Clinical and Laboratory Evaluations of Patients Diagnosed as Having Multisystem Inflammatory Syndrome Associated with Coronavirus Disease 2019 in Children: A Single Center Experience from Konya

Objective Multisystem inflammatory syndrome in children (MIS-C), characterized by fever, inflammation, and multiorgan dysfunction, was newly defined after severe acute respiratory syndrome coronavirus 2 infection. The clinical spectrum of MIS-C can be classified as mild, moderate, and severe. We aimed to evaluate demographics, clinical presentations, laboratory findings, and treatment modalities of patients with MIS-C according to clinical severity. Methods We performed a retrospective study of patients who were diagnosed as having MIS-C between September 2020 and October 2021 in the Necmettin Erbakan University Meram Faculty of Medicine, Türkiye. Results A total of 48 patients (24 females and 24 males) with a median age at diagnosis of 10.3 years (range: 42 months-17 years) were enrolled, the most common clinical severity of MIS-C was moderate. The common presentations of patients were fever (97%), nonpurulent conjunctivitis (89.6%), rashes (81.3%), fatigue (81.3%), strawberry tongue (79.2%), and myalgia (68.8%). The most common laboratory findings were lymphopenia (81.2%), thrombocytopenia (54.1%), elevated D-dimer levels (89.5%), C-reactive protein (CRP;100%), procalcitonin (97%), erythrocyte sedimentation rate (87.5%), ferritin (95.8%), interleukin 6 (IL-6) (86.1%), and probrain natriuretic peptide (pro-BNP) (97%). High levels of CRP, procalcitonin, pro-BNP, and urea were associated with the severity of MIS-C (p < 0.05). Fifteen of the patients were found to have pulmonary involvement. Ascites were the most common finding on abdominal ultrasonography (11 patients) and were not seen in a mild form of the disease. During the study period, two patients died. Conclusion It is important to make patient-based decisions and apply a stepwise approach in treating patients with MIS-C due to the increased risk of complications and mortality. © 2022. Thieme. All rights reserved.

Impact of the loss of Laboratory Developed Mass Spectrometry testing at a major academic medical center.

Background: Our laboratory historically performed immunosuppressant and definitive opioid testing in-house as laboratory developed (LDT) mass spectrometry-based tests. However, staffing constraints and supply chain challenges associated with the COVID-19 pandemic forced us to refer this testing to a national reference laboratory. The VALID Act could impose onerous requirements for laboratories to develop LDTs. To explore the potential effect of these additional regulatory hurdles, we used the loss of our own LDT tests to assess the impact on patient care and hospital budgets. Methods: Laboratory information systems data and historical data associated with test costs were used to calculate turnaround times and financial impact. Results: Referral testing has extended the reporting of immunosuppressant results by an average of approximately one day and up to two days at the 95th percentile. We estimate that discontinuing in-house opioid testing has cost our health system over half a million dollars in the year since testing was discontinued. Conclusions: Barriers that discourage laboratories from developing in-house testing, particularly in the absence of FDA-cleared alternatives, can be expected to have a detrimental effect on patient care and hospital finances.

A CASE OF LONG-TERM TOLERANCE AFTER KIDNEY TRANSPLANTATION.

We present a case of long-term organ functioning (ca.10 years) after allografting of a cadaveric kidney without usage of immunosuppressing drugs. In 2005, a patient suffering from a hypertensive form of chronic glomerulonephritis, have received an allogeneic graft of cadaveric kidney compatible for AB0 system, HLA antigens (A19, B07, DR04), and negative results of cross-match test. The graft function was immediately restored, with normalization of creatinine levels achieved 4-5 days after surgery. Immunosuppression with cyclosporine, solumedrol, cellcept, metypred and simulect was performed in the hospital. Pulse therapy with solumedrol was performed on the day +20 due to the development of initial rejection signs. The postoperative period proceeded without infectious complications. The patient was discharged being recommended to take cyclosporine, Cell-Sept and Metypred. Within a year after transplantation, the patient claimed for pain in the hip joint, and, therefore, metypred was completely canceled. Subsequently, the Cellcept was replaced with a Mayfortic. In 2007, the signs of coxarthrosis were revealed at computed tomography, followed by aseptic necrosis of the the right femur head. Deforming osteoarthritis of the right hip joint was detected, and the hip replacement surgery was suggested. In 2010, due to risk of side effects from ongoing immunosuppressive therapy, e.g., joint damage, the Mayfortic was canceled. In 2012, being in fear of original Sandimmun Neoral replacement by a generic drug, the patient completely refused cyclosporine therapy. In 2021, the endoprosthetics of the right hip joint was performed, and the surgical wound healed initially. Since 2012, the patient has not completely taken immunosuppressive therapy. Over this time period, the patient has never been admitted to the hospital for impaired functioning of the organ graft. Meanwhile, he monitored his graft function on regular basis undergoing biochemical analyses, clinical examination, ultrasound studies of the graft and made regular visits to the outpatient department. In 2021, a week after hip replacement, there was a slight increase in serum creatinine, followed by further increase to 230 mmol/L in 2021, and to 310 mmol/L in March 2022. In February 2022, the patient suffered mild respiratory infection (confirmed COVID-19). In March 2022, the first clinical signs of increasing nephropathy appeared, i.e., swelling of both lower extremities, with leukocytes in urine upon routine analysis, increased blood flow resistance in the main artery of the transplant shown by ultrasound study. Due to worsening of the patient's condition, he resumed taking the prescribed immunosuppressants. Copyright © 2022, SPb RAACI.

Incidence of COVID-19 hospitalization in patients with psoriasis taking systemic immunomodulators

Background: Current research on COVID-19-related outcomes in patients with psoriasis, particularly regarding influence of treatments, are subject to lack of comparator group, selection bias, and insufficient statistical power.1 Accordingly, it remains uncertain whether immunomodulatory treatments for psoriasis enhance or decrease the risk of severe COVID-19-related outcomes, including hospitalization. Objective(s): To compare the risk of COVID-19-related hospitalization according to immunomodulator treatment type in patients with psoriasis Methods: Retrospective cohort study of the Explorys database in the United States between March 1st, 2020 and December 31st, 2020. Psoriasis diagnosis was defined by at least 2 ICD-9 or ICD-10 diagnosis codes prior to March 1st, 2020. Drug exposure was classified as biologic or traditional immunosuppressive (methotrexate, cyclosporine, apremilast) treatment based on prescription order in the 3 months preceding March 1st, 2020. Biologic treatments included TNFalpha, IL-12/IL-23, IL-17A, IL-23 and JAK inhibitors. The primary outcome was defined as hospital admission with diagnosis of COVID-19 or positive lab test occurring between admission and discharge date. Propensity score weighting was used to compare COVID-19-related hospitalization between treatment groups, adjusting for comorbidities and demographic characteristics. Result(s): A total of 51,606 psoriasis patients aged 18-88 were included. Crude cumulative incidence of COVID-19 hospitalization per 1,000 psoriasis patients was 3.4 in the biologic group (9/2,669), 9.5 in the traditional immunosuppressive group (15/1,585), and 3.9 in those receiving neither drug class (184/47,352). Incidence was 4.7 (6/1,282) and 14 (13/898) per 1,000 patients among those receiving TNF-alpha inhibitors and methotrexate, respectively. After propensity-score weighting, risk of COVID-19-related hospitalization for patients receiving any biologic was lower than that of patients receiving traditional immunosuppressives (RR 0.39, 95% CI 0.16, 0.92), and those receiving neither drug class (RR 0.66, 95% CI 0.32, 1.34). TNF-alpha inhibitor use was associated with lower risk of hospitalization relative to methotrexate use (adjusted RR 0.39, 95% CI 0.14, 1.06). Adjusted relative risk of hospitalization for methotrexate users relative to those receiving neither drug class was 2.78 (95% CI 1.47, 5.26). Conclusion(s): During the first wave of the pandemic in 2020, psoriasis patients using biologics were at lower risk of COVID-19-related hospitalization compared to those using traditional immunosuppressives, particularly methotrexate. Methotrexate use was associated with a substantial increase in risk of hospitalization relative to those who did not receive systemic treatments.

COVID-19 associated Mucormycosis (CAM): Implications for perioperative physicians - A narrative review

Mucormycosis once considered a rare disease with an incidence of 0.005 to 1.7 per million, has become one of the greatest menaces during the coronavirus disease (COVID-19) pandemic. India alone has contributed to nearly 70% of the global caseload of COVID-associated mucormycosis (CAM) and it had even been declared as a notifiable disease. Second wave of COVID-19 pandemic saw a steep rise in the incidence of mucormycosis and these patients have been presenting to anesthesiologists for various surgical procedures due to its primary or secondary sequelae. Rhino-orbito-cerebral mucormycosis (ROCM) is the commonest manifestation and is caused by Rhizopus arrhizus. Injudicious use of corticosteroids in vulnerable patients could have been a major contributing factor to the sudden rise in ROCM during the pandemic. Concerns related to anesthetic management include COVID-19 infection and post COVID sequalae, common presence of uncontrolled diabetes mellitus, possibility of difficult mask-ventilation and/or intubation, various drug therapy-associated adverse effects, and interaction of these drugs with anesthetic agents. Thorough preoperative optimization, multidisciplinary involvement, perioperative care, and vigilance go a long way in improving overall outcomes in these patients. Copyright © 2022 Saudi Journal of Anesthesia Published by Wolters Kluwer - Medknow.

Tocilizumab as a promising treatment for MIS-C in JIA: Implications for countries with inaccessible anti-IL1 agents

Background: Multisystem inflammatory syndrome in children (MIS-C), causing high morbidity and mortality, is the hyperinflammatory response following COVID-19 infection (CI). According to the MISC management guideline, Anakinra (anti-IL1) is the preferable agent among other biologic agents: Infliximab, Tocilizumab (TCZ), and baricitinib if the patient is refractory to intravenous immunoglobulin (IVIG) and systemic corticosteroid (CS). However, these are not available in a number of countries, including Thailand. Our case represents refractory MIS-C in a systemic juvenile idiopathic arthritis (SJIA) patient responding well to TCZ. Method(s): Diagnostic investigations, including basic and immunological blood tests, and echocardiography assessment, were conducted. Result(s): A 12-year- old boy has been diagnosed with SJIA since he was 2 years old, according to the presentation of prolonged fever, hepatomegaly, and evanescent rash. CS, cyclosporin-a, and TCZ have been prescribed, and he has been in clinical remission off medication for two years. He experienced acute fever, rash, shortness of breath, nausea and vomiting for few days. Physical examination revealed a febrile boy with respiratory failure, compensated shock, and a generalized persistent maculopapular rash. The other was unremarkable. MIS-C was one of the possible diagnoses according to fever accompanied by more than two systems involved and his previous CI four weeks prior. Laboratory investigation revealed an elevated inflammatory response (Figure 1). The echocardiography was done by an experienced cardiologist with concern for myocardial dysfunction in MIS-C and showed a significant poor ejection fraction of the left ventricle of 42% under dobutamine, milrinone, and norepinephrine. Broad spectrum antibiotics and IVIG (1 g/kg/dose for two days) were initiated. After hemoculture did not report bacteria growth, pulse intravenous methylprednisolone (IVMP) 1000 mg for 3 days was given for the MIS-C treatment. After initial aggressive treatment with IVIG and pulse IVMP, the patient still has a high grade fever with laboratory revealed ongoing elevated inflammatory markers. The other possible causes of fever, such as infection and active SJIA were suspected. Immunological profiles returned with positive SAR-COV2 IgG, negative SAR-COV2 IgM, which confirmed the diagnosis of MIS-C with refractory to IVIG and CS. After multidisciplinary team discussion, TCZ was given. He had neither fever, dyspnea, nor heart failure. His clinical condition gradually improves together with laboratory parameters (Figure 1). Conclusion(s): In conclusion, our case demonstrated TCZ as a potential therapeutic agent in refractory MIS-C patients living in countries with limited access to anti-IL1 agents. The multidisciplinary care team together with prompt management is advisable to the best benefit of the patient. (Figure Presented).

Cyclosporin for treatment of refractory multisystemic inflammatory syndrome in a child.

Multisystemic inflammatory syndrome in children is an inflammatory condition with multiorgan dysfunction that manifest late in the course of Severe acute respiratory syndrome coronavirus 2 infection. We present a 12-year-old boy with a history of fever, vomiting, diarrhoea, and abdominal pain. He developed shock with ventricular dysfunction and pericardial effusion. He was diagnosed with multisystemic inflammatory syndrome in children and treatment with intravenous immunoglobulins, corticosteroids, and tocilizumab proved to be ineffective. Eventually, the patient responded to cyclosporin-A treatment. Multisystemic inflammatory syndrome in children has been treated with immunoglobulins and glucocorticoids and in refractory cases biologics and cyclosporin-A have been used. Intravenous and oral cyclosporin-A seems to be a safe and effective alternative treatment for refractory multisystemic inflammatory syndrome in children patients.