Favorable Clinical Course Research Articles

An alveolate kidney

Rationale: Emphysematous pyelonephritis is a life-threatening infectious disease that requires early diagnosis and treatment. The disease is often misdiagnosed due to its diversity of clinical manifestations. Patient's concern: A 62-year-old woman was admitted to the emergency department following a 12-hour history of abdominal pain and dyspnea. Physical examination showed percussion pain on the right costovertebral angle. Besides, she had a history of diabetes mellitus and urinary calculus. Diagnosis: Emphysematous pyelonephritis. Intervention: The patient accepted antishock therapy, tight glucose control, and broad-spectrum anti-infective therapy. After stabilization of the general condition, an ultrasound-guided percutaneous nephrostomy was performed. Outcome: Her conditions became stable over the following days. She presented a favorable clinical course, with normalization of renal function and positive improvements in imaging findings in a month. Lessons: Early diagnosis and rapid medical management are the keys to successful treatment. CT is an important method for the diagnosis of emphysematous pyelonephritis. For patients with severe lesions, percutaneous renal drainage combined with active anti-infection should be given in time.

Conventional and Atypical Deep Penetrating Nevus, Deep Penetrating Nevus-like Melanoma, and Related Variants.

Simple SummaryAtypical deep penetrating nevus (DPN) is a unique skin tumor with an uncertain biologic/metastatic potential that may be difficult to distinguish from DPN (an indolent lesion) and DPN-like melanoma (an aggressive lesion) based on the results of histomorphologic analysis and commonly employed molecular studies such as fluorescence in situ hybridization and comparative genomic hybridization alone. Herein, we review the clinical, histomorphological, immunohistochemical, molecular, and cytogenetic characteristics of the DPN spectrum of lesions to try to better understand the prognosis of these lesions and possible treatment approaches.Deep penetrating nevus (DPN) is an uncommon acquired melanocytic lesion with a distinct histopathological appearance that typically behaves in an indolent manner. The lesion is characterized by a symmetrical proliferation of epithelioid to spindled melanocytes associated with abundant melanophages and wedge-shaped extension to the deep reticular dermis and subcutis. Pronounced cytologic atypia and mitotic figures are usually absent, which helps distinguish DPN from melanoma with a deep penetrating growth pattern. Recently, the concept of atypical DPN has been proposed for lesions that demonstrate borderline histomorphologic features and may be associated with lymph node deposits but lack the copy number aberrations typical of melanoma by either fluorescence in situ hybridization or comparative genomic hybridization. While most of these lesions have a favorable clinical course, rare lesions may progress to melanoma. In this review, we summarize the current literature on atypical DPNs with uncertain behavior/metastatic potential and outline the characteristics that distinguish these lesions from conventional DPN and melanoma with DPN-like features.

Cardiac MRI Findings of Myocarditis After COVID-19 mRNA Vaccination in Adolescents

BACKGROUND. A possible association has been reported between COVID-19 messenger RNA (mRNA) vaccination and myocarditis. OBJECTIVE. The purpose of our study was to describe cardiac MRI findings in patients with myocarditis after COVID-19 mRNA vaccination. METHODS. This retrospective study included patients without known prior SARS-CoV-2 infection who underwent cardiac MRI between May 14, 2021, and June 14, 2021, for suspected myocarditis within 2 weeks of COVID-19 mRNA vaccination. Information regarding clinical presentation, hospital course, and events after hospital discharge were recorded. A cardiothoracic imaging fellow and cardiothoracic radiologist reviewed cardiac MRI examinations in consensus. Data were summarized descriptively. RESULTS. Of 52 patients without known prior SARS-CoV-2 infection who underwent cardiac MRI during the study period, five underwent MRI for suspected myocarditis after recent COVID-19 mRNA vaccination. All five patients were male patients ranging in age from 16 to 19 years (mean, 17.2 ± 1.0 [SD] years) who presented within 4 days of receiving the second dose of a COVID-19 mRNA vaccine. Troponin levels were elevated in all patients (mean peak troponin I value, 6.82 ± 4.13 ng/mL). Alternate possible causes of myocarditis were deemed clinically unlikely on the basis of medical history, physical examination findings, myocarditis viral panel, and toxicology screening. Cardiac MRI findings were consistent with myocarditis in all five patients on the basis of the Lake Louise criteria, including early gadolinium enhancement and late gadolinium enhancement (LGE) in all patients and corresponding myocardial edema in four patients. All five patients had a favorable hospital course and were discharged from the hospital in stable condition with improved or resolved symptoms after hospitalization (mean length of hospital stay, 4.8 days). Two patients underwent repeat cardiac MRI that showed persistent, although decreased, LGE. Three patients reported mild intermittent self-resolving chest pain after hospital discharge, and two patients had no recurrent symptoms after discharge. CONCLUSION. In this small case series, all patients with myocarditis after COVID-19 vaccination were male adolescents and had a favorable initial clinical course. All patients showed cardiac MRI findings typical of myocarditis from other causes. LGE persisted in two patients who underwent repeat MRI. These observations do not establish causality. CLINICAL IMPACT. Radiologists should be aware of a possible association of COVID-19 mRNA vaccination and myocarditis and recognize the role of cardiac MRI in the assessment of suspected myocarditis after COVID-19 vaccination.

Malignant transformation of central neurocytoma with dissemination 17 years after initial treatment: illustrative case.

BACKGROUNDCentral neurocytomas usually have a favorable clinical course, and gross total resection (GTR) results in long-term survival. Recurrences of central neurocytomas are usually local, and dissemination is extremely rare.OBSERVATIONSA 24-year-old man who presented with vomiting was found to have a mass in the right lateral ventricle. After GTR, he received whole-brain irradiation and chemotherapy and had remained disease-free on follow-up for years. The review of the initial tumor revealed central neurocytoma. Seventeen years later, he presented with deterioration of memory, and magnetic resonance imaging showed an enhanced lesion in the left hippocampus. The enhanced lesion was resected, and the histological examination revealed that the tumor was a disseminated atypical central neurocytoma with frequent mitoses. Although he was treated with chemotherapy, the disseminated tumor slowly grew and invaded the brain. Massive brain invasion occurred without enhanced lesions, and he died 27 months after the tumor recurrence.LESSONSIn this patient, a central neurocytoma disseminated after an extremely long period of time. Once neurocytomas disseminate and show aggressive behavior, patients usually follow a poor course. Patients with central neurocytomas should be followed up for a long time.

Нормотензивная гидроцефалия Хакима — Адамса (научный обзор и личное наблюдение)

В обзоре отражены современная трактовка термина «нормотензивная гидроцефалия», данные об этиологии, патогенезе, особенностях клинических проявлений, диагностики. Описаны подходы нейрохирургического и консервативного лечения. Представлено личное наблюдение клинического случая верифицированной нормотензивной гидроцефалии (синдрома Хакима — Адамса), особенностью которого были молодой возраст пациента, благоприятное клиническое и нейрорадиологическое течение заболевания после нейрохирургического и медикаментозного лечения. Согласно литературным данным, эта патология чаще всего встречается у лиц пожилого возраста и может быть причиной деменции, нарушения ходьбы и функции тазовых органов. В работе обоснована важность дальнейшего изучения нормотензивной гидроцефалии в клинической практике.

Myocarditis after RNA-based vaccines for coronavirus.

BackgroundThe incidence of myocarditis after RNA-based vaccines for coronavirus has gained social and medical interest. MethodsWe performed an intention-to-treat meta-analysis, following the PRISMA statement. After a systematic search, without language restriction, 9 publications were selected. Two were excluded (one was only in subjects with age 12–17 and other might had included subjects from a larger publication). We followed the PRISMA guidelines for abstracting data and assessing data quality and validity. Data was verified by 2 investigators. ResultsWe analyzed 17,704,413 subjects, from 7 studies, that included 627 cases of confirmed myocarditis). The incidence of myocarditis was 0.0035% (95% CI 0.0034–0.0035). Mean incidence rate was 10.69 per 100.000 persons-year. Cases reported from Israel represented 45.14% from total (283 out of the 627). Only 1 case of fatal myocarditis or death was reported. There was significant heterogeneity between results. The meta-regression analysis excluded mean age, region, number of cases or number of people included as sources of heterogeneity. No small-study effect was observed (p = 0.19). Conclusions and relevanceMyocarditis incidence after RNA vaccines is very rare (0.0035%) and has a very favorable clinical course.

Clinicopathological investigation of secretory carcinoma cases including a successful treatment outcome using entrectinib for high-grade transformation: a case report

BackgroundSecretory carcinoma (SC) of the salivary gland is a recently described malignant tumor harboring characteristic ETV6-NTRK3 gene fusion. SC generally has a favorable clinical course, and is currently regarded as a low-grade carcinoma. However, a small subset of SCs demonstrates aggressive clinical features with histologically high-grade transformed morphology, the molecular pathogenesis of which has not yet been elucidated. In this study, we performed a clinicopathological and molecular genetic study of patients with SC of the head and neck displaying various clinical characteristics to investigate the differences of pathological and molecular genetics between low-grade and high-grade components of SC.Case presentationThree cases with SC of the head and neck, including a conventional low-grade SC and two high-grade transformed SCs are described. High-grade transformed SCs with histological features such as nuclear polymorphism, distinctive nucleoli and increased mitotic activity developed locoregional recurrence and distant metastasis. Immunohistochemical analysis revealed that low- and high-grade components showed different expression patterns for S-100 protein and mammaglobin, whereas all examined components were positive for p-STAT5. p53-positive cell population was markedly higher in one case with high-grade transformed SC. The proliferative activity of high-grade components was markedly increased, with the Ki-67 labeling index ranging up to 30–32%. A fluorescence in situ hybridization study with an ETV6 (12p13) break apart probe revealed split signals in the nuclei in all 3 cases. A targeted next-generation sequencing-based fusion assay demonstrated that all 6 clinical samples from the 3 patients showed the presence of the ETV6-NTRK3 fusion transcripts. One patient with high-grade transformed SC showed a dramatic clinical response to the pan-TRK inhibitor, entrectinib, for the treatment of locoregional recurrence and pulmonary metastasis.ConclusionsHigh-grade transformed SC showed aggressive clinical and pathological features with increased Ki-67 labeling index. Molecular genetic study of gene rearrangement appears to be beneficial treatment as the presence of ETV6-NTRK3 translocation may represent a therapeutic target in SC, particularly the high-grade transformed type.

Continuous cyclosporine a infusion in patients with severe Kawasaki disease.

The efficacy and safety of continuous intravenous infusion of cyclosporine A (CICsA) in patients with intravenous immunoglobulin-resistant Kawasaki disease are unclear. Between 2010 and 2020, 83 patients with Kawasaki disease that was not responsive to intravenous immunoglobulin (total dose ≥ 4 g/kg) were enrolled. All patients were started on CICsA (3 mg/kg/day) and switched to oral cyclosporine A (CsA) (4-6 mg/kg/day). Treatment efficacy, occurrence of coronary artery lesions (CALs), and laboratory parameters were evaluated. Patients were divided into two groups according to CICsA response: the responder group (afebrile ≤24 h after CICsA without additional treatment) and the weak responder group (afebrile >24 h after CICsA requiring additional treatment). Fifty-five patients became afebrile within 24 and 74 h became afebrile in less than 72 h. Adverse events included hypertension in four and hyperkalemia in two patients. Thirty-nine patients were defined as responders and 44 patients as weak responders. There were no significant differences in CAL between the two groups. In weak responders, white blood cells, neutrophils, and C-reactive protein levels were higher, and albumin, immunoglobulin G, and CsA concentration were lower than in responders, indicating that weak responders had more severe inflammatory findings. However, there were no significant differences in CAL. Logistic regression analysis revealed that the response to treatment for CICsA was associated with immunoglobulin G levels at baseline and CsA concentrations the day after CICsA. Although CICsA required additional treatments in about half of the cases, a favorable clinical course was observed by using this strategy, especially for reducing CAL.

Parechovirus neonatal sepsis and meningitis – a (still) poorly recognised agent

Human parechovirus (HPeV), a Picornaviridae virus, is a microorganism associated with respiratory and gastrointestinal infections, in most cases with a benign clinical course. However, some serotypes have been recently associated with a more serious clinical outcome in young children, namely sepsis-like disease and meningitis. In this report, we describe the case of a previously healthy, 11-day-old infant in our Paediatric Emergency Department who presented with high fever, irritability and poor feeding. No other accompanying symptoms, such as respiratory, gastrointestinal or urinary, were shown by the patient. Family history unveiled an 18-month-old sibling with an upper respiratory tract infection. Physical examination was unremarkable. Laboratory testing revealed a normal total white cell count with lymphopenia and a maximum C-reactive protein value of 21.4 mg/L. Cerebrospinal fluid (CSF) analysis showed pleocytosis with high proteinorrachia and normal glycorrhachia. With the clinical suspicion of sepsis, she was hospitalized for clinical surveillance, and empirical antibiotics were administered. Although the bacteriological exams of blood and CSF were negative, RNA of an HPeV was detected in the CSF. She had a favourable clinical course, the cerebral ultrasound was normal, and the clinical follow-up showed adequate psychomotor development until today (18 months old). Recent publications suggested HPeV as one of the major agents of neonatal sepsis and meningitis. Similarly, several other studies reported significant neurological impairments in infants with HPeV infection. In line with these recent findings, we believe this clinical case further supports the need for more extensive research in viral aetiology and in particular of this, not so uncommon, agent in order to avoid unnecessary and potentially harmful interventions in newborns presenting with a sepsis-like clinical picture.

Hypothyroidism in Conakry: Epidemiological, Clinical and Therapeutic Aspects

Hypothyroidism is a frequent endocrine disorder that can occur at any age and predominantly affects women. The etiologies are diverse and may vary according to the geographical and socio-demographic context. The objective of our work was to describe the epidemiological, clinical and therapeutic characteristics of hypothyroidism in Conakry, Guinea. Materials and Method: This was a descriptive study with prospective data collection, over the period from December 2016 to May 2021. It focused on patients seen at the endocrinology consultation of Conakry University Hospital. Epidemiological, clinical, etiological, therapeutic, and evolutionary variables of patients diagnosed or followed-up for hypothyroidism were collected and analyzed. The diagnosis of hypothyroidism was defined by elevated TSH and/or decreased FT4/FT3. Results: Out of a total of 290 patients who consulted for thyroid pathology, hypothyroidism concerned 49 patients, i.e. , a frequency of 14%. Women were the most affected with a sex ratio of 0.13. The mean age of patients was 48.65 ± 19.93 years with extremes of 2 years and 80 years. Hypo-metabolic syndrome was the main clinical sign and was manifested mainly by constipation found in 48.89% of cases. TSH was elevated in all cases with a mean level of 24.56 ± 14.17 mIU/ml. Hypertension was the most frequently associated pathology (57%). Three etiological groups of hypothyroidisms were found. These were thyroidectomy in 42.85% of cases, thyroiditis in 34.69% of cases and post synthetic antithyroid hypothyroidism. All patients were treated with L-thyroxin, with a favorable clinical course. Follow-up was regular in 16 patients (32.65%). Conclusion: Hypothyroidism is common in this population, and primarily affects women. Thyroid surgery was the main cause of hypothyroidism in this work.

Tocilizumab as a Treatment for Cytokine Storm in COVID-19 Patients: A systematic review

Tocilizumab is a competitive interleukin-6 inhibitor agent that has been proposed to combat the COVID-19-related hyperinflammatory state, known as a cytokine storm. This systematic review was conducted to study the treatment of cytokine storm by Tocilizumab in COVID-19 patients. The search strategy (“COVID-19” OR “COVID19” OR SARS-CoV-2”) AND “tocilizumab” AND “cytokine storm” AND “inflammatory markers” AND (“ICU stay duration” OR “intensive care unit stay duration”) AND “mechanical ventilation requirement” AND (mortality OR death) were manually searched through Web of Science, Scopus, and PubMed databases spanned from March 2020 to November 2021. The inclusion criteria were: research articles, human study, clinical trial, and articles in English. The exclusion criteria were: review articles, case reports, early access, editorial materials, letters, short survey, in vivo or in vitro studies. Five articles were included in the analysis. There were four countries had conducted the studies (Italy, China, USA and Netherland) with different study designs (observational (80%) and randomized controlled trials (20%)) involving 649 patients (48% received TCZ) among moderate to severe COVID-19 patients. There were variabilities in the TCZ dosage given with some combination with other medication (methylprednisolone, azithromycin, hydroxychloroquine, lopinavir and ritonavir). TCZ reduce death cases significantly. It improves respiratory function, reduces the incidence of respiratory syndrome and less-invasive mechanical ventilation usage. The level of inflammatory markers such as C-reactive protein, ferritin and lactate dehydrogenase were significantly higher in the TCZ group. Tocilizumab may increase survival and favourable clinical course, improved hypoxia, accelerate respiratory recovery, lower hospital mortality, reduce the likelihood of invasive mechanical ventilation, improve clinical symptoms, represses the deterioration of patients (prolonging survival) and improve inflammation and immune cell function.

Early application of non-invasive ventilation for children with pulmonary edema after drowning.

The present study aimed to assess the efficacy of non-invasive ventilation (NIV) on the clinical course, oxygenation, need for invasive mechanical ventilation (IMV), and outcomes for children with pulmonary edema after drowning. We conducted a retrospective chart review. Children who were referred to the pediatric emergency department due to drowning-related pulmonary edema and underwent NIV between May 2014 and October 2020 were included. Demographics, vital signs, clinical findings, and results of laboratory and radiologic investigations were recorded. Patients were divided into six groups using the Szpilman classification system. The need for IMV, the need for pediatric intensive care unit admission, and the length of NIV treatment and stay in the pediatric intensive care unit were recorded for each patient. Twenty-five patients were enrolled. According to the Szpilman classification, 13 (52.0%) patients were evaluated as grade 3 and 12 (48.0%) as grade 4. All patients were treated with bi-level positive airway pressure in the spontaneous / timed mode. A significant increase in oxygen saturation (SpO₂) and SpO₂/fraction of inspired oxygen ratios was observed from the beginning of NIV treatment and this increase was also observed for the second and fourth hours. There was a decrease in respiratory rate at the fourth hour of NIV treatment. No patient subsequently deteriorated to require IMV. We have reported a favorable clinical course of drowning patients who underwent early use of NIV in the pediatric emergency department. Management of drowning patients with pulmonary edema by NIV with close follow-up can be successfully applied in selected cases.

THE IMPACT ON THE STATE OF HEALTH DUE TO THE SEPARATION OF MOTHER/INFANT

Introduction: Early maternal/infant separation can result in a series of traumatic emotional reactions from both the newborn and the mother. Material and methods: The authors propose conducting a study on the influence of mother/newborn separation in a neonatology and premature department. To undergo the study, a questionnaire was prepared and distributed both to mothers admitted separately from newborns and to mothers admitted in the same ward as newborns. The study included a group of 60 mothers, the group being divided into two groups: separated mothers/newborns and unseparated mothers/newborns. Results: The study reported that the separated mothers/newborns group had an average hospital stay of more than 10 days compared to the group of unseparated mothers/newborns where the average duration of hospitalization was 7 days. 83.3% of unseparated newborns had a favorable clinical course and only 6.67% had complications. In the group of separated newborns, 40% had a favorable evolution and 30% had complications. Regarding the behavioral changes occured in the newborns, comparing the results of the two groups, it appears that the group of separated newborns showed the most behavioral changes. The most common were crying (66.7%), followed by decreased appetite (13.3%), sleep disorders (10%) and weight loss (6.67%). The most common behavioral changes seen in mothers were decreased / lost of milk, anxiety states and sleep disorders. Conclusions: Maternal-infant separation has not only a negative impact on the child, but also on the mother with both short- and long-term effect.

285 A rare case of atypical, non-triggered takotsubo recurrence

Abstract Aims Takotsubo syndrome (TTS) is an acute and reversible heart failure syndrome that, at presentation, mimics acute myocardial infarction. The most common echocardiographic manifestation is the so-called ‘apical ballooning’, but other much less common wall motion patterns have been described. The pathophysiology of the syndrome is not fully understood, but there is considerable evidence that sympathetic stimulation plays a central role. The prevalence of this syndrome is higher in post-menopausal women and in most cases, but not invariably, precipitated by an emotional or physical triggering event. A close relation between brain and circulatory system has been observed and for this reason psychiatric and neurologic disorders are often recognized as precipitating conditions. Although many risk factor persist after the acute manifestation, Takotsubo recurrences do represent an exception, especially in the absence of a clear precipitating event. Methods and results A 70-year-old woman was admitted for anginal pain associated with ischaemic electrocardiographic alterations and elevation of cardiac biomarkers. The coronary angiography with left ventriculogram and the echocardiographic findings were consistent with a diagnosis of mid-ventricular Takotsubo. Cardiac magnetic resonance confirmed the absence of an ischaemic pattern or evidence of infectious myocarditis. This case represents a recurrence of TTS, in fact two years earlier the patient was hospitalized to our division for stress cardiomyopathy with typical apical ballooning. Also in the present occasion, she had a favorable clinical course, with a complete recovery of the cardiac function at subsequent evaluations. The unicity of this case lies above all in the absence of a clear trigger event. Although, an altered mental status was present because the patient suffered from anxiety and depression on pharmacological treatment, with periods of exacerbation but not in occasion of the recurrence. Conclusions TTS is not a benign condition, with recurrence being possible even in the absence of precipitating events. Based on registry data, annual rate of Takotsubo recurrence is 1.5–1.8% and is estimated to reach 4% in life. A variable TTS pattern at recurrence is common in up to 20% of cases. Our paper reports a unique case of recurrent Takotsubo syndrome with variable patterns of ventricular involvement, with neither physical nor psychological trigger. Nevertheless, for what concerns our case, the psychiatric condition the patient suffered from, could have played a role of permanent status of sympathetic activation, that in the end elicitates the occurrence of the syndrome. A better understanding of the pathophysiology of the syndrome is needed to find evidence-based therapeutic strategies that could prevent recurrence.

Immunohistochemical analysis of GFAP expression in the experimental sepsis-associated encephalopathy

Pathophysiology of sepsis-associated encephalopathy (SAE) is linked to blood-brain barrier breakdown, neuroinflammation and neurotransmitter imbalance in the brain. Astroglia, the most abundant cell population within the brain, plays the critical role in control of all kinds of homeostatic processes, thereby regulating the adaptive reactions of the brain to various challenges. Astroglia are highly heterogenous across the brain regions, therefore, damaging factors stimulate heterogenous astroglial reactivity and response in different brain regions. The aim of this study was determining immunohistochemical features of GFAP expression in various brain regions in the model of rodent experimental sepsis. Materials and methods. The experiment was performed in Wistar rats: control group of 5 sham-operated rats and the main group of 20 rats subjected to cecum ligation and puncture (CLP) procedure. The immunohistochemical study of GFAP expression in the sensorimotor cortex, subcortical white matter, hippocampal, thalamic and caudate nucleus/putamen regions was performed from 20 to 48 hours of the postoperative period. Results. Starting from the 12th hour after CLP, animals began display progressive increase in signs of periorbital exudation, piloerection, fever-/hypothermia, diarrhea, social isolation, lethargy, and respiratory impairment. In the period of 20–38 hours, 9 animals showed expressed previously listed symptoms and were euthanized (CLP-B – lethal group), 11 rats survived until 48 hours of the experiment (CLP-A – survived group). In the lethal group, starting from 20 to 38 hours after the CLP procedure, a significant (relative to control) regionally-specific dynamic increase in the level of GFAP expression was observed in the brain: in the cortex – by 465 %, in the subcortical white matter – by 198 %, in the hippocampus – by 250 %, from the 23rd hour – in the caudate nucleus/putamen by 18 %. In the thalamus, no significant changes in the level of GFAP expression were observed. In the cortex and hippocampus of survived animals, 48 h after CLP, higher values of GFAP expression were observed comparing to the group of non-survived animals. Conclusions. Under conditions of the experimental SAE, an early dynamic increase in the astroglial reactivity was observed in the cortex, hippocampus, white matter, and caudate nucleus/putamen of the brain with the most significant increase of indicators in the cortex and hippocampus, which potentially indicates relatively more vulnerable areas of the brain to damaging factors, as well as places of the most active intercellular interaction in the condition of systemic inflammation. Higher values of GFAP expression in the cortex and hippocampus of survived animals at 48 hours of the experiment, compared with indicators of non-survived group, indicate increased astroglial reactivity in these brain regions at the noted time period, accompanied by relatively more favorable clinical course of the disease.

MIS-A associated myocardial injury: The art of diagnosis and follow-up

Multisystem inflammatory syndrome in adults (MIS-A) is a rare but severe condition in adults with a clinical course similar to that described in children (MIS-C) following infection with the SARS-CoV-2 virus. Here we describe a case of a 21-year-old, otherwise healthy female who presented with chest pain and signs of sepsis six weeks after recovering from coronavirus disease 2019 (COVID-19). Early identification of MIS-A led to a favorable clinical course and full recovery. Given the highly variable disease presentation yet potentially deadly outcome, providers must remain vigilant to recognize and treat MIS-A early Keywords: MIS-A; myocardial inflammation; SARS-CoV-2; COVID-19 disease.

PATH-25. H3 K27M-MUTANT DIFFUSE NON-MIDLINE GLIOMA: REPORT OF A CASE WITH EXTENDED FOLLOW-UP

Abstract H3 K27M-mutant diffuse gliomas without midline involvement are extremely rare and their clinical behavior remains elusive due to limited reported follow-up data. We describe an H3 K27M-mutant diffuse non-midline glioma patient with extended follow-up. A 34-year-old woman presented with headache, memory loss, periods of changes in taste and smell, and confusion. Imaging studies revealed an 2.3 cm expansile T2/flair hyperintensity with patchy postcontrast enhancement centered in the left amygdala without associated restricted diffusion and no involvement of the midline structures. The tumor was debulked and consisted of a mitotically active infiltrating astrocytic glioma without tumor necrosis or microvascular proliferation, consistent with anaplastic astrocytoma. Targeted 187-gene neuro-oncology NGS testing detected an H3F3A K27M mutation along with a PTPN11 and a PPM1D mutation. FISH 1p/19q-codeletion testing was negative. MGMT promoter was unmethylated. The patient was treated with chemoradiation with temozolomide for 6 weeks followed by 12 cycles of temozolomide. Four years after initial resection, an area of increased post-contrast enhancement indicating tumor recurrence/progression was noted. Partial resection of the recurrent tumor revealed a mitotically active infiltrating astrocytic glioma with tumor necrosis consistent with glioblastoma. Molecular profiling of the recurrent tumor by the neuro-oncology NGS panel detected similar mutational profile (identical H3F3A K27M and PTPN11 mutation; different PPM1D mutation) with an additional SOS1 mutation. The patient completed 4 cycles of Lomustine and although clinically stable, imaging studies showed slight increase in residual tumor size concerning for tumor progression. Lomustine was discontinued, Bevacizumab therapy was initiated and patient was enrolled in clinical trial (NCT02525692). Despite tumor progression, this patient has had a relatively long disease course (5 years) suggesting that H3 K27M-mutant non-midline diffuse gliomas although molecularly similar, may follow a more favorable clinical course than their midline counterparts possibly due to the hemispheric location, which is more amenable for surgical resection.

Fucosyltransferase 2 Mutations Are Associated With a Favorable Clinical Course in Crohn's Disease.

Fucosyltransferase 2 (FUT2) participates in intestinal antigen secretion and bacterial adherence. FUT2 homozygous nonsense mutations (FUT2M) and subsequent nonsecretor status is associated with Crohn's disease (CD). The common null allele is rs601338. We assessed the relationship between FUT2M and disease course. In consecutive adult CD outpatients, clinical, biochemical, and genetic data were collected at baseline visits. Patients were longitudinally followed over 5 years. The primary outcome analyzed the relationship between FUT2M and rates of CD patients in persistent steroid-free clinical remission requiring neither surgery, biologics, nor immunomodulators. Sixty-two CD patients were recruited. FUT2M homozygotes (rs601338 or any mutation in linkage disequilibrium) were detected in 27% of CD (17/62). Patients with rs601338 mutations had higher rates of the primary outcome (homozygous: 46.6%, heterozygous: 28.0%, wild-type: 5.3%, P=0.02). Similar findings existed for CD patients with homozygous mutations in any single-nucleotide polymorphism for FUT2 (homozygous: 41.2%, heterozygous: 25.9%, wild-type: 5.6%, P=0.04). On multivariable analysis, rs601338 mutation was associated with the primary outcome (odds ratio=3.4, 95% confidence interval: 1.3-8.7, P=0.01), while other parameters were not. Mutation of rs601338 was associated with lower rates of penetrating disease (homozygous: 13.3%, heterozygous: 28.0%, wild-type: 52.6%, P=0.05) and particularly in high-risk patients (homozygous: 0%, heterozygous: 37.5%, wild-type: 83.3%, P=0.01). FUT2 mutation status is associated with a favorable clinical course in CD. Further confirmatory studies are needed.

Epi-P-05 - COVID-19 infection in patients with Sézary syndrome: report of three cases

Introduction:A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread worldwide during 2020, was declared as a public health emergency and potentially life-threatening. Patients with hematologic malignancies may have an increased risk of severe COVID-19, due to immunosuppression related to the underlying disease and its treatment. In the absence of specific data, potential risk factors for severe events of COVID-19 should be considered as for other community acquired respiratory virus (CARV) infections: >60 years, severe immunodeficiency, chemotherapy treatment. We present three patients with Sézary syndrome (SS) and COVID-19 infection.Objective:We aim to report the outcome of COVID-19 in patients with SS treated at the department of Dermatology of the Hospital Italiano de Buenos Aires.Methods and material:Patients with SS who were diagnosed positive for COVID19 infection, during worldwide pandemic in 2020. We collected retrospectively clinical data, SS evolution and treatment response.Case 1:A 58-year-old male with hypertension was diagnosed with SS stage IVA1 in July 2014, he received multiple systemic treatments such as extracorporeal photopheresis (ECP), IFN 2b, bexarotene, with partial response (PR) and eventually stable disease. In August 2020, he was hospitalized due to fever, dry cough and progressive cutaneous disease. SARS-CoV2 was confirmed, requiring invasive mechanical ventilatory (IMV) in the ICU and systemic corticosteroids. The clinical course improved with complete response (CR) of cutaneous disease and persistence of hematologic involvement. He was discharged 3 months later with no SARS-CoV-2 sequels.Case 2:A 66-year-old female with breast cancer in 2002 treated with RT and tamoxifeno was diagnosed with SS stage IVA1 in March 2012. She was treated with IFN 2b, TSEB, vorinostat and ECP with CR, relapse and then PR. In November 2020 she started chemotherapy due to cutaneous and nodal progression. A month later, she required hospitalisation and IMV due to dry cough and respiratory distress, SARS-CoV-2 was confirmed. She died 7 days later due to progression of respiratory distress.Case 3:An 86-year-old male with arterial hypertension was diagnosed with SS stage IVA1 in March 2017. He received ECP, methotrexate, with PR. In February 2021 he was hospitalized due to dry cough, headache with cutaneous disease relapse. Laboratory parameters showed pre-existing lymphopenia. SARS CoV-2 was confirmed. He was admitted to the ICU requiring IMV due to respiratory distress, and died 15 days after.Conclusions:Among our patients, two had several associated comorbidities and risk factors for a severe event of COVID-19, besides case 3 presented pre-existing lymphopenia at presentation. Case 1, despite his comorbidities and IMV, developed a favorable clinical course. To our knowledge there are many unknown factors and limited published studies, describing COVID-19 outcomes in patients with SS, most of them based on case reports.

Fingolimod as a first- or second-line treatment in a mini-series of young Hellenic patients with adolescent-onset multiple sclerosis: focus on immunological data.

Pediatric onset multiple sclerosis(POMS) is characterized by a highly active profile, often warranting treatment with high efficacy disease-modulating therapies (DMTs). Fingolimod, an oral sphingosine-1-phosphate receptor modulator, is the first Food and Drug Administration (FDA)- and European Medicines Agency (EMA)-approved DMT for the treatment of POMS. Our aim is to present real-world data of seven fingolimod-treated POMS-patients, recruited in a single MS center in Greece. Clinical and imaging/laboratory data from 7 Hellenic patients fulfilling the International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria for POMS diagnosis, who have received fingolimod treatment, were selected. Human leukocyte antigen (HLA) genotyping was performed with standard low-resolution sequence-specific oligonucleotide techniques. Three patients were treatment-naïve adolescents who received fingolimod as first-line treatment. Two experienced ongoing clinical and radiological disease activity and have been switched to natalizumab. The remaining cases were post-adolescent adults with POMS, where the vast majority experienced total/near-total disease remission. Fingolimod was generally well-tolerated. Two patients with high disease activity carried the HLA-DRB1*03 allele, while five patients were carriers of at least one of the HLA-DRB1*04, HLA-DRB1*13, and HLA-DRB1*14 alleles, which when not combined with HLA-DRB1*03 showed a trend towards a more favorable clinical course. Fingolimod responders showed a trend towards increased CD(16-56)+NK cell counts in immunophenotyping assays. Our preliminary results support that response of POMS patients to fingolimod may be partially dependent on age and previous DMT, with younger and treatment-naïve patients presenting worse outcomes. The role of immunogenetics and immunophenotyping in personalized treatment warrants investigation in larger and more diverse populations.