Corticosteroid Boluses Research Articles

Unraveling a Psychiatric Puzzle: Corticosteroid-Induced Psychosis in Addison’s Disease. A case report

IntroductionThe spectrum of neuropsychiatric adverse effects of corticosteroids ranges from unspecific symptoms to structured psychotic or affective episodes. We present the case of a 30-year-old woman admitted to our hospital due to behavioral alterations, coinciding with the initiation of treatment with corticosteroid boluses as part of a chemotherapy regimen for gastric adenocarcinoma. She had a previous diagnose of Addison’s disease, undergoing treatment with supplemental corticosteroids.Objectives1)To describe the clinical particularities of this case, focusing on the psychopathological aspects and their correlation with the corticoid treatment.2)To review the available literature regarding the clinical characteristics and management of corticosteroid-induced psychosis, with special interest in patients with adrenal insufficiency that require long term steroid supplementation.MethodsA review of the patient’s clinical history and complementary tests were carried out. Likewise, we reviewed the available literature in relation to the clinical presentation of corticosteroid-induced psychosis and its pharmacological management.ResultsThe patient was admitted to our hospital due to acute behavioural alterations, which temporally coincided with the 4th cycle of FOLFOX chemotherapy and corticosteroid boluses. She presented with incoherent speech, with non sequitur answers and glossolalia, as well as dysphoric affect and purposeless behavior. She presented a favorable clinical course after the initiation of treatment with antipsychotics and temporary suspension of corticosteroid treatment.Manic symptoms are the most common presentation of “corticosteroid-induced psychosis”, with the key characteristic being the temporal association with the corticosteroids administration. Although the discontinuation of steroids generally results in a sudden decrease in symptoms, additional treatment with antipsychotics such as haloperidol or olanzapine might be required for a symptomatic control. In patients with adrenal insufficiency, long-term treatment with lithium or anti-seizure treatments are effective strategies in relapse prevention when a higer steroid dose is required.Conclusions-Corticosteroid-induced psychosis is a well described clinical phenomenon, that usually presents with manic symptoms rather than psychotic experiences.-Progressive discontinuation of corticosteroid treatment usually results in complete cessation of symptoms, but additional psychopharmacological treatment might be required, especially in patients with adrenal insufficiency undergoing long-term corticosteroid treatment.-This case outlines the psychopathological richness in the presentation of corticosteroid-induced psychosis, and illustrates the challenges in the pharmacological management in patients with adrenal insufficiency.Disclosure of InterestNone Declared

Abstract 15799: Frequency and Etiology of Post-Operative Leukocytosis After Heart Transplantation

Introduction: Many factors contribute to post-operative leukocytosis after heart transplantation; it may be challenging to determine whether post-operative leukocytosis is caused by infection. Objective: To describe the frequency and causes of leukocytosis after heart transplantation. Methods: A representative sample of 207 of 308 patients who underwent heart transplant at our institution between 1/1/17 and 12/31/22 was examined. Leukocytosis was defined as a white blood cell (WBC) count peak >11 th/μL or a 30% increase in WBC if pre-transplant baseline was >11 th/μL. Leukocytosis was classified as early (post operative day [POD] 0-3), delayed (POD 4-7), or late (POD 8-60). Culture, biopsy, and other clinical data were used to adjudicate etiology. Groups were compared using χ 2 , Fisher’s, or t-test as indicated. Results: The sample was 27% female with a mean age of 51.2 (±12.6) years. A total of 404 leukocytosis episodes were identified affecting 204 patients. Common etiologies included: post-transplant surgery (47.0%), true infection (27.2%), corticosteroid bolus (4.0%), subsequent surgery (3.5%), rejection (3.0%), and thrombus (3.0%). Delayed (24/47) and late (59/146) leukocytosis were more likely to be associated with infection than early leukocytosis (27/211, p<0.0001 for both comparisons). Common causes of infection were: pneumonia (33%), bloodstream infection (20%), skin and soft tissue (12%), unknown (9%), urinary (5%), and colitis (3%). Post-operative infection was associated with increased hospital length of stay after transplantation (17 vs 46 days, p<0.0001), and increased in-hospital mortality (9.6% vs 2.7%, p=0.040). ECMO (p=0.08), non-ECMO temporary mechanical circulatory support (p=0.70), prior cardiac surgery (p=0.08), and donor bloodstream infection (p=0.40) were not associated with post-operative infection. There was no significant difference in cross clamp time (p=0.42), ischemic time (p=0.27), or age (p=0.07) in patients with vs without infection. Conclusion: Leukocytosis after transplant is nearly universal. Patients developing leukocytosis on POD ≥4 have a high rate of concurrent infection compared to those with early leukocytosis, which is in turn associated with increased LOS and in-hospital mortality.

ACUTE DISSEMINATED ENCEPHALOMYELITIS FOLLOWING VARICELLA INFECTION

Inflammatory demyelinating disease affecting the central nervous system(CNS). Early treatment is the key to neurological recovery. We reportthe case of a 4-year-old girl who developed cerebellar ataxia one week after a varicella rash. Cerebral MRI revealed bilateral lesions of the white matter in favor of ADEM. Corticosteroid boluses associated with antiviral treatment were administered and resulted in a remarkable clinical improvement. Long-term follow-up is essential for assessing prognosis.

A Case Report on Rasmussen Encephalopathy (RE)

Summary: Rasmussen's encephalitis (RE) is a rare and severe chronic inflammatory brain disease resulting in drug-resistant epilepsy and progressive hemispheric destruction with neurological deficit. ER is associated with deterioration of background EEG activity, progressive atrophy of the affected hemisphere on MRI and extensive PET hypometabolism over the affected hemisphere. We report the case of a 6-year-old girl who presented with pharmacoresistant epilepsy.
 Observation: A 6-year-old child with no particular medical history presented 6 months prior to admission with epilepsy resistant to all therapeutic classes (antiepileptic drugs). Clinical examination revealed left hemiparesis with facial involvement and constant left hemi-myoclonus.
 An EEG showed a pattern compatible with a continuous epileptic encephalopathy that could correlate with Rasmussen syndrome.
 Cerebral MRI Revealed: right cerebral hemiatrophy with secondary homolateral hippocampal sclero-atrophy, compatible with Rasmussen encephalitis.
 The patient received immunoglobulins and a corticosteroid bolus, but without improvement; she was therefore a candidate for surgical treatment.
 Rasmussen's encephalopathy is a rare and serious disease that can be responsible for paresis and cognitive decline. Its pathophysiology is still poorly defined, and it mainly affects children.

#5816 RAVULIZUMAB “DE NOVO” IN PEDIATRIC PATIENTS WITH ATYPICAL HEMOLITIC UREMIC SYNDROME: FIRST WORLDWIDE CASES

Abstract Background and Aims Ravulizumab is a long-acting C5 inhibitor that has recently demonstrated its effectiveness in adult and pediatric patients for the control of hemolytic uremic syndrome compared to eculizumab, allowing average annual infusion times of up to 70% less. There is still little evidence in the literature of naïve treatment with this drug in pediatrics. Method We present the first two pediatric cases worldwide with the use of de novo Ravulizumab: the first one in the onset of the disease and the second one, post-kidney transplant Results 13-year-old girl referred from another country with 1 week history of acute gastroenteritis with bloody stools, vomiting and compromise of consciousness. Deterioration of general condition, with laboratory tests compatible with thrombotic microangiopathy (TMA), evolves to anuria and convulsive episode requiring invasive mechanical ventilation, corticosteroid boluses, 6 plasmapheresis sessions and 4 intermittent hemodialysis. One Eculizumab dose (600 mg) was administered in the center of origin and STEC was isolated. At admission presented compromised renal function (AKI III), hemolytic anemia, thrombocytopenia, normal ADAMTS-13, negative direct Coombs and decreased complement. Brain MRI study shows images compatible with multiple foci of necrosis. Due to the persistent requirement of renal replacement therapy and persistent TMA, Ravulizumab was started with a loading dose (2400 mg) and a second dose after 2 weeks. The need for renal replacement therapy ceased with improvement of hemolysis and renal function. Genetic study showed mutation of uncertain significance in heterozygosis in exon 6 (c.881_883, p.Ala292del) with risk polymorphism for HUSa (deletion CFHR3-CFHR1) Case 2: 7-year-old girl (stage 5 CKD) in chronic hemodialysis 3 times/week secondary to aHUS (CD46 mutation) was admitted for kidney transplant from a living donor (father), performing hemodialysis session before surgical intervention. Low-intermediate immunological risk (PRA 0%, 9 HLA matches) and high CMV infectious risk (valganciclovir prophylaxis). Induction treatment: Basiliximab, tacrolimus, mycophenolate and steroids. First dose of Ravulizumab was infused the day before transplantation (900mg), well tolerated. 36 hours after presented acute pulmonary edema as well as a drop in hemoglobin (4g/dL). With normal laboratory hemolysis parameters, urgent abdominal-pelvic CT was performed due to suspicion of bleeding, confirming an active bleeding. Surgical reintervention was decided due to ureteral bleeding and the tunnel was redone with good results. The patient has had a favorable evolution of renal function, with a normal value of creatinine at discharge (0.43 mg/dl). Protein/Creatinine urine ratio (iPr/Cr) increases to a maximum of 8 mg/mg. Negative DSA levels but the option of renal biopsy was assessed and ruled out due to a decrease in proteinuria (iPr/Cr 0.51 mg/mg). She received second dose of ravulizumab after 2 weeks, remain stable with no data on recurrence of her underlying disease today. Conclusión: In the two patients, the initial treatment with Ravulizumab was satisfactory, both in the acute phase of the disease and in the immediate post-transplantation. In the first case we observed a functional recovery from the first dose with no notable adverse effects up today, as in the post-transplant patient, maintaining a good control of TMA despite more spaced dosing (8 weeks). The inclusion of this drug in the therapeutic arsenal opens a new safe treatment route in pediatric patients with HUSa

Nephrotic Syndrome: Epidemiological, Clinical, Paraclinical and Therapeutic Profile

Background: End-stage kidney disease has several causes, including nephrotic syndrome (NS). Steroid- resistant nephrotic syndrome (SRNS) children are a difficult subset of nephrotic syndrome patients who frequently respond poorly to conventional immunosuppression. Objective: The goals of our research are to analyze the different types of nephrotic syndrome, to study the epidemiological, clinical and paraclinical profile, as well as to present the difficulty in managing steroid-resistant nephrotic syndrome. Methods: Our study is a cross-sectional analysis of all patients hospitalized or followed in consultation, who were diagnosed with a nephrotic syndrome at the pediatric B department of the university hospital center Mohamed VI in Marrakech, from January 2011 to January 2022. Results: We gathered 447 instances, with an annual incidence of 41 cases. The children's ages varied from 12 days to 16 years, with an average of 5 years and 9 months. Pure nephrotic syndrome was found in 302 patients and 145 patients were carriers of impure nephrotic syndrome. In our study, 81.5% of patients had nephrosis as the cause of deseas. Secondary NS was seen in 11% of the patients, infant form was found in 6% and 1.5% of cases were congenital. The treatment was mainly based on oral corticosteroid therapy. 71.4% of the patients were corticosensitive of which 45.3% became corticodependent while 28.6% of the cases were corticoresistant. Corticosteroid boluses were used in 53% of cases. Immunosuppressants were prescribed in 31.5% of patients. Conclusion: In children, nephrotic syndrome is a common and chronic illness. It is of particular interest because of the frequency of nephroses, multiple relapses, the difficulties of management and the psychological and school impact on the child.

Predictors factors of atlanto-axial subluxation in Tunisian patients with rheumatoid arthritis.

The aim of this study was to describe clinical and imaging features of atlantoaxial subluxation (AAS) and the associated risk factors in patients with rheumatoid arthritis (RA). We conducted a retrospective and comparative study including 51 RA patients with AAS and 51 RA patients without AAS. Atlantoaxial subluxation was defined by the presence of an anterior C1C2 diastasis on the cervical spine radiograph in hyperflexion and/or an anterior, posterior, lateral or rotatory C1C2 dislocation on MRI with/without inflammatory signal. In G1, clinical presentations revealing AAS were mainly neck pain (68.7%) and neck stiffness (29.8%). MRI revealed: diastasis C1C2 (92.5%), periodontoid pannus (92.5%), odontoid erosion (23.5%), vertical subluxation (9.8%) and spinal cord involvement (7.8%). A collar immobilisation and corticosteroid boluses were indicated in 86.3% and 47.1% of cases. C1-C2arthrodesis was performed in 15.4% of cases. Atlantoaxial subluxation was significantly associated with: age at disease onset (p=0.009), history of joint surgery (p=0.012), disease duration (p=0.001), rheumatoid factor (p=0.01), anti-cyclic citrullinated peptide (p=0.02), erosive radiographic status (p<0.005), coxitis (p<0.001), osteoporosis (p=0.012), extra-articular manifestations (p<0.001), and high disease activity (p=0.001). Multivariate analysis identified RA duration (p<0.001,OR=1.022 CI[1.01-1.034]) and erosive radiographic status (p=0.01, OR=21.236 CI[2.05-219.44]) as predictive factors of AAS. Our study showed that longer disease duration and joint destruction are the major predictive factors of AAS. Early treatment initiation, tight-control and regular monitoring of cervical spine involvement are required in these patients.

Long-term Prolonged-release Tacrolimus-based Immunosuppression in De Novo Kidney Transplant Recipients: 5-Y Prospective Follow-up of Patients in the ADVANCE Study.

ADVANCE was a 24-wk, randomized, open-label, phase-4 study. De novo KTPs received PR-T with basiliximab and mycophenolate mofetil and were randomized to receive an intraoperative corticosteroid bolus plus tapered corticosteroids until day 10 (arm 1) or an intraoperative corticosteroid bolus (arm 2). In this 5-y, noninterventional follow-up, patients received maintenance immunosuppression according to standard practice. The primary endpoint was graft survival (Kaplan-Meier). Secondary endpoints included patient survival, biopsy-confirmed acute rejection-free survival, and estimated glomerular filtration rate (4-variable modification of diet in renal disease). Follow-up study included 1125 patients. Overall graft survival at 1 and 5 y posttransplantation was 93.8% and 88.1%, respectively, and was similar between treatment arms. At 1 and 5 y, patient survival was 97.8% and 94.4%, respectively. Five-year graft and patient survival rates in KTPs who remained on PR-T were 91.5% and 98.2%, respectively. Cox proportional hazards analysis demonstrated similar risk of graft loss and death between treatment arms. Five-year biopsy-confirmed acute rejection-free survival was 84.1%. Mean ± standard deviation values of estimated glomerular filtration rate were 52.7 ± 19.5 and 51.1 ± 22.4 mL/min/1.73 m2 at 1 and 5 y, respectively. Fifty adverse drug reactions were recorded, probably tacrolimus-related in 12 patients (1.5%). Graft survival and patient survival (overall and for KTPs who remained on PR-T) were numerically high and similar between treatment arms at 5 y posttransplantation.

Abnormal Alpha-1 Antitrypsin Levels and Other Risk Factors Associated with Lung Function Impairment at 6 and 12 Months after Hospitalization Due to COVID-19: A Cohort Study.

Respiratory function deficits are common sequelae for COVID-19. In this study, we aimed to identify the medical conditions that may influence lung function impairment at 12 months after SARS-CoV2 infection and to analyze the role of alpha-1 antytripsin (AAT) deficiciency (AATD). A cohort study was conducted on hospitalized COVID-19 pneumonia patients in Granada (Spain) during the first infection wave who were referred to a post-COVID-19 hospital clinic. The patients were monitored with three follow-up visits from May 2020 to May 2021. Previous medical history, hospital admission data, baseline parameters and physical examination data were collected at the first visit. Pulmonary function tests were performed at 6 and 12 months together with the determination of AAT level and AATD genotype. After 12 months, 49 out of 157 patients (31.2%) continued to have lung function impairment. A multivariate analysis showed a statistically significant association of lung function impairment with: higher Charlson index; pneumonia with a central and/or mixed distribution; anemia on admission; time in intensive care; need for corticosteroid boluses; abnormal respiratory sounds at 6 months; elevated lactate dehydrogenase at 12 months; abnormal AAT; and MZ genotype. Our results suggest that these medical conditions predispose COVID-19 patients to develop long-term lung function sequelae.

Rescue therapy for symptomatic spinal cord ischemia after thoracic endovascular aortic repair

ObjectiveSpinal cord ischemia (SCI) after thoracic endovascular aortic repair (TEVAR) can cause permanent neurologic deficits and poor long-term survival. Targeted treatment of new SCI symptoms after TEVAR (rescue therapy [RT]) might improve/resolve neurologic symptoms but few data characterize the association of specific interventions with SCI outcomes. We evaluated the effectiveness of post-TEVAR RT at our tertiary aortic center. MethodsOur institutional TEVAR database was reviewed for SCI incidence and details of RT. This included cerebrospinal fluid drainage (CSFD), medical therapy, and optimization of spinal cord oxygen delivery. SCI outcomes were categorized at discharge as paralysis/paraparesis and temporary/permanent. ResultsNine hundred forty-three TEVAR procedures were performed in 869 patients from 2011 to 2020. Post-TEVAR SCI occurred in 7.8% (n = 74) with permanent paraplegia in 1.5%. Older patient age, chronic obstructive pulmonary disease, and previous abdominal aortic surgery were predictive of SCI. Half (n = 37) of SCI episodes resulted in only temporary paralysis/paraparesis. Rescue postoperative cerebrospinal fluid drains were implanted in 3.7% (n = 35) of procedures and was predicted by higher American Society of Anesthesiologists class, lower serum hemoglobin level, elevated international normalized ratio, bilateral iliac artery occlusion, nonelective procedures, and penetrating atherosclerotic ulcer/intramural hematoma indication. The most commonly used RTs were emergent placement of or increased drainage from an existing cerebrospinal fluid drain (87.8%), induced/permissive hypertension (77.0%), corticosteroid bolus (36.5%), and naloxone infusion (33.8%). Neurologic improvement occurred in 68.9% (n = 51/74). New/increased drainage was associated with improved SCI outcome. ConclusionsPermanent paraplegia from post-TEVAR SCI is rare (1.5%). Older patients with comorbidities carry greater post-TEVAR SCI risk. SCI symptoms improved/resolved with CSFD and multimodal RT in 68.9% of patients, but no intervention was independently associated with improvement. TEVAR centers should have robust protocols for timely and safe CSFD placement to augment RT strategies for SCI.

Clinical and Biological Characteristics of a Griscelli Syndrome Type 2: About a Case Report

Introduction: Griscelli Syndrome (GS) is a rare autosomal recessive genetic disorder, characterized by a partial albinism that can be associated with early-onset severe psychomotor retardation, and normal immune status (type 1), or associated with an immune deficiency (type 2). GS type 2 results from mutations in the RAB27A gene, leading to immune deficiency. GS type 2 has a grave prognosis because of a rapidly fatal macrophage activated syndrome. Case Report: A 3-month-old infant having a family history of first-degree consanguinity in the parents and history of silvery gray hair in two uncles, Admitted to our department for management of a prolonged fever and an anemic syndrome. Hair on the scalp, eyebrows, and eyelashes were silvery gray and had a metallic sheen. The lymphocyte sub typing showed a severe combined immune deficiency. Histological examination of the hair showed enlarged, hyper pigmented basal melanocytes with sparse pigmentation of adjacent keratinocytes in favor of a Griscelli syndrome. The evolution was marked by clinical worsening, respiratory distress. On the biological level, a macrophage activation syndrome was retained in front of a hyperferritinemia, a hypertriglyceridemia and hepatic cytolysis. The patient received broad-spectrum antibiotic therapy, antivirals and antifungals, corticosteroid boluses 3 days in a row and an immunoglobulin infusion. Unfortunately, the patient died of septic shock. Conclusion: Type 2 GS is a rare genetic disease with a poor prognosis, which must be diagnosed early to allow better support. The only curative treatment is bone marrow transplantation.

52 Use of corticosteroids in childhood systemic lupus erythematosus: experience from a pediatric rheumatology center

BackgroundChildhood-onset Systemic Lupus Erythematosus (cSLE) is a rare but severe multisystem autoimmune/inflammatory disease that can affect any organ system and cause significant damage, disability and/or death. Corticosteroids are one of the important therapeutic weapons for childhood Systemic Lupus Erythematosus (SLE). Prednisone doses are increased during flare-ups of lupus disease, and then progressively reduced to reach a threshold dose in order to avoid the harmful effects of this treatment in growing children. The oral route is by far the most used over prolonged periods, however corticosteroid boluses are recommended in the treatment of severe acute attacks of the disease.ObjectiveAssess the use of corticosteroids in childhood systemic lupus erythematosus (SLE) and the risk of steroid-related damage.MethodsPatients with childhood -onset SLE (n = 83) treated at paediatric rheumatology centre were followed for 36 months. Information on medication use, disease activity as measured by SLEDAI was collected.ResultsEighty-three (83) patients were studied. Female: male ratio was 1:49. Mean ages at lupus onset and diagnosis were respectively: 10, 12 (±3,88_ and 11, 3 (±3,62) years. Corticosteroids were used in 92% of cases in oral form and on 37% of cases as a bolus of high dose intravenous methylprednisolone. The indication of corticoids bolus was significantly related to severe forms (p = 0,001), high disease activity (p = 0, 00008), and macrophage activation Syndrome (p = 0, 0006). The doses varied between 0.5–1 g/1.73m2. The mean initial disease activity in these patients was 30 ± 10, while that found after taking the treatment was 12.9 ± 15. The decrease was statistically significant (p = 0, 000001). More than half of our patients were on high dose oral corticosteroids (2 mg/kg/d) and only 1/5 of the patients benefited from a dose of (1 mg/kg/day). The use of corticosteroids has been associated with significant side effects, including growth delay (22%), cushingoid obesity (58%), stretch marks (49%), osteoporosis (33%), femoral head osteonecrosis (1%), infections (54%). The association of certain side effects with a high dose of oral corticosteroids (2 mg/kg/day) was significant in this case cushingoid obesity (p = 0, 0003), stretch marks (p = 0.014).ConclusionCorticosteroids are the mainstay of therapy for prompt control of acute disease related inflammation in patients with SLE; they remain the first-line treatment for significant lupus manifestations, especially severe forms and life-threatening situations Higher dosage and longer duration of therapy, which are common in SLE, result in greater risk of adverse effects. Their use wisely is the guarantee of a better response and the reduction of deleterious effect.

Multisystemic Inflammatory Syndrome in Children (Disease with Several Faces): About 2 Cases in the Pediatric Intensive Care Unit in Rabat Children Hospital

Since the advent of the COVID 19 pandemic, very few severe cases have been described in the pediatric population and very few have required admission in intensive care unit (ICU). However, a new entity has emerged worldwide including multi-systemic inflammatory disease in children related to COVID infection called PIMS or MIS-C for multisystemic inflammatory syndrome in children. We report the case of two children admitted to the Pediatric Intensive Care Unit of the Rabat Children's Hospital for a severe multisystemic inflammatory syndrome related to an undetected COVID-19 infection; the first case presented a Status epilepticus while the second case was in shock due to myocarditis. The diagnosis of MIS-C was made with reference to WHO criteria and treatment was based on corticosteroid bolus only, due to lack of IV Ig. The evolution was favorable for both patients.

ACUTE DISSEMINATED ENCEPHALOMYELITIS AFTER RABIES VACCINATION: ONE CASE REPORT

Acute disseminated encephalomyelitis (ADEM) is an inflammatory autoimmune demyelinating disease of the central nervous system (CNS). There is no typical clinical presentation of ADEM. The combination of multiple neurological disorders occurring during infections or vaccination should alarm the clinician. We report a case of ADEM in a 37-year-old patient, occurred 2 months after an anti-rabies vaccine shot. The diagnosis was concluded as we had the anti-rabies vaccination 2 months before the onset of symptoms, clinical symptoms (of encephalomyelitis) and the outcome of nuclear magnetic resonance imaging (bilateral and symmetrical signal abnormalities of both capsules and both Putamens, hyposignal in T1, hypersignal in T2 and FLAIR). IV corticosteroid boluses were administered, followed by oral corticosteroid therapy then gradual dose reduction. Clinical evolution was marked by improving of consciousness, disappearance of the motor deficit and the persistence of irreversible blindness. ADEM is a rare and serious condition of the central nervous system. Early management is the key to avoid complications.

Late acute cellular rejection after switch to everolimus monotherapy at 11 months following liver transplantation

BackgroundAcute cellular rejection beyond the 6th month posttransplant is an uncommon complication after liver transplantation. The inadequate immunosuppression (IS) remains the main risk factor. We report a case of acute cellular rejection after a switch to everolimus monotherapy at 11 months following liver transplantation.Case presentationThis was a 69-year-old man who underwent liver transplantation after hepatocellular carcinoma. The initial immunosuppression was a combination of three immunosuppressive drugs (corticosteroids + tacrolimus + mycophenolate mofetil). The corticosteroid therapy was stopped at the 4th month posttransplant. Serious side effects of the immunosuppressive drugs (agranulocytosis and renal dysfunction), which occurred 4 months after transplantation, required a reduction and then a discontinuation of tacrolimus and mycophenolate mofetil. Everolimus was introduced as a replacement. The patient was consulted at 11 months after liver transplantation, 1 month after stopping the two immunosuppressive drugs, for liver function test abnormalities such as cytolysis and anicteric cholestasis. A moderate late acute cellular rejection was confirmed by a liver biopsy. A satisfactory biological evolution was observed following corticosteroid boluses and optimization of basic immunosuppressive drugs.ConclusionLate acute cellular rejection remains an uncommon complication, observed mostly in the first year after liver transplantation. The main risk factor is usually the decrease of immunosuppression.

P082 Appendicular syndrome revealing Kawasaki-like syndrome: a case report

BackgroundWith the wide spread of the current SARS-CoV-2, It was found that about 2% of children was affected according to several studies, However, a small number of children with Covid-19 develop a significant systemic inflammatory response similar to Kawasaki disease, a new disease entity called multisystem inflammatory syndrome.MethodsA 12-year-old child, without a notable pathological history, who presented to the emergency, during the SARS-CoV-2 pandemic, for management of a pseudo-appendicular syndrome. Our patient was initially assessed by the surgical team due to his query acute abdomen. The pain had been evolving for 3 days associated with several episodes of bilious vomiting in a context of fever at 38.5°. Abdominal examination noted abdominal tenderness and defence. Extradigestive signs were not reported, The Lab Testing objectified a CRP at 235, elevated white blood cells at 18 180, an abdominal ultrasound was requested returning without particularities. Faced with the persistence of bilious vomiting, surgical exploration was indicated objectifying a catarrhal appendix. A pediatric opinion was requested, the clinical examination shows conscious child who presents infra cervical lymphadenopathy with a fever at 38 associated with an erythematous skin rash on the back and aseptic conjunctivitis. The Lab Testing objectified an important inflammatory syndrome, a acute kidney and heart failure a Covid 19 serology was requested with positive IGG, négative IGM, PCR covid test was negative, given the unavailability of In immunoglobulins, the treatment was based on corticosteroid bolus then relay by oral corticosteroid associated with an anti-inflammatory treatment, gastric protection by proton pump inhibitors, treatment of heart and acute kidney failure. The evolution was marked by clinical and biological improvementDiscussionCoronavirus 2 (SARS-CoV-2) infection among children and adolescents, is mainly responsible for mild respiratory symptoms, in contrast to the severe forms reported in adults [7]. A systemic inflammatory syndrome mimicking kDa, temporally associated with infection with SARS-CoV-2 (Kawa-COVID-19) has recently been described as a serious illness sometimes requiring intensive care (44%). The median age is older (> 5 years), the frequency and severity of myocarditis are very different from classic kDa, abdominal pain and/or diarrhea were more frequently (81%) reported than in classic kDa, heart failure, pneumonia, neurological and renal impairment, associated with elevated CRP, hyperferritinemia are more common in Kawasaki-Like syndrome [10]. Some investigations must be systematically realized urgently to diagnose potentially fatal complications. These include testing for myocarditis, patients should benefit from careful monitoring and treatment with IV Ig 2 g/kg should be administered rapidly and seems to be effective in the majority of cases, associated anti-inflammatory therapy, such as steroids is necessaryConclusionPediatricians should be aware of these atypical presentations of COVID-19 infection for early diagnosis.

Infectious complications and graft outcome following treatment of acute antibody-mediated rejection after kidney transplantation: A nationwide cohort study.

Acute antibody-mediated rejection (AMR) remains a challenge after kidney transplantation (KT). As there is no clear-cut treatment recommendation, accurate information on current therapeutic strategies in real-life practice is needed. KT recipients from the multicenter Swiss Transplant Cohort Study treated for acute AMR during the first post-transplant year were included retrospectively. We aimed at describing the anti-rejection protocols used routinely, as well as patient and graft outcomes, with focus on infectious complications. Overall, 65/1669 (3.9%) KT recipients were treated for 75 episodes of acute AMR. In addition to corticosteroid boluses, most common therapies included plasmapheresis (56.0%), intravenous immunoglobulins (IVIg) (38.7%), rituximab (25.3%), and antithymocyte globulin (22.7%). At least one infectious complication occurred within 6 months from AMR treatment in 63.6% of patients. Plasmapheresis increased the risk of overall (hazard ratio [HR]: 2.89; P-value = 0.002) and opportunistic infection (HR: 5.32; P-value = 0.033). IVIg exerted a protective effect for bacterial infection (HR: 0.29; P-value = 0.053). The recovery of renal function was complete at 3 months after AMR treatment in 67% of episodes. One-year death-censored graft survival was 90.9%. Four patients (6.2%) died during the first year (two due to severe infection). In this nationwide cohort we found significant heterogeneity in therapeutic approaches for acute AMR. Infectious complications were common, particularly among KT recipients receiving plasmapheresis.

Transplant rejections associated with immune checkpoint inhibitors: A pharmacovigilance study and systematic literature review

BackgroundSolid organ transplant recipients are at increased risk of cancer due to long-term immunosuppression. Immune-checkpoint inhibitors (ICI) showed clinical benefits but increased risk of transplant rejection. Our work aims to assess the main features of reported rejection events. MethodsA disproportionality analysis of the World Health Organisation pharmacovigilance database, VigiBase, to identify drugs associated with rejection events. The estimate of this analysis is the information component for which the lower end of the 95% credibility interval (IC025) indicates significance when positive. We combined a systematic literature review of case reports to obtain additional information regarding treatment management and histopathological findings. ResultsA total of 96 reports of transplant rejections following ICI were included, including kidney (n = 65), liver (n = 23), cornea (n = 2) and heart (n = 5). The main indication reported for ICI was malignant melanoma (39/89, 43.8%). The time to onset between first ICI administration and rejection was 21 [interquartile range: 13; 56] days. Kidney transplant rejection was associated with nivolumab (IC025 = 1.32), pembrolizumab (IC025 = 1.17) and ipilimumab (IC025 = 0.33); while liver transplant rejection was mostly over-reported with nivolumab (IC025 = 1.95). Overall, anti-PD-1 and anti-PD-L1 were more involved than anti-CTLA-4 drugs (93.0% versus 7.0%). Subsequent mortality was 36.5% and involved liver-transplant recipients more than other organ recipients (p < 0.0001). When performed, all biopsies reported acute cellular rejections, but only a few showed concomitant antibody-mediated lesions (6/28, 21.4%). Management mainly consisted in intravenous corticosteroid boluses and ICI cessation. ConclusionICI-associated transplant rejections were mostly reported in kidney and liver transplant recipients. Rejections were T-cell mediated with low participation of humoral response.

Blood test dynamics in hospitalized COVID-19 patients: Potential utility of D-dimer for pulmonary embolism diagnosis.

BackgroundA higher incidence of thrombotic events, mainly pulmonary embolism (PE), has been reported in hospitalized patients with COVID-19. The main objective was to assess clinical and laboratory differences in hospitalized COVID-19 patients according to occurrence of PE.MethodsThis retrospective study included all consecutive patients hospitalized with COVID-19 who underwent a computed tomography (CT) angiography for PE clinical suspicion. Clinical data and median blood test results distributed into weekly periods from COVID-19 symptoms onset, were compared between PE and non-PE patients.ResultsNinety-two patients were included, 29 (32%) had PE. PE patients were younger (63.9 (SD 13.7) vs 69.9 (SD 12.5) years). Clinical symptoms and COVID-19 CT features were similar in both groups. PE was diagnosed after a mean of 20.0 (SD 8.6) days from the onset of COVID-19 symptoms. Corticosteroid boluses were more frequently used in PE patients (62% vs. 43%). No patients met ISTH DIC criteria. Any parameter was statistically significant or clinically relevant except for D-Dimer when comparing both groups. Median values [IQR] of D-dimer in PE vs non-PE patients were: week 2 (2010.7 [770.1–11208.9] vs 626.0 [374.0–2382.2]; p = 0.004); week 3 (3893.1 [1388.2–6694.0] vs 1184.4 [461.8–2447.8]; p = 0.003); and week 4 (2736.3 [1202.1–8514.1] vs 1129.1 [542.5–2834.6]; p = 0.01). Median fold-increase of D-dimer between week 1 and 2 differed between groups (6.64 [3.02–23.05] vs 1.57 [0.64–2.71], p = 0.003); ROC curve AUC was 0.879 (p = 0.003) with a sensitivity and specificity for PE of 86% and 80%, respectively.ConclusionsAmong hospitalized COVID-19 patients, D-dimer levels are higher at weeks 2, 3 and 4 after COVID-19 symptom onset in patients who develop PE. This difference is more pronounced when the fold increase between weeks 1 and 2 is compared.

Identification of Predictive Markers and Outcomes of Late-onsetPneumocystis jiroveciiPneumonia in Kidney Transplant Recipients

AbstractBackgroundIn the era of prophylaxis, Pneumocystis pneumonia (PCP) has become a late-onset opportunistic infection requiring indications for prolonged prophylaxis to be defined. The primary objective of our study was therefore to evaluate risk factors associated with late-onset PCP. The secondary objective was to assess the impact of this infection on graft and patient survival.MethodsWe conducted a French case-control study in Bordeaux and Toulouse center by matching 1 case to 1–2 controls from the same center based on the transplant date and the type of induction treatment.ResultsSeventy cases and 134 controls were included. PCP occurred at a median of 3 years after transplantation. The total lymphocyte count and CD4+ and CD8+ T-lymphocyte values were lower in the cases than in their matched controls on the day of infection and annually up to 4 years earlier. The covariables independently associated with PCP were the total lymphocyte count 1 year before Pneumocystis, mTOR inhibitors used as maintenance immunosuppressive drugs, and the administration of corticosteroid boluses used in acute rejection. A total lymphocyte count threshold &amp;lt;1000/µL offered the best predictive value for infection occurrence. PCP was associated with high incidence of graft loss and patient death (30% and 17% respectively, 3 years after PCP).ConclusionsPneumocystis pneumonia has dramatic consequences in kidney transplant recipients; a targeted prophylaxis based on simple criteria, such as chronic lymphopenia and/or history of corticosteroid boluses, could be useful to avoid life-threatening complications.