MALIGNANT HYPERTENSION AFTER COVD-19 VACCINE INJECTION

Case;40 y/o male. Clinical course;The patient was transferred to our university hospital because of DOE and severe headache. He had been well and had no history of hypertension or obesity. He had experienced the COVID-19 vaccine injection two week before this visit. After the injection he had been experienced high fever and general fatigue as well as 7 kg of weight loss. On examnation, it was found that he had severe hypertension (190/110 mmHg) and hypertensive optic fundi. On chest X-ray, cardiomegaly and bilateral lung infiltrations was evident and biochemical data indicated renal dysfunction (serum creatinine 2.35 mg/dl), high levels of plasma renin activity (39.1 ng/ml/hour normal;0.6-3.9) and aldosterone concentration (176 pg/ml normal;4.0-82.1), and inflammatory changes (CRP = 23 mg/dl). We also found that increased levels of LDH and decreased levels of hemoglobin which indicated hemolytic anemia and thrombotic microangiopathy. After the control of high blood pressure by intravenous administration of Calcium channel blockades, We performed renal biopsy, which had a finding of diffuse findings of onion skin lesion and global glomerular sclerosis compatible with the diagnosis of malignant hypertension. Any secondary etiologies including renal artery disease or collagen disease had not been identified. Seven days after the admission, we started hemodialysis for this patient because of the renal failure was not resolved. We also had startred ACE inhibitors. We stopped the diuretics and minimized the ultrafiltration. Twenty-five days after the admission the patients was withdrawn from dialysis with the urine volume around 2000 ml/day and the serum creatinine concentration 5.29 mg/dl. He was discharged without any aid of dialysis and with small number of anti-hypertensives. Four months after the discharge, his serum creatinine concentration was 3.36 mg/dl and his blood pressure was 139/85 mmHg with the ACE inhibitor and calcium channel blockades. Conclusions;The case suggested that the malignant hypertension might be triggered by COVID-19 vaccine injection, which is of clinical importance.

An Overview About Pediatric Type 1 Diabetes Mellitus

Background: Diabetes mellitus (DM) represents one of the most common metabolic diseases in the world, with rising prevalence in recent decades. Most cases are generally classified into two major pathophysiological categories: type 1 diabetes mellitus (DM1), which progresses with absolute insulin deficiency and can be identified by genetic and pancreatic islet autoimmunity markers, and type 2 diabetes mellitus (DM2), which is the most prevalent form and involves a combination of resistance to the action of insulin with an insufficient compensatory response of insulin secretion. In the last two decades, in parallel with the increase in childhood obesity, there has also been an increase in the incidence of DM2 in young people in some populations. Other forms of diabetes may affect children and adolescents, such as monogenic diabetes (neonatal diabetes, MODY – maturity onset diabetes of the young, mitochondrial diabetes, and lipoatrophic diabetes), diabetes secondary to other pancreatic diseases, endocrinopathies, infections and cytotoxic drugs, and diabetes related to certain genetic syndromes, which may involve different treatments and prognoses. DM1 is considered an immuno-mediated disease that develops as a result of gradual destruction of insulin-producing pancreatic beta cells that eventually results in their total loss and complete dependence on exogenous insulin. Clinical presentation can occur at any age, but most patients will be diagnosed before the age of 30 years

Characteristics of post-covid syndrome in elderly patients with rheumatic diseases

Purpose: To compare the frequency of occurrence of various symptoms of post-covid syndrome (PCS) in groups of patients with rheumatic diseases (RD) of the elderly to young. Material(s) and Method(s): The study involved 89 patients with RD who underwent COVID-19, verified by RT-PCR for SARS-CoV- 2 RNA, for the period from 05/15/2020 to 12/01/2021. Participants in the study, after talking with the research physician, completed questionnaires on past COVID-19 and post-COVID syndrome (PCS). The information was supplemented with data from discharge records after inpatient treatment for COVID-19. Result(s): The data obtained were differentiated depending on the age of the participants: <60 years (group 1), N = 69 and >=60 years (group 2), N = 20. Both groups were dominated by women (82.6% and 85%). The average age in group 1 was 41.9 +/- 11.6 years, in group 2 -68.5 +/- 5.1 years. 33 (47.8%) patients in group 1 and 10 (50%) in group 2 noted the development of PCS. In group 1, the following symptoms of PCS prevailed: memory impairment -in 17 (51.5%) patients, fatigue, weakness -in 14 (42.4%), problems with concentration -in 14 (42.4%), arthralgia -in 12 (36.4%) %, shortness of breath during physical exertion -in 11 (33.3%), drowsiness -in 10 (30.3%), irritability -in 9 (27.3%). In group 2, the most common memory impairment -in 8 (80%) patients, weakness, fatigue -in 7 (70%), arthralgia -in 7 (70%), problems with concentration -in 6 (60%), weight loss -in 5 (50%), irritability -in 5 (50%), sleep disturbance -in 5 (50%). The frequency of occurrence of different manifestations of PCS did not differ significantly between the groups. On average (median), each patient in group 1 noted 4 [2;8], group 2 -10 [8.25;12.5] symptoms of PCS at the same time, but the differences did not reach statistical significance. Conclusion(s): The frequency of occurrence of various clinical manifestations of PCS did not have statistically significant differences between the study groups. In a comparative assessment, the group of elderly patients noted a greater number of symptoms of PCS at the same time.

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).

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).

Tsukamurella and mycobacterium tuberculosis pneumonia co-infection

Case Report: Tsukamurella species are aerobic, partially acid fast saprophytes commonly isolated from soil and water. They are opportunistic pathogens known to infect multiple organs and can contribute to significant pathologies such as bacteremia, peritonitis, and respiratory tract infections. Moreover, Tsukamurella shares certain characteristic properties to Mycobacterium tuberculosis and Actinomyces species, including the acid fast stain, which can contribute to misdiagnosis of patients. A 68 year old female patient presented to the ED for shortness of breath, fatigue, and weight loss for 6 months. The patient's past medical history includes pulmonary fibrosis, type 2 diabetes, coronary artery disease with stent, hyperlipidemia, hypertension, and M. tuberculosis infection when she was 3 years old in Finland. On admission, labs revealed thrombocytosis (reactive 555 000/microL), leukocytosis (14 450/microL), and microcytic anemia (9.4 microg/dl). Moreover, C reactive protein was elevated and procalcitonin was normal (0.06 microg/l);a COVID-19 PCR was negative. An X-ray revealed severe patchy and interstitial infiltrates throughout both lungs with parenchymal scarring and pleural thickening in the periphery of the left mid-lung zone with multifocal pneumonia. Blood and sputum cultures were performed under the impression of pneumonia, and treatment with azithromycin and ceftriaxone was started. A M. tuberculosis infection was suspected due to a positive AFS. Further chest CT suggested multifocal pneumonia within the left lung in addition to apparent cavitary lesions versus bulla, a chronic interstitial lung disease with traction bronchiectasis, calcified right lower lung nodule, and calcified hilar lymph nodes suggesting a history of granulomatosis diseases. A bronchoscopy with Bronchoalveolar lavage was performed. The initial sputum specimen direct smear showed acid-fast stain positive with Actinomyces growth, and Penicillin G was added to the treatment. Samples were sent to the state department lab, and biopsy revealed granulomatous inflammation negative for malignant cells. One month later, the patient's sputum culture showed Tsukamurella for High-performance liquid chromatography (HPLC). Moreover, a rifampicin sensible M. tuberculosis complex by NAA was also positive six weeks later. The patient was started on a complete TB regimen and continued in the outpatient pulmonology clinic with the addition of levofloxacin for three months and rifampicin substituted for rifabutin. As demonstrated in the case above, a Tsukamurella infection can present similarly to a Mycobacterium infection. Patients may be misdiagnosed or potentially be co-infected. Our patient was further tested and appropriately treated for Tsukamurella after further extensive diagnostic screenings. Due to a high rate of missed cases, it is important to keep Tsukamurella infection on the differential diagnosis as the patient presentation may initially appear to be a Mycobacterium or other pulmonary infection. Copyright © 2023 Southern Society for Clinical Investigation.

Systemic lupus erythematosus in a 36-year old Filipino male after SARS-COV- 2 vaccination

Background: Systemic lupus erythematosus (SLE), a multisystem autoimmune disease more common in females, is associated with autoantibodies against different autoantigens forming immune complexes. Inadequate removal of these complexes from the host triggers inflammatory response which causes tissue damage. Some antiviral vaccines have been associated with the onset of SLE. Few cases of SLE occurring after SARS-CoV- 2 vaccines have been reported. Herein, we describe a case of new-onset SLE associated with COVID-19 vaccine. Case Summary: A previously well 36-year- old male with unremarkable family history of autoimmune disease started to develop muscle and joint pains, hair thinning, and ecchymoses 2 months after receiving second dose of inactivated SARS-CoV- 2 vaccine. He was subsequently admitted after consultation due to thrombocytopenia (platelet count of 58). He was given high dose steroid with tapering dose during the entire 14 days admission with significant increase of platelet count after 72 hours of repeat complete blood count. He went consult at rheumatology clinic a month after due to persistent joint and muscle pains, and progression of hair fall with associated facial rash, oral ulcers, easy fatigability and weight loss. Physical exam disclosed an ambulatory well-built male with normal vital signs, alopecia, malar rash, oral ulcers, joint tenderness and no objective muscle weakness. Complete blood counts and Anti-smith were within normal. Urinalysis, Antinuclear antibody (ANA), Anti-SSA, Anti-SSB, complement factor 3 (C3), and Anti-dsDNA were positive. He was managed with tapering prednisone and hydroxychloroquine with significant improvement at time of this report. Conclusion(s): Development of autoimmune reaction following COVID-19 vaccine has been described extensively;however, evidence of autoimmunity following vaccination seems to be lacking at present. Pathomechanisms include defective elimination and/or control of self-reactive lymphocytes resulting in over-stimulation of the immune system leading to clinical manifestations strikingly similar to the infection itself. Management approach to these autoimmune reactions address the immune hyper-stimulation with immunosuppressive or immuno-modulating agents including steroids and hydroxychloroquine.

Kikuchi-Fujimoto disease following COVID-19 infection in a 13-year- old girl

Background/Purpose: Kikuchi-Fujimoto disease (KFD) is a rare, self-limited histiocytic necrotizing lymphadenitis. Although it is of uncertain aetiology, it is associated with viral infections and autoimmune diseases. Hence, it is crucial to identify KFD from other conditions with lymphadenopathy. Here we present a case of KFD after COVID-19 infection. Method(s): Medical records were traced and reviewed Results: A previously healthy 13-year- old girl was admitted in April 2022 with four weeks of fever, dry cough, loss of weight, followed by 1 week history of painful cervical lymphadenopathy and nonspecific maculopapular rash. She received her second dose of Covid 19 vaccine in January 2022. Unfortunately, she was diagnosed with CAT II, COVID 19 infection in March 2022. There was no history of allergy, recent traveling and cat scratch injury. Clinically there was no strawberry tongue, erythema of the lips, conjunctivitis or distal extremities changes to suggest Kawasaki disease. She was initially diagnosed with infection related lymphadenitis, treated with oral azithromycin for three days and intravenous ceftriazone for one week with no improvement. Her laboratory results showed hypochromic microcystic anaemia with leucopenia, raised inflammatory markers and lactate-dehydrogenese levels. Extensive workup for infection was unremarkable. Immunology test showed ANA, ANCA, ENA were negative with normal complements. Ultrasound abdomen was normal. Excisional lymph node biopsy revealed confluent areas of necrosis surrounded by histiocytes (CD68+) with absent of neutrophils. No granuloma or atypical lymphoid cells seen. Based on histopathology report, diagnosis of KFD was established. As she was not able tolerate orally, IV hydrocortisone was started and subsequently switched to oral prednisolone. She responded well to corticosteroids with fever subsided within a day and cervical lymphadenopathy reducing in size and resolved in one month. Prednisolone was able to taper off by two months. She showed complete recovery with no recurrence during follow-up. Conclusion(s): In persistent febrile painful lymphadenopathy, excision lymph node biopsy is essential to establish definite diagnosis. This case highlights the possible association between COVID-19 and KFD.

New Onset Type 1 Diabetes Mellitus in the Setting of COVID-19 Infection in a 5-Month- Old Infant

Objectives To report a case of new onset Type 1 Diabetes Mellitus (T1DM) and Diabetic Ketoacidosis (DKA) in a 5-month-old female who was positive for SARS-CoV-2 (COVID-19) infection, which may be a novel precipitant for autoimmunity at a very young age. Methods Case Report Results A 5-month-old term Caucasian female with no significant past medical history presented to the emergency department with Kussmaul respirations and altered mental status. She had one day of presumed viral respiratory symptoms and decreased oral intake. She also had a 5% weight loss (0.31 kg) and polyphagia for one month. Her presenting bloodwork included a blood glucose of >600 mg/dL, pH 6.901, bicarbonate 3.8 (22-28 mmol/L), potassium 5.5 (3.3-5.1 mmol/L), white blood cell count 47.9 (6-17.5 x10

Central diabetes insipidus following immunization with anti-COVID19 BNT162b2 Comirnaty vaccine

Introduction: The coronavirus disease 19 (COVID19) pandemic urged to develop new vaccines to reduce the morbidity and mortality associated with this disease. Recognition and report of potential adverse effects of these novel vaccines (especially the urgent and life-threatening ones) is therefore essential. Case Presentation: A 16-year-old boy presented to the Paediatric Emergency Department with polyuria (9 liters per day), polydipsia and concomitant weight loss (- 6 Kg) over the last four months. His past medical history was unremarkable. Onset of symptoms was referred to be few days after second dose of anti- COVID19 BNT162b2 Comirnaty vaccine. The patient was admitted to the Paediatric Department. The physical exam was normal, without neurological abnormalities. Auxological parameters were within normal limits (height -0.12 SDS, weight +0.35 SDS). Daily fluid balance monitoring confirmed polyuria and polydipsia (IN 6,250 L / OUT 7,100 L). Biochemistry laboratory analysis and urine culture were normal (Sodium levels 141 mEq/L). Serum osmolality was 297 mOsm/Kg H2O (normal values 285-305), whereas urine osmolality was 80 mOsm/Kg H2O (normal values 100-1100), suggesting diabetes insipidus. Hormonal tests showed no significant impairment of anterior pituitary function. Test with Desmopressin was performed and confirmed the diagnosis of central diabetes insipidus. Brain MRI revealed pituitary stalk enlargement (4 mm) with contrast enhancement, and loss of posterior pituitary bright spot on T1 weighted imaging. Even in absence of pituitary enlargement, those signs were consistent with neuroinfundibulohypophysitis. Immunoglobulin levels were normal. Low doses of oral Desmopressin were sufficient to control patient's symptoms, normalizing serum and urinary osmolality values and daily fluid balance at discharge. Brain MRI after 2 months showed stable thicken pituitary stalk and detectable small posterior pituitary. Due to persistence of polyuria and polydipsia, therapy with Desmopressin was adjusted by increasing dosage and number of daily administrations. Clinical and neuroradiological follow-up is still ongoing. Conclusion(s): Hypophysitis is a rare disorder characterized by lymphocytic, granulomatous, plasmacytic, or xanthomatous infiltration of the pituitary gland and stalk. Common manifestations are headache, hypopituitarism, and diabetes insipidus. To date, only time correlation between SARS-CoV-2 infection and development of hypophysitis and subsequent hypopituitarism has been reported. Further studies will be needed to deepen a possible causal link between anti-COVID19 vaccine and diabetes insipidus.

Impact of Covid-19 pandemic on the efficacy of outpatient counseling in childhood obesity management

Introduction: The Covid-19 pandemic drastically modified social life and lifestyle in particular among children and adolescents, promoting sedentary behaviors and unhealthy eating habits. In this scenario, the effectiveness of the outpatient approach for pediatric obesity may decrease. Objective(s): Aims of this study were to assess the rate and the factors associated with outpatient drop-out by comparing two groups of children and adolescents with obesity evaluated at the pediatric endocrinology outpatient clinic before and during the Covid-19 pandemic, respectively, and to evaluate how Covid-19 pandemic influenced the weight status and lifestyle of children and adolescents with obesity. Result(s): One hundred and forty-five children and adolescents with obesity were evaluated, including 80 subjects (mean age 11.6 +/- 2.3 years) evaluated before the Covid-19 pandemic (group A) and 65 subjects (mean age 11.8 +/- 2.7 years) in the period straddling the Covid-19 pandemic (group B). Anamnestic (dietary habits, physical activity, screen time, family history of obesity), socio-cultural (economic status, employment and schooling of parents, household composition, place of living) and clinical (weight, height, BMI, waist circumference) data were analyzed at baseline (T0) and at 12-months (T1) in-person assessment. Glico-lipids biochemical profile was assessed at T0. The drop-out rate did not differ significantly between the two groups. BMI SDS at T0 (OR=2.52;p=0.004), female sex (OR=0.41;p=0.035) and incomplete household (OR=5.74;p=0.033) significantly influenced drop-out in both groups. BMI SDS, not significantly different between the two groups at T0, was significantly higher in group B than group A at T1. Consistently, weight loss between T0 and T1 was significantly greater among group A patients compared to group B (p=0.031). Hours spent in physical activity decreased significantly in group B from T0 to T1 and were significantly lower than group A at T1. Screen time increased significantly in group B from T0 to T1 and were significantly greater than group A subjects at T1. The consumption of sugary drinks and snacks was significantly greater in group B than group A at T1. Hours spent in physical activity (OR=2.27, p=0.038) and group A belonging (OR=0.16, p=0.028) significant influence weight loss. Conclusion(s): Our study documented that the Covid-19 pandemic, although it has not affected the drop-out rate of obese children, negatively influenced lifestyle and reduced the effectiveness of outpatient counseling in childhood obesity treatment.

CASPR-2 Antibody Associated Autoimmunity in the Setting of COVID-19 (Infection, Vaccination, or Both?) and Chronic Lymphocytic Leukemia: Case Report and Review of the Literature

Objective To report a case of Anti-Contactin-Associated Protein-like2 (CASPR-2) autoimmunity in a patient with low-grade Chronic Lymphocytic Leukemia (CLL) following COVID-19 vaccination and infection. Background Anti-CASPR2 antibody disorder has been associated with neoplastic disorders like thymoma. Recent reports enlist COVID-19 as apotential trigger of CASPR2 autoimmunity. While the clinical presentations are similar, management differs based on the underlying etiology. Design/Methods We review a case of anti-CASPR2-antibody associated disorder with concurrent low grade CLL and recent history of COVID-19 vaccination and infection. Additionally, we review the literature and discuss the therapeutic challenges. Results A 73-years old male presented with five months of progressive fatigue, weight loss, diffuse sweating, muscle cramps, and neuropathic pain. He eventually developed bilateral upper and lower facial weakness. Patient contracted a mild COVID-19 infection two months prior and COVID- 19 vaccination one month prior to his symptom onset. His exam was remarkable for bilateral facial weakness, diffuse fasciculations and sensory neuropathy on his trunk and extremities. His diagnostic work up including bone marrow biopsy was consistent with a chronic lymphocytic leukemia (CLL)-like immunophenotype. Cerebrospinal fluid (CSF) analysis was remarkable for five WBC (lymph-dominant) and protein of 74 mg/dl. Serum paraneoplastic panel revealed positive CASPR2 antibody with a titer of 1:100. Magnetic Resonance Imaging (MRI) of the brain showed enhancement of bilateral cranial nerve VII. After lack of clinical response to IV methylprednisone (1 gram for 5 days), patient was treated with a single cycle of IV immunoglobulin (IVIG). He had complete recovery of his symptoms except for residual facial weakness. He remains stable at his six months post-treatment follow-up. Conclusions Anti-CASPR2 associated autoimmunity following COVID-19 infection or in the setting of CLL has previously been reported. However, cranial neuropathy in association with CASPR2 antibody has never been. A trial of IVIG could be beneficial in patients with viral-spike protein-induced autoimmunity and CLL who do not otherwise meet the criteria for CLL treatment.

A Single-Centre Experience of Telephone Assessment of Patients Referred to Two Week-Wait Colorectal Surgery Clinics in England

Aim: Despite Covid-19, hospitalsin the England, United Kingdom continued to assess and manage patients referred on two week-wait (2WW) suspected cancer referral pathways. Most index clinic assessments of such patients were conducted viatelephone. We retrospectively evaluated adistrict general hospital experience of managing patients on a 2WW suspected lower gastrointestinal tract (LGIT)cancer referral pathway, initially assessed via telephone Method: Data were obtained using a prospectively maintained database and electronic patient records. LGIT 2WW referrals between 01/06/2020to 31/10/2020 were included. Data were retrospectively collated and analysed using Excel (Microsoft Corporation, USA) Results: A total 757 patients (median age = 70, interquartile range = [59-79], female = 47.2%) were identified. The majority (n = 629,83.1%) were white Caucasian. All patients were initially assessed virtually and only 3 (0.4%) were re-assessed face-to- face for their index appointment. Sixteen (2.1%) missed at least one prior appointment. The most common presenting complaints included change in bowel habit, rectal bleeding, weight loss, anaemia and abdominal pain, and 415 (54.8%), 269 (35.5%) underwent endoscopy and imaging respectively as the first investigation. Forty four (5.8%) patients had malignant pathology with the majority (n = 37,84.1%) being colorectal in origin. Of those diagnosed with a primary colorectal malignancy 25 (67.6%) underwent surgical or endoscopic treatment, 3 (8.1%) were referred to chemoradiotherapy and 8 (21.6%) were referred for palliation. Conclusion(s): Patients referred on the 2WW LGIT pathway continued to be assessed and managed despite Covid-19. Index telephone clinic assessments are perhaps as effective a tool as face-to- face assessments, for patients referred on this pathway. This warrants further investigation.

Early Clinical Interventions Dictate Favorable Outcomes: A Case of Lemierre Syndrome

INTRODUCTION: Lemierre's syndrome (LS) is characterized by fever, sore throat, neck swelling and tenderness, and septic thrombophlebitis of the jugular vein. It remains a fatal disease as serious complications commonly arise. DESCRIPTION: 20-year-old male patient with not known past medical history endorsed 1 week of sore throat, emesis, loose stools, weight loss as well as dyspnea associated with bilateral, non-pleuritic chest pain, night sweats, myalgias and subjective fever sensation. Patient was initially hypoxic, hypotensive, tachycardic, tachypneic and febrile, with scleral icterus, lymphadenopathy of neck and jaw bilaterally, enlarged tonsils, and diffuse abdominal tenderness. Laboratory results showed leukocytosis with neutrophile predominance, anemia, thrombocytopenia, elevated inflammatory markers. There was also pre-renal acute kidney injury, elevated alkaline phosphatase and hyperbilirubinemia. SARS-CoV-2 tests were negative. Initial computerized tomography (CT) of the chest showed extensive peripheral ground-glass nodules and rounded consolidations, with lower lobe predominance. Admission to medical ICU was warranted. Initial blood cultures showed no identification of speciation;Ceftriaxone was started with satisfactory response. However, patient developed worsening shortness of breath, orthopnea, rightsided neck pain and erythema. Repeat imaging showed new airspace opacities in both lungs with cavitation consistent with septic emboli, and thrombophlebitis of right jugular vein with no abscess. At that point, blood cultures grew Fusobacterium necrophorum and metronidazole was started. A four-week course was completed upon discharge with satisfactory response. DISCUSSION: Lemierre's syndrome remains as a rare but potentially fatal entity. Internal jugular vein (IJV) thrombophlebitis occurs through infection of the lateral pharyngeal space. Pulmonary metastases are common. Metronidazole comprises the foundation of the treatment given its tissue penetration and activity against all strains of Fusobacterium spp. Data regarding anticoagulation efficacy is limited. Clinicians should maintain high clinical suspicion, and a multidisciplinary approach with broad collaboration among specialties is imperative to aid early diagnosis and better clinical outcomes.

The Impact of COVID-19 on nursing home residents? clinical, functional, and psychosocial outcomes

Background. Data on COVID-19 related nursing home infections and mortality accumulated at a rapid pace;yet little is known about the impact of nursing homes' response to COVID-19 on resident clinical, functional, and psychosocial outcomes. Methods. We examined aggregated Minimum Data Set (MDS) assessments to describe resident outcomes using an interrupted times series methodology for three timeframes: pre-COVID (1/2019 to 2/2020), pandemic (3/2020-12/2021), and vaccination (1/2021-6/2021). Data included 307,558 federally mandated resident MDS assessments from 60,846 resident in 489 nursing homes in a Mid-Western state. We calculated MDS based quality measures (QM) using definitions available from Centers for Medicare and Medicaid Services. Each QM-based outcome was fit to a logistic regression model using the method of generalized estimating equations. Results. None of the QMs displayed a statistically significant trend pre-COVID. The prevalence of excessive weight loss and ADL decline increased sharply during the pandemic and reversed that trend with vaccination. Pressure ulcers among high-risk residents followed a similar trend, although pandemic and vaccination-related regression parameters for thatQMwere only marginally significant (p = .08). Pain worsened during the pandemic and vaccination period approaching significance (p=.07). Antipsychotic medication use worsened in the pandemic (p< .001) and did not improve in the vaccination period. Other QMs including any fall, fall with major injury, and incontinence did not exhibit statistically significant change in trend. Prevalence Profiles Circles: Observed proportions, Dashed Line: Model expected value, Solid Lines: 95% confidence limits for expected values Conclusion. We noted significant changes in QMs for antipsychotic use, ADL loss, andweight loss, with the latter two improving in the vaccination period. Isolation, disease outbreaks, and staffing issues in facilities could have affected theseQMs. Data variability may have limited our ability to detect other changes. Antipsychotics may have increased with the need to reduce wandering and other behaviors common in the nursing home population;behaviors high risk for spreading COVID-19. Why antipsychotic use did not improve during the vaccination period is less clear. Data beyond June of 2021 may help clarify the pattern of antipsychotic use. (Figure Presented).

Prophylactic and Therapeutic Activity of AZD7442 (Tixagevimab/ Cilgavimab) in SARS-CoV-2 Hamster Challenge Models

Background. AZD7442-a combination of 2 human, extended-half-life, SARS-CoV-2-neutralizing monoclonal antibodies (mAbs) (tixagevimab/cilgavimab)-has received US Food and Drug Administration emergency use authorization for COVID-19 prevention in immunocompromised individuals. We evaluated the effect of AZD7442 in prevention and treatment settings in Syrian hamsters challenged with SARS-CoV-2. Methods. Hamsters received intraperitoneal isotype control mAb (2 mg) or AZD7442 (0.002-2 mg) 1 day before intranasal (IN) SARS-CoV-2 challenge (USA-WA1/2020;1x105 plaque-forming units) in prevention;OR control mAb (5 mg) or AZD7442 (0.5-5 mg) 1 day after IN SARS-CoV-2 challenge in treatment. The impact of AZD7442 on lung viral RNA and pathology and AZD7442 serum levels was assessed on Days 3 and 7 post infection. Body weight was recorded daily through Day 7. Results. With AZD7442 prevention, lower lung viral loads were observed compared to controls;at Day 3 post infection, lowest infectious virus titer and viral subgenomic mRNA (sgmRNA) levels were seen with doses >=0.2 mg AZD7442. Concomitantly, increased serum levels of AZD7442 were observed. By Day 7, infectious virus titer and sgmRNA fell below the level of detection (LOD) at all doses tested. Moreover, AZD7442 at doses >=0.2 mg protected hamsters from weight loss versus controls. Lung pathology scores (scale: 0 [normal] to 25 [most severe]) were generally dose dependent, with mean scores of < 2 for AZD7442 versus 10 for controls, indicating less SARS-CoV-2-induced inflammation and alveolar damage in hamsters given AZD7442. Lower AZD7442 doses were associated with mean pathology scores similar to controls. With AZD7442 treatment, infectious virus titers were below the LOD at Day 3 post infection and at Day 7 for sgmRNA, for all doses tested. Mean lung pathology score was <2 for AZD7442 versus 12 for controls. AZD7442 doses >=0.5 mg protected against weight loss relative to controls. Conclusion. In a SARS-CoV-2 challenge model, AZD7442 administered as prevention or treatment led to significantly lower lung viral loads and improved lung pathology, without weight loss. There was also no evidence that AZD7442 mediated antibody-dependent enhancement of disease or infection.

Efficacy of a Polyclonal Ovine Fab (PR020) Against SARS-CoV-2 Infection

Background. Passive immune therapies may be useful in mitigating severe COVID-19. The hamster model has been successfully used to study efficacy of COVID-19 treatments. Our objective with this research is to demonstrate initial efficacy of a new polyclonal ovine Fab raised against the SARS-CoV-2 spike protein (PR020) as a treatment for COVID-19. Methods. Hamsters were treated with PR020 via intraperitoneal route at a dose of 120 mg/kg or a vehicle control once every 24 hours for 8 days, starting 1 day prior to viral challenge with Victoria/1/2020 SARS-CoV-2. Sampling to detect viral RNA and clinical observations were taken throughout the challenge phase. Necropsy occurred 1 day following the last dose of PR020, and tissues were assessed for histopathology and viral RNA. Results. Hamsters receiving vehicle alone lost weight more rapidly than the PR020 group (Figure 1, p< 0.05 day 4 onward). Clinical illness scores for the PR020 group were lower compared to control animals (Figure 2, p< 0.05 day 3 onward). While viral shedding assessed by throat swab did not differ between groups, viral RNA levels in lung tissue was significantly lower in PR020-treated animals (Figure 3, p< 0.05). PR020-treated animals also showed significantly less pathological changes in the lung compared to controls (Figure 4, p=0.0022). (Figure Presented) Conclusion. Treatment with PR020 resulted in a positive clinical outcome (e.g. less weight loss and lower clinical signs). While treatment appeared to have little effect in the nasopharynx, there was a positive effect in the lower respiratory tract, with substantially less viral RNA in the lungs of the group given PR020 and a decrease in the lung histopathology, including consolidation.

An unusual recurrent case of Cryptococcal sacroilitis in an immunocompetent elderly female in Rajasthan, India

Background: Cryptococcus lives in the environment all over the globe. Although it spreads via inhalation route still most of the exposed individuals never get sick as the majority of cases are seen in immunocompromised. Objective of this clinical case report is to highlight the rare fungal etiology associated with iliac bone abscess to avoid incorrect diagnosis and prompt management of case. Case Presentation: A 70-year-old elderly female presented with hip pain for a month duration, not relieved with analgesics in September, 2021. In MRI a well-defined irregularly marginated hyperintense focal lesion was found in left iliac bone with joint effusion suggestive of infective etiology, tubercular, or less likely metastasis. CT-guided biopsy reported occasional hyphae-like fragments giving an impression of acute on chronic osteomyelitis with suspicion of fungalinfection.Culture reported Cryptococcus ne oformans.Fungal markers and Beta-dglucan were indeterminate and Galactomannan was found negative for the sample. Extrapulmonary TB was ruled out by AFB staining, MGIT Culture, and GeneXpert MTB. Bone scan, tumor markers, and PET scan ruled out osteolytic lesion secondary to metastasis. Though PET Scan and HRCT thorax confirm pulmonary involvement giving a picture of bilateral interstitial lung disease along with multiple enlarged lymph nodes. Patient serum was found negative for HIV, HBV, and HCV. Liver and renal function tests were within normal range and in hematology, ESR was raised (50;normal range:0-20). Patient is hypertensive with HbA1c of 5.3. There was no history of travel, avian exposure, weight loss, and COVID-19 infection. Patient was started on voriconazole and considering generalized lymphadenopathy, a therapeutic trial of anti-tubercular therapy was started which was stopped within a week on patient non-compliance. Abscess resolved with voriconazole and patient was discharged. In February 2022, Patient presented with similar complaints. CT scan of this fluctuant nodule depicted hypoechoic lesion which was ultrasound-guided drained.Sections show many rounds of oval fungal organism which were found PASpositive with mucicarmine and alcian blue positive capsule.Budding yeast cells were seen on KOH mount and India ink preparation demon-strated capsule which was confirmed by Cryptococcal Antigen test giving an overall impression in favor of Cryptococcosis. Patient was started on oral fluconazole and Injection liposomal amphotericin B 250 mg for 14 days. Discussion and Conclusion(s): This is the first case of skeletal Cryptococcosis at our institution which was managed by antifungals without surgical debridement resulting in resolution of abscess. Isolated focal iliac bone cryptococcosis is unusual but may occur in immunocompetent with everyday exposure to the organism. Herein, Patient had bilateral lung involvement along with multiple lymphadenopathies with no evidence of TB bacilli which inferences that the isolate most likely originated from environmental bird droppings and has disseminated from pulmonary lesion to the iliac bone. The radiological findings of iliac cryptococcosis abscess were nonspecific.A definitive diagnosis was made on histopathological and fungal examinations of ultrasound-guided drained abscess. Patient will be followed in the near future for relapse or any other medical issues related to the case.