Infeccao Aguda Por Citomegalovirus Associada a Glomerulonefrite Rapidamente Progressiva No Paciente Em Terapia De Manutencao Para Leucemia Pro Mielocitica Aguda Com Fusao Pml Rara

Objetivo: O presente estudo tem por objetivo relatar caso de infeccao aguda por citomegalovirus associada a glomerulonefrite rapidamente progressiva no paciente em terapia de manutencao para leucemia pro mielocitica aguda. Relato de caso: Paciente masculino de 25 anos, sem comorbidades, em seguimento no servico de hematologia da UNIFESP por quadro de Leucemia Pro Mielocitica Aguda (diagnostico em julho/2021), em protocolo de manutencao desde janeiro/2022 com 6-mercaptopurina, metotrexato e ATRA, em remissao morfologica e molecular, evolui com quadro de febre diaria ha 10 dias associada a odinofagia e tosse, com linfopenia, sem alteracoes ao exame fisico e rastreio infeccioso ambulatorial negativo. Solicitadas pesquisas de Citomegalovirus, Parvovirus, Epstein-Barr e SARS-Cov-2, suspensos os farmacos do protocolo de manutencao e indicada internacao hospitalar. Sem melhora do quadro relatado acima, paciente evoluiu com pancitopenia associada a um aumento de DHL e ferritina, sem figuras de hemofagocitose no aspirado de medular, alem de sindrome nefrotica e lesao renal rapidamente progressiva KDIGO III com indicacao de dialise. Visto tambem que nao haviam esquizocitos em sangue periferico, alteracoes no coagulograma ou outras disfuncoes organicas. Constatadas sorologias IgM e IgG positiva para CMV alem de carga viral serica elevada para CMV, confirmando a infeccao aguda por CMV associada a glomerulonefrite rapidamente progressiva. A biopsia renal demonstrou podocitos com alteracoes degenerativas, ausencia de depositos glomerulares e infiltrado linfocitario intersticial. Apos tratamento adequado com ganciclovir paciente evoluiu com melhora da febre e retorno da funcao renal de base. Discussao: Em individuos imunocompetentes a infeccao assintomatica pelo citomegalovirus e comum, e quando ocorrem sintomas ha um quadro clinico semelhante a mononucleose infecciosa, que pode cursar com sintomas de vias aereas superiores associados a linfadenopatia, esplenomegalia e linfopenia. No contexto clinico dos pacientes imunossuprimidos e mais comum que ocorra uma reativacao viral que pode levar a lesao organica aguda com acometimento de orgao unico ou lesao multissitemica. E descrito em literatura que a infeccao por citomegalovirus associada a lesao renal aguda exclusiva esta mais associada ao contexto do paciente imunossuprimido pos transplante renal em uso de drogas com maior potencial imunossupressor, diferentemente do caso relatado. Conclusao: A partir das manifestacoes clinicas e do rastreio infeccioso direcionado as infeccoes oportunistas que acometem o paciente imunossuprimido foi possivel associar o quadro de glomerulonefrite rapidamente progressiva a infeccao aguda por CMV, quadro pouco conhecido na pratica clinica, visto a predilecao para doenca invasiva em sistema nervoso central, retina, trato gastrointestinal e trato respiratorio. Alem disso, notou-se que nesse caso o tratamento com Ganciclovir foi efetivo neste tipo de apresentacao clinica, visto o retorno da funcao renal de base apos o tratamento adequado. Copyright © 2022

Eyeing up the pandemic: A literature review of the ocular manifestations of COVID-19

Background Since the onset of SARS-CoV-2, this novel virus has been the focus of many studies seeking to improve the ability of healthcare systems to withstand pandemics against it. COVID-19 has pulmonary and cardiovascular implications, but its ocular effects remain a subject of debate. Objectives The objective of our narrative review is to explore the ophthalmic manifestations of COVID-19, identify research gaps, and act as a guide for further research in the field. Methods The literature search involved original studies published from January 1, 2020, up until August 20, 2021, on the PubMed database. Title and screening and full text review were conducted by two independent researchers, with a third researcher resolving conflicts. Studies that met the set inclusion criteria were used for data synthesis. Results The preliminary search generated 59 articles, with 25 being data extracted. Conjunctivitis, epiphora and ocular irritation were consistently stated anterior segment manifestations. Posterior segment implications were mostly subclinical, including cotton-wool spots and retinal nerve-fiber layer thinning, but some cases were more detrimental, such as central retinal vein occlusion, posterior segment inflammation, retinal hemorrhages, and fungal infiltration. RT-PCR tests were unreliable in detecting SARS-CoV-2 infection in ocular tissues, potentially due to methodological limitations. Conclusion Anterior segment findings were significant manifestations of the novel coronavirus, but a clear resolution of posterior segment findings is yet to be made. In the absence of reliable COVID-19 ocular sample tests, all links made to SARS-CoV-2 etiology remain tentative;further research must be directed to the field with modified testing strategies. Copyright © 2022 University of Jordan,Deanship of Scientific Research. All rights reserved.

PERSISTENT POST-DISCHARGE SYMPTOMS after COVID-19 in RHEUMATIC and MUSCULOSKELETAL DISEASES

Background: The COVID-19 pandemic continues worldwide and has had a strong impact on public health. As the pandemic evolves, efforts have been inten-sifed to identify persistent symptoms associated with the infection once resolved have intensifed. Objectives: We aimed to describe persistent symptoms and sequelae in patients with rheumatic and musculoskeletal diseases (RMD) after admission due to Covid-19. We also compared the role of autoimmune rheumatic diseases (ARD) with that of non-autoimmune rheumatic and musculoskeletal diseases (NARD) in persistent symptoms and sequelae. Methods: We performed an observational study of patients with RMD who attended a rheumatology outpatient clinic in Madrid and required admission to hospital due to Covid-19 (1st March-30th May 2020) and survived. The study began at discharge and ran until 1st October 2020. The main outcomes were persistence of symptoms and sequelae related to Covid19. The independent variable was the RMD group (ARD and NARD). The covariates were sociode-mographic data, clinical fndings, and treatment. We ran a multivariate logistic regression model to assess the risk of the main outcomes by RMD group. Results: We included 105 patients, of whom 51.5% had ARD and 68.57% reported at least 1 persistent symptom. The most frequent were dyspnea, fatigue, and chest pain. Sequelae were recorded in 31 patients. These included lung damage in 10.4% of patients, lymphopenia in 10%, central retinal vein occlusion (1 patient), and optic neuritis (1 patient). Two patients died. Eleven patients required readmission owing to Covid-19 problems (16.7% ARD vs 3.9% NARD;p=0.053). No statistically signifcant differences were found between RMD groups in the fnal models. Conclusion: Many RMD patients have persistent symptoms, as in other populations. Lung damage is the most frequent sequela. Compared to NARD patients, ARD patients do not seem to differ in terms of persistent symptoms or sequelae, although ARD patients might generate more readmissions due to Covid-19.

45th Annual Meeting of the American Society of Neuroimaging

The proceedings contain 31 papers. The topics discussed include: brain abscess appearing 20 years post craniotomy;postoperative diffusion restriction in the proximal optic nerve: optic neuropathy or central retinal artery occlusion?;magnetic resonance imaging as a prognostic disability marker in clinically isolated syndrome: a systematic review;bilateral internuclear ophthalmoplegia caused by unilateral infarction;neuroaspergillosis in a patient with chronic lymphocytic leukemia as progressively worsening ischemic infarct;neuroimaging in mitochondrial short-chain enoyl-coa hydratase 1 deficiency: a progressive encephalomyelopathy starting in utero;childhood-onset neurodegeneration with brain atrophy: imaging findings of a rare diagnosis;multiple sclerosis associated with Balo-like lesions post-coronavirus disease 2019;and within-subject reproducibility of quantitative proton density mapping.

Retinal Manifestations in Rhinoorbito-cerebral Mucormycosis: A Cross-sectional Study

Introduction: Rhino-orbito-cerebral Mucormycosis (ROCM) is an uncommon but devastating fungal infection caused by Mucoraceae family fungi, which are angiotropic and filamentous, with significantly high morbidity and mortality despite treatment. Post Coronavirus Disease-2019 (COVID-19), there was a sudden surge in ROCM cases nationwide due to immunologically and metabolically compromised status. Aim: To describe retinal manifestations in ROCM in a tertiary eye care centre of Northern India. Materials and Methods: An analytic, cross-sectional and hospital-based study was conducted in Regional Institute of Ophthalmology, PGIMS Rohtak, Haryana, India, from May 2021 to September 2021. This study was conducted on 200 admitted patients of RCOM in the institute, which was only designated Nodal centre in Haryana, India. Detailed history was recorded in every patient regarding presenting symptoms, history of COVID-19, hospital stay, oxygen inhalation, steroid intake and immunisation. Thorough ocular examination was done in every patient including visual acuity, ocular movements and pupillary reactions. Dilated fundus examination was done by Indirect Ophthalmoscopy (IDO) for posterior segment evaluation. Contrast Enhanced Magnetic Resonance Imaging (CE-MRI) brain with orbit and Paranasal Sinus (PNS) was done in every patient to see the extent of spread and planning further management. Results: Out of 200 patients of ROCM, majority of patients (64/200) were of 51-60 year age group (32%) followed by 41-50 year age group (28%). Out of 200 cases of ROCM, 146 patients (73%) had history of COVID-19 infection in past and 134 (67%) patients had history of hospital stay during COVID-19 infection. Oxygen (O2) supplementation was given to 98 patients either at home or during hospital stay. History of steroid intake was present in 34 patients and 46 patients received injection Remedsivir. Only 12 patients had vaccine against COVID-19 and none of them were fully vaccinated. Most common presenting symptom was unilateral nasal stiffness (22%) followed by loss of vision (17%). Most common predisposing factor was Diabetes Mellitus (DM) in 78 patients (39%) followed by steroid intake in 34 patients (17%). Out of 200 patients, only 60 patients had retinal manifestations and most common was Central Retinal Artery Occlusion (CRAO) (35/60) and the main mechanism is the direct infiltration of central retinal artery due to angioinvasion of fungi from the orbit. Conclusion: CE-MRI brain with orbit is an important tool in diagnosing and monitoring progression of RCOM but it cannot provide information regarding retinal findings like CRAO, central retinal venous occlusion (CRVO), disc pallor and optic atrophy. Thus, the fundus examination of every ROCM patient should be emphasised, as it not only helps in categorising ROCM but also tells about the visual potential of affected eye. Patients with CRAO and combined vascular occlusion should be considered for exenteration on urgent basis, so that intracranial spread can be prevented and patient's life can be saved.

Modern a COVID-19 Vaccine-Induced Immune Thrombosis of Central Retinal Artery-Report of a Case

Objective: To report a rarely isolated central retinal artery occlusion (CRAO) following Coronavirus disease 2019 (COVID-19) Vaccine Moderna (mRNA-1273). Background: COVID-19 caused by severe acute respiratory syndrome coronavirus was firstly reported in Dec 2019 and became pandemic as of Mar 2020. Fortunately, novel rapidly developed COVID-19 vaccines are capable of lessening the pandemic effectively. As billions of people vaccinated, however, COVID-19 vaccine-induced thrombosis (VIT) are gradually emerging. Design/Methods: A previously healthy 70-year-old man presented with acute painless visual loss of the right eye five days after the first dose of Moderna vaccine. On examination of the right eye, visual acuity (VA) was counting finger at 15 cm. Fundoscopy revealed a diffuse whitened retina with cherry-red spot. Optical coherence tomography (OCT) showed hyperreflectivity. Screening tests for platelet and D-Dimer levels were unremarkable. CRAO was treated with clopidogrel and hyperbaric oxygen therapy. The serum level of anti-platelet factor-4 (PF4) antibody was 73.34 ng/ml (ref, 0-49.99 ng/ml).Two months later, VA was counting finger at 10 cm3 and OCT revealed hyperreflectivity and mild inner retina atrophy Results: COVID-19 vaccine-induced thrombosis and thrombocytopenia (VITT) based on the victims receiving AstraZeneca and Johnson & Johnson vaccines is through autoimmune antibody against PF4. VITT is typically manifested within 6-24 days post-vaccination;thrombotic sites are in the cerebral sinus, portal vein, splanchnic vein, and pulmonary emboli;as well as thrombocytopenia and increased level of D-Dimer. Our patient had isolated CRAO five days post-Moderna vaccination but normal platelet count and D-Dimer level. Moreover, VIT with isolated CRAO was not published on PubMed. Conclusions: VIT could occur in the unusual site such as CRAO in our case. Normal platelet and D-Dimer levels might not be sensitive tools to exclude VIT. Suspected patient with thrombotic event after COVID-19 vaccines should have anti-PF4 antibody test to assure an effective treatment.

Acute and sub-acute ocular manifestations in pediatric patients with COVID-19: A systematic review

Background: The coronavirus disease 2019 (COVID-19) pandemic has been the most challenging health problem in the last 2 years. Post-COVID-19 multisystem inflammatory syndrome of children (MIS-C) is a severe post-COVID-19 complication in pediatric patients. Ocular manifestations may be the first presentation of MIS-C, wherein prompt treatment may improve outcomes. In this systematic review, we aimed to summarize the acute and sub-acute ocular manifestations in pediatric patients with laboratory-confirmed COVID-19. Methods: We included all online primary studies, with no language restriction and published between January 1, 2019 and November 18, 2020, reporting any acute or sub-acute ocular manifestations in children with laboratory-confirmed COVID-19. PubMed/MEDLINE was searched using the following MeSH and Emtree terms: “eye,” “ophthalmologic,” “ocular,” “vision,” “conjunctivitis,” “severe acute respiratory syndrome coronavirus 2,” “SARS-CoV-2,” “corona,” “2019-nCoV,” “COVID19,” and “COVID.” The eligibility and quality of the selected records were assessed by two independent reviewers as per the Cochrane Handbook for Systematic Review. Results: A total of 1,192 records were identified electronically. Seven papers were extracted from the reference lists of the eligible records. Thirty-six papers met the inclusion criteria and were categorized into two subgroups according to acute or sub-acute presentation of ocular manifestations. Among 463 pediatric patients with COVID-19, 72 (15.5%) had acute ocular manifestations. There was one patient with central retinal vein occlusion and another with photophobia and diplopia associated with meningoencephalitis. Among 895 pediatric patients with post-COVID-19 MIS-C, 469 (52.4%) had ocular manifestations, which only included non-purulent conjunctivitis. Conclusions: Ocular manifestations have been reported in less than one-fifth of pediatric patients with acute COVID-19. Furthermore, conjunctivitis was the only ocular manifestation reported in half of the patients with MIS-C, and it may be missed easily due to its non-purulent nature. During the COVID-19 pandemic, pediatricians and health workers must remain vigilant for early detection of signs of this potentially fatal post-COVID-19 inflammatory syndrome.

Catastrophic covid-19 in a pregnant woman

Case Report We report here a case of a 26-year-old woman at week 29 of a pregnancy who was transferred to our hospital for OBGYN care after on the same day she presented to an outside facility for one day of vaginal bleeding. At the transferring facility she was noted to be hypertensive with concerns for pre-eclampsia, acute kidney injury and non-reactive nonstress test. She had not had any pre-natal care or screenings done. Upon arrival she was normotensive but became obtunded and emergently taken to the OR. She was found to have a 50% placental abruption with uterine atony, hemorrhaging, and unfortunately fetal demise. She tested positive for SARS-CoV-2 on screening though she had no initial respiratory symptoms. Following extubation, she was noted to have very labored breathing, continued disorientation, and repeatedly stated that she was blind. She was subsequently re-intubated both to protect her airway and due to her work of breathing. Chest imaging showed bilateral patchy opacifications of her lungs and she was initiated on treatments for COVID19 pneumonia. She was lymphopenic at this time with an absolute lymphocyte count of 800 cells/mm. She had not been vaccinated against SARS-CoV-2. Over her hospitalization, she underwent extensive workup. For her complaints of vision loss she underwent ophthalmologic exam which did not find uveitis or other changes consistent with syphilis but rather for ischemic central retinal vein occlusions. She had persistent hypoxic respiratory failure and ultimately necessitated tracheostomy due to prolonged dependence of mechanical ventilation support. Approximately 1 month after her hospitalization, she developed a new left lower lung opacification as well as scattered tree-in-bud nodular findings on chest CT imaging. On bacterial and culture workup she grew methicillin-susceptible Staphylococcus aureus as well as Aspergillus species (identification still pending). She was treated with a short course of cefazolin for bacterial pneumonia and was started on a 3-month course of isavuconazonium sulfate for probable COVID-19-associated pulmonary aspergillosis (CAPA). After a two-month long hospitalization, she had gradual clinical improvement and was transferred to a skilled nursing facility for long-term care. In this case, the devastating impact of COVID-19 disease in a young, unvaccinated, and pregnant woman is clearly seen, as are multiple sequelae. She unfortunately lost her pregnancy and developed severe visual impairments and several opportunistic respiratory infections. Her placental abruption, ischemic retinal vein occlusions and pulmonary aspergillosis were all felt to be directly attributable to her COVID19 disease. The case presented here serves as a cautionary tale that even the young are at risk for severe COVID-19 disease. Healthcare professionals should continue to advocate for screening and vaccination for these high-risk individuals.

And quickly there were ten: DADA2, experience from a center in Mumbai, India

Introduction: The number / phenotype of DADA2 continues to expand rapidly though series from Asia are scant. Objectives: Share experience with 10 DADA2 patients (9 unrelated families) identified over 2 years. Methods: We diagnosed the first case in April 2019 following which we recalled and diagnosed 4 more patients on renewed suspicion. In 2, their phenotypes did not match the initial provisional diagnosis of primary CNS vasculitis and inflammatory bowel disease (IBD) respectively while 2 had been treated as classic PAN. 4 patients were diagnosed prospectively on clinical suspicion and 1in whom we suspected syndromic bone dysplasia with inflammatory features was a diagnostic surprise. Results: 7/10 are males. Age of onset ranged from 4 months - 17 years 9 months. Referrals were by varied specialists including primary pediatrician, pediatric hematologist, ophthalmologist, adult neurologist and urosurgeon. Medium-vessel dominated disease was seen in 6 patients and in 3 we suspected a systemic autoinflammatory disease (SAID) {1-febrile relative of a previously diagnosed DADA2 patient, 1-IBD-like with cutaneous vasculitis,1- early onset prolonged fever with granulomatous mediastinal adenitis suspected Blau syndrome} and 1 patient with progressive deforming symmetric inflammatory arthropathy and acquired micrognathia. Cutaneous features were the commonest;seen in 7 patients and stroke was seen in 3. Other systems involved were musculoskeletal (5- including the bone dysplasia mimic described above),renal (4- notable were renal artery stenosis and perinephric hematoma), gastrointestinal (2- notable was bowel perforation), while ocular involvement was seen in 2 (notable being central retinal artery occlusion and episcleritis). Hematological features were seen in 5 and included pure red cell aplasia, persistent leucopenia and thrombocytopenia in 1 patient each and anemia in 2 (notable-unexplained anemia of infancy). None of the patients had exclusive hematological disease or immunodeficiency. 5 were homozygous for p.G47R variant and 2 are compound heterozygous with p.G47R and splice mutation c.753+2T>A and p.G47R and p.H219P respectively. Of those with p.G47R variant 4 belong to Agarwal community in whom endogamy is known. 2 patients born of a first cousin marriage (and even related three generations higher) have a homozygous pathogenic variant p.G358R. The patient with symmetrical skeletal affliction has a homozygous pathogenic variant in p.R169Q. All 4 patients in whom ADA2 enzyme assay was performed were deficient. 4 patients are on etanercept originator molecule and 6 on etanercept biosimilar with treatment duration varying between 2 weeks to 116 months and no drug side effects. 9 patients are in clinical remission off steroids and growing well with no restriction of activities of daily living. 2 have residual hypertension. 1 unvaccinated patient contracted COVID 19 and recovered uneventfully. Conclusion: Since our first case in 2019, DADA2 is now the commonest SAID in our cohort (10/44). Due to its initial presentation to varied specialists we need to spread awareness to increase diagnosis. We report an unusual phenotype mimicking a bone dysplasia and alert colleagues that the classic phenotype originally described is being overshadowed by a wide spectrum. The p.G47R mutation is the commonest in our series and seen in the endogamous Agarwal community. The disease is very responsive to etanercept and treatment is progressively affordable with etanercept biosimilar. Residual hypertension may be seen with renal involvement and 1 patient with COVID19 on etanercept recovered uneventfully.