases.There were 76 patients tested for antinuclear antibodies;29 （38.16%）were negative, 18 （23.68%）had a 1/80 titre, and 29（28.16%） had a titre greater than 1:80. The 31 covid patients were positive for ANA. In the high-titer group, 19 patients with rheumatic diseases were positive for COVID-19, and 12 patients had an exacerbation of the rheumatic diseases (6 of whom had previously had pulmonary fibrosis). Of 31 covid patients, only two were non-rheumatic patients, and both were elderly, aged 85 and 100, respectively.Fifty-six patients had ENA results, and 29 for positive antibodies, 8 for ds-DNA antibodies, 2 for anti-Sm antibodies, 6 for anti-nucleosome antibodies, 12 for anti-U1RNP antibodies, 2 for anti-Scl-70 antibodies, 12 for anti-SS-A antibodies, 3 for anti-mitochondrial M2 antibodies, 2 for anti-centromere antibodies, 1 for anti-Po antibodies, and one for anti-Jo-1 antibody. All 56 patients had rheumatic diseases, and no new patients were found.There were 62 patients with ANCA data. P-ANCA was positive in 12 cases(19.35%), and MPO-ANCA was positive in 2 cases. An 85-year-old non-rheumatic COVID-19 patient was P-ANCA positive. She had a history of hypertension, colon cancer, CKD3, coronary heart disease, and atrial flutter.In the anticardiolipin antibodies group, there were 62 patients;only 6 were positive, and 2 were rheumatic patients infected with COVID-19. Antiphospholipid antibodies were detected in 33 patients, and a-β2GPI was tested in one patient, an 82-year-old COVID-19 patient with gout, diabetes, and cerebral infarction in the past. We did not find a statistical difference in the above results.ConclusionWe have not found a correlation between SARS-CoV-2 and serum autoantibodies of rheumatic immune diseases. It needs large samples and an extended follow-up to research.AcknowledgementsThis work was supported by Scientific and Technological Planning Project of Guangzhou City [202102020150], Guangdong Provincial Basic and Applied Basic Research Fund Project [2021A1515111172], National Natural Science Foundation of China Youth Fund [82201998] and Third Affiliated Hospital of Sun Yat-Sen University Cultivating Special Fund Project for National Natural Science Foundation of China [2022GZRPYQN01].Disclosure of Interestsone declared.

Risk factors affecting outcome of rhino-orbital-cerebral mucormycosis in COVID-19 patients

Background: Mucormycosis is a serious life-threatening fungal infection that recently made severe sudden and devastating surge during the second wave of the COVID-19 epidemic with a mortality rate of up to 50%. Although the causality link between COVID-19 and rhino-orbito-cerebral mucormycosis (ROCM) remains unclear, many factors including poor diabetes control, high doses of steroids, viral-induced lymphopenia, and cytokine storm have been attributed to ROCM in patients with COVID-19. Orienting to risk factors and early recognition of this potentially fatal opportunistic infection is the key to optimal management and improved outcomes. In these contexts, we conducted a prospective study for 33 patients admitted to our tertiary hospital to determine the risk factors for ROCM in patients with COVID-19 and the cumulative mortality rates. Result(s): This study found a statistically significant relation between the fate of death in COVID-MUCOR patients who had presented fever, ophthalmoplegia, facial skin necrosis, and visual loss with those who received dose of steroid to control their respiratory symptoms P < 0.001. Death from COVID-MUCOR was statistically significant related to the prolonged interval from the onset of the symptoms to start of treatment and intervention. Also, it was found that there was a significant decrease in duration between COVID-19 infection and the start of mucormycosis (days) with incidence of DKA on admission. Nineteen (57.6%) of the patients had uncontrolled diabetes mellitus (hemoglobin A1C (HbA1c) of > 7.0%). Conclusion(s): Mucormycosis epidemic was precipitated by a unique confluence of risk factors: diabetes mellitus, widespread use of steroids, and perhaps SARS-CoV-2 infection itself. Restricting steroid use in patients with severe COVID-19 requiring oxygen therapy, and screening for and optimally controlling hyperglycemia, can prevent COVID-MUCOR in a large majority.Copyright © 2023, The Author(s).

Case Series of Burkholderia Pseudomallei Causing Melioidosis (Pulmonary, Cerebral, and Splenic Abscess)

Burkholderia pseudomallei is soil saprophytic Gram-negative bacilli that cause a fatal disease called melioidosis. Melioidosis is capable of causing cutaneous infection and systemic infections in the respiratory tract, cardiovascular, gastrointestinal, urinary, skin and soft tissue, and musculoskeletal and central nervous systems. Here, we report rare forms of pulmonary, cerebral, and splenic abscess case series of melioidosis caused by B. pseudomallei. Imported cases have been reported among tourists, immigrants, and soldiers who returned from endemic areas. The acquisition of infection is through percutaneous, inhalation, and ingestion of contaminated water;person-to-person transmission is very rare. Melioidosis cases are primarily found in the rainfall season and are usually associated with risk factors such as diabetes, alcoholism, and chronic renal diseases. However, 20-26% of cases were not associated with predisposing conditions. The identification is based on colony morphology, Gram stain, antibiotic susceptibility testing, and other supportive automated and molecular assays when we suspect B. pseudomallei. There are two phases, the intensive and eradication phases, in managing melioidosis. In the intensive phase, ceftazidime for 2 weeks showed efficacy in almost 50% of cases, and the eradication phase treatment with co-trimoxazole and doxycycline or amoxicillin/clavulanic acid for 3-6 months showed an excellent response. The improper clinical diagnosis and management of B. pseudomallei can lead to complications. Hence, early diagnosis with microbiological approaches such as culture, biochemical reactions, or automated systems available and antimicrobial sensitivity testing will cure the patient quickly without mortality.Copyright © 2023 The Authors.

Clinical course and diagnosis of cerebral vein and sinus thrombosis associated with COVID-19 in young and middle-aged patients.

Cerebral venous thrombosis (CVT) is a form of cerebrovascular disorders that is difficult to recognize, it is potentially a life threatening condition and requires timely anticoagulant therapy. In the era of the COVID-19 pandemic, there is a steady increase in CVT (4.2% vs. 0.5-1%). At the same time, mortality in patients with CVT on the background of COVID-19 significantly exceeds the mortality in patients with CVT without COVID-19 (45.5% vs. 15%). Objective(s): to study the clinical course of CVT, to determine the diagnostic value of radiological methods and the significance of genetic risk factors for thrombosis in the development of CVT in young and middle-aged patients against the background of COVID-19. Material and methods. Seven patients were examined: six women (five of them of reproductive age) and one man, aged 26 to 57 years (mean age 37 years). The main clinical and neurological manifestations of CVT, the results of laboratory examination, neuroimaging, and the data of molecular genetic analysis of risk factors for thrombosis were analyzed. Results. The course of COVID-19 was severe in one case, and moderate in the rest of cases. The interval between the onset of COVID-19 symptoms and the development of CVT ranged from 7 to 25 days. In three cases CVT had an acute course and was accompanied by the development of a stroke (in two cases, hemorrhagic stroke was noted, in one case, multifocal ischemic stroke), in other cases, a subacute course of CVT was noted. Genetic risk factors for thrombosis were identified in all patients. Conclusion. The diagnosis of CVT in the era of the COVID-19 pandemic is particularly difficult, since the most common symptom of CVT - headache (90%) - can be regarded as a manifestation of COVID-19. At the same time, timely diagnosis of CVT and immediate initiation of anticoagulant therapy are associated with a relatively favorable prognosis.Copyright © 2023 Ima-Press Publishing House. All rights reserved.

Diagnostic and Therapeutic Challenges of Concurrent Intracranial Hemorrhage and Cerebral Venous Thrombosis in a Patient With Acute Lymphoblastic Leukemia: A Case Report and Literature Review.

Cerebral venous sinus thrombosis (CVST) is a cerebrovascular condition due to the thrombosis of cerebral venous sinuses, leading to intracranial hemorrhage, increased intracranial pressure, focal deficit, seizure, toxic edema, encephalopathy, and death. The diagnosis and therapeutic approach of CVST remain challenging because of its highly nonspecific clinical presentation including headaches, seizures, focal neurologic deficits, and altered mental status, etc. Anticoagulation is the mainstay of CVST treatment and should be started as soon as the diagnosis is confirmed. Here, we present the case of a 34-year-old male construction worker who presented to the emergency department with a complaint of right chest wall pain and swelling. He was admitted to the hospital following a diagnosis of anterior chest wall abscess and mediastinitis. During hospitalization, his complete blood count revealed pancytopenia with blast cells, and bone marrow biopsy revealed 78.5% lymphoid blasts by aspirate differential count and hypercellular marrow (100%) with decreased hematopoiesis. He developed concurrent CVST and intracranial hemorrhage while receiving CALGB10403 (vincristine, daunorubicin, pegaspargase, prednisone) with intrathecal cytarabine induction chemotherapy for acute lymphoblastic leukemia (ALL). The patient failed two standard chemotherapy for ALL and achieved remission while on third-line chemotherapy with an anti-CD19 monoclonal antibody, blinatumomab. Although this patient had an MRI scan of the brain with multiple follow-up non-contrast CT scans, it was CT angiography that revealed CVST. This showed the diagnostic challenge in CVST, with CT and MRI venography having excellent sensitivity in diagnosing CVST. Risk factors for CVST in our patient were ALL and its intensive induction chemotherapy with pegaspargase.

Cerebral blood flow in patients recovered from mild COVID-19.

BACKGROUND AND PURPOSE: Cerebral hypoperfusion has been described in both severe and mild forms of symptomatic Coronavirus Disease 2019 (COVID-19) infection. The purpose of this study was to investigate global and regional cerebral blood flow (CBF) in asymptomatic COVID-19 patients. METHODS: Cases with mild COVID-19 infection and age-, sex-, and race-matched healthy controls were drawn from the Aging Brain Consortium at The University of South Carolina data repository. Demographics, risk factors, and data from the Montreal Cognitive Assessment were collected. Mean CBF values for gray matter (GM), white matter (WM), and the whole brain were calculated by averaging CBF values of standard space-normalized CBF image values falling within GM and WM masks. Whole brain region of interest-based analyses were used to create standardized CBF maps and explore differences between groups. RESULTS: Twenty-eight cases with prior mild COVID-19 infection were compared with 28 controls. Whole-brain CBF (46.7 ± 5.6 vs. 49.3 ± 3.7, p = .05) and WM CBF (29.3 ± 2.6 vs. 31.0 ± 1.6, p = .03) were noted to be significantly lower in COVID-19 cases as compared to controls. Predictive models based on these data predicted COVID-19 group membership with a high degree of accuracy (85.2%, p < .001), suggesting CBF patterns are an imaging marker of mild COVID-19 infection. CONCLUSION: In this study, lower WM CBF, as well as widespread regional CBF changes identified using quantitative MRI, was found in mild COVID-19 patients. Further studies are needed to determine the reliability of this newly identified COVID-19 brain imaging marker and determine what drives these CBF changes.

Rising Incidence of Post Covid Rhinocerebral Mucormycosis: An Otolaryngologists Prospective.

Mucormycosis or grimmer popular name, "black fungus" has evolved public concern in context of covid-19 pandemic, Covid Associated Mucormycosis (CAM) seen in Covid-19 pandemic and as a post covid sequelae. The present study was conducted to find out the incidence of the Mucormycosis, and to study its association with post-covid status and co-morbidities. A retrospective study conducted at tertiary care centre over a period of four months, involving all patients with mucormycosis of the paranasal sinuses suffering from or having a history of coronavirus disease. 59 patients had CAM, 47 patients had rhino-orbital Mucormycosis, followed by nasal and paranasal Mucormycosis in 8 patients, 3 patients with rhino-orbital-cerebral Mucormycosis, and one patient with pulmonary Mucormycosis. Diabetes mellitus was present in all 59 patients, 60.41% who had HbA1c > 10 (range 7-15), and 39.58% had HbA1c < 10 with range 6-13. Only 8.33% had controlled diabetes status, uncontroled hypertension and diabetes was seen in 34.02%. All patients were started with IV amphotericin B anti-fungal drug, and followed by oral posaconazole. Depending upon the extent of the disease surgical debridement was done in 52 patients. All patients had history of steroid intake. 7 mortality was there. Uncontrolled diabetes, over-zealous use of steroids, uncontrolled underlying primary disease or co-morbidities, prolonged hospitalization in intensive care unit or normal wards, and hyperventilation all these factors together aggravated the CAM. So it's proper management based on, prompt diagnosis, reversal of predisposing condition with proper medical and aggressive surgical debridement remain the corner stone for this deadly CAM.

Advances in Management of the Stroke Etiology One-Percenters.

PURPOSE OF REVIEW: Uncommon causes of stroke merit specific attention; when clinicians have less common etiologies of stoke in mind, the diagnosis may come more easily. This is key, as optimal management will in many cases differs significantly from "standard" care. RECENT FINDINGS: Randomized controlled trials (RCT) on the best medical therapy in the treatment of cervical artery dissection (CeAD) have demonstrated low rates of ischemia with both antiplatelet and vitamin K antagonism. RCT evidence supports the use of anticoagulation with vitamin K antagonism in "high-risk" patients with antiphospholipid antibody syndrome (APLAS), and there is new evidence supporting the utilization of direct oral anticoagulation in malignancy-associated thrombosis. Migraine with aura has been more conclusively linked not only with increased risk of ischemic and hemorrhagic stroke, but also with cardiovascular mortality. Recent literature has surprisingly not provided support the utilization of L-arginine in the treatment of patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS); however, there is evidence at this time that support use of enzyme replacement in patients with Fabry disease. Additional triggers for reversible cerebral vasoconstriction syndrome (RCVS) have been identified, such as capsaicin. Imaging of cerebral blood vessel walls utilizing contrast-enhanced MRA is an emerging modality that may ultimately prove to be very useful in the evaluation of patients with uncommon causes of stroke. A plethora of associations between cerebrovascular disease and COVID-19 have been described. Where pertinent, authors provide additional tips and guidance. Less commonly encountered conditions with updates in diagnosis, and management along with clinical tips are reviewed.

Ischemic stroke in the setting of supratherapeutic International Normalized Ratio following coronavirus disease 2019 infection: a case report.

BACKGROUND: SARS-CoV-19 infection is associated with an increased risk of thrombotic events. We present a case of acute middle cerebral artery ischemic stroke in a patient with SARS-CoV-19 infection despite being on warfarin with supratherapeutic INR (International Normalized Ratio). CASE PRESENTATION: A 68-year-old Caucasian female with multiple comorbidities was admitted to the hospital with symptoms of upper respiratory tract infection. A rapid antigen test confirmed the diagnosis of COVID-19 pneumonia, and intravenous remdesivir was initiated. On the fifth day of admission, the patient experienced sudden onset confusion, slurred speech, left-sided hemiplegia, right-sided eye deviation, and left-sided facial droop. Imaging studies revealed an occlusion of the distal anterior M2 segment of the right middle cerebral artery, and an MRI of the brain confirmed an acute right MCA infarction. Notably, the patient was receiving warfarin therapy with a supratherapeutic INR of 3.2. CONCLUSIONS: This case report highlights the potential for thromboembolic events, including stroke, in patients with COVID-19 infection, even when receiving therapeutic anticoagulation therapy. Healthcare providers should be vigilant for signs of thrombosis in COVID-19 patients, particularly those with pre-existing risk factors. Further research is necessary to understand the pathophysiology and optimal management of thrombotic complications in COVID-19 patients.

SARS-CoV-2 vaccination induced cerebral venous sinus thrombosis: Do megakaryocytes, platelets and lipid mediators make up the orchestra?

The COVID-19 vaccines comprised of adenoviral vectors encoding the Spike (S) glycoprotein of SARS-CoV-2 are highly effective but associated with rare thrombotic complications. The adenovirus vector infects epithelial cells expressing the coxsackievirus and adenovirus receptor (CAR). The S glycoprotein expressed locally stimulates neutralizing antibody and cellular immune responses. These vaccines have been associated with thromboembolic events including cerebral venous sinus thrombosis (CVST). S glycoprotein stimulates the expression of cyclooxygenase-2 (COX-2) and leads to massive generation of thromboxane A2 in COVID-19. Megakaryocytes express CAR and we postulate that S glycoprotein stimulated generation of thromboxane A2 leads to megakaryocyte activation, biogenesis of activated platelets and thereby increased thrombogenicity. Cerebral vein sinuses express podoplanin, a natural ligand for CLEC2 receptors on platelets. Platelets traversing through the cerebral vein sinuses could be further activated by thromboxane A2-dependent podoplanin-CLEC2 signaling, leading to CVST. A prothrombotic hormonal milieu, and increased generation of thromboxane A2 and platelet activation in healthy females compared to males is consistent with increased risk for CVST observed in women. We propose that antiplatelet agents targeting thromboxane A2 receptor signaling such as low-dose aspirin merit consideration for chemoprophylaxis when administering the adenovirus based COVID-19 vaccines to young adults at risk of thrombosis provided there are no contraindications.

COVID-19 and Mucormycosis of Orofacial Region: A Scoping Review.

During the second wave of coronavirus disease, or COVID-19, infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus in the year 2021 around the globe, there is a surge in the number of cases of mucormycosis or "Black Fungus" that is directly/indirectly associated with COVID-19. In this review article, mucormycosis of the orofacial region has gained importance from the maximum published literature (45 articles) from various databases like PubMed, Google Scholar, Scopus, Web of Science, and Embase. Rhino-orbital cerebral mucormycosis (ROCM) is a fatal condition associated with COVID-19 among categories of mucormycosis such as pulmonary, oral, gastrointestinal, cutaneous, and disseminated. ROCM targets the maxillary sinus, also involving teeth of the maxilla, orbits, and ethmoidal sinus. These are of particular interest to dentists and oral pathologists for proper diagnosis and identification. Co-morbid conditions, especially diabetes mellitus type II, have to be monitored carefully in COVID-19 patients as they have a higher risk of developing mucormycosis. In this review article, various presentations of COVID-19-linked mucormycosis are mentioned having particular emphasis on pathogenesis, signs and symptoms, clinical presentation, various diagnostic modalities including histopathology, radiology like CT and MRI, serology, tissue culture, various laboratory investigations, treatment protocols, management with prognosis, and so on. Any suspected case of mucormycosis needs quick detection and treatment since it progresses quickly due to the destructive course of infection. Long-term follow-up along with proper care is a must to detect any kind of recurrence.

The effect of motor learning-based telerehabilitation on quality of life of children with cerebral palsy during the COVID-19 pandemic.

BACKGROUND: During the pandemic, the access of children with cerebral palsy (CP) to rehabilitation services was adversely affected due to the significant risk of infection. AIMS: We assessed whether the effect of a motor learning-based treatment provided via a telerehabilitation method on the quality of life of children with cerebral palsy during the COVID-19 period was equivalent to face-to-face treatment. METHODS: Distance exercises were explained by a physiotherapist to the patients in the telerehabilitation group, and motor learning-based treatment was applied by their families; the physiotherapist followed the sessions with video conferencing. Motor learning-based treatment was offered to the face-to-face group by a physiotherapist in the clinic. RESULTS: In the comparison between the groups, there was a significant difference in the parameters of play activities, pain-hurt, fatigue, eating activities, and speech communication activities after treatment (p<0.05). However, in the test performed by considering the nonhomogeneous parameters before the treatment, no time-dependent difference was found in the repeated measurements before and after the treatment in all parameters (p>0.05). CONCLUSION: Motor learning-based treatment provided using the telerehabilitation method has a positive effect on the quality of life of children with CP, but the results are similar to face-to-face treatment.

Rhino-Orbito-Cerebral Mucormycosis—The Bane of the ‘Black Fungus'

Rhino-orbito-cerebral mucormycosis (ROCM) is an infection of the nasal passages and orbit caused by ubiquitous fungi of the order Mucorales. These fungi are known to affect patients with phagocyte and neutrophil dysfunction. Patients with uncontrolled diabetes, solid-organ, haematological malignancies and organ transplant recipients on immunosuppressive therapy are especially susceptible. The disease is being seen with alarming frequency in patients with COVID-19 infection or those who have recently recovered from it. Poor glycaemic control due to the indiscriminate use of steroids has been strongly implicated. Patients present with periocular pain, oedema, numbness or skin discoloration along with symptoms of the nasal blockade. Direct microscopy of a deep nasal swab taken from the involved mucosa reveals broad aseptate or pauci-septate fungal hyphae, clinching the diagnosis. CT scan of the paranasal sinuses and orbit would reveal a hyperdense lesion involving the nasal turbinates and sinuses with extension into the orbit. Lack of contrast enhancement indicates necrosis of the tissues. The treatment involves administration of systemic antifungals (Amphotericin B, Posaconazole and isavuconazole) and aggressive surgical debridement of involved tissues. In spite of all measures, the mortality rate is about 46% in these patients. Strict diabetic control and judicious prescription and monitoring of systemic steroids in the setting of COVID-19 infection, keeping a high index of suspicion with early detection of the disease can go a long way in improving the prognosis. © The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd. 2021.

Development of an integrated telerehabilitation model in children with cerebral visual impairment in South India during the COVID-19 pandemic - A pilot study.

Purpose: Coronavirus disease 2019 (COVID-19) pandemic affected the in-person rehabilitation/habilitation services in families with children with cerebral visual impairment (CVI) in India. This study aimed to develop a structured and family-centered telerehabilitation model alongside conventional in-person intervention in children with CVI to observe its feasibility in the Indian population. Methods: This pilot study included 22 participants with a median age of 2.5 years (range: 1-6) who underwent a detailed comprehensive eye examination followed by functional vision assessment. The visual function classification system (VFCS) was administered to the children and the structured clinical question inventory (SCQI) to the parents. Every participant underwent 3 months of telerehabilitation including planning, training, and monitoring by experts. At 1 month, the parental care and ability (PCA) rubric was administered to the parents. After 3 months, in an in-person follow-up, all the measures were reassessed for 15 children. Results: After 3 months of Tele-rehabilitation there were significant improvements noted in PCA rubric scores (P<0.05). Also, statistically significant improvements were noted in functional vision measured using SCQI and VFCS scores (P<0.05) compared to baseline. Conclusion: The outcomes of the study provide the first steps towards understanding the use of a novel tele-rehabilitation model in childhood CVI along-side conventional face-to-face intervention. The added role of parental involvement in such a model is highly essential.

Cerebral small vessel disease pathology in COVID-19 patients: A systematic review.

Cerebral small vessel disease (CSVD) is the leading cause of vascular cognitive impairment and is associated with COVID-19. However, contributing factors that often accompany CSVD pathology in COVID-19 patients may influence the incidence of cerebrovascular complications. Thus, a mechanism linking COVID-19 and CSVD has yet to be uncovered and differentiated from age-related comorbidities (i.e., hypertension), and medical interventions during acute infection. We aimed to evaluate CSVD in acute and recovered COVID-19 patients and to differentiate COVID-19-related cerebrovascular pathology from the above-mentioned contributing factors by assessing the localization of microbleeds and ischemic lesions/infarctions in the cerebrum, cerebellum, and brainstem. A systematic search was performed in December 2022 on PubMed, Web of Science, and Embase using a pre-established search criterion related to history of, or active COVID-19 with CSVD pathology in adults. From a pool of 161 studies, 59 met eligibility criteria and were included. Microbleeds and ischemic lesions had a strong predilection for the corpus callosum and subcortical/deep white matter in COVID-19 patients, suggesting a distinct CSVD pathology. These findings have important implications for clinical practice and biomedical research as COVID-19 may independently, and through exacerbation of age-related mechanisms, contribute to increased incidence of CSVD.

A case report overlapped vaccine and COVID-19 in disseminated atherosclerosis.

Coronavirus disease 2019 (COVID-19) has become a part of our lives now and we have no more effective way of coping than a vaccine. COVID-19 is a disease that causes severe thrombosis outside the respiratory tract. Vaccines also protect us in this respect, but in some rare cases, thrombosis has been found to develop after vaccination (much less frequently than COVID-19). What was interesting in our case was that it showed how a disaster could happen under three factors that predispose to thrombosis. A 65-year-old female patient with disseminated atherosclerosis was admitted to the intensive care unit with complaints of dyspnea and dysphasia. In the evening of the day, the patient had the vaccination 2 weeks ago, she had active COVID-19. On examination, lower extremity pulses could not be detected. The patient's imaging and blood tests were performed. Multiple complications such as embolic stroke, venous and arterial thrombosis, pulmonary embolism, and pericarditis were observed in the patient. This case may give consideration to anticoagulant therapy studies. We give effective anticoagulant therapy in the presence of COVID-19 in patients at risk of thrombosis. Can anticoagulant therapy be considered after vaccination in patients at risk of thrombosis such as disseminated atherosclerosis?

Brain hypoxia, neurocognitive impairment, and quality of life in people post-COVID-19.

OBJECTIVE: Systemic hypoxia occurs in COVID-19 infection; however, it is unknown if cerebral hypoxia occurs in convalescent individuals. We have evidence from other conditions associated with central nervous system inflammation that hypoxia may occur in the brain. If so, hypoxia could reduce the quality of life and brain function. This study was undertaken to assess if brain hypoxia occurs in individuals after recovery from acute COVID-19 infection and if this hypoxia is associated with neurocognitive impairment and reduced quality of life. METHODS: Using frequency-domain near-infrared spectroscopy (fdNIRS), we measured cerebral tissue oxygen saturation (StO2) (a measure of hypoxia) in participants who had contracted COVID-19 at least 8 weeks prior to the study visit and healthy controls. We also conducted neuropsychological assessments and health-related quality of life assessments, fatigue, and depression. RESULTS: Fifty-six percent of the post-COVID-19 participants self-reported having persistent symptoms (from a list of 18), with the most reported symptom being fatigue and brain fog. There was a gradation in the decrease of oxyhemoglobin between controls, and normoxic and hypoxic post-COVID-19 groups (31.7 ± 8.3 µM, 27.8 ± 7.0 µM and 21.1 ± 7.2 µM, respectively, p = 0.028, p = 0.005, and p = 0.081). We detected that 24% of convalescent individuals' post-COVID-19 infection had reduced StO2 in the brain and that this relates to reduced neurological function and quality of life. INTERPRETATION: We believe that the hypoxia reported here will have health consequences for these individuals, and this is reflected in the correlation of hypoxia with greater symptomology. With the fdNIRS technology, combined with neuropsychological assessment, we may be able to identify individuals at risk of hypoxia-related symptomology and target individuals that are likely to respond to treatments aimed at improving cerebral oxygenation.

Outcomes of transcutaneous retrobulbar Amphotericin B (TRAMB) as an adjuvant therapy for rhino-orbital-cerebral mucormycosis (ROCM) following COVID-19.

PURPOSE: To assess the outcomes of transcutaneous retrobulbar Amphotericin B (TRAMB) for rhino-orbital-cerebral-mucormycosis (ROCM) post-COVID-19, as an adjuvant to standard systemic antifungal therapy. METHODS: In this prospective cohort study involving ROCM patients with clinical/radiological orbital involvement, 44 eyes with ROCM stage ≥ 3B received TRAMB for 7 consecutive days with liposomal Amphotericin-B (3.5 mg/ml) with a minimum clinical and radiological follow-up of 3 months. All patients received standard systemic antifungal therapy also as per institutional protocol. Data pertaining to demography, systemic status, clinical involvement, imaging, surgical/medical management were also recorded. Potential eyes for exenteration were excluded. Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 12 Given name: [Mahendra Kumar ] Last name [Garg]. Also, kindly confirm the details in the metadata are correct.All author names are presented accurately. Details in the metadata are correct. Thank you. RESULTS: Forty-four eyes of 42 patients were included, out of which 30 had diabetes mellitus & 22 had received steroid/oxygen treatment during COVID-19 infection. Forty eyes showed improvement or stable disease on follow-up on radiology. Four eyes which showed progression of the disease in orbit were reaugmented with TRAMB. No patient required exenteration. Subconjunctival haemorrhage occurred in six eyes and temporary blurring of vision in four eyes after TRAMB which resolved spontaneously. CONCLUSION: TRAMB, as an adjuvant to standard systemic antifungal therapy, is associated with a significant reduction or stabilisation of orbital involvement. TRAMB should be considered as an adjuvant therapy for ROCM to reduce disease progression as well as to preserve globe or sight. It has a promising role in preventing potential orbital exenterations.

COVID-associated rhinocerebral mucormycosis: a retrospective analysis of presentation and outcomes.

OBJECTIVES: To comprehensively analyse the disease presentation and mortality of COVID-associated rhino-orbito-cerebral mucormycosis. METHODS: A retrospective analysis of the demographics, clinical and radiographic findings was performed. A binary logistic regression analysis was performed to examine the survival of patients with mucormycosis from hypothesised predictors. RESULTS: A total of 202 patients were included in this study. Statistical significance was demonstrated in the predilection to the male gender, recent history of SARS-COV-2, history of use of corticosteroid and hyperglycemia in this cohort of CAM. The mortality rate was 18.31%. Advanced age, raised HbA1c and intra-orbital extension were found to be predictors adversely affecting survival. CONCLUSION: Early diagnosis, aggressive surgical therapy, early and appropriate medical therapy can help improve outcomes. LEVEL OF EVIDENCE: Level 4.

Relationship between cognitive dysfunction and the promoter methylation of PER1 and CRY1 in patients with cerebral small vessel disease.

Background and purpose: The prevalence of cerebral small vessel disease (CSVD) is increasing due to the accelerating global aging process, resulting in a substantial burden on all countries, as cognitive dysfunction associated with CSVD is also on the rise. Clock genes have a significant impact on cognitive decline and dementia. Furthermore, the pattern of DNA methylation in clock genes is strongly associated with cognitive impairment. Thus, the aim of this study was to explore the connection between DNA promoter methylation of PER1 and CRY1 and cognitive dysfunction in patients with CSVD. Methods: We recruited patients with CSVD admitted to the Geriatrics Department of the Lianyungang Second People's Hospital between March 2021 and June 2022. Based on their Mini-Mental State Examination score, patients were categorized into two groups: 65 cases with cognitive dysfunction and 36 cases with normal cognitive function. Clinical data, 24-h ambulatory blood pressure monitoring parameters, and CSVD total load scores were collected. Moreover, we employed methylation-specific PCR to analyze the peripheral blood promoter methylation levels of clock genes PER1 and CRY1 in all CSVD patients who were enrolled. Finally, we used binary logistic regression models to assess the association between the promoter methylation of clock genes (PER1 and CRY1) and cognitive dysfunction in patients with CSVD. Results: (1) A total of 101 individuals with CSVD were included in this study. There were no statistical differences between the two groups in baseline clinical data except MMSE and AD8 scores. (2) After B/H correction, the promoter methylation rate of PER1 was higher in the cognitive dysfunction group than that in the normal group, and the difference was statistically significant (adjusted p < 0.001). (3) There was no significant correlation between the promoter methylation rates of PER1 and CRY1 in peripheral blood and circadian rhythm of blood pressure (p > 0.05). (4) Binary logistic regression models showed that the influence of promoter methylation of PER1 and CRY1 on cognitive dysfunction were statistically significant in Model 1 (p < 0.001; p = 0.025), and it still existed after adjusting for confounding factors in Model 2. Patients with the promoter methylation of PER1 gene (OR = 16.565, 95%CI, 4.057-67.628; p < 0.001) and the promoter methylation of CRY1 gene (OR = 6.017, 95%CI, 1.290-28.069; p = 0.022) were at greater risk of cognitive dysfunction compared with those with unmethylated promoters of corresponding genes in Model 2. Conclusion: The promoter methylation rate of PER1 gene was higher in the cognitive dysfunction group among CSVD patients. And the hypermethylation of the promoters of clock genes PER1 and CRY1 may be involved in affecting cognitive dysfunction in patients with CSVD.