Intravenous Immunoglobulin Research Articles

P.056: High-dose intravenous immunoglobulin for BK virus DNAemia protects against BK nephropathy but not acute rejection.

P.056: High-dose intravenous immunoglobulin for BK virus DNAemia protects against BK nephropathy but not acute rejection.

51955 A patient’s view of switching from intravenous to subcutaneous immunoglobulin for the management of recalcitrant systemic lupus erythematosus

51955 A patient’s view of switching from intravenous to subcutaneous immunoglobulin for the management of recalcitrant systemic lupus erythematosus

Immunoglobulins as Tools for Passive Immunization in Preventive Healthcare

Immunoglobulins have emerged as an important tool in passive immunization for the prevention and treatment of infectious diseases. Immunoglobulins are the proteins produced by B cells that bind to specific pathogens, neutralize them, and facilitate their removal by the immune system. In preventive healthcare, immunoglobulins are used for primordial, primary, secondary, tertiary, and quaternary prevention of infectious diseases. This work was designed to carry out an extensive literature search to provide useful information on immunoglobulins as the tools of passive immunization in preventive healthcare. Relevant and accurate literatures were sourced from the World Health Organization. Centers for Disease Control and Prevention, National Center for Disease Control, PubMed, Scopus, PLoS One, and NATURE journals: Primordial prevention aims to prevent the emergence and spread of risk factors for infectious diseases. Immunoglobulins can be used to prevent the spread of infectious diseases by targeting the pathogens that cause them. The primary prevention aims to prevent the initial infection of individuals at risk of acquiring infectious diseases. Immunoglobulins can be used as prophylaxis to prevent the onset of infection in high-risk individuals. The secondary prevention aims to reduce the severity and duration of infectious diseases. Immunoglobulins can be used to treat infectious diseases and prevent complications. The tertiary prevention aims to prevent the recurrence and complications of infectious diseases. Immunoglobulins can be used to prevent the recurrence of infections in individuals who have already been infected. Quaternary prevention aims to prevent the overuse, misuse, and abuse of medical interventions. Immunoglobulins can be used to prevent the development of antibiotic resistance by reducing the use of antibiotics. However, the use of immunoglobulins in preventive healthcare is not without challenges. The cost-effectiveness of immunoglobulin therapy, long-term safety, and the potential for cross-infection are some of the challenges that need to be addressed. Further research is needed to optimize the use of immunoglobulins in preventive health-care delivery. Immunoglobulins are valuable tools in passive immunization for the prevention and treatment of infectious diseases in preventive healthcare. Their use can help reduce the burden of infectious diseases and improve public health outcomes. Keywords: Immunoglobulins, passive immunization, preventive healthcare.

Anti-LGI1 Antibody-Associated Encephalitis Misdiagnosed as Schizophrenia: A Case Report.

Anti-leucine-rich glioma-inactivated 1 (LGI1) antibody-associated encephalitis is a rare but clinically significant form of autoimmune encephalitis, predominantly affecting middle-aged men. Its heterogeneous clinical presentation often leads to misdiagnosis, commonly as other neurological or psychiatric disorders. This report details the case of a 46-year-old male who initially presented with depressive symptoms, personality changes, and visual hallucinations. Over time, his condition progressed to include memory impairment, disorganized behavior, and seizures. Initially misdiagnosed with schizophrenia, the correct diagnosis of LGI1 antibody-associated encephalitis was eventually established through positive serum and cerebrospinal fluid (CSF) tests for LGI1 antibodies. Neuroimaging findings revealed characteristic bilateral temporal lobe lesions. The patient demonstrated marked improvement following treatment with methylprednisolone and intravenous immunoglobulin, ultimately achieving significant recovery. This case highlights the critical importance of comprehensive antibody testing and neuroimaging in patients presenting with nonspecific psychiatric and neurological symptoms to prevent misdiagnosis and delays in appropriate treatment. The article also reviews the pathogenesis, clinical manifestations, diagnostic approaches, and therapeutic strategies for LGI1 antibody-associated encephalitis, aiming to enhance clinical awareness and optimize patient outcomes.

Therapeutic agents for steroid-refractory immune checkpoint inhibitor-related myocarditis: a narrative review.

Immune checkpoint inhibitors (ICIs) have become one of the cornerstones of current oncology treatment, and immune checkpoint inhibitor-related myocarditis (IRM) is the most fatal of all immune checkpoint inhibitor-related adverse events (irAEs). Methylprednisolone pulse therapy (500-1,000 mg/day) is the initial treatment for IRM recommended by almost all relevant guidelines. However, subsequent treatment regimens remain unclear for patients who do not respond to methylprednisolone pulse therapy (who are defined as steroid-refractory patients). We propose a potential treatment approach for steroid-refractory IRM. The PubMed and the Cochrane Library databases were searched using keywords related to IRM. Relevant English-language articles published from January 2000 to February 2024 were included in this narrative review. Abatacept is the preferred choice for the treatment of isolated steroid-refractory IRM. For rapidly progressive or interleukin-6 abnormally elevated steroid-refractory IRM, alemtuzumab or tocilizumab/tofacitinib are the preferred therapeutic agents, respectively. For steroid-refractory IRM comorbid with myositis or comorbid with myasthenia gravis, abatacept + ruxolitinib/mycophenolate mofetil (MMF)/intravenous immunoglobulin (IVIG), or MMF + pyridostigmine/IVIG are the preferred therapeutic agents, respectively. The pathogenesis of steroid-refractory IRM and the treatment regimen remain unclear. A large number of studies need to be conducted to validate or update our proposed treatment approach.

Submicron immunoglobulin particles exhibit FcγRII-dependent toxicity linked to autophagy in TNFα-stimulated endothelial cells

In intravenous immunoglobulins (IVIG), and some other immunoglobulin products, protein particles have been implicated in adverse events. Role and mechanisms of immunoglobulin particles in vascular adverse effects of blood components and manufactured biologics have not been elucidated. We have developed a model of spherical silica microparticles (SiMPs) of distinct sizes 200–2000 nm coated with different IVIG- or albumin (HSA)-coronas and investigated their effects on cultured human umbilical vein endothelial cells (HUVEC). IVIG products (1–20 mg/mL), bare SiMPs or SiMPs with IVIG-corona, did not display significant toxicity to unstimulated HUVEC. In contrast, in TNFα-stimulated HUVEC, IVIG-SiMPs induced decrease of HUVEC viability compared to HSA-SiMPs, while no toxicity of soluble IVIG was observed. 200 nm IVIG-SiMPs after 24 h treatment further increased ICAM1 (intercellular adhesion molecule 1) and tissue factor surface expression, apoptosis, mammalian target of rapamacin (mTOR)-dependent activation of autophagy, and release of extracellular vesicles, positive for mitophagy markers. Toxic effects of IVIG-SiMPs were most prominent for 200 nm SiMPs and decreased with larger SiMP size. Using blocking antibodies, toxicity of IVIG-SiMPs was found dependent on FcγRII receptor expression on HUVEC, which increased after TNFα-stimulation. Similar results were observed with different IVIG products and research grade IgG preparations. In conclusion, submicron particles with immunoglobulin corona induced size-dependent toxicity in TNFα-stimulated HUVEC via FcγRII receptors, associated with apoptosis and mTOR-dependent activation of autophagy. Testing of IVIG toxicity in endothelial cells prestimulated with proinflammatory cytokines is relevant to clinical conditions. Our results warrant further studies on endothelial toxicity of sub-visible immunoglobulin particles.

Therapeutic Potential of Salvia miltiorrhiza Root Extract in Alleviating Cold-Induced Immunosuppression.

The interaction between environmental stressors, such as cold exposure, and immune function significantly impacts human health. Research on effective therapeutic strategies to combat cold-induced immunosuppression is limited, despite its importance. In this study, we aim to investigate whether traditional herbal medicine can counteract cold-induced immunosuppression. We previously demonstrated that cold exposure elevated immunoglobulin G (IgG) levels in mice, similar to the effects of intravenous immunoglobulin (IVIg) treatments. This cold-induced rise in circulating IgG was mediated by the renin-angiotensin-aldosterone system and linked to vascular constriction. In our mouse model, the cold-exposed groups (4 °C) showed significantly elevated plasma IgG levels and reduced bacterial clearance compared with the control groups maintained at room temperature (25 °C), both indicative of immunosuppression. Using this model, with 234 mice divided into groups of 6, we investigated the potential of tanshinone IIA, an active compound in Salvia miltiorrhiza ethanolic root extract (SMERE), in alleviating cold-induced immunosuppression. Tanshinone IIA and SMERE treatments effectively normalized elevated plasma IgG levels and significantly improved bacterial clearance impaired by cold exposure compared with control groups injected with a vehicle control, dimethyl sulfoxide. Notably, bacterial clearance, which was impaired by cold exposure, showed an approximately 50% improvement following treatment, restoring immune function to levels comparable to those observed under normal temperature conditions (25 °C, p < 0.05). These findings highlight the therapeutic potential of traditional herbal medicine in counteracting cold-induced immune dysregulation, offering valuable insights for future strategies aimed at modulating immune function in cold environments. Further research could focus on isolating tanshinone IIA and compounds present in SMERE to evaluate their specific roles in mitigating cold-induced immunosuppression.

Efficacy of tocilizumab in highly relapsing MOGAD with an inadequate response to intravenous immunoglobulin therapy: A case series

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory disease affecting the central nervous system that may require long-term immunotherapy in relapsing cases. While immunotherapies utilized in neuromyelitis optica spectrum disorder have shown varying efficacy in MOGAD, intravenous immunoglobulin G (IVIG) recently emerged as a promising treatment. Tocilizumab, a monoclonal antibody that targets the interleukin-6 (IL-6) receptor, has been reported to be effective in refractory MOGAD in several case studies, where tocilizumab was introduced primarily due to rituximab failure. This retrospective study was conducted in a single center and focused on MOGAD patients receiving tocilizumab therapy, who have shown limited response to various immunotherapies, including intravenous immunoglobulin G (IVIG) maintenance. This study included four patients, three adults, and one child. They experienced a median of 9 attacks (range 6-9) throughout their disease course despite at least two immunotherapies. All patients transitioned to tocilizumab after experiencing a median of two relapses (range 1-3) while on IVIG maintenance for a median of 21.9 months (range 21.3-49.6 months). Following the monthly tocilizumab administration at a dose of 8g/kg, all patients remained relapse-free with a median follow-up duration of 25.0 months (range 9.8-51.3 months) without reported adverse events. Targeting the IL-6 pathway appears to offer therapeutic benefits in highly relapsing MOGAD patients who poorly respond to IVIG maintenance therapy.

Pediatric Chronic Inflammatory Demyelinating Polyneuropathy: Challenges in Diagnosis andTherapeutic Strategies.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare autoimmune neurological disorder seen in both pediatric and adult populations. CIDP typically presents with progressive and persistent weakness over at least 4 weeks in addition to sensory symptoms in the extremities. Although CIDP shares common clinical features between children and adults, it sometimes presents as a distinct clinical entity in children that requires close attention and recognition. A major caveat when diagnosing a child with CIDP is the clinical and diagnostic overlap with inherited neuropathies, most commonly Charcot-Marie-Tooth disease (CMT). Demyelinating CMT (dCMT) and CIDP might share similar clinical presentations, and sometimes it might be difficult to differentiate them on the basis of the electrodiagnostic findings or cerebrospinal fluid (CSF) albumino-cytological dissociation. This indeed merits early consideration for genetic testing in patients who do not respond to conventional CIDP therapies. Current treatment options for CIDP include intravenous immunoglobulins (IVIG), corticosteroids (CS), and plasmapheresis (PLEX). The need for novel therapies is essential in instances where patients continue to have symptoms despite the standard therapies or due to adverse effects of long-term use of standard therapies such as CS. This paper reviews the challenges in the diagnosis of CIDP in children and the current as well as novel therapies for CIDP.

Intravenous immunoglobulin improves live birth rates in patients with unexplained recurrent pregnancy loss

This real-world study aimed to assess the clinical efficacy and safety of intravenous immunoglobulin (IVIG) in treating unexplained recurrent pregnancy loss (uRPL) patients. A total of 238 patients with uRPL were enrolled in this retrospective study. According to the treatment, patients were assigned into treatment group (n=184, receiving IVIG+low molecular weight heparin [LMWH]) and control group (n=54, only LMWH). The primary outcome was the live birth rates (LBR) after 24 weeks of gestation. In addition, we performed subgroup analyses to assess the LBR in uRPL patients with age (≥30 years or <30 years), body mass index (BMI, 18–24 kg/m2 or ≥24 kg/m2), number of previous pregnancy losses (2 or ≥3), gestational week of first medication, and IVIG medication regimen during pregnancy. The LBR showed a significant increase after IVIG treatment compared to the control group (77.7 % vs. 53.7 %, P=0.001). Multivariable logistic regression indicated that IVIG was associated with increased LBR (aOR=4.383, 95 %CI 2.024–9.489). Besides, we observed a significantly lower incidence of decreased platelet count (1.6 % vs. 7.4 %, P=0.049) in the treatment group. Subgroup analyses showed that IVIG treatment was associated with improved LBR in uRPL patients with age of <30 years (aOR=4.012, 95 %CI 1.428–11.266), previous pregnancy losses ≥3 times (aOR=17.327, 95 %CI 2.525–118.921), and BMI of 18–24 kg/m2 (aOR=8.914, 95 %CI 2.985–26.618). IVIG treatment significantly improves the LBR in uRPL patients. These findings from real-world data provide evidence for the safety and efficacy of IVIG as a viable treatment for uRPL patients in clinical practice.

Infections in Children with Acute Lymphoblastic Leukemia.

Background and Objectives: Infections are the most common and potentially life-threatening complications of the treatment of children with acute lymphoblastic leukemia (ALL). The aim of this study was to determine epidemiological, clinical, and microbiological characteristics of infections in pediatric patients with ALL. Materials and Methods: Twenty-three children (16 males and 7 females, with a mean age of 5.9 years (range of 1.3 to 12.2 years)) with ALL, treated at the Division of Hematology, Oncology, and Clinical Genetics, Department of Pediatrics, Clinical Hospital Center Rijeka, Croatia, from 1 January 2015 to 31 December 2020, were included in the study. Results: One hundred and four infectious episodes (IEs) were reported (an average of 4.5 IE per patient). IEs were more frequent in the intensive phases of antileukemic treatment. Neutropenia was present in 48 IEs (46.2%) with a duration greater than 7 days in 28 IEs (58.3%). The respiratory tract was the most common infection site (48.1%). We documented 49 bacterial (47.1%), 4 viral (3.9%), 4 fungal (3.9%), and 10 mixed isolates (9.6%), while in 37 IEs (35.6%), a pathogen was not isolated. The most common causes of bacteremia were coagulase-positive staphylococci. The most frequent empirical therapy was third- and fourth-generation cephalosporins, followed by piperacillin/tazobactam. The modification of first-line antimicrobial therapy was performed in 56.9% of IEs. Granulocyte-colony stimulating factor was administered in 53.8% of IEs, and intravenous immunoglobulins were administered in 62.5% of IEs. One patient required admission to the intensive care unit. No infection-related mortality was reported. Conclusions: ALL patients have frequent IEs. Close monitoring, the identification of risk factors, the rapid empirical use of antibiotics in febrile neutropenia, and the timely modification of antimicrobial therapy play key roles in reducing infection-related morbidity and mortality in children with ALL.

Multi-modal immune dynamics of pre-COVID-19 Kawasaki Disease following intravenous immunoglobulin

Despite progress, the molecular mechanisms underlying Kawasaki Disease (KD) and intravenous immunoglobulin's (IVIG) ability to mitigate the inflammatory process remain poorly understood. To characterize this condition, plasma proteomic profiles, flow cytometry, and gene expression of T cell subsets were investigated in longitudinal samples from KD patients and compared with two control groups. Systems-level analysis of samples in the acute phase revealed distinctive inflammatory features of KD, involving mainly Th-1 and Th-17 mediators and unveiled a potential disease severity signature. APBB1IP demonstrated an association with coronary artery involvement (CAI) and was significantly higher in CAI+ compared to CAI- patients. Integrative analysis revealed a transient reduction in CD4+ EM T cells and a comprehensive immune activation and exhaustion. Following treatment, Tregs at both frequency and gene expression levels revealed immune dynamics of recovery. Overall, our data provide insights into KD, which may offer valuable information on prognostic indicators and possible targets for novel treatments.

Clinical Impact of Community-Acquired Respiratory Viruses in Patients With Solid Organ Transplants

Community-acquired respiratory viruses (CARVs) are associated with poor outcome in solid organ transplant recipients. We reviewed some of these outcomes such as respiratory support, length of stay, admission to the intensive care unit, steroid use, and 30-day all-cause mortality. Multihospital, single center, retrospective review of electronic health records from January 1, 2014, to December 31, 2019. Twenty-three solid organ transplant recipients (20 male and 3 female) who tested positive for CARVs were identified. The mean age at admission was 60 years, average length of stay was 8 days with 2 patients needing >2 weeks. Six patients required intensive care unit and 8 required supplemental oxygen support. CARV distribution was rhinovirus in 48%, parainfluenza in 29%, metapneumovirus in 12%, respiratory syncytial virus in 0.03%, adenovirus in 0.03%, and non-novel coronavirus in 0.06%. All patients were immunosuppressed, intravenous immunoglobulins were used in 3 patients, antivirals in 7 patients (ribavirin in 6 and oseltamivir in 1), and steroids in 10 patients. Twelve patients had transplant organ biopsy with 5 showing acute cellular rejection. Thirty-five percent of patients died within 1 year (2 during the same admission). Transplant recipients are at a high risk of infections, especially CARVs, which may increase morbidity and mortality. In our observational study, we assessed patients with solid organ transplants who were admitted and tested positive for CARVs, and the associated impact on their clinical course. Careful analysis of the results will help us to emphasize the importance of timely diagnosis and treatment in specific populations.

Diffuse alveolar hemorrhage in patients with systemic lupus erythematosus: data from the Spanish society of rheumathology Lupus Register (RELESSER).

Diffuse alveolar hemorrhage (DAH) is a rare complication with high mortality in patients with systemic lupus erythematosus (SLE). Early diagnosis and treatment are essential to improve patient prognosis.To determine the characteristics of patients with DAH and their mortality in a Spanish cohort of patients with SLE. Patients from the RELESSER (Spanish Society of Rheumatology Lupus Register) who had had at least one confirmed episode of DAH were included. Epidemiological, clinical, and laboratory characteristics were analyzed. 4024 patients were included in the RELESSER register, 37 (0.9%), had at least one recorded episode of DAH. Only further data for 14 patients could be analyzed. In total, 92.9% were women, and for 4 (28.6%) DAH coincided with the debut of SLE. More than 80% of patients had renal involvement and thrombocytopenia. The most frequent manifestations were dyspnea (85.7%) and hypoxemia (100%), with the classic triad of hemoptysis, anemia and pulmonary infiltrates, appearing in 6 (46.2%) patients. The most frequently used treatments were glucocorticoids (85.7%) and cyclophosphamide (69.2%); plasmapheresis was utilized in 5 patients (35.7%) and 8, (57.1%) received intravenous immunoglobulins; 12 (85.7%) patients required admission to the ICU and 5 (35.7%) died. Tobacco use, history of lupus nephritis (LN), concomitant infection, and treatment with cyclophosphamide were more frequent in patients who died. DAH is rare in patients with SLE; in up to one-third of patients, it may appear at the onset of the disease. Some factors, such as smoking, a history of LN, treatment with cyclophosphamide, or concomitant infection, are more prevalent in patients with an unfavorable outcome.

Prior carbapenem exposure increases the incidence of ventilator-associated pneumonia in critically Ill children

BackgroundPrior antibiotic exposure has been identified as a risk factor for VAP occurrence, making it a growing concern among clinical practitioners. But there is a lack of systematic research on the types of antibiotics and the duration of exposure that influence VAP occurrence in children at current.MethodsWe retrospectively reviewed 278 children admitted to the Pediatric Intensive Care Unit (PICU) and underwent invasive mechanical ventilation (MV) between January 2020 and December 2022. Of these, 171 patients with MV duration ≥ 48 h were included in the study, with 61 of them developing VAP (VAP group) and the remaining 110 as the non-VAP group. We analyzed the relationship between early antibiotic exposure and VAP occurrence.ResultsThe incidence of VAP was 21.94% (61/278). The VAP group had significantly longer length of hospital stay (32.00 vs. 20.00 days, p<0.001), PICU stay(25.00 vs. 10.00 days, p<0.001), and duration of mechanical ventilation(16.00 vs. 6.00 days, p<0.001) compared to the non-VAP group. The mortality in the VAP group was significantly higher than that in the non-VAP group (36.07% vs. 21.82%, p = 0.044). The VAP group had a significantly higher rate of carbapenem exposure (65.57% vs. 41.82%, p = 0.003) and duration of usage (9.00 vs. 5.00 days, p = 0.004) than the non-VAP group. Vancomycin and/or linezolid exposure rates (57.38% vs. 40.00%, p = 0.029) and duration (8 vs. 4.5 days, p = 0.010) in the VAP group were significantly higher than that in the non-VAP group, either. Multivariate logistic regression analysis identified the use of carbapenem (≥ 7 days) (OR = 5.156, 95% CI: 1.881–14.137, p = 0.001), repeated intubation (OR = 3.575, 95% CI: 1.449–8.823, p = 0.006), and tracheostomy (OR = 5.767, 95% CI:1.686–19.729, p = 0.005) as the independent risk factors for the occurrence of VAP, while early intravenous immunoglobulin (IVIG) was a protective factor against VAP (OR = 0.426, 95% CI: 0.185–0.98, p = 0.045).ConclusionPrior carbapenem exposure (more than 7 days) was an independent risk factor for the occurrence of VAP. For critically ill children, reducing carbapenem use and duration as much as possible should be considered.

Efgartigimod combined with steroids as a fast-acting therapy for myasthenic crisis: a case report

BackgroundGeneralized myasthenia gravis (gMG) can be managed with acetylcholinesterase inhibitors (AChEis; e.g., pyridostigmine), corticosteroids, other immunosuppressive drugs (e.g., tacrolimus), and their combinations. Intravenous immunoglobulin (IVIg) or plasmapheresis (PLEX) may be administered if symptoms persist. PLEX and IVIg are also mainstays of treatment for myasthenic crisis. Recently, efgartigimod was approved in Japan for treating adults with gMG (irrespective of the antibody status) who do not have a sufficient response to corticosteroids and nonsteroidal immunosuppressive therapies. Efgartigimod is generally safe and well tolerated. However, since phase III trials of efgartigimod excluded those with myasthenic crisis, the efficacy of efgartigimod in treating myasthenic crisis is still unclear. Moreover, there are no reports that efgartigimod therapy can reduce the dose of corticosteroids needed to achieve a minimal manifestation status.Case presentationWe report the case of a 70-yeat-old woman with gMG who developed a myasthenic crisis. After she was diagnosed with gMG, the patient had been treated with oral corticosteroids and tacrolimus for 1 year. However, she refused to continue taking the medication, and two weeks later, she developed ptosis, dysphagia and dyspnea. The patient was intubated and treated with efgartigimod in combination with steroid therapy, and she recovered without PLEX or IVIg. Afterward, when she experienced worsening of fatigue and increased levels of anti-acetylcholine receptor antibodies, efgartigimod therapy was effective. The patient achieved minimal manifestation status even after the reduction of corticosteroids and showed improvements in the Myasthenia Gravis Activities of Daily Living scales after 4 cycles of efgartigimod infusion.ConclusionsOur case suggests that efgartigimod can be an alternative drug for achieving minimal manifestation status in patients with myasthenic crisis. Considering its strong efficacy and safety, efgartigimod could be expanded to use as bridging therapy in the acute and chronic phases of gMG.

A case report of elevated bromide levels from pyridostigmine bromide for treatment of myasthenia gravis.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Elevated serum bromide levels can cause dermatological, gastrointestinal, and neurological abnormalities. As bromide and chloride are both halogens, bromide may interfere with chloride assays, causing a falsely high serum chloride concentration and a low or negative anion gap. There is a paucity of data describing bromide toxicity from high doses of pyridostigmine bromide (PB). This case report describes a patient with an elevated bromide level with neurological symptoms from a therapeutic dose of PB. A 37-year-old male with myasthenia gravis secondary to type B2 thymoma status following thymectomy presented in myasthenic crisis. He required mechanical ventilation and was managed with steroids, intravenous immune globulin, plasmapheresis, and PB. On day 9, the patient experienced acute agitation. He had an anion gap of 2 mEq/L and a chloride concentration of 109 mEq/L. The plasma creatinine concentration was 0.63 to 1.15mg/dL and urine output was 0.76 to 1.79mL/kg/h throughout his admission. All other laboratory values were normal. The daily dose of PB was 660mg on day 9, but the patient received 76mg of intravenous PB over the first few days of his admission with the largest dose in 24 hours equal to 48mg. On day 10, the patient's bromide level was 37 μg/mL. His agitation was initially managed with quetiapine, followed by PB dose reduction. To our knowledge, there are 2 cases in the literature of bromide toxicity secondary to PB. These patients experienced neurological symptoms with bromide levels of 88 to 90 μg/mL. Bromide concentrations of more than 12 μg/mL are associated with a higher risk of neuronal dysfunction demonstrated as disturbances on an electroencephalogram, and levels greater than 50 μg/mL are considered toxic. While our patient's bromide level was not as high as those previously reported, no other causes for his agitation were identified. Elevated bromide levels from therapeutic PB can occur, and monitoring of these levels should be considered.

A rare case of hemolytic disease-associated thrombocytopenia mimicking alloimmune thrombocytopenia: Salvaging a precious baby

Abstract: Thrombocytopenia associated with hemolytic disease of fetus and newborn (HDFN) is usually mild-to-moderate severity. Neonatal alloimmune thrombocytopenia (NAIT) is one of the leading causes of severe thrombocytopenia in neonates. We describe a rare case of very severe thrombocytopenia (5 g/L) with bleeding manifestations associated with HDFN mimicking NAIT. The baby was a preterm female, born to a 34-year-old multiparous mother with a bad obstetric history and multiple alloantibodies (anti-D, anti-C, anti-E, and anti-Jka). She was managed with phototherapy, exchange transfusion with phenotype-matched packed red blood cells, random donor platelets and intravenous immunoglobulin as platelet crossmatching could not provide compatible platelets. NAIT was ruled out with human platelet antigen (HPA) genotyping of the baby, the mother, and the father. It was concluded that the very severe thrombocytopenia might be due to HDFN after ruling out the other causes. HDFN can rarely cause very severe thrombocytopenia. However, when a newborn presents with severe/very severe thrombocytopenia, NAIT is to be ruled out with HPA genotyping, even in resource-limited settings, to plan out subsequent pregnancies.

JAK inhibition in Down Syndrome Regression Disorder

Down Syndrome Regression Disorder (DRSD) is an uncommon but devastating condition affecting primarily adolescents and young adults with Down syndrome (DS). Individuals with DS display a dysregulated immune system associated with hyperactive interferon signaling, which is associated with a high incidence of autoimmune conditions. While the cause of DSRD is unknown, increasing evidence indicates that it may have an immune basis, and some individuals with DSRD have responded to intravenous immunoglobulin therapy. This case series describes three individuals with probable DSRD who received the JAK inhibitor tofacitinib and saw improvement in DSRD symptoms across multiple domains of neurological function.

Perioperative Use of IgM-Enriched Immunoglobulins in Liver Transplantation Recipients at High Risk for Infections: A Preliminary Study.

Background: Infections frequently occur after orthotopic liver transplantation (OLT) and are associated with increased mortality. In 2018, we introduced perioperative administration of intravenous immunoglobulin enriched in IgM as an optional therapy in recipients at a high risk of infection. This preliminary study evaluated whether this preparation reduced infections in the early post-transplantation period. Methods: Adult patients with a high risk of postoperative infections who underwent OLT between January 2014 and December 2021 in our center were included in the study. The primary outcome was the occurrence of new postoperative bacterial and fungal infections within the first 30 days after OLT. Results: Ninety recipients at a high risk of postoperative infections who underwent OLT were included, of whom 51 (57%) received IgM preparation. Patients treated and not treated with IgM were similar in terms of demographics, model of end-stage liver disease score, and risk factors for postoperative infections. The occurrence of new infections was lower (absolute risk reduction (ARR) 21.2%; p = 0.038) in patients who received IgM than in those who did not. Multivariate analysis adjusted for confounders (OR 0.348; p = 0.033) and propensity score-based matching analysis (ARR 21.2%, p = 0.067) confirmed an association between IgM preparation and lower occurrence of postoperative infections. The 90-day mortality rate was lower (ARR 13.4%, p = 0.018) in patients who received IgM preparation. Conclusions: In OLT recipients at high risk for infections, perioperative administration of an IgM-enriched preparation seems to reduce the development of new infections within the first 30 days after OLT.