Received Plasma Exchange Research Articles

Vitamin B12 Deficiency in Thrombotic Thrombocytopenic Purpura-Like Cases.

Thrombotic microangiopathies (TMA) are characterized by a triad of microangiopathic hemolytic anemia, thrombocytopenia, and organ damage which occur in the setting of endothelial damage and platelet activation. Vitamin B12 (cobalamin) deficiency could lead to a picture that resembles TMA, termed metabolic mediated TMA (MM-TMA). A 60-year-old female was brought to the hospital after she was found unresponsive. On presentation, she was pale, lethargic, tachycardic, and febrile. Laboratory investigations revealed normocytic anemia, thrombocytopenia, and elevated bilirubin. Blood smear revealed schistocytes and tear drop cells. Given the presence of hemolytic anemia, thrombocytopenia, acute renal failure, and altered mental status, a presumptive diagnosis of thrombotic thrombocytopenic purpura (TTP) was made with a PLASMIC score of 7 indicating high risk. She received plasma exchange, caplacizumab, and intravenous methylprednisolone. Given the patient's low level of vitamin B12, she was initiated on intramuscular cyanocobalamin 1000 μg daily. The encephalopathy resolved and renal function improved. On day 6, ADAMTS13 activity was normal ruling out the diagnosis of TTP. Accordingly, plasmapheresis, steroids, and caplacizumab were discontinued. With continued aggressive B12 replacement, hemolysis resolved indicating severe vitamin B12 deficiency was the likely culprit of this patient's microangiopathic hemolytic anemia. This case serves to highlight the variable presentation of vitamin B12 deficiency. Severe vitamin B12 deficiency can even mimic TTP. If patients have markers of hemolysis, a low vitamin B12 level, and low reticulocyte count we should consider vitamin B12 deficiency as a likely cause of microangiopathic hemolytic anemia as early detection allows for early initiation of appropriate management. Vitamin B12 deficiency can be a cause of thrombotic microangiopathy.

Outcomes of patients with thrombotic thrombocytopenic purpura treated in an intensive care unit.

Background Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder characterized by widespread microthrombosis that can predispose to multiple organ failure. The literature is sparse on the outcomes of critically ill patients with TTP managed in intensive care units (ICUs). We aimed to determine the mortality of ICU patients admitted with TTP and evaluate the predictors of survival. We also compared the incidence of nosocomial infection among those who did or did not receive plasma exchange (PE). Methods We conducted a retrospective study in a tertiary ICU. Two authors screened patients for eligibility from the hospital information system based on peripheral smear reports. Adult critically ill TTP patients managed in ICU were included. Patients with a diagnosis of haemolytic uraemic syndrome, autoimmune causes of haemolysis and pregnancy-related conditions, etc. were excluded. Two authors extracted data from medical charts. No imputation of missing variables was done. Non-parametric statistics were used to report data. Statistical analyses were performed using Stata version 16. Results Of the 535 records that were screened, 33 patients were deemed eligible. Mortality among TTP patients was 14 (42%). The women to men ratio was 7:3. At admission, greater degree of anaemia, thrombocytopenia, and higher lactate dehydrogenase levels were observed in non-survivors compared to survivors (5.4 g/dl [4.8-7.1] v. 7.6 g/dl [6.1-8.9], p=0.05; 17x103 μl v. 21x103 μl, p=0.63; and 2987 (1904-3614) U/L v. 2126 U/L (1941-3319), p=0.71; respectively]. Nineteen (57%) patients had acute kidney injury (AKI), of which 11 survived: 6 recovered completely from renal failure and 5 progressed to end-stage renal disease. Nosocomial infection rates were not different among those receiving and not receiving PE therapy (7 [33%] v. 3 [25%], respectively). Conclusion TTP is more common in women and has a high mortality. Older age, low haemoglobin and higher platelet transfusions are predictors of poor survival. Nosocomial infection rates were similar irrespective of receiving PE therapy.

Visual Function Improvement after Plasma Exchange Therapy for Acute Optic Neuritis in Neuromyelitis Optica Spectrum Disorders: Case Series and Review.

Neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder (NMOSD) are autoimmune-mediated central nervous system disorders distinguished by the presence of serum aquaporine-4 IgG antibody (AQP4-Ab). The clinical panel comprises severe optic neuritis (ON) and transverse myelitis, which can result in incomplete recovery and a high risk of recurrence. This study aimed to evaluate the visual outcomes of three patients with severe acute ON in NMOSD that was non-responsive to intravenous methylprednisolone (IVMP), who received plasma exchange therapy (PLEX). We included three patients (P1, P2 and P3) with severe acute ON who had no improvement after IVMP treatment and were admitted to the ophthalmology department at the Emergency University Hospital Bucharest from January 2022 to September 2023. All three patients with ON were diagnosed in accordance with the criteria described by the Optic Neuritis Treatment Trial. All the subjects were experiencing their first attack. The mean recruitment age was 35.3 ± 7.71. All patients were seropositive for the AQP4 antibody. All patients were tested for serum myelin oligodendrocyte glycoprotein (MOG) antibody but only one showed a positive test (P3). Lesions visible in orbital MRI indicated the involvement of retrobulbar, canalicular and/or intracranial segments. All three subjects had no response or incomplete remission after an IVMP protocol (5 days of 1000 mg intravenous methylprednisolone in sodium chloride 0.9%). The mean time from onset of optic neuritis to PLEX was 37.6 days. The PLEX treatment protocol comprised five cycles of plasma exchange treatment over 10 days, with a plasma exchange session every other day. An amount of 1 to 1.5 volumes of circulating plasma were dialyzed for 2-4 h. At 1 month after the completion of PLEX therapy, BCVA and VF parameters were improved in all three patients. The treatment of ON remains subject to debate and is somewhat controversial. Plasma exchange must be considered as a rescue therapy when IVMP is insufficient for AQP4-ON patients. This study revealed that PLEX treatment effectively improves the visual outcomes of patients experiencing their first attack of severe acute isolated ON after high-dose IVMP treatment. This study suggests that PLEX may be associated with improved visual outcomes in NMOSD acute optic neuritis.

Case-series of patients treated with anti-NMDAR encephalitis at Semmelweis University

Introduction Anti-NMDAR encephalitis is an autoimmune disorder, characterized by neuropsychiatric symptoms, such as mood instability, psychosis, catatonia, dyskinesia, seizures and vegetative lability. Psychiatric symptoms usually occur in the initial phase, therefore almost half of the patients are first observed at a psychiatric unit, however in later phases the patients’ condition often show progression with the characteristic neurological symptoms, such as perioral dyskinesia and seizures. Although, early recognition and treatment is essential to reach good outcomes, delay in the diagnostic process often happens due to the unspecific early symptoms and the lack of knowledge of this disorder amongst psychiatrists. Moreover, there are cases, where neurological symptoms do not appear, which can lead to diagnostic failure and mismanagement of these patients. Since anti-NMDAR encephalitis is a rare condition, it is important to treat such cases in specific centres, where sufficient knowledge and multidisciplinary approaches are available.ObjectivesOur aim was to gather all patients’ data treated with anti-NMDAR encephalitis at two departments (Neurology and Psychiatry) of Semmelweis University. We wanted to analyse psychiatric manifestations of the disorder in details and follow these symptoms long term, with special interest on the cognitive symptoms.One of our aims was to follow-up these patients and measure antibody titres in their serum, to be able to asses, whether there was any association between prolonged serum positivity and cognitive impairment.MethodsWe have retrospectively analysed data of previous cases and prospectively followed up recently hospitalised patients.Neurocognitive assessment had been conducted by the same psychologist, all the patients were followed up by the same interdisciplinary team, including a neurologist and two psychiatrists. Laboratory tests (autoimmune antibody essays) were conducted by the Immunological Laboratory at Semmelweis University.ResultsAltogether, 13 female patients were treated with anti-NMDAR encephalitis in the past ten years at Semmelweis University. All of them received plasma exchange, iv. steroids and azathioprine. 8 out of the 13 needed ventilation and intensive care treatment. 2 of these patients have mild psychiatric symptoms as residual symptoms, and 1 of them is still in the recovery stage, currently experiencing mild cognitive symptoms.Only two patient had ovarian teratomas out of the 13, which is a lower number than expected from previous studies. 4 out of 12 had positive antibody titre at follow up, one patient is still at recovery stage, however her antibody titres are still very high.ConclusionsSemmelweis University is one of the largest centre treating patients with anti-NMDAR encephalitis in Hungary. We had altogether 13 patients in the last ten years, with very good outcome, since all of them recovered, although 2 have residual symptoms.Disclosure of InterestNone Declared

Real-World Experience With Avacopan in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis

Postmarketing data on outcomes of avacopan use in antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) are lacking. We performed a multicenter retrospective analysis of 92 patients with newly diagnosed or relapsing AAV who received therapy with avacopan. The coprimary outcome measures were clinical remission at 26 and 52 weeks. We use descriptive statistics and univariate logistic regression to assess outcomes and predictors of remission, respectively. Of the 92 patients, 23% (n = 21) had a baseline estimated glomerular filtration rate (eGFR)< 15 ml/min per 1.73 m2 and 10% on kidney replacement therapy at baseline. Among those with kidney involvement, mean (SD) enrollment eGFR was 33 (27) ml/min per 1.73 m2 with a mean (SD) change of+12 (25) and+20 (23) ml/min per 1.73 m2 at weeks 26 and 52, respectively. In addition to avacopan, 47% of patients received combination therapy of rituximab and low-dose cyclophosphamide, and 14% of patients received plasma exchange (PLEX). After induction, the median (interquartile range [IQR]) time to start avacopan was 3.6 (2.1-7.7) weeks, and the median time to discontinue prednisone after starting avacopan was 5.6 (3.3-9.5) weeks. Clinical remission was achieved in 90% of patients at week 26 and 84% of patients at week 52. Of the patients, 20% stopped avacopan due to adverse events, with the most common being elevated serum aminotransferases (4.3%). A high rate of remission and an acceptable safety profile were observed with the use of avacopan in the treatment of AAV in this postmarketing analysis, including the populations excluded from the ADVOCATE trial.

Thrombotic Microangiopathy as a Life-Threatening Complication of Long-Term Interferon Beta Therapy for Multiple Sclerosis: Clinical Phenotype and Response to Treatment-A Literature Review.

Thrombotic microangiopathy (TMA) has been observed in some patients receiving interferon beta (IFNβ) therapy for relapsing-remitting multiple sclerosis, but little is known about its clinical features and outcomes. We searched the literature to identify cases with IFNβ-related TMA and assessed their pattern of organ involvement, the presence of prodromal manifestations, the treatments used, and the outcomes. Thirty-five articles met the inclusion criteria, and data of 67 patients were collected. The median duration of IFNβ therapy before the diagnosis of TMA was 8 years, and 56/67 (84%) presented with acute kidney injury (AKI), of which 33 required acute dialysis. All but three patients had manifestations during the four weeks before TMA onset, including flu-like symptoms, headache, and worsening blood pressure control. In only two patients, ADAMTS13 activity was reduced, while 27% had low C3 levels. However, none showed causative genetic mutations associated with development of atypical hemolytic uremic syndrome. All patients discontinued IFNβ, 34 (55%) also received plasma exchange, and 12 (18%) received eculizumab. Complete renal recovery was achieved by 20 patients (30%), while 13 (20%) developed end-stage renal disease. Among those with AKI requiring dialysis, eculizumab therapy was associated with a significantly reduced risk of ESRD compared with plasma exchange. Therefore, TMA with features of aHUS mainly occurs after prolonged treatment with IFNβ and is preceded by prodromes, which may lead to an early diagnosis before life-threatening complications occur. Eculizumab appears beneficial in cases with severe kidney involvement, which supports a role of the complement system in the pathogenesis of these forms.

Anti-glutamic acid decarboxylase antibodies-associated cerebellar ataxia: A treatable ataxia

Abstract Background: Anti-glutamate decarboxylase 65 antibody-associated cerebellar ataxia (anti-GAD65Ab-associated CA) is the most widely studied immune-mediated CA. There are few case series evaluating the clinical, radiological, treatment profile, and outcome of anti-GAD65Ab-associated CA. Objective: To study the clinical, radiological profile, associated neoplasm, treatment outcome, and prognosis in patients diagnosed with anti-GAD65Ab-associated CA. Methods: A retrospective descriptive analysis of a cohort of patients diagnosed with anti-GAD65Ab-associated CA was performed and analyzed. Results: Thirteen patients were selected for the analysis with female predominance (70%). The mean age at presentation was 47.5 ± 11.1 years (range, 29–65 years), and the median duration of the symptoms was 4 months. All 13 patients (100%) had gait ataxia. Ten patients had limb ataxia along with gait ataxia (75%). Seven patients had cerebellar dysarthria (54%). Four patients (31%) had gaze-evoked jerky nystagmus. Five patients (39%) were diagnosed with type 2 diabetes mellitus, and one patient had hypothyroidism in addition to type 2 diabetes mellitus. Brain magnetic resonance imaging was normal in seven (54%) patients, and pure cerebellar atrophy was observed in six patients. One patient was detected with a colon neoplasm. All 13 patients received intravenous methylprednisolone, followed by oral steroids over 3 months. Six patients (50%) received plasma exchange along with intravenous methylprednisolone. Favorable outcomes (modified Rankin scale score ≤2) were observed in five patients and poor outcomes in two; six patients were lost to follow-up after the first admission. Conclusion: Anti-GAD65Ab-associated CA presents as subacute to chronic progressive CA with a favorable outcome with immunotherapy. Anti-GAD antibodies should be assessed in serum or cerebrospinal fluid in patients presenting subacute to chronic sporadic CA. The occurrence of a systemic neoplasm is rare in anti-GAD65Ab-associated CA.

Validation of the Plasmic Score and Development of a Novel Predictive Model for Thrombotic Thrombocytopenic Purpura: Exploring Socioeconomic Disparities and Outcomes

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy with a mortality rate up to 90% if left untreated. The PLASMIC score is a clinical prediction tool used to estimate the pretest probability of severe ADAMTS13 deficiency. Female sex, black ethnicity, and obesity have been identified as potential risk factors for TTP, however, definitive evidence for this is lacking. Our goal was to externally validate the PLASMIC score at our institution, explore the role of socioeconomic factors on TTP outcomes, and potentially identify a more accurate predictive model for TTP. Methods: We conducted a retrospective analysis of patients admitted to our institution in Cleveland, Ohio with suspected TTP between January 2000 and January 2023. Any patient who had an ADAMTS13 test ordered was included in the study. The PLASMIC score was retrospectively calculated based on admission labs and correlated with ADAMTS13 levels. Logistic regression analysis was performed to identify potential predictors of TTP with effect measured by odds ratio (OR) and its 95% confidence interval (CI). The performance of 5 predictive models was summarized using the area under the curve (AUC) and compared using Delong's test (Figures 1.1&amp;1.2). We also examined the relationship between age, race, average income, and underlying chronic diseases with TTP outcomes including length of hospital stay, number of blood transfusions, treatment options, lowest hemoglobin level during admission, and lowest platelet count during admission. Overall survival (OS) was calculated from admission to death or last follow-up for surviving patients and was evaluated using Kaplan-Meier method and Cox model. Results: We identified a cohort of 47 patients who underwent ADAMTS13 testing. The average age was 50 years old with 62% females and 44.7% identifying as African American. A total of 47% of patients were diagnosed with TTP and had ADAMTS13 levels below 10%. Our analysis revealed that the PLASMIC score was predictive of TTP with OR = 3.05 (P=0.003). When the PLASMIC score was dichotomized into a low-intermediate range (0-5) and a high range (6-7), the model predicted severe ADAMTS13 deficiency (at cutoff point -0.1088028) with a positive predictive value of 75%, negative predictive value of 69.6%, sensitivity of 72%, and specificity of 72.7%. Among the five predictive models compared (Figures 1.1 &amp; 1.2) the final multivariable model that included sex and four components of the PLASMIC score (Active Cancer, Mean Corpuscular Volume, International Normalized Ratio, and Creatinine) was found to be the most accurate in predicting TTP, with an AUC 0.88. In patients with TTP, 94% received plasma exchange and 100% received systemic steroids as treatment. Only 6 TTP patients (31.5%) received rituximab, and 2 patients (10.5%) received intravenous immunoglobulin. The use of multiple treatment options was significantly higher in older patients (P=0.017), obesity (P=0.002), and those with higher average income (per 1% increase, P=0.006). The length of hospital stay was associated with older age (P=0.015), hyperlipidemia (P=0.037), and the presence of underlying autoimmune disease (P=0.009). There was no statistically significant correlation between race and any of the adverse outcomes. Patients diagnosed with TTP had a significantly better OS compared to patients without TTP (P=0.011). The OS of patients who underwent plasmapheresis was slightly better, although the difference was not statistically significant (P=0.067). Conclusion: Our study validates the original PLASMIC score as a reliable predictor of severe ADAMTS13 deficiency. However, we propose a new multivariable model that incorporates sex and four components of the original PLASMIC score (Active Cancer, Mean Corpuscular Volume, International Normalized Ratio, and Creatinine) as a better predictor for TTP. Further multicenter studies with larger sample sizes are necessary to validate this new model. We also identified socioeconomic disparities, such as patients with higher income who received multiple lines of treatment compared to lower income patients. Notably, patients diagnosed with TTP had lower mortality possibly due to prompt diagnosis and effective management at our institution and/or the presence of more severe alternative diagnoses in the non-TTP group.

Acquired hyperexcitable peripheral nerve disorders: Clinical and laboratory features, therapeutic responses, and long-term follow-up.

Hyperexcitable peripheral nerve disorders (HPNDs) are rare. Although their clinical and laboratory features have been well studied, information on treatment and follow-up is limited. The aim of this study is to explore the long-term clinical, investigative, and therapeutic profile of patients with acquired HPNDs. This study retrospectively analyzed patients from a single tertiary care center with HPND (January 2012 to January 2022). Patients were recruited according to published inclusion and exclusion criteria. Details of clinical features, diagnostic tests, therapeutic interventions, and follow-up were recorded. This study included patients with follow-up of 2 or more years. A total of 32 patients (M = 26, F = 6) were studied. The common clinical features included myokymia, neuropathic or shock-like pain, cramps, sleep disturbances, encephalopathy, cerebellar ataxia, and seizures. A total of 81.25% of patients responded favorably to corticosteroids and membrane stabilizers. Among the nonresponders, five received intravenous immunoglobulin (IVIG), and one received plasma exchange (PLEX). Two patients required rituximab due to poor responses to the above treatments. The mean duration of response was 6 weeks (4-24 weeks) from the initiation of treatment. All patients had favorable outcomes, reaching clinical remission within 1-5 years from the initiation of treatment. Only two patients had relapses. Immunotherapy could be stopped in 78% of patients within 3 years and 100% by 5 years. Chronic immunosuppression starting with corticosteroids is required for satisfactory outcomes of HPNDs. These disorders usually run a monophasic course, and relapses are uncommon.

Clinical application of blood purification in polymyositis/dermatomyositis.

We investigated the clinical efficacy and safety of blood purification technology in patients with polymyositis/dermatomyositis. In a study of 22 patients, 10 cases received blood purification treatment (5 cases received plasma exchange, 5 cases received plasma HA280 immunoadsorption), and 12 cases served as the control group. A 3-month follow-up was conducted to compare the clinical manifestations and laboratory examination. Symptoms and signs of patients in treatment group were significantly improved, and the hormone usage was lower than the control group. For patients with normal creatine kinase level and ferritin level below three times the upper limit of normal, there was a positive correlation between their N/L values and MDAAT scores. The results of this study suggest that blood purification therapy, including plasma HA280 immunoadsorption and plasma exchange, is an effective and safe treatment for patients with polymyositis/dermatomyositis, offering assistance in reducing hormone usage in the long-term.

Analysis of the relation between cerebrospinal fluid antibody titers and clinical characteristics in pediatric patients with anti-N-methyl-D-aspartate receptor encephalitis

ObjectiveThis retrospective study aimed to investigate the relationship between cerebrospinal fluid (CSF) antibody titers of N-methyl-d-aspartate receptor (NMDAR), and clinical characteristics in pediatric patients with anti-NMDAR encephalitis. MethodsThe clinical and laboratory characteristics of hospitalized patients with anti-NMDAR encephalitis, stratified by antibody titers in CSF and disease severity, were retrospectively studied. The demographics, clinical characteristics, main accessory examinations, immunotherapy, and prognosis of patients were recorded, and each observed indicator was statistically analyzed. ResultsA total of 103 pediatric anti-NMDAR encephalitis patients were enrolled in the study, including 41 males (39.8%) and 62 females (60.2%) with a mean age of 8.0 ± 4.0 years. The proportion of patients with cognitive dysfunction and the positive pathogen was higher in the high-titer group than in the low-titer group (p = 0.023, p = 0.042). Consciousness disturbance that occurred as an initial symptom or during the course in the severe group was higher than in the non-severe group (p = 0.002, p < 0.001). More patients in the high-titer group received plasma exchange (PE) than in the low-titer group (p = 0.022). The cure rate of patients was higher with PE (65.2%) than with Corticosteroids and (or) intravenous immunoglobulin (58.1%). ConclusionsPatients with symptoms of disturbance of consciousness may be severer. The severity in pediatric anti-NMDAR encephalitis patients was not correlated with anti-NMDAR antibody titers. Patients with high CSF antibody titers had a better prognosis after early PE therapy.

Efficacy of Rituximab Combined with Plasma Exchange in the Treatment of Thrombotic Thrombocytopenic Purpura (TTP)

Objective: To analyze the curative effect of rituximab combined with plasma exchange in the treatment of thrombotic thrombocytopenic purpura. Methods: 70 patients with thrombotic thrombocytopenic purpura that were treated in our hospital from January 2022 to January 2023 were selected for this study. They were divided into two groups according the treatment method they were about to receive. The patients in the control group received plasma exchange. The observation group was given rituximab in addition to plasma exchange. Then, the therapeutic effects of the two groups were observed, and the incidence of adverse reactions was compared. Results: The rate of effectiveness of the treatment received in observation group and the control group was 97.14% and 82.86%, respectively. The treatment received in observation group had a better therapeutic effect (P &lt; 0.05). The incidence of adverse reactions in the observation group (22.86%) was lower than that of the control group (5.71%) , with P &lt; 0.05. Conclusion: Rituximab combined with plasma exchange is relatively more effective than plasma exchange alone, with less adverse reaction, making it a viable treatment option.

Overlap syndrome of anti-aquaporin 4 positive neuromyelitis optica spectrum disorder and primary Sjögren's syndrome: a systematic review of individual patient data.

Central nervous system (CNS) involvement can occur in primary Sjögren's syndrome (pSS) due to co-existing neuromyelitis optica spectrum disorder (NMOSD) which has a highly relapsing course requiring indefinite immunosuppression, and if not diagnosed early, damage accrual occurs over time leading to permanent disability and morbidity. In this review, we describe and outline the clinical course and outcomes of anti-aquaporin 4 (AQP4) antibody seropositive NMOSD with pSS overlap cases. To investigate the co-existence of AQP4 + NMOSD with pSS, we conducted a review of individual patient data from case reports and case series found in major databases. The study extracted clinico-demographic features, imaging and laboratory profiles, treatment approaches, and outcomes of these patients. Inclusion criteria for the review required patients to have positivity for anti-AQP4 or NMO-IgG autoantibodies in the blood and/or cerebrospinal fluid (CSF) and exhibit at least one manifestation of both pSS and NMOSD. In this overlap between AQP4 + NMOSD and pSS, 44 patients were included of whom 41 (93.2%) were females. The mean age of pSS onset was 44.8 ± 18.4years and NMOSD onset was 43.2 ± 19.8years. In 20 (45.5%) patients, NMOSD preceded pSS onset, 13 (29.5%) NMOSD occurred after pSS onset, and 11 (25%) patients had a simultaneous presentation. 31 (70.5%) patients experienced acute transverse myelitis, 21 (47.7%) optic neuritis, 14 (31.8%) cerebral syndrome, 10 (22.7%) acute brainstem syndrome, 5 (11.4%) area postrema syndrome, and 2 (4.5%) diencephalic clinical syndromes. For the treatment of acute phase, 40 (90.9%) patients received intravenous methylprednisolone, 15 (34.1%) received plasma exchange, and 10 (22.7%) received intravenous immunoglobulin; and for the induction/maintenance therapy, 16 (36.4%) patients received cyclophosphamide, 6 (13.6%) received rituximab, 16 (36.4%) received azathioprine, and 10 (22.7%) received mycophenolate mofetil. Disease course was monophasic in 2 (4.5%) and relapsing in 27 (61.4%) patients. At median (IQR) follow-up duration of 2.4 (6) years, 39 (88.6%) patients showed improvement, 3 (6.8%) showed stabilization and 2 (4.5%) showed worsening of their NMOSD manifestations. In this overlap syndrome of AQP4 + NMOSD and pSS, patients have a neurologically disabling disorder that can mimic neurological manifestations of pSS, frequently occurs prior to the onset of pSS, has a relapsing course, responds well to immunosuppressants, and necessitates indefinite treatment. Collaborative multicentre studies are needed to clarify the natural history and outcomes of this rare overlap syndrome.

Placental transmission of MOG-IgG to neonate from mother with MOGAD (P13-5.026)

Placental transmission of MOG-IgG to neonate from mother with MOGAD (P13-5.026)

Clinical characteristics and management of immune checkpoint inhibitor-related cardiotoxicity: A single-center experience.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy in the past decade and amplify T-cell-mediated immune responses by disrupting immunoinhibitory signals. The augmented T-cell immune response has led to a range of immune-related adverse effects (irAEs). Immune-related cardiotoxicity has been reported in case series but has been underappreciated due to difficulties in diagnosis. This article describes epidemiological, clinical presentation, subtype, and treatment data and a new systematic framework for the clinical management of cardiotoxicity. Data were extracted for cancer patients who received ICIs in a single center between January 1, 2020, and February 28, 2022. ICI-associated cardiotoxicity was clinically diagnosed based on clinical presentations, biochemical biomarkers, and imaging features. We identified a total of 12 (2.46%) cases of ICI-related cardiotoxicity from 487 patients who received PD-1 or PD-L1 inhibitors. All patients were diagnosed with advanced or metastatic solid tumors. The severity of ICI-related cardiotoxicity ranged from subclinical cardiac abnormalities (subclinical type) with only asymptomatic troponin-I (TnI) elevations (25.0%) to symptomatic cardiac abnormalities (clinical type) (75.0%). Patients with symptomatic cardiac abnormalities had several manifestations, including tachyarrhythmia (16.7%), bradyarrhythmia (41.7%), or cardiac failure (8.3%). The median immunotherapy exposure time was 1.5 doses (range: 1 to 5), and the median time from the initial immunotherapy to the onset of ICI-related cardiotoxicity was 33.5 days (IQR: 20.3 to 46.8). Most patients, including those with subclinical cardiac abnormalities, were administered systemic corticosteroids (58.3%). One (8.3%) patient was put on mechanical ventilation, one (8.3%) received plasma exchange therapy, one (8.3%) was implanted with a pacemaker, and one (8.3%) was admitted to the ICU. Three patients with symptomatic cardiac abnormalities (25.0%) died, and other patients presented with significant clinical improvement with good outcomes. ICI-related cardiotoxicity is uncommon but critical with a high mortality rate and poor prognosis, especially for a small group of patients with symptomatic cardiac abnormalities. More attention should be given to cardiotoxicity associated with ICIs, and these patients should be given baseline examinations and biochemical analyses before and after the initiation of immunotherapy, intensive cardiac assessments, an accurate and rapid diagnosis, and timely multidisciplinary management with immunosuppressive agents and other necessary clinical interventions.

Clinical characteristics of pediatric allogeneic hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA): a retrospective single-center analysis

ObjectivesTo investigate the clinical features of thrombotic microangiopathy associated with allogeneic hematopoietic stem cell transplantation in children.MethodsA retrospective analysis of continuous clinical data from HSCT received in the Department of Hematology and Oncology of Wuhan Children's Hospital from August 1, 2016 to December 31, 2021.ResultsDuring this period, 209 patients received allo-HSCT in our department, 20 (9.6%) of whom developed TA-TMA. TA-TMA was diagnosed at a median of 94 (7–289) days post-HSCT. Eleven (55%) patients had early TA-TMA within 100 days post-HSCT, while the other 9 (45%) patients had TA-TMA thereafter. The most common symptom of TA-TMA was ecchymosis (55%), while the main signs were refractory hypertension (90%) and multi-cavity effusion (35%). Five (25%) patients had central nervous system symptoms (convulsions and lethargy). All 20 patients had progressive thrombocytopenia, with 16 patients receiving transfusion of platelets that was ineffective. Ruptured red blood cells were visible in only two patients with peripheral blood smears. Cyclosporine A or Tacrolimus (CNI) dose was reduced once TA-TMA was diagnosed. Nineteen cases were treated with low-molecular-weight heparin, 17 patients received plasma exchange, and 12 patients were treated with rituximab. TA-TMA-related mortality percentage in this study was 45% (9/20).ConclusionPlatelet decline and/or ineffective transfusion post-HSCT should be considered an early indicator of TA-TMA in pediatric patients. TA-TMA in pediatric patients may occur without evidence of peripheral blood schistocytes. Aggressive treatment is required once diagnosis is confirmed, but the long-term prognosis is poor.

A multi-subgroup predictive model based on clinical parameters and laboratory biomarkers to predict in-hospital outcomes of plasma exchange-centered artificial liver treatment in patients with hepatitis B virus-related acute-on-chronic liver failure.

Postoperative risk stratification is challenging in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) who undergo artificial liver treatment. This study characterizes patients' clinical parameters and laboratory biomarkers with different in-hospital outcomes. The purpose was to establish a multi-subgroup combined predictive model and analyze its predictive capability. We enrolled HBV-ACLF patients who received plasma exchange (PE)-centered artificial liver support system (ALSS) therapy from May 6, 2017, to April 6, 2022. There were 110 patients who died (the death group) and 110 propensity score-matched patients who achieved satisfactory outcomes (the survivor group). We compared baseline, before ALSS, after ALSS, and change ratios of laboratory biomarkers. Outcome prediction models were established by generalized estimating equations (GEE). The discrimination was assessed using receiver operating characteristic analyses. Calibration plots compared the mean predicted probability and the mean observed outcome. We built a multi-subgroup predictive model (at admission; before ALSS; after ALSS; change ratio) to predict in-hospital outcomes of HBV-ACLF patients who received PE-centered ALSS. There were 110 patients with 363 ALSS sessions who survived and 110 who did not, and 363 ALSS sessions were analyzed. The univariate GEE models revealed that several parameters were independent risk factors. Clinical parameters and laboratory biomarkers were entered into the multivariate GEE model. The discriminative power of the multivariate GEE models was excellent, and calibration showed better agreement between the predicted and observed probabilities than the univariate models. The multi-subgroup combined predictive model generated accurate prognostic information for patients undergoing HBV-ACLF patients who received PE-centered ALSS.

Rapidly progressive glomerulonephritis secondary to anti-GBM disease associated with MPO-ANCA: a case report

BackgroundAnti-glomerular basement membrane (GBM) disease and ANCA-associated vasculitis (AAV) diseases are rare. It is associated with variable renal manifestations and increased mortality, thus requiring early aggressive treatment to minimize adverse outcomes and improve prognosis.Case presentationWe present the case of a male patient with 1-month onset of asthenia, adynamia, oliguria, and weight loss. Initial laboratory findings were indicative of severe kidney dysfunction. The urinalysis showed active sediment, but the urinary tract ultrasound was unaltered. As these findings were consistent with rapidly progressive glomerulonephritis, he received steroid pulses, and given the severity of the condition, renal replacement therapy was initiated. Other diagnostic tests revealed MPO-ANCA antibody levels of 26 mg/dl, pANCAs 1/320, and anti-GBM of 8 mg/dl. Kidney biopsy evidenced necrotizing glomerulonephritis with extracapillary proliferation in 90% of the glomeruli. The patient received plasma exchange (PE) therapy and intravenous (IV) cyclophosphamide (CYC) cycles; however, he presented with severe alveolar hemorrhage requiring the completion of 21 PE sessions and 3 CYC boluses. Pulmonary symptoms resolved, but the patient persisted dependent on dialysis. During the outpatient follow-up, monthly CYC were prescribed until circulating antibody levels were normal; however, the patient did not recover full kidney function and remained dependent on renal support.ConclusionsAnti-GBM and AAV diseases are rare; therefore, anti-GBM antibodies should be screened simultaneously in patients with ANCA positive, especially in older patients, due to the early morbidity and mortality typical of anti-GBM disease with comparable disease severity it represents.

Impact of Acute Coronary Syndrome on Clinical Outcomes in Patients With Thrombotic Thrombocytopenic Purpura.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening clinical syndrome characterized by microangiopathy and a variable degree of end-organ ischemic damage. Cardiac involvement has been recognized as a major cause of mortality in these patients. In this study, we queried the National Inpatient Sample (NIS) for all patients hospitalized with thrombotic microangiopathy from 2002 to 2017, who also received plasma exchange (PLEX) during the same admission. A total of 6,214 patients with TTP were identified. We stratified patients based on whether or not they had acute coronary syndrome (ACS) during admission. ACS was documented in 6.3% of patients. Compared with patients without ACS, those with ACS were relatively older (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.02-1.03) and had a relatively higher prevalence of heart failure (OR, 2.02; 95% CI, 1.53-2.67)and coronary artery disease (OR, 2.69; 95% CI, 2.03-3.57). Certain complications were more prevalent in the ACS group including acute cerebrovascular accident (OR, 3.33; 95% CI, 2.94-3.78), acute heart failure (OR, 1.91; 95% CI, 1.67-2.19), acute kidney injury (OR, 1.76; 95% CI, 1.59-1.95), cardiogenic shock (OR, 2.15; 95% CI, 1.72-2.69), and respiratory failure (OR, 1.48; 95% CI, 1.32-1.66). Despite wider utilization of therapeutic plasmapheresis and improved supportive management of patients with TTP, associated morbidity and mortality remain significant.We demonstrate from this large retrospective cohort that ACS is an independent predictor of higher morbidity and mortality in TTP patients.

A retrospective study on acquired demyelinating diseases in children

Background: Acquired demyelinating diseases (ADS) соnstitute а heterogeneous grоuр of central nervous system disorders of autoimmune origin that causes significant physical and cognitive disabilities. Early recognition and prompt management causes significant improvement in acute episodes of demyelinating disorders. Methods: 33 children diagnosed with demyelinating disorders at Lokmanya Tilal municipal medical college and hospital in Mumbai were enrolled. The study was conducted between January 2013 and November 2022. Demographic data, clinical profile, CSF study, serum antibody, radiological findings were collected and results were analyzed. Statistical Data was analysed using statistical software GraphPad in Stat.V3.0. Data were presented in tables and figures whenever needed. P value &lt;0.05 considered as significant. Results: Of 33 patients, 21 (63%) were cases of acute disseminated encephalomyelitis (ADEM), 6 (18.1%) of transverse myelitis (TM), 1 case of ADEM + TM (3%), 3 (9%) of neuromyelitis optica, 1 (3%) of Optic neuritis and 1 (3%) of multiple sclerosis. ADEM patients presented with encephalopathy and multifocal neurological deficits, 40% were MOG positive. Two patients were of multiphasic ADEM. Patients of transverse myelitis had paraparesis or quadriparesis and sensory + bladder involvement. Patients with NMO presented with bilateral visual impairment with limb weakness and bladder involvement. Steroids were the primary treatment, 3 patients (9%) required intravenous immunoglobulin (IVIG) and 1 (3%) patient received plasma exchange therapy. Conclusions: ADEM is the most common ADS. Early diagnosis and management with steroids therapy improves outcome in most of the patients. Non response to steroids warrants second line treatment options like IV Immunoglobulin (IVIG) or Therapeutic plasma exchange.