Fulminant varicella infection complicated by disseminated intravascular coagulation following influenza-A case report

Objectives: Varicella is common infectious disease mainly in childhood, usually is a mild, self-limited illness and complications are usually rare. The incubation period for this disease is generally 14- 16 days but may vary from 7 to 21 days. Varicella in the adults with comorbidities or immunosuppressed children may be severe and prolonged with complications. Method(s): A case report of a 6-year-old girl hospitalized for new-onset manifestations of disseminated vesicular exanthema, the manifestations of which occurred mainly on the chest, back, capillitium, oral cavity, and genital area. The child was suffering from abdominal, knee and lumbosacral pain at that time. The patient's history revealed that 10 days prior to the cutaneous manifestations, she had influenza with bronchopneumonia requiring oxygen therapy, steroids and antibiotics. Result(s): The condition progressed within 48 h, complicated by the development of multi-organ failure, coagulopathy with the development of disseminated intravascular coagulopathy over the course of antiviral, antibiotic and antifungal therapy. Laboratory parameters included high elevation of C-reactive protein, il-6, leukocytosis, neutrophilia and highly elevated liver enzymes. Varicella infection was confirmed by detection of herpes zoster virus - polymerase chain reaction (PCR) from vesicles. The patient received intravenous immunoglobulin therapy at a dose of 2 g/L and fresh frozen plasma, thrombocyte concentrate. The girl was intubated with analogization. Laboratory parameters subsequently revealed high anti CoV-2 positivity, high CoV-2 IgG positivity and negative CoV-2 IgM. The patient's condition did not preclude the course of multisystem inflammatory syndrome in children (MIS-C) corticosteroids were added to the treatment at a dose of 1 mg/kg weight. Patient's condition stabilized after 1 month. Discussion(s): Our case report presents an example of fulminant complicated life-threatening course of varicella. Even in common respiratory infections, we must think about the risk and consequences of coinfections and post-infectious complications such as in our case especially influenza and COVID-19.

SARS-COV-2 Infection in Children and Young People in Bulgaria - A Prospective, Single-Center, Cohort Study

Compared to other respiratory viruses, the proportion of hospitalizations due to SARS-CoV-2 among children is relatively low. While severe illness is not common among children and young individuals, a particular type of severe condition called multisystem inflammatory syndrome in children (MIS-C) has been reported. The aim of this prospective cohort study, which followed a group of individuals under the age of 19, was to examine the characteristics of patients who had contracted SARS-CoV-2, including their coexisting medical conditions, clinical symptoms, laboratory findings, and outcomes. The study also aimed to investigate the features of children who met the WHO case definition of MIS-C, as well as those who required intensive care. A total of 270 patients were included between March 2020 and December 2021. The eligible criteria were individuals between 0-18 with a confirmed SARS-CoV-2 infection at the Infectious Disease Hospital "Prof. Ivan Kirov"in Sofia, Bulgaria. Nearly 76% of the patients were <= 12 years old. In our study, at least one comorbidity was reported in 28.1% of the cases, with obesity being the most common one (8.9%). Less than 5% of children were transferred to an intensive care unit. We observed a statistically significant difference in the age groups, with children between 5 and 12 years old having a higher likelihood of requiring intensive care compared to other age groups. The median values of PaO2 and SatO2 were higher among patients admitted to the standard ward, while the values of granulocytes and C-reactive protein were higher among those transferred to the intensive care unit. Additionally, we identified 26 children who met the WHO case definition for MIS-C. Our study data supports the evidence of milder COVID-19 in children and young individuals as compared to adults. Older age groups were associated with higher incidence of both MIS-C and ICU admissions.Copyright © 2023 P. Velikov et al., published by Sciendo.

Cutaneous Adverse Drug Reactions of COVID-19 Vaccines: A Cross-Sectional Study of the Largest Healthcare System in Taiwan

Objectives: Potential cutaneous adverse drug reactions (cADRs) associated with COVID-19 vaccinations are well-known. However, comprehensive evaluation including detailed patient characteristics, vaccine types, signs and symptoms, treatments and outcomes from such cADRs are still lacking in Taiwan. Method(s): A cross-sectional study was conducted from December 2019 to October 2022 to analyze spontaneous ADR reporting data from Taiwan's largest multi-institutional healthcare system. Physicians and pharmacists initially ensured the data quality and completeness of the reported ADR records. Subsequently, we applied descriptive statistics to analyze the patient cohort based on demographic characteristics, administered COVID-19 vaccines, clinical manifestations, and patient management. Result(s): We identified 242 cADRs from 759 reported COVID-19 vaccine-related ADRs, 88.3% of which were judged as "possible" using the Naranjo Scale. The mean age of patients with cADRs was 48.1+/-17.5 years, with the majority (44.2%) of cADRs reported in the 40-64yr old age group. cADRs were more common in women (68.2%) and most of the patients had no history of allergy to vaccines (99.6%). Oxford/AstraZeneca (58.6%) accounted for the most reported brand of COVID-19 vaccines. Patients developed cADRs within 1 to 198 days (median = 5.5 days), and mostly after first-dose vaccination (77.8%). The most frequently reported cADR was rash/eruption (18.7%), followed by itchiness/pruritus (11.7%) and urticaria (9.2%), mainly affecting the lower limbs (23.8%) and upper limbs (22.6%). Medications were prescribed for 65.1% of the cADRs, and signs and symptoms were resolved within 1 to 167 days (median = 7 days) after treatment with oral antihistamines (23.0%), topical corticosteroids (14.6%) or oral corticosteroids (14.4%). Conclusion(s): Our findings provide comprehensive details regarding COVID-19 vaccine-related cADRs in Taiwan. Certain groups, especially women and the middle-aged, who reported a relatively higher rate of cADRs, may benefit from pre-vaccination counseling about the risks of cADRs and the use of appropriate medications.Copyright © 2023

A Case of a Relapsing Remitting Macrophage Activating Syndrome After Covid-19 Vaccine In a Teenager with UNC13D Heterozygous Variant of Uncertain Significance

Introduction: Macrophage activation syndrome (MAS) is a severe hyper inflammatory condition caused by the over-activation and proliferation of T cells, NK cells and macrophages. It is often associated with complications of rheumatic/immune diseases. We present a case of a 15-year-old female who experiences recurrent episodes of MAS without any known definitive underlying etiology. Case Presentation: A 15-year-old previously healthy female developed fatigue, fevers, myalgia, chest pain, splenomegaly and lymphadenopathy 10 days after receiving her first Pfizer COVID-19 vaccine. Her symptoms recurred 10 days after receiving the second dose. Her myocarditis, MIS-C, and infectious work up was negative except for positive EBV IgG. Laboratory studies revealed anemia, hypertriglyceridemia, hypofibrinogenemia, and hyperferritinemia. She initially responded to decadron;however, her symptoms recurred with steroid taper. Bone marrow biopsy revealed hemophagocytosis. Whole exome sequencing (WES) revealed a heterozygous variant of uncertain significance in UNC13D c.962C>A (p.Thr321Asn). She had multiple re-admissions with significantly elevated inflammatory markers, including extremely high IL2-R, IL-18 and CXCL9. Each episode was complicated by an acute viral infection. She responds to high dose steroids, anti-IL-1, and JAK inhibitors. Nonetheless, it has been difficult to wean decadron without triggering a flare. She continues to require increasing doses of baricitinib. Discussion(s): MAS may be seen as a complication of rheumatic diseases, as well as inborn errors of immunity. However, none of these conditions have been diagnosed in this patient despite extensive testing, including WES. The degree of her immune dysregulation has been very severe making her disease process unpredictable and extremely difficult to control. She has frequent flares precipitated by viral infections or attempts at adjusting her immunomodulators. Weaning her medications has been challenging as she continues to require increasing doses of baricitinib and corticosteroids. The UNC13D gene is associated with autosomal recessive familial hemophagocytic lymphohistiocytosis type 3 (FHL3). Our patient is heterozygous for an UNC13D variant of uncertain significance. Additional genetic inquiries with whole genome sequencing to help elucidate the underlying etiology of her severe condition is being conducted. We hypothesize she developed MAS due to a combination of genetic predisposition, prior EBV infection, and immune stress associated with the COVID-19 vaccine. [Formula presented] [Formula presented] [Formula presented]Copyright © 2023 Elsevier Inc.

Drugs that aggravate the course of COVID-19: really?.

The safety of NSAIDs, corticosteroids and renin-angiotensin inhibitors in COVID-19 is challenged. NSAIDs may interfere with the defense process against viral infection and are best avoided. Systemic corticosteroids have not shown benefit in viral infection, including other coronavirus;thus they should be avoided, unless prescribed for another indication. The benefit-risk ratio is however clearly in favor of continuing inhaled corticosteroids in patients with asthma or COPD. ACE inhibitors and sartans upregulate the expression of angiotensin-converting enzyme 2 (ACE2), the pulmonary receptor for SARS-CoV-2. Any possible clinical impact of these treatments on COVID-19 infection remains to be clarified;in the meantime, they should be continued.Copyright © 2020 Editions Medecine et Hygiene. All rights reserved.

Anosmia and COVID-19.

Anosmia associated or not with dysgeusia seems to be a frequent symptom in cases of infection with SARS-CoV-2 responsible for COVID-19. It can be the initial symptom of the disease or remain isolated in pauci-symptomatic patients. Waiting for scientific confirmation and in the context of the current pandemic, it seems essential to consider any patient with a new anosmia as being infected with SARS-CoV-2 until proven otherwise. These patients should therefore isolate themselves and remain alert to the occurrence of other symptoms suggestive of the infection and/or be tested. Topical and systemic corticosteroids and nose washes are contraindicated. The natural course of anosmia seems to be favorable in most cases.Copyright © 2020 Editions Medecine et Hygiene. All rights reserved.

Postnatal SARSCOV2 Infection in Neonates, Characteristics and Outcomes: An Observational Study

Background: Many aspects of the severe acute respiratory syndrome coronavirus 2 (SARSCoV2) pandemic in 2019 have been unclear, especially in newborns, and reports of neonatal diseases are usually associated with perinatal infection. Objective(s): The purpose of this study was to evaluate clinical and para-clinical manifestations in newborns that contracted the infection after birth. Method(s): This observational research was conducted from October 2020 to March 2022 to examine postnatal SARSCoV2 infection in infants admitted to the NICU or neonatal ward at the Children's Medical Center in Tehran, Iran. Inclusion in the study was open to neonates who had positive RT-PCR results postnatally. Result(s): In total, 55 newborns were confirmed to have postnatal SARSCOV2. Fever was the most frequently observed symptom, with 35 (61%). Necrotizing enterocolitis was seen in 18% of neonates, and 30% of them were preterm. Neutropenia was seen in 34% of cases, with five cases having severe neutropenia. All neonates had a normal platelet count. Twenty percent of patients showed C-reactive protein higher than 6 mg/L. Two newborns had co-existing bacterial urinary tract infections. Our neonates didn't require antiviral, anticoagulant, or corticosteroid medications, and they recovered while receiving only supportive care. Everyone in the group of newborns was discharged without complications, and there were no deaths. Conclusion(s): The high rate of fever, high C-reactive protein, and neutropenia in SARSCoV2 neonates suggests that more observational research is needed to compare these symptoms to bacterial sepsis to avoid the overuse of antibiotics in these patients.Copyright © 2023, Author(s).

Report of the Association Between Multisystem Inflammatory Syndrome and Severe Myocarditis

Introduction: The people worldwide have been affected by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection since its appearance in December, 2019. Kawasaki disease-like hyperinflammatory shock associated with SARS-CoV-2 infection in previously healthy children has been reported in the literature, which is now referred to as a multisystem inflammatory syndrome in children (MIS-C). Some aspects of MIS-C are similar to those of Kawasaki disease, toxic shock syndrome, secondary hemophagocytic syndrome, and macrophage activation syndrome. Case Presentation: This study reported an 11-year-old boy with MIS-C presented with periorbital and peripheral edema, abdominal pain, elevated liver enzymes, severe right pleural effusion, moderate ascites, and severe failure of right and left ventricles. Conclusion(s): Due to the increasing number of reported cases of critically ill patients afflicted with MIS-C and its life-threatening complications, it was recommended that further studies should be carried out in order to provide screening tests for myocardial dysfunction. Adopting a multidisciplinary approach was found inevitable.Copyright © 2023, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

Isometric thumb extension exercise as part of a multimodal intervention for de Quervain's syndrome: A randomised feasibility trial

Introduction: de Quervain's syndrome is a painful condition commonly presented to hand therapists. Exercise is utilised as an intervention, but isometric exercise has not been investigated. We aimed to assess the feasibility and safety of isometric thumb extension exercise for de Quervain's syndrome and to explore differences between high-load and low-load isometric exercise. Method(s): This parallel-group randomised clinical feasibility trial included individuals with de Quervain's syndrome. All participants underwent a 2 week washout period where they received an orthosis, education, and range of motion exercises. Eligible participants were then randomised to receive high or low-load isometric thumb extension exercises, performed daily for 4 weeks. Feasibility and safety were assessed by recruitment and drop-out rates, adherence, adverse events, and participant feedback via semi-structured interviews. Secondary outcomes included patient-reported outcomes for pain and function, and blinded assessment of range of motion and strength. Result(s): Twenty-eight participants were randomised. There were no drop-outs after randomisation, and no serious adverse events. Adherence to exercise was 86.7%, with 84% of participants stating they would choose to participate again. There were clinically and statistically significant improvements in pain and function over time (p < 0.001) but not in range of motion or strength. There were no statistically significant between-group differences. Conclusion(s): Isometric thumb extension exercise within a multimodal approach appears a safe and feasible intervention for people with de Quervain's syndrome. A large multi-centre trial would be required to compare high- and low-load isometric exercises. Further research investigating exercise and multimodal interventions in this population is warranted.Copyright © The Author(s) 2023.

A case of erythema nodosum after vaccination against COVID-19.

A case report of 52-years-old male with erythema nodosum, fever and malaise that developed seven days after second dose of mRNA vaccine Comirnaty (Pfizer-BioNTech) against coronavirus SARS-CoV-2. The most common causes of erythema nodosum were ruled out and the patient was treated with systemic corticotherapy with a very good effect. Because of the time association between the development of erythema nodosum and the second dose of mRNA vaccine, findings of high titres of anti-SARS-CoV-2 IgG antibodies in the blood, the case was reported to national regulation authority (State Institute for Drug Control) as a possible side effect of the mRNA vaccine Comirnaty.Copyright © 2021, EEZY Publishing, s.r.o.. All rights reserved.

Development of warm autoimmune hemolytic anemia after initiation of Ruxolitinib in a patient with STAT1 gain-of-function mutation

Introduction: STAT1 gain-of-function (GOF) disease is associated with chronic mucocutaneous candidiasis (CMC) and a broad spectrum of infectious, inflammatory, and vascular manifestations. The Janus Kinase inhibitor ruxolitinib has been used successfully for CMC and autoimmune phenomena. We describe a case of warm autoimmune hemolytic anemia (WAIHA) in a patient with STAT1 GOF disease after initiating ruxolitinib. Case report: A 36-year-old man with STAT1 c.850G>A (p.Glu284Lys) mutation presented with CMC as well as recurrent viral and bacterial infections, lymphadenopathy, enteritis, nodular regenerative hyperplasia (NRH) and splenomegaly. Immune workup confirmed a combined immunodeficiency with hypogammaglobulinemia and T-cell lymphopenia. Ruxolitinib was initiated at 5 mg twice daily (due to pre-existing thrombocytopenia) with up titration over 3 months to 20 mg twice daily. He improved with weight gain, increased energy, resolution of chronic anemia, and improved lymphadenopathy and splenomegaly on imaging. Serum CXCL9 only minimally decreased from 4660 pg/ml to 3990 pg/ml. Soon after reaching ruxolitinib 20 mg twice daily, he developed JC viremia, prompting dose reduction to 15 mg BID. Within two weeks, he developed a non-COVID upper respiratory tract infection followed by fatigue, shortness of breath with ambulation, and dark urine. Emergency evaluation revealed warm antibody positive hemolytic anemia with a hemoglobin of 5 g/dL, and worsened thrombocytopenia. He was treated with blood transfusions, pulse steroids, and high-dose IVIG with stabilization but continued hemolysis. Due to the JC viremia, there was concern to give rituximab with increased PML risk. Bone marrow showed trilineage hematopoiesis, a mild increase in megakaryocytes and RBC precursors, and a loss of B-cell progenitors with retention of mature B cells. His B and T lymphocyte numbers had increased since prior to ruxolitinib, with a predominance of Tfh1-cells (58.7% of total Tfh-cells). He was started on sirolimus with a slow taper of prednisone with continued stable hemoglobin and platelets, and resolution of hemolysis after 3 months. Conclusion(s): To our knowledge, this is the first case of a STAT1 GOF patient developing WAIHA while receiving ruxolitinib therapy. Treatment choices were complicated by the risks of PML. Sirolimus combined with ruxolitinib allowed wean of corticosteroid and subsequent resolution of hemolysis.Copyright © 2023 Elsevier Inc.

Comparative effectiveness and safety of a pharmacist-managed protocol for the transition from intravenous to subcutaneous insulin

Purpose: To evaluate the effectiveness and safety of a pharmacist-managed protocol for transitioning critically ill patients from intravenous (iv) to subcutaneous insulin compared with a provider-managed process. Method(s): This single-center, retrospective, observational study included patients admitted to the medical or surgical/trauma intensive care unit who received a continuous infusion of iv insulin from January 2019 to April 2021. Patients were excluded if they were less than 18 years of age, pregnant, incarcerated, or received iv insulin for the diagnosis of diabetic ketoacidosis, hyperglycemic hyperosmolar state, calcium channel blocker or beta blocker overdose, or hypertriglyceridemia. The primary outcome was the percentage of blood glucose (BG) concentrations within the target range of 70-150 mg/dL from 0 to 48 h following transition to subcutaneous insulin. Secondary outcomes included percentage of BG concentrations within goal range following transition at 0-12 h and 12-24 h, incidence of hypo- and hyperglycemia, and percentage of patients requiring dose adjustments after initial transition. Result(s): A total of 110 unique patients were included with 70 patients in the provider-managed group and 40 patients in the pharmacist-managed group. On average, pharmacists transitioned patients to 63% basal insulin based on their 24-h total day dose of insulin. The pharmacist-managed group achieved glycemic control in 53% of transitions at 12 h, 40% at 24 h, and 47% from 0 to 48 h, while the provider group achieved glycemic control in 25% of transitions at 12 h, 12% at 24 h, and 18% from 0 to 48 h (p < 0.001 for all time points). As for safety end points, the pharmacist-managed group demonstrated lower rates of hypoglycemia (p = 0.001), severe hypoglycemia (p = 0.332), hyperglycemia (p < 0.001), and severe hyperglycemia (p < 0.001) compared with the provider-managed group. Conclusion(s): Pharmacists can effectively and safely transition critically ill patients from iv to subcutaneous insulin utilizing a standardized protocol.Copyright © 2023 Pharmacotherapy Publications, Inc.

Chilblain lupus erythematosus associated with systemic lupus erythematosus: A classic diagnosis in a current epidemiological context

Objectives: Chilblain lupus erythematosus (LE) is a rare chronic cutaneous lupus erythematosus (CCLE) characterized by the appearance of violaceous plaques in acral regions most exposed to cold. The isolated form affects middle-aged women, while the familial form manifests in early childhood and is associated with mutations in the TREX1 gene. Result(s): A 13-year-old adolescent, with no relevant family history, was referred in March 2021 for suspected chilblain-like lesions associated with COVID-19 infection. The patient presented with multiple violaceous papules on hands and feet. The lesions were slightly painful. Small hyperkeratotic papules were also observed on finger pads. Physical examination also revealed some aphthae affecting the lips. No other systemic symptoms were reported. A skin biopsy and blood tests were performed due to presumed chilblain LE with probable systemic involvement. Histology revealed basal vacuolar damage and intense perivascular and periadnexal lymphocytic inflammatory dermal infiltrate. Remarkably, mucin was noted among the collagen bundles. Leukopenia and positive ANA antibodies (titre 1:320) were detected. Complement levels were normal. SARS-CoV2 infection was ruled out. Skin lesions disappeared within 1 month under topical corticosteroids. Hydroxychloroquine was afterwards started by Rheumatology without recurrence of skin symptoms until last follow-up. Discussion(s): We present an uncommon case of an adolescent with systemic LE presenting as chilblain LE. Chilblain LE can be accompanied by other discoid CCLE. It can progress to systemic LE in up to 20% of patients, especially when concomitant CCLE is present. This rare presentation of CCLE should be differentiated from typical chilblain and other resembling lesions, such as SARS-CoV2-associated chilblain and acral purpuric lesions (COVID toes). The Mayo Clinic diagnostic criteria can be helpful, particularly in this last SARS-CoV2 outbreak scenario, when the reporting of similar skin lesions has been significant.

COPD Exacerbation Profile in Chile: Preliminary Results from Integramedica Cohort 2018-2020

Objectives: To describe demographic characteristics, comorbidities, and exacerbations in a cohort of patients with COPD in Chile. Method(s): Retrospective cohort study using INTEGRAMEDICA (a network of ambulatory medical centers) electronic medical records of patients with COPD aged >=40 years at index with data available one year before (baseline) and after (follow-up) index. Index date was fixed at 28-Feb-2019 to avoid including data from the COVID-19 pandemic. Moderate and severe exacerbations were defined as prescription of systemic corticosteroid/antibiotics and emergency visit/hospitalization, respectively. Result(s): In total, 19,000 patients were included. In the baseline period, 86% (n=16,400) had no moderate or severe exacerbations (NMSE), 13% (n=2,503) had only moderate exacerbations (OME) and <1% (n=96) had >=1 severe exacerbation (SEV). Mean age/proportion of females was: 64 years/60% (total cohort), 65 years/59% (NMSE), 61 years/67% (OME) and 73 years/62% (SEV). The four most frequent comorbidities were: hypertension (total: 17.6%;NMSE: 16.2%;OME: 26.0%;SEV: 24.0%), asthma (total: 8.9%;NMSE: 7.8%;OME: 15.3%;SEV: 17.7%), diabetes type 1/2 (total: 6.3%;NMSE: 5.9%;OME: 9.1%;SEV: 7.3%) and congestive heart failure (total: 3.2%;NMSE: 3.2%;OME: 2.9%;SEV: 4.2%). The proportion of patients with >=1 moderate/severe exacerbation during follow-up was 14% (total), 10% (NMSE), 38% (OME) and 35% (SEV). The severe exacerbation rate was 2.00 per 1,000 person-years in the overall population and increased based on exacerbation history (NMSE: 0.91;OME: 1.60;SEV: 197.92) Conclusion(s): Preliminary results indicate that severe exacerbations were more frequent in patients with a history of SEV compared with patients with a history of OME or NMSE. In addition, comorbidities were more frequent in patients with a history of exacerbation. To improve patient health outcomes, strategies with a multisectoral approach should be prioritized as COPD can coexist with, and be aggravated by, other chronic comorbidities. Funding(s):GSK [209968].Copyright © 2023

High-Dose Steroids in COVID-19 Related Acute Respiratory Distress Syndrome: A Proposed Protocol

Introduction: The introduction of dexamethasone in the treatment of COVID-19 began in late 2020 after evidence emerged demonstrating that treatment with corticosteroids reduced mortality in those infected with severe COVID-19.1 Current guidelines suggest the use of Dexamethasone 6mg OD for 7-10 days for those requiring oxygen. A small proportion of patients in the intensive care unit do not respond to the usual dosing of dexamethasone. A treatment often advocated following discussion with the regional ECMO centre was high-dose steroid therapy.2-3 No guidance existed regarding the use of high-dose steroids in ARDS secondary to COVID-19. We believed there was inconsistency in patient selection, screening, dosing and monitoring. A protocol was needed to simplify this process. Objective(s): To develop a simple protocol for the use of high-dose steroids in COVID-19 related ARDS that provided the user with information on: 1. When to consider high-dose steroids 2. The precautions that should be taken to exclude infection prior to commencing high-dose steroids 3. The monitoring required while receiving high-dose steroids 4. A proposed treatment regimen Methodology and Results: A literature review of treatment regimens for high-dose steroids in COVID-19 ARDS was undertaken. We also included trials involving non-COVID-19 ARDS.3-4 A local evidence-based protocol for the use of high-dose steroids in COVID-19 related ARDS was designed. Following peer review by the wider MDT the protocol was first trialled, reviewed, and then adopted. An extended guideline with scientific context together with a quick reference bedside poster were launched. Conclusion(s): The protocol provided a user-friendly summary of the information required to safely use high-dose steroids for the treatment of COVID-19 related ARDS. The algorithm has now been adopted in several units and has been submitted for consideration as a network wide resource. Feedback from users has been positive and we will seek to review and update this guidance as further evidence emerges in this evolving condition.

Acenocoumarol-Induced Diffuse Alveolar Hemorrhage: A Case Report.

Diffuse alveolar hemorrhage (DAH) is bleeding into the alveolar spaces of the lung. DAH is often associated with systemic autoimmune diseases, coagulation disorders, drugs, inhaled toxins, or transplantation. This study describes a rare case of acenocoumarol-induced DAH, a pulmonary disorder, which has not been reported before. A 48-year-old male presented with a history of rheumatic heart disease with mitral stenosis with moderate mitral regurgitation status post mitral valve replacement. He was taking acenocoumarol but did not keep his prothrombin time-international normalized ratio (PT-INR) monitoring and came to the hospital with complaints of cough, hemoptysis, and breathlessness. Chest x-ray and high-resolution computed tomography (HRCT) thorax were done which revealed diffuse patchy opacities and pulmonary hemorrhage, respectively. After nine days of hospital stay with appropriate management with corticosteroids, antibiotics, and intravenous fluids, the patient was doing well.

Rheumatic Fever Revealed by Pulmonary Involvement: A Case Report.

Rheumatic fever (RF) is a significant public health problem in underdeveloped countries, and its diagnosis is based on modified Jones criteria. However, there are rare manifestations not included in these criteria that can complicate this condition. We present a case report of a 21-year-old Moroccan female with RF revealed by pulmonary involvement. The patient had no known rheumatic fever. She presented with a two-week history of joint pain, severe chest pain, and shortness of breath. On clinical examination, she was febrile with a palpable left knee joint effusion. Laboratory tests indicated elevated levels of inflammation markers and moderate hepatic cytolysis. The thoracic CT scan revealed extensive bilateral alveolar-interstitial parenchymal involvement. The left knee joint puncture showed an inflammatory fluid without germs or microcrystals. Antibiotic therapy with ceftriaxone and gentamycin was ineffective. Echocardiography revealed rheumatic poly valvulopathy with mitral valve narrowing and moderate to severe mitral insufficiency. Streptolysin O antibody levels were high. The diagnosis of RF complicated by rheumatic pneumonia was made. Treatment with amoxicillin and prednisone led to favorable outcomes.

Intermediate- to high-dose dexamethasone versus low-dose dexamethasone in patients with COVID-19 requiring respiratory support: a systematic review and meta-analysis of randomized trials.

The present review critically appraised the randomized clinical trials that compared mortality outcomes between intermediate- to high-dose dexamethasone and low-dose dexamethasonein patients with COVID-19 and reported pooled mortality risk estimates associated with these two dosing regimens of dexamethasone. The systematic searching of electronic databases was limited to randomized clinical trials that compared mortality outcomes between intermediate- to high-dose dexamethasone with low-dose dexamethasone in patients with COVID-19 requiring respiratory support. The primary outcome of interest in this review was all-cause mortality. A total of eight trials with 1800 patients randomized to receive intermediate to high-dose dexamethasone and 1715 patients randomized to low-dose dexamethasone were included. The meta-analysis of six trials revealed no significant difference in the risk of 28-day all-cause mortality between intermediate- to high-dose dexamethasone and low-dose dexamethasone (odds ratio 1.16, 95% confidence interval, 0.77-1.74). Similarly, the meta-analysis of five trials revealed no significant difference between the two doses regarding 60-day all-cause mortality (odds ratio 0.96, 95% confidence interval 0.74-1.26). The results suggest intermediate- to high-dose dexamethasone to be as effective as low-dose dexamethasone in reducing the risk of mortality among patients with COVID-19 requiring respiratory support. However, higher dexamethasone doses could expose patients with COVID-19 to an increased risk of adverse events, such as hyperglycemia.

Factors Associated With Prolonged Ventilation in Patients Receiving Prone Positioning Protocol With Muscle Relaxants for Severe COVID-19 Pneumonia.

BACKGROUND: Prone positioning and neuromuscular blocking agents (NMBAs) are frequently used to treat severe respiratory failure from COVID-19 pneumonia. Prone positioning has shown to improve mortality, whereas NMBAs are used to prevent ventilator asynchrony and reduce patient self-inflicted lung injury. However, despite the use of lung-protective strategies, high death rates in this patient population have been reported. METHODS: We retrospectively examined the factors affecting prolonged mechanical ventilation in patients receiving prone positioning plus muscle relaxants. The medical records of 170 patients were reviewed. Subjects were divided into 2 groups according to ventilator-free days (VFDs) at day 28. Whereas subjects with VFDs < 18 d were defined as prolonged mechanical ventilation, subjects with VFDs ≥18 d were defined as short-term mechanical ventilation. Subjects' baseline status, status at ICU admission, therapy before ICU admission, and treatment in the ICU were studied. RESULTS: Under the proning protocol for COVID-19, the mortality rate in our facility was 11.2%. The prognosis may be improved by avoiding lung injury in the early stages of mechanical ventilation. According to multifactorial logistic regression analysis, persistent SARS-CoV-2 viral shedding in blood (P = .027), higher daily corticosteroid use before ICU admission (P = .007), delayed recovery of lymphocyte count (P < .001), and higher maximal fibrinogen degradation products (P = .039) were associated with prolonged mechanical ventilation. A significant relationship was found between daily corticosteroid use before admission and VFDs by squared regression analysis (y = -0.00008522x2 + 0.01338x + 12.8; x: daily corticosteroids dosage before admission [prednisolone mg/d]; y: VFDs/28 d, R2 = 0.047, P = .02). The peak point of the regression curve was 13.4 d at 78.5 mg/d of the equivalent prednisolone dose, which corresponded to the longest VFDs. CONCLUSIONS: Persistent SARS-CoV-2 viral shedding in blood, high corticosteroid dose from the onset of symptoms to ICU admission, slow recovery of lymphocyte counts, and high levels of fibrinogen degradation products after admission were associated with prolonged mechanical ventilation in subjects with severe COVID-19 pneumonia.