ID: 219407 The Cardiac Patient and Neuromodulation, When Anticoagulation Dictates the Intervention

Introduction: Patients with cardiac comorbidities present unique challenges for undergoing interventional pain procedures. Consensus guidelines on safe anticoagulation management are categorized by procedure, patient specific bleeding risk factors, and class of anticoagulation (Table 1, Table 2).1 Specifically, some procedures occur in close proximity to the spinal cord, require large gauge needles and styletted leads, while others are in compressible locations with minimal tissue disruption. Further, pain-induced hypercoagulation increases the risk of thrombo-vascular events.1 This accentuates the importance of interdisciplinary perioperative coordination with the prescribing cardiologist. Case: A 71-year-old male with past-medical-history of CABG, bilateral femoral-popliteal bypass, atrial fibrillation on apixaban and ticagrelor, and multiple cardiac stents presented with intermittent shooting axial back pain radiating to right buttock, lateral thigh, and calf, worsened with activity. MRI demonstrated thoracic myelomalacia, multi-level lumbar disc herniation, and moderate central canal stenosis. An initial multi-model treatment approach utilizing pharmacologic agents, physical therapy, ESI's, and RFA failed to alleviate symptoms. After extensive discussion with his cardiologist, he was scheduled for a three-day SCS trial. Ticagrelor and apixaban were held throughout the 3-day trial and for 5 and 3 days prior, respectively, while ASA was maintained. Successful trial with tip placement at T6 significantly improved function and pain scores (Figure 1). Upon planned percutaneous implant, the cardiologist recommended against surgical implantation and holding anticoagulation. Alternatively, the patient underwent bilateral lumbar medial branch PNS implant with sustained improvement in lower back symptoms. However, he contracted COVID, resulting in delayed lead explanation (>60 days) without complication. Conclusion(s): Interventional pain practice advisories are well established for anticoagulation use in the perioperative period.1,2 However, there is limited high-quality research on the appropriate length to hold anticoagulation prior to surgery for high thrombotic risk patients. Collegial decision making with the cardiologist was required to avoid deleterious procedural complications. However, they may be unfamiliar with the nuances between interventions or between trial and implant. Prospective studies have shown that low risk procedures, such as the PNS, may not require holding anticoagulants.3 Other case data has demonstrated post-SCS epidural hematoma with ASA use after being held for 1-week prior to surgery. Our patient was unable to undergo SCS implant and instead elected for a lower risk procedure with excellent efficacy. 4 However, delayed PNS lead extraction due to COVID19 hospitalization presented further risk of infection and lead fracture.5 PNS may prove to be an appropriate treatment option for patients who are anticoagulated and are not SCS candidates. Disclosure: Elliot Klein, MD,MPH: None, Clarence Kong, MD: None, Shawn Sidharthan, MD: None, Peter Lascarides, DO: None, Yili Huang, DO: NoneCopyright © 2023

Characterizing the Blood Pressure Response to Physical Counterpressure Manoeuvres Using Surface Electromyography in Adults With Long Covid

Orthostatic intolerance (OI) is common in Long Covid. Physical counterpressure manoeuvres (PCM) may improve OI in other disorders. We characterised the blood pressure-rising effect of PCM using surface electromyography (sEMG) and investigated its association with fatigue in adults with Long Covid. Participants performed an active stand with beat-to-beat hemodynamic monitoring and sEMG of both thighs, including PCM at 3-minutes post-stand. Multivariable linear regression investigated the association between change in systolic blood pressure (SBP) and change in normalised root mean square (RMS) of sEMG amplitude, controlling for confounders including the Chalder Fatigue Scale (CFQ). In 90 participants (mean age 46), mean SBP rise with PCM was 13.7 (SD 9.0) mmHg. In regression, SBP change was significantly, directly associated with change in RMS sEMG ( 0.25 , 95% CI 0.07-0.43, P = 0.007);however, CFQ was not significant. PCM measured by sEMG augmented SBP without the influence of fatigue. Copyright © 2013 IEEE.

Covid-19 Vaccine-Induced Myositis

Background/Aims Through the COVID pandemic there have emerged reports of autoimmunity or new rheumatic diseases presenting in patients after they had COVID-19. This is thought to be caused by cross-reactivity of the COVID-19 spike protein to human antigens. Given the use of mRNA COVID-19 vaccinations which express the spike protein we might expect to see presentation of new rheumatic diseases following their use. We discuss a case where this appears to have occurred. Methods Our patient is a 24-year-old male with mixed phenotype acute leukaemia who had been treated with allogenic stem cell transplant and was currently in remission. He presented with fevers, palpitations, myalgia and bilateral arm and leg swelling. Symptoms began the day after receiving the first dose of an mRNA COVID-19 vaccination (Pfizer/BioNTech.) There were no other symptoms or recent change in medications. Physical examination revealed tender oedema in his forearms, biceps and thighs bilaterally with sparring of the hands. He had reduced power with shoulder (MRC 3/5), elbow (4), wrist (4+) and hip (4) movements. Observations revealed tachycardia and fevers up to 40C. Results Laboratory studies showed markedly elevated C-reactive protein (202), creatinine kinase (6697) and troponin (593) whilst investigations for infection were negative. An autoimmune panel was positive for anti- PM-SCL-75-Ab. An electrocardiogram showed sinus tachycardia. Echocardiogram was normal. Bilateral upper limb dopplers revealed no deep vein thrombus. An MRI of his thighs showed diffuse symmetrical oedema within the muscles, in keeping with an inflammatory myositis. A quadricep muscle biopsy showed evidence of MHC class 1 up-regulation, suggesting an inflammatory process. In addition, there were numerous macrophages evident in the endomysium. While this can be seen in graft-versus-host disease (GVHD), they would usually be found in the perimysium. After discussion between haematology, rheumatology and neurology, this was felt to be a case of vaccine induced myositis and myocarditis. Autoimmune myositis was thought to be less likely due to the relative sparing of the hands and the absence of Raynaud's phenomenon. 1 gram of intravenous methylprednisolone was then given for 3 days. The patient had a marked response with defervescence, improving laboratory markers, improved myalgia and decreased limb swelling. The patient was stepped down to a reducing regime of prednisolone and discharged. Due to relapse whilst weaning he has started on mycophenalate mofetil and rituximab and now continues to improve. Conclusion There are case reports of myositis following COVID-19 vaccination but our patient's case is complicated by the differential diagnosis of GVHD and concurrent myocarditis. Ongoing work is needed to clarify the exact link between vaccination and the presentation of a new inflammatory myositis, but it is important to recognise and start treatment early in order to preserve muscle bulk and ensure recovery.

Outside The Box But All Squeezed In: A 23- year-old Man With Progressive Dyspnea After Overseas Travel

Case Presentation: A 23-year-old previously healthy man presented with progressive dyspnea. Physical examination revealed jugular venous distension and lower extremity edema. Laboratory testing demonstrated elevated B-type natriuretic peptide (193 pg/mL) and normal high sensitivity troponin. Echocardiogram revealed small pericardial effusion, respiratory variation in diastolic flow across the mitral valve, diastolic septal bounce, and annulus reversus (Figure). The differential diagnosis for constrictive pericarditis was broadly considered in the context of a recent febrile illness and frequent travel to Hawaii and Vietnam;we included infectious, autoimmune, and malignant etiologies. Cardiac magnetic resonance imaging revealed thickening and diffuse enhancement in the pericardium as well as ventricular interdependence. Chest CT identified hilar and anterior mediastinal lymphadenopathy. Laboratory testing was positive for QuantiFERON gold and negative for COVID-19, HIV, and ANA. Transbronchial biopsy demonstrated non-necrotizing granulomas with negative acid-fast bacilli smear, culture, and polymerase chain reaction for mycobacterial DNA. Reexamination identified a red-brown plaque on the patient's thigh;biopsy showed granulomatous inflammation and rod-shaped organism with positive FITE staining. A presumed unifying diagnosis was made of extrapulmonary tuberculosis (TB) complicated by constrictive pericarditis. Discussion(s): Despite being a primarily pulmonary disease, systemic involvement can occur with TB with the heart being one of the most common extrapulmonary sites. This case highlights 1) the utility of extra-cardiac diagnostic testing (e.g., dermatologic biopsy) in the diagnosis of constrictive pericarditis, and 2) the diagnostic challenge associated with extrapulmonary TB, particularly paucibacillary disease that requires a detailed social history with "out-of-the-box" thinking.

Tixagevimab/Cilgavimab Im and Iv for Covid-19: A Randomized Controlled Activ-2 Trial

Background: Within the ACTIV-2/A5401 platform (NCT04518410), the safety and efficacy of tixagevimab/cilgavimab (T/C), an anti-SARS-CoV-2 monoclonal antibody combination, was studied in outpatients with COVID-19. Intravenous (IV) and intramuscular (IM) administration of T/C were assessed. Method(s): Non-hospitalized adults >=18 years enrolled within 10 days of positive SARS-CoV-2 test and symptom onset. Participants at higher risk of disease progression were eligible for IV T/C 300mg (150mg each component) or placebo;all were eligible for IM T/C 600mg (300mg each) administered to the lateral thigh or placebo. Co-primary outcomes were: time to symptom improvement through day 28;nasopharyngeal (NP) SARS-CoV-2 RNA below lower limit of quantification (LLoQ) on days 3, 7 or 14;and treatment emergent Grade >=3 adverse events. Result(s): Between February and May 2021, 223 participants (106 T/C, 117 placebo) initiated study intervention and were included in the IM analysis and 114 participants (58 T/C, 56 placebo) in the IV analysis;the IV study was stopped early for administrative reasons. Both studies enrolled 45% Latinx;the IM and IV populations included 12% and 19% Black participants, 49% and 59% female sex at birth, and median age was 39 and 44 years, respectively, all of which were balanced between active vs placebo for each. Median (IQR) days from symptom onset at enrollment was 6 (4, 7). There were no differences in time to symptom improvement comparing IM T/C to placebo (median 8 (IQR 7, 12) vs 10 (8, 13) days;p=0.35) or IV T/C to placebo (11 (9, 15) vs 10 (7, 15) days;p=0.71). A significantly greater proportion (80%) in the IM T/C arm had NP SARS-CoV-2 RNA below LLoQ at day 7 compared to placebo (65%), but not days 3 or 14, overall p=0.003 across visits. Secondary and post-hoc analyses revealed antiviral effects within the smaller IV study. There was no difference in Grade >=3 AEs with either administration route. Fewer participants were hospitalized who received T/C vs placebo (4 vs 7 in IM group;0 vs 4 in IV group), neither group reaching statistical significance. Conclusion(s): Tixagevimab/cilgavimab administered IM or IV was well-tolerated and demonstrated antiviral activity and a trend towards fewer hospitalizations, but did not change time to symptom improvement in mild-to-moderate COVID-19 compared to placebo. Monoclonal antibodies administered intramuscularly to the thigh may present a valuable alternative for early SARSCoV-2 infection. Virologic Outcomes of Tixagevimab/Cilgavimab treatment 600mg IM (panels A and B) or 300mg IV (panels C and D) versus placebo.

Protein S Deficiency with Favourable Foetomaternal Outcome: A Case Report

Protein S is a multifunctional plasma protein, whose deficiency, results in a rare congenital thrombophilia, inherited in an autosomal dominant pattern. It can aggravate the hypercoagulable state of pregnancy, when it presents in parallel with the condition, leading to adverse maternal outcomes and foetal loss. A 35-year-old female third gravida having previous 2 deliveries by Lower Segment Caesarean Section (LSCS) presented to emergency at 10 weeks pregnancy with chief complaints of pain and swelling in left thigh since 4-5 days. After thorough investigations and work-up, the patient was diagnosed with Protein S deficiency. She was managed conservatively and was delivered by elective LSCS with bilateral tubal ligation at 38 weeks of gestation with good foetal and maternal outcomes.The rarity of Protein S deficiency along with the successful outcome of the pregnancy makes this a unique case.Copyright © 2023 Journal of Clinical and Diagnostic Research. All rights reserved.

Neutralizing Carbapenem Resistance by Co-Administering Meropenem with Novel ß-Lactam-Metallo-ß-Lactamase Inhibitors.

Virulent Enterobacterale strains expressing serine and metallo-ß-lactamases (MBL) genes have emerged responsible for conferring resistance to hard-to-treat infectious diseases. One strategy that exists is to develop ß-lactamase inhibitors to counter this resistance. Currently, serine ß-lactamase inhibitors (SBLIs) are in therapeutic use. However, an urgent global need for clinical metallo-ß-lactamase inhibitors (MBLIs) has become dire. To address this problem, this study evaluated BP2, a novel beta-lactam-derived ß-lactamase inhibitor, co-administered with meropenem. According to the antimicrobial susceptibility results, BP2 potentiates the synergistic activity of meropenem to a minimum inhibitory concentration (MIC) of ≤1 mg/L. In addition, BP2 is bactericidal over 24 h and safe to administer at the selected concentrations. Enzyme inhibition kinetics showed that BP2 had an apparent inhibitory constant (Kiapp) of 35.3 µM and 30.9 µM against New Delhi Metallo-ß-lactamase (NDM-1) and Verona Integron-encoded Metallo-ß-lactamase (VIM-2), respectively. BP2 did not interact with glyoxylase II enzyme up to 500 µM, indicating specific (MBL) binding. In a murine infection model, BP2 co-administered with meropenem was efficacious, observed by the >3 log10 reduction in K. pneumoniae NDM cfu/thigh. Given the promising pre-clinical results, BP2 is a suitable candidate for further research and development as an (MBLI).

An 81-Year-old Woman With Proximal Weakness

An 81-year-old woman developed progressive proximal weakness and myalgias several months following a COVID-19 infection. She was admitted to her local hospital for progressive weakness, peripheral edema, and exertional dyspnea. Neurology evaluation noted proximal arm and leg weakness. She had creatine kinase 740 U/L, white blood cells 21,000/mL (with abnormal differential), and abnormal antibody serologies. Additional diagnostic testing obtained included a thigh MRI and muscle biopsy. During her COVID-19 admission, a mediastinal mass had been detected, which was increased in size on this current admission. Notably, she had a remote history of an incidentally discovered mediastinal mass, which had been incompletely resected 18 years prior. At neuromuscular follow-up one month later, she reported improvement in peripheral edema and dyspnea but ongoing weakness. Strength exam noted symmetric Medical Research Council grade 4 weakness in neck flexion/extension, shoulder abduction, elbow flexion/extension, wrist extension, hip flexion/abduction/extension, and knee flexion. She had no fatiguability and no facial or bulbar weakness. Remainder of her neuromuscular examination was unremarkable. Her white blood cell count differential remained abnormal but had improved from her initial presentation. Her recent muscle biopsy slides were reviewed again. Bone marrow biopsy and mediastinal mass biopsy were obtained. A unifying diagnosis was made, and she was started on therapy with resolution of her weakness, myalgias, and abnormal cell counts.

First reported case of parvovirus triggering painful widespread livedoid vasculopathy: another virus causing hypercoagulability?

Livedoid vasculopathy (LV) is a noninflammatory thrombotic disease caused by occlusion of dermal small vessels associated with systemic autoimmune disorders and coagulopathies. However, LV is often reported as being 'idiopathic', despite extensive investigation. We report a case of severe LV in an otherwise healthy 27-year-old woman, associated with parvovirus infection. The patient presented with a short history of a livedoid rash initially covering her torso, which spread to acral sites. Burning pains in the lower limb caused reduced mobility;systemically, she remained well and stable throughout. Examination revealed generalized acral skin pallor, livedoid patches of violet erythema and purpura with deep serpiginous ulcerations over extensor aspects of upper and lower limbs with a more broken/racemosa nonulcerated livedoid appearance on the trunk. On admission a transaminitisareas continued to ulcerate. Codeine was present with a creatine kinase of 1569 U L.1, but other blood test results were unremarkable including erythrocyte sedimentation rate, complement, cryoglobulins, antinuclear antibodies, antineutrophil cytoplasmic antibodies, extractable nuclear antigen, rheumatoid factor, myositis screen, antiphospholipid screen and thrombophilia screen. Parvovirus IgG and IgM were both positive and tested for, as the patient's young daughter had recently been diagnosed with 'slapped cheek disease'. Magnetic resonance imaging of the thighs showed a diffuse mild myositis;electromyography, nerve-conduction studies, barium swallow and computed tomography of the chest, abdomen and pelvis were all normal. An incisional skin biopsy was performed, which revealed a blood vessel with organizing (Solimani F, Mansour Y, Didona D et al. Development of severe pemphigus vulgaris following SARS-CoV-2 vaccination with BNT162b2. J Eur Acad Dermatol Venereol 2021;35: e649- 51) have been reported. The main proposed mechanisms for AstraZeneca vaccine-induced pemphigus could be a hyperimmune reaction in genetically predisposed individuals, with eventual formation of anti-desmoglein antibodies. An alternative hypothesis is that vaccine components could act as foreign antigens resulting in a cross-reaction with pemphigus antigens. The close association of COVID-19 vaccination with the acute onset of pemphigus in our patient, as well as exacerbations after subsequent vaccine administration, is more than coincidental. Considering the recent pandemic with COVID-19 and the widespread administration of the COVID-19 vaccine, continued observation and documentation of true adverse events is essential.

Guillain-Barre syndrome: An autoimmune disorder post-COVID-19 vaccination?

SARS-CoV-2 causes Coronavirus Disease 2019 (COVID-19), an infectious condition that can present none or one or more of these symptoms: fever, cough, headache, sore throat, loss of taste and smell, aches, fatigue and musculoskeletal pain. For the prevention of COVID-19, there are vaccines available including those developed by Pfizer, Moderna, Sinovac, Janssen, and AstraZeneca. Recent evidence has shown that some COVID-19-vaccinated individuals can occasionally develop as a potential side effect Guillain-Barre syndrome (GBS), a severe neurological autoimmune condition in which the immune response against the peripheral nerve system (PNS) can result in significant morbidity. GBS had been linked previously to several viral or bacterial infections, and the finding of GBS after vaccination with certain COVID-19, while rare, should alert medical practitioners for an early diagnosis and targeted treatment. Here we review five cases of GBS that developed in different countries after COVID-19 vaccination.Copyright © 2021

A contrasting diagnosis: iododerma

An 86-year-old woman presented to the emergency department with acute shortness of breath. She was treated with intravenous furosemide for acute-on-chronic heart failure. Her past medical history included atrial fibrillation, hypertension, diverticulosis and hypothyroidism. Rivaroxaban and levothyroxine were her only long-term medications. On day 5 of hospital admission, she developed painful haemorrhagic and purulent bullae on her dorsal hands, head and neck. These evolved to large suppurative, vegetative plaques over a 72 h period and she developed additional lesions on her trunk, upper back and thighs. The patient had routine blood tests, which showed a raised C-reactive protein at 260 mg L-1, and an acute kidney injury with a glomerular filtration rate of 54 mL-1 min-1. She had a negative COVID-19 swab, and swabs from the lesions for bacterial culture and viral polymerase chain reaction were negative. She had a normal serum protein electrophoresis, immunoglobulin, antinuclear antibody and antineutrophil cytoplasmic antibody. She had computed tomography of her chest 24 h prior to the onset of her lesions, which showed mild bilateral pleural effusions in keeping with fluid overload secondary to heart failure. A biopsy taken from her hand showed orthokeratosis and parakeratosis, and there was bulla formation subepidermally. There was a dense neutrophilic infiltrate with microabscess formation with scattered eosinophils and lymphocytes. There was no evidence of vasculitis. Direct immunofluorescence was negative and a tissue culture for atypical mycobacteria was negative. The patient was commenced on high-dose intravenous methylprednisolone at 500 mg for 3 days followed by 40 mg prednisolone orally for 1 week, but there was a limited response. Our initial differential was Sweet syndrome or pyoderma vegetans;however, the patient had no fevers and no risk factors (malignancy, inflammatory disease, infection, etc.). She also had no response to high-dose oral prednisolone. Given the timing of her CT examination in relation to her acute dermatosis and the use of radioiodine for contrast, we assessed the patient's serum iodine and urine iodine. These were both high at 1.02 mmol L-1 (reference interval 0.32- 0.63) and 3.46 mmol L-1 (reference interval 0.0-2.43), respectively. A diagnosis of iododerma was made. The patient's eruption slowly resolved and at 12 weeks there was evidence of postinflammatory skin changes only. Her urine and serum iodine were rechecked, and both had normalized. In the last 20 years there have been approximately 20 case reports of iododerma. Most have been following iodine contrast use in patients with abnormal kidney function, like our patient. Most describe an acneiform eruption that subsequently evolves to vegetative plaques (Chalela JG, Aguilar L. Iododerma from contrast material. N Engl J Med 2016;374: 2477). Iododerma is largely a diagnosis of exclusion, but histopathology and urine and serum iodine levels can help support diagnosis.

Pregnancy-Related Acquired Haemophilia A: Description of Two Recent Cases

Introduction: Acquired haemophilia A (AHA), characterized by neutralizing autoantibodies against factor VIII (FVIII), is a rare disorder (1.5/million/y). Pregnancy-relatedAHAis an even rarer disorder affecting 0.03/million/y with an incidence of 1 case/350000 births. Aim(s): to describe two pregnancy-related AHA presented at the same year of 2022. Method(s): We evaluate data from two women (patient 1 and 2) with AHA diagnosed within 1 year following childbirth. Result(s): Two women, patient 1 (P1) and P2 with 32 and 33-year old respectively, presented AHA seven (P1) and six (P2) months after delivery. They had no relevant medical history, except for COVID-19 vaccination fifteen days before the development of bleeding in P1, and late-pregnancy COVID-19 infection in P2. They had no complications related to childbirth. The bleeding events in both patients were haematuria and apparently spontaneous hematomas in the upper limb, requiring no haemostatic treatment. Laboratorial investigation, demonstrated in P1 a FVIII activity of 0.026 IU/ml and a FVIII antibody titer of 26 Bethesda Units (BU), and in P2 a FVIII activity of 0.005 IU/ml and a FVIII antibody titer of 34 BU. Concomitant disorders were excluded. The patients started eradication of the inhibitors with prednisone (1mg/kg/day orally). In P1, inhibitor titer was 0 BU and FVIII> 0.5 IU/ml after 8 weeks of immunosuppression. During eradication period, the P2 had a hematoma in right thigh treated with bypassing agent (FEIBA), but the inhibitor titer was 0 BU and FVIII>0.5 IU/ml after 1 month of inhibitor eradication. Curiously, P2 with FVIII< 0.01 IU/ml and a higher inhibitor titer than P1 had a faster response to prednisolone therapy (4 vs. 8 weeks). Currently, prednisone has been completely withdrawn in P1 and the prednisone dosage is being gradually reduced in P2. Discussion/Conclusion: Data from these two women with pregnancyrelated AHA are similar to previously described cases and expand the knowledge about this rare disorder. The peculiarity of this report is due to the emergence of two cases of a disease with markedly low incidence, in the same local and year, raising the question of whether there were new acquired factors (as immunological triggers such as COVID-19 infection or vaccination) that could be involved in the modification of the natural history of the disease. It cannot be excluded the possibility that these two cases were a coincidence.

Impact of Intramuscular Injection Site on Sotrovimab Pharm Aco Kin Etics

BACKGROUND: Sotrovimab, a dual-action Fc-engineered human immunoglobulin G (IgG1) mAb, binds to a conserved epitope on the SARS-CoV- 2 receptor binding domain and was developed to treat mild to moderate COVID-19. A high concentration formulation is being evaluated to offer the potential for IM administration at lower volumes and at different injection sites. METHOD(S): COSMIC (NCT05280717) is a phase 1, open-label healthy volunteer study comprising three parts. Part A is an ongoing randomized, parallel group study investigating the relative bioavailability, safety, and tolerability of two concentrations of sotrovimab administered at different injection sites. A total of 215 subjects were randomized in a 2:2:1:1 ratio into 4 treatment arms: dorsogluteal injection (62.5 mg/mL), or 100 mg/mL administered as dorsogluteal, thigh, or deltoid injection(s). PK will be evaluated for 24 weeks post-dose. RESULT(S): Preliminary PK is available from 50 participants who received a 500 mg IM dose of sotrovimab of the higher concentration (100 mg/mL). Administration into thigh or deltoid resulted in higher geometric mean Cmax and AUCD1-15 and lower inter-subject variability compared to 100 mg/mL dorsogluteal. Following gluteal, thigh, or deltoid injections, the geometric mean (%CV) Cmax was 44.8 mug/mL (63.3), 70.9 mug/mL (35.5), and 65.1 mug/mL (27.1), respectively, and the geometric mean (%CV) AUCD1-15 was 534 day*mug/mL (67.5), 814 day*mug/mL (39.7), and 782 day*mug/mL (26.3), respectively. Median Tmax was earlier following thigh (4 days) and deltoid (5.5 days) injection than gluteal (7 days) injection. CONCLUSION(S): Administration of sotrovimab into thigh or deltoid muscles may improve exposure and reduce inter-subject variability compared to gluteal IM administration. These data may inform IM injection site selection for mAbs.

Popper's Dermatitis: A Unique Form of Contact Dermatitis In the MSM Community

Rationale: Men who have sex with men have different contact allergen exposures compared to men who have sex with women due to cultural differences in the LGBTQ+ community. Poppers, a common name for volatile alkyl nitrates, are used more frequently in the MSM community as recreational inhalants. We aimed to identify common anatomic sites and contact allergens associated with popper's dermatitis in the MSM community. Method(s): Covidence, Embase, MEDLINE, PubMed, Web of Science, and Google Scholar were searched to identify relevant articles studying allergic contact dermatitis associated with poppers in the MSM population. Search terms included 'allergic' or 'contact dermatitis' or 'patch testing' or "poppers" or 'Men who have sex with men'. Date, geographical or language restrictions were not used. No exclusion criteria was used. Result(s): : Common allergens associated with popper's dermatitis in the MSM community included amyl nitrate (N=7), isobutyl nitrate (N=3), isopropyl nitrate (N=2), and fragrance mix (N=5). Common anatomic sites included perioral regions (N=3), chest (N=2), nasal orifices (N=3), cheeks (N=5), penis (N=1), and lateral thigh (N=1). Conclusion(s): Sexual orientation is a relevant factor for dermatologists/allergists to consider, as the standard patch test series does not include common allergens associated with popper's dermatitis which disproportionally affects the MSM community. Our community needs to include gender and sexuality demographics when collecting patch test data.Copyright © 2022

When and What to Consider Knee Arthroscopy Surgery in Post-COVID 19 Infected Patients

Coronavirus disease 19 (COVID-19) is the worst pandemic ever recorded in history, as of this day more than 545 million people infected and more than 6 million cumulative deaths. COVID 19 is primarily respiratory disease, however non-respiratory presentations that could be manifested are venous and arterial thromboembolic events. Both pulmonary embolism (PE) and deep vein thrombosis (DVT) are the most frequently thrombotic events in COVID-19. Knee arthroscopy surgery is the one of the most common orthopedic surgical procedures nowadays, with the most common procedures are meniscectomy, meniscal repair and cruciate ligament reconstruction. Although knee arthroscopy is known to be a safe procedure, several complications could be found with the 3 most common complications are DVT, effusion and synovitis, and PE. We reported a case series of four patients with DVT post knee arthroscopy anterior cruciate ligament reconstruction during 2021. The DVT diagnosis was retained on clinical presentation and elevated of D-dimer testing. The patient's mean age was 35,25 years, and all of the patients had no risk factors of DVT, although they had COVID-19 infection within 3 months before surgery. The most common clinical presentation was swelling on the lower leg (around the ankle) with slightly pain and numbness. Only one patient had severe pain around the thigh. All of the patients had elevated D-dimer testing result with mean of D-dimer 1250 (normal value < 500). Only one patient had sonography testing and found proximal DVT. One of the patients had DVT at post operative day (POD) 3, one at POD 4 and the other two at POD 5. Three of the patients improved with oral anticoagulant therapy using rivaroxaban (XARELTO). In one patient the symptom was not improved after two days oral anticoagulant therapy and underwent thrombectomy by vascular surgeon. DVT is the most common complication of knee arthroscopy and also the most common non-respiratory events of COVID-19 infection. Routinely administration of thromboprophylaxis agent was not recommended, pre-operative risk assessment of DVT should be used, especially in post-COVID 19 patients.

Melanized (dematiaceous) fungal infections simulating skin cancer in African organ transplant recipients

Fungi are the most frequent skin infections in organ transplant recipients (OTRs) and usually present as superficial mycoses. Deeper infections are much less common, potentially more serious and the incidence is higher in the first few months post-transplant. We report two African OTRs with deep fungal infections caused by dematiaceous (melanized, pigmented or black) fungi, who both presented with suspected skin malignancies. A 60-year-old Nigerian man developed a painful, ulcerated, amelanotic, bleeding nodule on his right fourth toe 2 months after renal transplantation. Clinical differential diagnoses included Kaposi sarcoma (KS), amelanotic acral melanoma and subungual squamous cell carcinoma (SCC). However, histology showed pseudoepitheliomatous hyperplasia, extensive mixed inflammation, multinucleated giant cells and pigmented septate hyphae with rounded 'budding' forms. Periodic acid-Schiff, Grocott and Masson-Fontana stains were positive, and Alcian blue stain was negative, consistent with infection by a dematiaceous fungus. Fungal 18S polymerase chain reaction (PCR) was positive and culture identified Nigrograna mackinnonii. Treatment with oral itraconazole was supervised virtually during the COVID-19 pandemic. After 6 months there was minimal response and he opted for amputation of the digit. A 61-year-old Nigerian man presented 2 months after renal transplantation with a 2-cm diameter nodule on his left thigh at the site of a previous burn. This failed to respond to antibiotics. Magnetic resonance imaging was suggestive of possible malignancy, but surgery was deferred because of the COVID-19 pandemic. Two months later the lesion was 5 cm in diameter and verrucous with an 8-cm sessile, purplish plaque on his right forearm. Atypical KS, lymphoma and chronic burns-associated SCC were all considered. However, histology from both lesions was similar to the first patient. Fungal culture and 18S PCR confirmed infection with the dematiaceous fungus Alternaria alternata. At his request, the right thigh lesion was excised. The lesion on his forearm has partially responded to 8 months of ongoing oral itraconazole. In our African OTR cohort, KS is more common than deep fungal infection. However, despite this suspicion of skin malignancy, both patients had phaeohyphomycoses caused by dematiaceous fungi. Characterized by the presence of melanin in their cell walls, > 130 species of these plant pathogens and soil saprophytes are implicated in human disease, particularly in immunocompromised individuals. Although localized skin diseases (phaeohyphomycoses, chromoblastomycosis and mycetoma) are the most common manifestations, rare disseminated, central nervous system and pulmonary infections may prove fatal. Although uncommon, deep fungal infection should be considered in atypical skin lesions in OTRs;histology, tissue culture and fungal PCR are critical to confirming this diagnosis.

Unusual case of a free anterolateral thigh flap partial necrosis in a COVID-19 positive young male following extremity reconstruction.

Free flap procedure provides an overall success rate of 97%, which decreases to 85% in hypercoagulable states. COVID-19, as a pro-thrombotic disorder, therefore seems detrimental to free flap survival. We encountered a case of unique pattern of free flap partial failure in a young male who underwent extremity reconstruction. The patient was diagnosed as COVID-19 positive on the 3rd day post-reconstruction. The flap survived well for the first 7 days post-operatively, but gradually the skin got necrosed and the subcutaneous fat layer was preserved when debriding. To our knowledge, this is the only case in which the skin of the free flap of a COVID-19 positive patient was necrosed almost entirely subsequently, while the subcutaneous fat was relatively preserved.

Perforated Appendicitis Presenting as a Soft Tissue Infection of the Thigh: An Example of Successful Non-Operative Management.

Perforated appendicitis is a rare but serious clinical scenario typically requiring urgent surgical intervention. Herein, we discuss the case of a 62-year-old woman with COVID-19 and ruptured retrocecal appendicitis presenting as a right lower extremity soft tissue infection that was successfully managed using non-operative measures. This unique case illustrates the feasibility of conservative care - rather than urgent surgical intervention - in the treatment of an atypical presentation of complicated appendicitis in a high-risk patient.

Systemic lupus erythematosus cutaneous flare following COVID-19 vaccination: A case report

Objective: To present a case of a SLE cutaneous flare following COVID-19 vaccination in a patient with low disease activity Background: Disease flare in a patient with underlying autoimmune rheumatic disease (AIRD) after vaccination had already been experienced with other vaccines, such as influenza, hepatitis B, and HPV vaccines. Given the relatively unknown safety profile of the COVID-19 vaccine among patients with AIRD, the probability of a disease flare is not a remote possibility. Several case reports available had already reported few cases of AIRD disease flare following vaccination, some of which requiring escalation of the treatment regimen. Molecular mimicry, as had been described with other vaccines, is still implicated as the possible explanation for such a phenomenon. Case: A 57 year old female with systemic lupus erythematosus with nephritis since 1994 with low disease activity, maintained on hydroxychloroquine and low dose methylprednisolone daily who developed multiple well-defined elevated erythematous and pruritic plaques on both thighs, spreading to the face, scalp, trunk, and extremities 3 weeks after receiving her first dose of viral vector vaccine. Work-ups included eosinophilia on CBC, elevated ESR, anti-dsDNA, ferritin, and LDH, with low C3, with proteinuria and hematuria on urinalysis. She was admitted and her glucocorticoid was increased and tapered accordingly. Skin punch biopsy with alcian blue staining was also done which revealed interface dermatitis consistent with lupus erythematosus. Few days after increasing her glucocorticoid, cutaneous lesions gradually resolved and she was discharged improved. She received her second dose of vaccine 2 months after her first dose with no reported incidents of adverse events. Conclusion(s): This is one of the few cases of a reported SLE flare confirmed by disease activity index and biopsy-confirmed skin rashes. The development of such an adverse reaction to a vaccine may be relatively low but still possible due to intricate interaction of the immune system and vaccine.

Rare case of post-COVID transverse myelitis

Case Report: Acute transverse myelitis (TM) is a rare inflammatory disease that typically presents asweakness, sensory alterations, and bowel or bladder dysfunction. Among the causes of TM are infections, paraneoplastic syndromes, or autoimmune conditions of CNS. Postinfectious TM can develop secondary to a viral or bacterial infection. SARS-CoV-2 is a recently discovered viral illness, and sequelae due to COVID-19 infection are still being studied. There is scarce literature relating the two conditions, and it is imperative to raise awareness. A 72-year-old man with hypertension and GERD, completely independent in ADL, was brought to the ED with sudden onset of bilateral lower extremity weakness. He reported symptoms started with difficulty climbing stairs that rapidly progressed to inability to ambulate independently and were associated with bilateral thigh soreness. Nine days prior, he developed fever and generalized malaise, and two days later, SARS-CoV-2 PCR and Ag tests were positive. He received azithromycin, Paxlovid, and dexamethasone as treatment. Upon evaluation, the patient was afebrile and hemodynamically stable. Neurological examination was remarkable for spasticity and hyperreflexia at bilateral lower limbs, clonus, preserved motor strength with adequate sensation to soft touch, and intact vibration and proprioception in all extremities. Cranial nerves were intact. These findings were consistent with an upper motor neuron lesion. On imaging, the Head CT scan was unremarkable. Thoracic/Lumbar Spine MRI was significant for distal thoracic and conus areas with central homogeneous brightness compatible with nonspecific myelitis. Laboratories showed leukocytosis without neutrophilia or bandemia, thrombocytosis, and elevated CRP. HIV and RPR tests were negative. A lumbar puncture for CSF analysiswas remarkable for mild monocytic pleocytosis (7 cell/muL), an increased level of total proteins (56 mg/dL), and normal glucose (57 mg/dL). CSF culture and gram stain were negative. CSF cytology yielded few lymphocytes and few monocytes and was negative for malignant cells. The meningoencephalitis panel was negative. Based on these findings, a clinical diagnosis of postinfectious myelitis secondary to COVID-19was made. The patient was treated with intravenous Methylprednisolone 1 g daily for five days. On follow-up, lower extremity weakness resolved completely, and he resumed his daily physical activities. Patients with COVID-19 infection can present with neurologic manifestations such as headache, myalgias, dizziness, dysgeusia, and anosmia. This case hopes to raise awareness of less commonly known neurological manifestations of SARS-CoV-2 infection and how the early recognition of symptoms can help expedite the diagnosis and treatment of the condition to avoid long-term sequelae. [Figure presented] Copyright © 2023 Southern Society for Clinical Investigation.