Administration Of Immunoglobulin Research Articles

KNOWLEDGE AND SKILLS OF NURSES REGARDING ORPHAN DISEASES

Introduction. The role of the nurse in providing comprehensive and individualized care to patients with rare diseases is one ofthe key roles. Nurses work closely with physicians and patients and play an educational role for patients and their families, facilitating coordination, monitoring and continuity of care. Therefore, nurses should have a certain range of knowledge and skills regarding the most common rare diseases.The aim of research was to determine the knowledge and skills of nurses regarding some specifi c rare diseases.Material and methods. An anonymous and voluntary survey of nurses was conducted at the regional children’s clinical hospitalfrom April to May 2023. A total of 63 nurses from the hospital participated in the survey. The questionnaire consisted of 27 questions related to the sociodemographic data of the respondents and rare diseases. The most common rare diseases encountered in the practice of nurses at the hospital were primary immunodefi ciencies (PID), spina bifi da (SB), cystic fi brosis, and juvenile idiopathic arthritis.The research results are presented in the form of descriptive statistics. Comparisons of frequency parameters were made using the Chi-square test. Diff erences between parameters were considered statistically signifi cant at p<0.05. Statistical analysis of the survey results was performed using the statistical package STATISTICA 10.0 and Microsoft Excel 2003 spreadsheet editor.The research and the publication of the materials were approved by the Bioethics Committee of the I. Horbachevsky Ternopil National Medical University (protocol № 73 dated 03.04.2023).The study was conducted within the framework of the research project of the Department of Children’s Diseases with PediatricSurgery of the I. Horbachevsky Ternopil National Medical University “Improvement of methods of diagnostics, treatment and rehabilitation of the most common children’s diseases”, registration number 0122U000039.Results. The majority of respondents were female (96.8%), between the ages of 31 and 50 (63.5%), and employed in the hospitalsetting (90.5%). Most were experienced workers with more than 20 years of experience (52.4%). Overall, the majority of respondents (71.0%) correctly identifi ed which diseases are rare. The percentage of correct answers regarding knowledge of rare diseases ranged from 47.9% for PID to 77.5% for SB, while correct answers regarding skills ranged from 41.3% for SB to 63.0% for PID. Overall, nurses demonstrated better knowledge than skills regarding rare diseases (p=0.0003). The most problematic issues were that HIV/AIDS was classifi ed as PID (31.7%), lack of knowledge about standards of neurogenic bladder control in children with SB (49.2%), unfamiliarity with the technique of subcutaneous immunoglobulin administration (87.3%), and bowel cleansing procedures in children with SB (95.2%), as well as infection control in patients with cystic fi brosis (66.1%).Conclusion. The study revealed a lack of awareness among nurses regarding certain rare diseases. The lowest level of knowledge was found for primary immunodefi ciencies. There is a need to improve nurses’ knowledge and skills regarding rare diseases, which can improve the quality of care for rare disease patients and their families. The development of educational interventions for nurses can help to increase their awareness of rare diseases.

Аutoimmune encephalitis associated with anti-LGI-1 antibodies

Autoimmune encephalitis associated with anti-LGI-1 antibodies is a new type of autoimmune neurological disease.We present a description of a clinical case — this disease in a patient who was hospitalized at the Republican Scienti fi c and Practical Center for Neurology and Neurosurgery. During the analysis of blood and cerebrospinal fl uid for the presence of antibodies to autoimmune encephalitis, antibodies — IgG to anti-LGI-1 in the blood and cerebrospinal fl uid were detected. Conducted immune therapy, including intravenous administration of glucocorticosteroids, plasmapheresis and intravenous immunoglobulin led to a pronounced positive dynamics in the patient’s condition. Follow-up data indicate that the patient returned to her previous work after a course of therapy.

Immune-mediated hemolysis after administration of human intravenous immunoglobulin in a dog: a case report

A 10-year-old spayed female Maltese presented with purpura and hematemesis. Initial laboratory evaluation revealed immune-mediated thrombocytopenia, but evidence of hemolytic anemia was not identified. Three milligrams of human intravenous immunoglobulin (hIVIG) was administered for 3 hours following prednisolone and mycophenolate mofetil. A pale mucous membrane was identified, and the packed cell volume decreased by 3%. Blood film examination revealed significant spherocytosis with auto-agglutination. Blood transfusions and immunosuppression were continued for 4 days, and hIVIG was discontinued. This report describes a case of increased immune-mediated hemolysis after hIVIG administration, possibly due to new-onset immune-mediated hemolytic anemia or enhanced immunogenicity.

Fetal RHD Screening in RH1 Negative Pregnant Women: Experience in Switzerland.

RH1 incompatibility between mother and fetus can cause hemolytic disease of the fetus and newborn. In Switzerland, fetal RHD genotyping from maternal blood has been recommended from gestational age 18 onwards since the year 2020. This facilitates tailored administration of RH immunoglobulin (RHIG) only to RH1 negative women carrying a RH1 positive fetus. Data from 30 months of noninvasive fetal RHD screening is presented. Cell-free DNA was extracted from 7192 plasma samples using a commercial kit, followed by an in-house qPCR to detect RHD exons 5 and 7, in addition to an amplification control. Valid results were obtained from 7072 samples, with 4515 (64%) fetuses typed RHD positive and 2556 (36%) fetuses being RHD negative. A total of 120 samples led to inconclusive results due to the presence of maternal or fetal RHD variants (46%), followed by women being serologically RH1 positive (37%), and technical issues (17%). One sample was typed false positive, possibly due to contamination. No false negative results were observed. We show that unnecessary administration of RHIG can be avoided for more than one third of RH1 negative pregnant women in Switzerland. This reduces the risks of exposure to a blood-derived product and conserves this limited resource to women in actual need.

Induced Abortion and the Risk of Rh Sensitization

While population-level data suggest Rh immunoglobulin is unnecessary before 12 weeks' gestation, clinical evidence is limited. Thus, guidelines vary, creating confusion surrounding risks and benefits of Rh testing and treatment. As abortion care in traditional clinical settings becomes harder to access, many people are choosing to self-manage and need to know if ancillary blood type testing is necessary. To determine how frequently maternal exposure to fetal red blood cells (fRBCs) exceeds the most conservative published threshold for Rh sensitization in induced first-trimester abortion. Multicenter, observational, prospective cohort study using high-throughput flow cytometry to detect circulating fRBCs in paired maternal blood samples before and after induced first-trimester abortion (medication or procedural). Individuals undergoing induced first-trimester abortion before 12 weeks 0 days' gestation were included. Paired blood samples were available from 506 participants who underwent either medical (n = 319 [63.0%]) or procedural (n = 187 [37.0%]) abortion. Induced first-trimester abortion. The primary outcome was the proportion of participants with fRBC counts above the sensitization threshold (125 fRBCs/5 million total RBCs) after induced first-trimester abortion. Among the 506 participants, the mean (SD) age was 27.4 (5.5) years, 313 (61.9%) were Black, and 123 (24.3%) were White. Three of the 506 participants had elevated fRBC counts at baseline; 1 of these patients had an elevated fRBC count following the abortion (0.2% [95% CI, 0%-0.93%]). No other participants had elevated fRBC counts above the sensitization threshold after induced first-trimester abortion. The median change from baseline was 0 fRBCs, with upper 95th and 99th percentiles of 24 and 35.6 fRBCs, respectively. Although there was a strong association between the preabortion and postabortion fRBC counts, no other baseline characteristic was significantly associated with postabortion fRBC count. Induced first-trimester abortion is not a risk factor for Rh sensitization, indicating that Rh testing and treatment are unnecessary before 12 weeks' gestation. This evidence may be used to inform international guidelines for Rh immunoglobulin administration following first-trimester induced abortion.

Comparison of Demographic, Clinical, and Echocardiographic Features Between Complete and Incomplete, and Early and Late Presenters of Kawasaki Disease: A 10-Year Single-Center Experience.

The diagnosis of Kawasaki disease(KD)is based mainly on clinical findings and supported by laboratory tests. Complete KD fulfills the main clinical criteria, while incomplete KD includes patients with fewer main criteria and compatible laboratory or echocardiographic findings. The study compares the demographic, clinical, laboratory, and echocardiographic parameters between the complete and incomplete KD and early and late presenters. Moreover, it describes the coronary manifestations of the study population. A retrospective review of all patients admitted with a diagnosis of KD during the period from January 2010 to September 2020 was conducted. Clinical presentation, laboratory features, echocardiographic observations, and follow-up data were examined. Moreover, the patients were further classified as early presenters (presented within 10 days of fever onset) and late presenters (presented after 10 days of disease onset). A comparison between complete and incomplete KD and early and late presenters was performed for demographic, clinical, and echocardiographic features. A total of 76 patients were admitted with a diagnosis of KD.The median age of presentation was 28 months, with a range of five to 144months, and the median timing was seven days, with a range of one to 30days. The median follow-up period was six weeks, with a range of one to 192weeks. Complete KD was present in 38 patients (50%), and 38 (50%) had incomplete KD.Skin manifestations, oral mucosal changes, skin desquamation, conjunctivitis, and lymphadenopathy were present more in patients with complete KD than incomplete ones. Complete and incomplete diseases did not differ regarding coronary artery lesions. Of the patients,53 (70%) presented 10 days or less after the onset of fever, and 23 (30%) presented after the 10th day of disease onset. Comparison between early and late presenters revealed significantly greater mucus membrane changes and lymphadenopathy manifestations among the early presenters and coronary artery lesions among the late presenters. The clinical features of KD should prompt early referral for evaluation, echocardiography, and early administration of intravenous immunoglobulin to prevent coronary artery complications. The complete form of Kawasaki does not have more frequent coronary artery lesions than the incomplete form. Additionally, late presenters may be at increased risk for coronary artery abnormalities than early presenters.

Isolated Neutropenia Due to Immune Checkpoint Inhibitors.

In this article, we explore the correlation between immune checkpoint inhibitors (ICIs) and neutropenia. Immune checkpoint inhibitors have revolutionized cancer treatment and management by maximizing the innate abilities of the immune system. However, this therapeutic potential is accompanied by a range of immune-related adverse effects (irAEs), including neutropenia, which is a rare but potentially life-threatening side effect of this mode of cancer treatment. Through an in-depth analysis of various case reports, we have compiled a detailed table summarizing the occurrences of neutropenia associated with different ICIs, the grades of neutropenia, treatments used, and patient outcomes. Management of neutropenia must include an approach based on early diagnosis of the condition and a treatment based on its severity. This review discusses different therapeutic interventions, ranging from the administration of corticosteroids and intravenous immunoglobulin (IVIG) to the use of granulocyte colony-stimulating factor (filgrastim) and, in very severe cases, a stem cell transplant. We have also enlisted salient side effects caused by these interventions.Our findings emphasize that while neutropenia is a relatively rare adverse effect of ICIs, its severity necessitates increased awareness among healthcare professionals. As ICIs continue to be seen as an integral component of cancer therapy, a comprehensive understanding of neutropenia as a side effectand its management is critical for optimizing patient outcomes. A crucial purpose of this review is to highlight the need to achieve a balance between acquiring the therapeutic benefits of various treatment strategies for irAEs and considering their potential side effects, especially with the use of steroids. Achieving this equilibrium is very important in optimizing patient care during immunotherapy, as these irAE management options can bothmitigate the neutropenia triggered by ICIs and potentially give rise to secondary complications. Therefore, a careful assessment of the risks and benefits associated with each treatment approach is essential in tailoring irAE management.

Insights into Facilitated Subcutaneous Immunoglobulin Use in Patients with Secondary Immunodeficiency Diseases: A FIGARO Subgroup Analysis.

The Facilitated Immunoglobulin Administration Registry And Outcomes (FIGARO) Study was a European, multicenter, prospective, observational study conducted across Europe designed to provide insights on the clinical use and tolerability of facilitated subcutaneous immunoglobulin (fSCIG). Data herein are reported for the cohort of patients with secondary immunodeficiency (SID), with a subgroup analysis by age. The SID cohort included 31 patients: 1 pediatric, 15 adult, and 15 older adult patients. Over the 36-month observation period, the median monthly dose of fSCIG (30 g) and median monthly infusion volume per patient (300 mL) remained constant in both adult-age cohorts. Serum trough levels tended to increase over time. Most patients required only one infusion site and could receive the full dose every 3-4 weeks. There was a trend toward self-administration at home. In the adult group, infusion site inflammation and headache were reported at the inclusion visit (n = 1 each), with no adverse drug reactions reported at any of the follow-up visits. No acute severe bacterial infections were reported during the study follow-up. These results demonstrate the feasibility and tolerability of fSCIG use in patients with SID and the flexibility of administration settings including self-administration at home in patients aged ≥65 years.

Parvovirus B19 infection after kidney transplantation: A single centre experience

BackgroundParvovirus B19 is an uncommon cause of anaemia in kidney transplant recipients (KTRs). The study aims to determine the incidence, clinical presentation, laboratory findings and outcome of parvovirus B19-related anaemia in KTR. MethodWe conducted a 12-year retrospective, single-centre study describing the clinical profile of KTRs with parvovirus B19-related anaemia. ResultAmongst the 714 patients who underwent kidney transplantation between January 2011 and January 2023, (cumulative follow-up: 1287 patient-years), six females and one male, developed parvovirus B19-related anaemia. The incidence proportion (risk) is 0.98% with an incidence rate of 5.43 cases per 1000 patient-year. The median duration from transplant to development of anaemia was 6 weeks (range: 4–40 weeks). The mean fall in haemoglobin was 2.88 ± 1.55 gm/dl; concomitant leukopenia and thrombocytopenia were observed in 57.1 and 28.6% of patients. Three patients responded to a reduction in immunosuppression, the four non-responders required the administration of low-dose intravenous immunoglobulin. The mean duration from initiation of therapy to a sustained rise in haemoglobin was 7.71 ± 2.62 weeks. None of the patients had a relapse of the infection. ConclusionsParvovirus B19 infection is an uncommon cause of post-transplant refractory anaemia. The key to successfully managing such patients includes a high index of suspicion, early diagnosis and reduction of immunosuppression with or without administration of intravenous immunoglobulin.

Evaluation of Various Analytical Methods for Quantification of Rabies Antigen

Background: Rabies is a zoonotic viral disease caused by rabies virus. Rabies virus has special inclination towards central nervous system (CNS) where it causes life threatening acute encephalitis. Perhaps being extremely fatal, rabies can be 100% prevented by early, effective and complete post exposure prophylaxis (PEP). PEP for rabies include immediate toileting of bite wound, administration of rabies immunoglobulins (severe exposures), and a full course of anti-rabies vaccination (ARV). As ensuring the absence of any variations in the primary nucleotide sequence of the viral backbone after successive propagation in human cell lines is crucial to ensure that the expression vector does not produce variants of the antigen during production of vaccine, the present study was conducted with an aim to evaluate various analytical methods for quantification of rabies antigen. Method: Various analytical methods the Western Blot technique, the Sodium Dodecyl Sulphate Agarose Gel Electrophoresis(SDS-PAGE), ELLA method, the Enzyme-linked immunosorbent assay (ELISA) and extinction coefficient were used for quantification of rabies antigen. Results: When results of these tests were analyzed, it was observed that these analytical methods are easy, cost effective, accurate and most importantly rapid for quantification of rabies antigen. Conclusion: On the basis of observations noted in this study, Western Blot technique, the Sodium Dodecyl Sulphate Agarose Gel Electrophoresis(SDS-PAGE), ELLA method, the Enzyme-linked immunosorbent assay (ELISA) and extinction coefficient can be reliably recommended as analytical methods for quantification of rabies antigen..

Retrospective analysis of children diagnosed with Kawasaki disease.

The aim of our study was to evaluate the long-term impacts of Kawasaki disease on our patients regarding coronary involvement demographic characteristics, treatment regimens, and clinical course. Our study included 104 patients diagnosed and hospitalized with Kawasaki disease in our center, from January 2004 to January 2019. In our study, patients were divided into three groups according to coronary artery involvement. Patients in group 1 had no echocardiographic findings, while the ones in group 2 had coronary artery dilatation and ones in group 3 had coronary artery aneurysm (CAA). Among 104 patients, the median age was 9.15 (3.0-22.0) years, and 61 of the patients were male while 43 of the patients were female. With a wide range of 1.50-16.50 years of follow-up time, the median diagnosis age of our patients was 31 months (3.0-164.0). Fever duration (median day 10 (5-21), p = 0.025) was statistically significantly higher in group 3. Blood C-reactive protein (CRP) levels, white blood cell (WBC) counts, and neutrophil counts were significantly higher in group 3. There was a statistically significant difference between patients in group 3 and group 2 in which the lowest strain deformation values were in the patients of group 3. In contrast to group 1, the time for initiation of IVIG therapy is significantly prolonged both in group 2 (median: 9.5 days, p = 0.028) and group 3 (median: 10 days, p = 0.036). In our study, serum CRP levels, WBC count, and neutrophil count were higher in patients with coronary artery abnormalities, in agreement with the previous studies. In the light of our results, we consider that the most important determining factor for the development of coronary artery aneurysm is the time of intravenous immunoglobulin (IVIG) administration.

Antiviral mechanisms of two broad-spectrum monoclonal antibodies for rabies prophylaxis and therapy.

Rabies is an acute and lethal encephalomyelitis caused by lyssaviruses, among which rabies virus (RABV) is the most prevalent and important for public health. Although preventable through the post-exposure administration of rabies vaccine and immunoglobulins (RIGs), the disease is almost invariably fatal since the onset of clinical signs. Two human neutralizing monoclonal antibodies (mAbs), RVC20 and RVC58, have been shown to be effective in treating symptomatic rabies. To better understand how these mAbs work, we conducted structural modeling and in vitro assays to analyze their mechanisms of action, including their ability to mediate Fc-dependent effector functions. Our results indicate that both RVC20 and RVC58 recognize and lock the RABV-G protein in its pre-fusion conformation. RVC58 was shown to neutralize more potently the extra-cellular virus, while RVC20 mainly acts by reducing viral spreading from infected cells. Importantly, RVC20 was more effective in promoting effector functions compared to RVC58 and 17C7-RAB1 mAbs, the latter of which is approved for human rabies post-exposure treatment. These results provide valuable insights into the multiple mechanisms of action of RVC20 and RVC58 mAbs, offering relevant information for the development of these mAbs as treatment for human rabies.

Rising Kawasaki disease incidence in New Zealand: analysis of national population incidence and outcomes 2000–2017

ObjectiveThe recent epidemiology of Kawasaki disease (KD) in New Zealand (NZ) is unknown. Our aim was to describe the incidence, seasonal variation, long-term outcomes and mortality for KD in NZ.DesignRetrospective...

Combined effect of medical therapy and rehabilitation in Chronic Ataxic Neuropathy with anti-Disialosyl IgM Antibodies (CANDA): a case report.

Chronic Ataxic Neuropathy with anti-Disialosyl IgM Antibodies (CANDA) is a rare form of immune-mediated sensory ataxic neuropathy. We describe the case of a 45-year-old man, who was diagnosed with CANDA in October 2018. Since then, he has been treated with monthly courses of intravenous immunoglobulin administration (IV Ig) and, in October 2022, he underwent plasmapheresis, reporting a sudden worsening of clinical and motor picture. After a new IV Ig cycle admission, the patient was hospitalized to perform intensive rehabilitation, involving two individual sessions per day (90 minutes each) for 5 days a week. During hospitalization it was registered a relevant improvement in the muscle strength of the lower limbs (LLs). Furthermore, progressive improvements were recorded both in patient's motor performance and in his level of autonomy in activities of daily living. These results had a positive impact on his quality of life and made it possible to reduce the frequency of IV Ig treatments. This is the first case in literature reporting the combined effect of rehabilitation treatment and medical therapy in CANDA neuropathy.

Subcutaneous immunoglobulin 20% (Ig20Gly) treatment regimens in pediatric patients with primary immunodeficiencies – real-world data from the IG TATRY study

ABSTRACT Background Subcutaneous administration of immunoglobulins is associated with fewer systemic adverse events and easier infusion compared to intravenous administration. Ig20Gly is a 20% immunoglobulin formulation effective and safe in patients with primary immune deficiency diseases (PIDDs). Real-world data are scarce, therefore our study aimed to examine the real-life treatment regimen and clinical outcomes of Ig20Gly in Polish children with PIDDs. Researchdesign We retrospectively analyzed the medical documentation of 75 pediatric patients aged 0–17 years (mean 9.9) who received Ig20Gly (Cuvitru®; Baxalta US, Inc.; part of Takeda, MA, U.S.A.). Results The median exposure to treatment of the study population was 22.3 months. At the end of the study, 59 (78.7%) were still on Ig20Gly. The median monthly dose was 0.40 g/kg. The median treatment interval was 7.7 days. Most patients (96%) used one infusion site. The median infusion rate increased with patient age. The median IgG level in the study population, 8.0 g/L, was stable. There was one case of serious bacterial infection. Conclusion This is the largest, long-term real-world study to date on the treatment patterns of Ig20Gly in pediatric patients with PIDDs. The results of this study support the feasibility and tolerability of Ig20Gly usage in PIDD patients across the pediatric age spectrum. Trial registration The trial is registered at ClinicalTrials.gov (NCT04636502).

Adenovirus Infection in Hematopoietic and Solid Organ Paediatric Transplant Recipients: Treatment, Outcomes, and Use of Cidofovir.

human adenovirus (hAdV) infection constitutes an important cause of morbidity and mortality in transplant recipients, due to their immune status. Among drugs currently available, cidofovir (CDF) is the most prescribed. Retrospective study of hAdV infection in paediatric transplant recipients from a tertiary paediatric centre, describing characteristics, management, and outcomes, and focused on the role of CDF. 49 episodes of infection by hAdV were detected during a four-year period: 38 episodes in patients that received allogeneic hematopoietic stem cell transplantation (77.6%) and 11 in solid organ transplant recipients (22.4%). Twenty-five patients (52.1%) were symptomatic, presenting mainly fever and/or diarrhoea. CDF was prescribed in 24 patients (49%), with modest results. CDF use was associated with the presence of symptoms resulting in lower lymphocyte count, paediatric intensive care unit admission, and high viral load. Other therapeutic measures included administration of intravenous immunoglobulin, reducing immunosuppression, and T-lymphocyte infusion. Despite treatment, 22.9% of patients did not resolve the infection and there were three deaths related to hAdV infection. All-cause mortality was 16.7% (8 episodes) by 30 days, and 32.7% (16 episodes) by 90 days, of which, 3 episodes (3/16, 18.8%) were attributed to hAdV directly. hAdV infection had high morbidity and mortality in our series. CDF use is controversial, and available therapeutic options are limited. Transplant patients with low lymphocyte count are at higher risk of persistent positive viremias, and short-term survival of these patients was influenced by the resolution of hAdV infection.

Treatment with intravenous immunoglobulin in a subclinical neonatal myocarditis – Review of the literature and a case report

Myocarditis is an inflammatory disease of the myocardium that is associated with significant morbidity and mortality. We present the case of a male infant born at 38 weeks gestational age detected with subclinical myocarditis. The diagnosis was suggested by the raised cardiac enzymes, small voltages on electrocardiogram and biventricular hypertrophy on echocardiography. The newborn was managed with supportive, immunomodulatory therapy, diuretics and anti-platelet agents (Aspirin). Early intravenous immunoglobulin administration may have helped to reduce morbidity and mortality, even if administration of intravenous immunoglobulin is not yet clearly established in the neonatal population.

Side-by-side Comparative Study of the Immunogenicity of the Intramuscular and Intradermal Rabies Post-exposure Prophylaxis Regimens in a Cohort of Suspected Rabies Virus Exposed Individuals.

All World Health Organization (WHO) pre-qualified rabies vaccines for humans are inactivated tissue culture rabies virus formulations produced for intramuscular (IM) administration. Due to costs and vaccine shortage, dose-saving intradermal (ID) administration of rabies post-exposure prophylaxis (PEP) is encouraged by WHO. This study compared the immunogenicity of the ID 2-site, 3-visit Institut Pasteur Cambodge (IPC) PEP regimen to the IM 1-site, 4-visit 4-dose Essen regimen using Verorab vaccine (Sanofi). The development of neutralizing antibodies (nAbs) and T cell response was assessed in 210 patients with a category II or III animal exposure in a rabies-endemic country. At day 28, all participants developed nAbs (≥0.5 IU/mL), irrespective of PEP scheme, age, or administration of rabies immunoglobulin. T cell response and nAb titers were similar for both PEP schemes. This study demonstrated that the 1-week ID IPC regimen is as effective as the 2-week IM 4-dose Essen regimen in inducing an anti-rabies immune response under real-life PEP.

Prevention and management of adverse events during treatment with bispecific antibodies and CAR T cells in multiple myeloma: a consensus report of the European Myeloma Network.

T-cell redirecting bispecific antibodies (BsAbs) and chimeric antigen receptor T cells (CAR T cells) have revolutionised multiple myeloma therapy, but adverse events such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS), cytopenias, hypogammaglobulinaemia, and infections are common. This Policy Review presents a consensus from the European Myeloma Network on the prevention and management of these adverse events. Recommended measures include premedication, frequent assessing for symptoms and severity of cytokine release syndrome, step-up dosing for several BsAbs and some CAR T-cell therapies; corticosteroids; and tocilizumab in the case of cytokine release syndrome. Other anti-IL-6 drugs, high-dose corticosteroids, and anakinra might be considered in refractory cases. ICANS often arises concomitantly with cytokine release syndrome. Glucocorticosteroids in increasing doses are recommended if needed, as well as anakinra if the response is inadequate, and anticonvulsants if convulsions occur. Preventive measures against infections include antiviral and antibacterial drugs and administration of immunoglobulins. Treatment of infections and other complications is also addressed.

MR‐template‐based volumes‐of‐interest generation in individual brain PET of mouse Alzheimer model not only without MR but also without spatial normalization

AbstractBackgroundThe spatial normalization (SN) of individual mouse brain PET or MRI onto template brain space is one of prerequisites for precise quantitative analysis of positron emission tomography (PET) of mouse brains. This has recently been exploited by deep learning‐based approaches, but is still challenging. Moreover, most of them are based on SN using MR templates, which is not always available in both clinical and preclinical studies.MethodIn this study, we propose a new only PET‐based deep learning‐based image generation approach to resolve MR‐less PET SN problem. We generated individual‐brain‐specific cortical volumes‐of‐interest (VOI) based on inverse‐spatial‐normalization (iSN) and deep convolutional neural network (deep CNN) models with input of PET images instead of MR images. We applied the proposed methods to the mutated amyloid precursor protein and presenilin‐1 mouse model of Alzheimer’s disease. Eighteen mice underwent T2‐weighted MRI and F‐18 FDG PET scans twice, before and after the administration of human immunoglobulin or antibody‐based treatments. Specifically, skull‐stripped PET images were used as the model inputs and iSN‐based cortical (target) and cerebellar (reference) VOIs were used as the labels. We compared our CNN‐based VOI with conventional (template‐based) VOI by both qualitative (visual) assessment and quantitative correlation analysis of mean cortical SUVR (i.e., cortical uptake normalized by cerebellar uptake) estimated by both methods.ResultIn qualitative visual assessment, there was no visible difference between CNN‐based VOI and template‐based VOI. The mean count obtained by CNN‐based VOI and template‐based VOI were highly significantly (P<0.001) correlated in target VOI (i.e., cortex).ConclusionSince our deep CNN‐based method successfully generated target VOI, showing concordant results with that of conventional VOI methods in mean count correlation analysis, we believe we have established methods of template‐based VOI not only without spatial normalization but also without MR.