Use Of Intravenous Immunoglobulin Research Articles

The impact of institutional measures on optimal use of intravenous immunoglobulin.

Intravenous immunoglobulin (IVIG) shortage represents an emerging issue in transfusion medicine. Limited data are available to determine effective strategies for optimal use. The objective of this retrospective observational study was to determine the impact of institutional measures on IVIG use at a large academic center. IVIG infusions from November 26, 2018 to September 25, 2022 were categorized according to their appropriateness (Recommended, Option of treatment, or Unrecommended), based on provincial guidelines, and separated into three phases: Reference, Transition, and Post-Implementation phases, the latter following the adoption of restrictive measures, including mandatory standardized order forms, a blood bank gatekeeping strategy, and the creation of a stewardship committee. A total of 5431 IVIG infusions were administered to 544 patients, accounting for 295,033 g. The most common indication categories were neurology (30.4%), immunology (29.0%), and hematology (17.4%). From Reference to Post-Implementation phase, IVIG infusions decreased from 2275 to 2000 with unrecommended indications dropping from 9.5% to 7.4% (p = 0.01), and a global reduction of 23.0% (from 131,163 g to 100,936 g of IVIG). Decrease in chronic immunomodulation accounted for 48.3% of total reduction (14,610 g of 30,227 g), whereas single-use immunomodulation, 40.5% (12,237 g of 30,227 g). Moreover, an absolute reduction of 16.9% was observed in orders exceeding the recommended doses (20.8% to 3.9%; p < 0.0001). Together, the unrecommended and excessive IVIG doses decreased from 19,975 g (15.2%) to 6670 g (6.6%). A global reduction in IVIG use and a preferential decrease in the unrecommended orders were observed, most likely attributable to the bundle of restrictive strategies implemented.

When is the use of intravenous immunoglobulin appropriate in immune thrombocytopaenia?

Intravenous immunoglobulin (IVIg) is the gold standard treatment for severe cases of immune thrombocytopaenia (ITP). However, its cost, limited duration of efficacy and market supply tension have led French guidelines to reserve IVIg for ITP patients with formal contra-indications to corticosteroids, with French bleeding score ('Khellaf score') > 8, and corticosteroid-resistant patients either with Khellaf score ≤ 8 or in preparation for an invasive procedure or during pregnancy. We studied the prescribing practices of IVIg for ITP in real-life conditions and assessed their compliance with French guidelines. A monocentric retrospective study was conducted between 2016 and 2020 among 114 patients hospitalized in our unit, for a total of 208 IVIg treatments. In 37% of cases, the Khellaf score was >8, validating IVIg prescription according to French guidelines. In the remaining cases, reasons noted for use of IVIg included corticosteroid resistance (33.7%), preparation for an invasive procedure (8.5%), context of pregnancy (6.6%) and contra-indication to corticosteroids (3.3%). After analysis, IVIg prescription was considered valid according to current French guidelines in 84.4% of cases. Non-compliant IVIg prescription was more frequent in younger patients (p = 0.027). Concomitant anti-coagulation was also noted as an argument for IVIg prescription outside of the current French guidelines.

The role of intravenous immunoglobulin in autoimmune diseases with dermatological implications.

Intravenous immunoglobulin (IVIG) therapy has emerged as a promising treatment option for various dermatological autoimmune diseases due to its immunomodulatory potential and low incidence of severe side effects. Despite its widespread use, the mechanism of action of IVIG in treating autoimmune diseases remains a topic of debate. IVIG is derived from the plasma fractionation of a large pool of donors, primarily consisting of the IgG isotype. Its main mechanisms of action involve neutralizing circulating autoantibodies via the F(ab')2 portion, inhibiting complement-mediated tissue destruction, and reducing the half-life of circulating autoantibodies through the Fc portion. This paper explores the growing utilization of IVIG as an off-label therapy in dermatological autoimmune or immune-mediated diseases, including autoimmune bullous disease (AIBS), dermatomyositis (DM), lupus erythematosus (LE), systemic sclerosis, scleromyxedema, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), pyoderma gangrenosum (PG), and necrobiotic xanthogranuloma (NXG). In this context, the sole large prospective, randomized trial was the 2022 ProDERM study, which demonstrate efficacy of IVIG in improving cutaneous manifestations among 95 DM patients compared to the placebo group. Moreover, although considered off-label, the use of IVIG is regarded as the first-line therapy for patients with scleromyxedema. As a first line of therapy, IVIg is only approved for Kawasaki Disease (KD) in the setting of vasculitis. The treatment in all other indications is mostly considered as adjuvant therapy only after failure of immunosuppressive therapy or in the presence of contraindications.

Rational use of immunoglobulins (IVIgs and SCIgs) in secondary antibody deficiencies.

Immunoglobulins for intravenous use (IVIgs) and subcutaneous use (SCIgs) can prevent recurrent and severe infections in patients with secondary antibody deficiencies that are frequently linked to haematological/oncological malignancies as well as other clinical conditions and their respective treatments. Even so, as IVIgs and SCIgs are costly and their supply is limited, their clinical use must be optimised. The aim of this position paper is to provide structured practical guidance on the optimal use of IVIgs and SCIgs in secondary antibody deficiencies, particularly in haematological and oncological practice. The authors agree that the occurrence of severe infections is a prerequisite for the use of IVIgs. Serum IgG levels in general as well as IgG subclass levels can be additional indicators of whether a patient could benefit from IVIgs. Responsiveness to vaccines can help to identify immunodeficiency. Patients with chronic lymphocytic leukaemia or multiple myeloma who are receiving respective treatment, especially B-cell depletion therapy, but also some patients with autoimmune diseases are prone to antibody deficiencies and need IVIgs. For the optimal use of IVIgs and to maximise their potential benefit, the indication must be individually assessed for each patient. As a primary treatment goal, the authors define a sufficient prophylaxis of severe infections, which can be supported by normalising IgG levels. If the initiated treatment is insufficient or linked to intolerable adverse reactions, switching the product within the class of IVIgs or changing to a different batch of the same product can be considered. Pausing treatment can also be considered if there are no infections, which happens more frequently in summer, but treatment needs to be resumed once infections return. These structured recommendations for IVIg treatment in patients with secondary antibody deficiency may provide guidance for clinical practice and therefore help to allocate IVIgs to those who will benefit the most, without overusing valuable resources.

Transfusion-related acute lung injury (TRALI) following intravenous immunoglobulin infusion in a rituximab immunosuppressed patient with long-shedding SARS-CoV-2

BackgroundTransfusion-related acute lung injury (TRALI) is a rare life-threatening complication of blood product transfusion. Intravenous immunoglobulin (IVIG)-related TRALI is scarcely reported.Case presentationA 63-year-old male patient suffering from multiple sclerosis treated with half-yearly rituximab infusions, was hospitalized due to dry cough, daily fever and shivering for seven days despite antibiotic therapy. Because of the history of COVID-19 one month prior without the symptoms having improved since, persistent bilateral multifocal areas of ground glass opacities in chest computed tomography and positive SARS-CoV-2 PCR from bronchoalveolar lavage with a cycling time of 30.1 COVID-19 due to long-shedding SARS-CoV-2 under immunosuppression with rituximab was diagnosed. He received treatment with nirmatrelvir und ritonavir and because of diagnosed IgG deficiency additionally a single dose of 20 g IVIG. During the IVIG infusion, the patient acutely developed tachycardia, hypotension, fever, chills, and hypoxemic respiratory failure due to pulmonary edema. TRALI was promptly diagnosed, and the patient was transferred to the intensive care unit for non-invasive ventilation for less than 24 h. The patient was discharged home from regular ward 72 h later in a good general condition and no remaining symptoms of TRALI.ConclusionIVIG-related TRALI is a rare but life-threating condition and prompt recognition is lifesaving. Due to an increased use of IVIG not only in long-shedding SARS-CoV-2, an increase of TRALI incidence is expected.

Outcomes of intravenous immunoglobulin treatment of immunocompromised patients with viral respiratory infections

BackgroundLimited guidelines exist for treating immunocompromised patients hospitalized for acute viral respiratory infection. Little is known about clinical and economic benefits of intravenous immunoglobulin (IVIG) administration in patients with acute viral respiratory infections. ObjectiveTo compare clinical and economic outcomes among immunocompromised patients hospitalized with viral respiratory infections who received IVIG with those who did not. MethodsWe performed a retrospective cohort study on all patients hospitalized for a respiratory viral infection between 2011 and 2016 at 2 large academic centers including data on age, sex, virus species, immunosuppression type, and receipt of IVIG. Outcomes included death, hospital readmission, length of stay (LOS) in the hospital, and LOS in the intensive care unit (ICU). ResultsA total of 270 patient admissions were reviewed, and 35.6% received IVIG. The average age was 40.6 years, 50% were female, and 74% were transplant patients. The most common virus was rhinovirus (50.7%). Use of IVIG was significantly associated with a shorter ICU LOS (β = −0.534, P = .012) and a longer hospital LOS (β = 0.887, P < .01). IVIG administered within 48 hours of hospitalization (n = 229) was associated with a shorter ICU LOS (β = −2.08, P = .001) and a shorter hospital LOS for patients hospitalized at least 2 days (β = −0.461, P = .007). There were no significant differences in readmission rates or death. ConclusionThis double-center, retrospective cohort analysis is one of the first studies to evaluate the effect of IVIG on immunocompromised patients hospitalized with respiratory viral infections. IVIG was associated with a shorter hospital and ICU LOS, especially when administered within 48 hours of admission.

Prophylactic intravenous immunoglobulin use in allogeneic stem cell transplantation; does intravenous immunoglobulin affect survival, sepsis, and engraftment time?

Abstract: BACKGROUND: Stem cell transplant recipients have an increase in various infections depending on the immunosuppression. The purpose is to explore the effect of the use of proflactıc intravenous immunoglobulin (IVIG) on transplant recıpıents. OBJECTIVE: It was aimed to examine the effect of IVIG on allogeneic stem cell transplantation. MATERIALS AND METHODS: In this study, sepsis status, infection focus causing sepsis, neutrophil and platelet engraftment time of patients the length of stay in the hospital at the time of the stem cell transplant, if the patient died, how many days after the transplant the event developed, and the data of the bone marrow transplant unit were reviewed retrospectively. One hundred and eleven patients who were given IVIG (400 mg/kg/week IVIG intravenous was given to the patients as a weekly prophylactic up to 100 days starting on the 7th day after transplantation) and 190 patients who did not receive IVIG were included in the study. RESULTS: There was no statistically significant difference between the IVIG groups in terms of gender, diagnosis, donor characteristics, and event (P &gt; 0.05). Sepsis was observed significantly less in patients who were given IVIG compared to patients who were not given IVIG (P &lt; 0.001). While it was observed that IVIG did not have a significant effect on platelet engraftment and discharge times (P &gt; 0.05), neutrophil engraftment time was significantly higher in patients given IVIG compared to patients not given IVIG (P &lt; 0.009). It was observed that the use of IVIG in patients with sepsis did not have a positive effect on survival. (with sepsis hazard ratio [HR]: 3.890 P = 0.001, IVIG given HR: 3.244 P = 0.035). CONCLUSION: It was observed that the use of IVIG in allogeneic stem cell transplantation was associated with a decrease in sepsis, but the use of IVIG did not have a positive effect on survival and could prolong neutrophil engraftment.

Impact of Intravenous Immunoglobulin Replacement Therapy on Hypogammaglobulinemia and Infection in Lung Transplant Recipients

Secondary hypogammaglobulinemia (HGG) from immunosuppression therapy in lung transplant recipients has been associated with increased mortality, morbidity and higher risk of infection. Intravenous immunoglobulin (IVIG) for the treatment of HGG post-lung transplant is not well studied with conflicting evidence regarding efficacy. This single-center, retrospective cohort study analyzed adult lung transplant recipients with HGG receiving ≥1 dose of IVIG 0.3-0.5 g/kg. Resolution of HGG (IgG &gt; 600 mg/dL within 30 days of IVIG) was evaluated for optimal dose and duration of IVIG therapy. Incidence of infection, patient survival, rejection, and chronic lung allograft dysfunction-free survival at 1 year were compared between resolved and persistent HGG. Results demonstrated majority of patients 46/58 (79.3%) achieved HGG resolution. Severe HGG (IgG &lt; 400 mg/dL) was significantly associated with persistent HGG (50.5% vs 15.2%, p = 0.02), with comparable cumulative IVIG dose and duration between both groups (p = 0.96 and p = 0.39, respectively). No other variables correlated with HGG resolution. Overall infection rates were similar between groups (69.6% vs 58.3%, p = 0.50), suggesting HGG resolution did not correlate with incidence of infection. Lastly, use of IVIG for the treatment of HGG appears to be safe with minimal incidence of thrombosis found within each group.

Effect of intravenous immunoglobulin on mortality in hospitalized patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials.

We performed a meta-analysis of randomized controlled trials (RCTs) to summarize the overall effect of intravenous immunoglobulin (IVIG) on mortality outcomes among hospitalized coronavirus disease 2019 (COVID-19) patients. We systematically searched electronic databases up to June 1, 2023. Pooled odds ratio (OR) of mortality with a 95% confidence interval (CI) was generated using a random-effects model. The risk of bias was appraised using the Cochrane risk-of-bias Version 2 tool for randomized trials. Nine RCTs were included: three RCTs had an overall low risk of bias, four RCTs had some concerns in the overall risk of bias, and two RCTs trials had an overall high risk of bias. The use of IVIG indicated a significant reduction in the odds of mortality (pooled OR = 0.69; 95% CI 0.50-0.96) relative to nonuse of IVIG. Subgroup analysis in patients with a severe course of COVID-19 revealed no significant reduction in the odds of mortality (pooled OR = 0.58; 95% CI 0.29-1.16). We suggest exercising caution when interpreting effectiveness of IVIG in reducing mortality among hospitalized patients with COVID-19. Our findings emphasize for larger trials with rigorous study designs to better understand the impact of IVIG, particularly in those with severe COVID-19.

Off-label use of intravenous immunoglobulin g in a highly complex pediatric hospital in Argentina. A prospective observational study

The World Health Organization recommends prioritizing safe and effective drugs proven by clinical or epidemiological studies. However, in population groups with little research, a drug can be used for an indication or pharmaceutical form different from that approved by the regulatory agency (off-label), extrapolating data from studies in adults and exposing pediatric patients. to develop an Adverse Drug Reaction (ADR) due to safety considerations that have not been systematically studied. Intravenous immunoglobulin (IVIg), a high-cost drug, is used with scant evidence in some low-prevalence pathologies. This paper describes and analyzes the off-label use of IVIg at the J. P. Garrahan Pediatric Hospital. Observational, descriptive, prospective study on off-label indications of IVIg. The sampling technique was non-probabilistic and for convenience during 7 months. 305 IVIg infusions were studied, corresponding to 111 patients. The indication classification showed that 22% (n=67) of the infusions were off-label. In neurology there was a higher percentage of off-label indications (46%) and within them 45% corresponded to the use in neurological disorders. 81% of the doses indicated off-label were in the range 0.8-1g/kg. The off-label infusions presented 61.5% (n=8) of the ADRs. Those from the Neurology service represented 87.5%; 75% being from the "Neurological disorders" group. In some cases, IVIg was indicated in an off-label manner, finding a statistically significant relationship with the appearance of ADR. This finding motivates the proposition of new hypotheses to carry out more studies.

P.014 Intravenous immunoglobulin use for central nervous system disorders in British Columbia: implementation of a provincial screening program

Background: Intravenous Immunoglobulin (IVIg) use for Central Nervous System (CNS) conditions has increased over the last decade. In many CNS disorders, robust evidence for IVIg efficacy is still lacking. Building on the success of the British Columbia (BC) Neuromuscular IVIg utilization initiative, Guidelines for IVIg use in CNS conditions were developed. A provincial screening program was launched in 2023. Methods: For CNS IVIg, requests, diagnosis, dosing, consultation letters and treatment questionnaires were reviewed. Patient management was compared to provincial guidelines. A letter was sent to the ordering physician with the results of the review and treatment recommendations when management differed significantly from guidelines. Review of the first year’s cases was conducted. Results: Over the first 11 months of the program, 79 IVIg renewal requests were reviewed. The most common diagnoses were antibody mediated autoimmune encephalitis, severe drug resistant non-surgical epilepsy and Susac’s syndrome. Recommendations included dose reduction, discontinuation of IVIg, or initiation of alternative therapies for many of the requests. Conclusions: IVIg may be effective in the management of some CNS inflammatory conditions. A physician-led utilization program in BC with targeted education to ordering physicians promotes best practice. Review of year one data will inform a quality improvement cycle to optimize the guidelines.

NAVIGATING THE UNCHARTED WATERS: MANAGING CONCURRENT CYTOMEGALOVIRUS MYOCARDITIS AND ALLOGRAFT REJECTION IN A PATIENT WITH HEART TRANSPLANTATION

Abstract A 49–year–old female with hypertrophic cardiomyopathy underwent orthotopic heart transplantation. She was cytomegalovirus(CMV)–positive and received a heart from a CMV–negative donor, so prophylaptic therapy was not administered. Initial immunosuppression included cyclosporine and induction with Basiliximab in a steroid–free regimen. The first routine biopsy (EMB) showed mild focal cellular rejection (grade 1A) and C4d positivity with granular aspect. Mycophenolate mofetil (MMF) was added. The second EMB, 7 days later, showed mild diffuse cellular rejection (grade 1B) and diffuse C4d positivity. Anti–HLA donor–specific antibodies (DSA) had increased anti–B13 levels (MFI=21298) compared to pre–transplantation tests. Echocardiography showed a normal ejection fraction (LVEF) and mild concentric hypertrophy (LVH). Treatment included pulse methylprednisolone therapy (1 g/day for three days) followed by oral prednisone with a slow tapering regimen, and increased MMF. CMV count weekly monitored was negative. The next two EMBs performed one week apart from each other described a grade 1A mild focal pattern while the 5th EMB (1 month and 2 weeks post–transplant) showed a grade 1A rejection together with focal mild fibrosis and eosinophils, so we replaced cyclosporine with tacrolimus, increased MMF and prednisone. At this time, the patient had no overt clinical signs of CMV infection but a CMV–PCR of 100847 IU/mL so ganciclovir 5 mg/Kg bid was started and CMV–PCR decreased to 42308 IU/mL after 1 week. Subsequently, she developed sinus tachycardia, mildly reduced LVEF, moderate LVH and diastolic dysfunction. Troponin was elevated. A new EMB revealed interstitial edema, diffuse ischemic injury, and eosinophilic inclusions suggesting CMV myocarditis. Treatment involved down–titrating MMF and Prednisone, administering standard intravenous immunoglobulin (IVIG), and high–dose Ganciclovir (7.5 mg/Kg bid). Leukopenia subsequently led to Ganciclovir down–titration. In the next days, the patient improved, CMV cleared, and leukocyte count normalized. She was discharged on Tacrolimus, MMF, Prednisone and Valganciclovir. Subsequent tests showed no cellular or antibody–mediated rejection (AMR), no CMV inclusions, recovered cardiac function, and markedly reduced anti–B13 DSA (MFI 3000). This case raises some concerns: in this context, the use of IVIG in the treatment of CMV infection and AMR appears reasonable, in support of antiviral and immunosuppressive therapy.

THE POTENTIAL OF HUMAN PLASMA AND HUMAN BLOOD PRODUCTS FOR IMMUNE PROTECTION

Intravenous Immunoglobulin (IVIg) were used for the first time at the late seventies for treatment of patient with primary and secondary immunodeficiencies. Тhe first observations opened a wide field for basic and clinical research leading to a rapidly expanding use of IVIg for the treatment of patients with multiple diseases. The immunoglobulin preparations contain large amount of intact form of IgG molecules with comparable values of subclasses as in native plasma. Тhose properties account for the normal half-life of injected immunoglobulin of three weeks, and its ability to react normal with the complement components and with the specific Fcγ-receptors on the surface of phagocytes and lymphocytes. IVIg is produced from plasma pules from several thousand donors, which leads to wide spectre of variable regions of IgG molecules in the product. Some of the antibodies in the product can recognize bacterial, virus and fungal antigens are essential in replacement therapy in patients with antibody deficiency. А good understanding of the molecular and cellular basis of the immunoregulatory actions of intravenous immunoglobulin preparations is important for optimizing their use in inflammatory diseases for conducting new clinical observations.

Absence of Anti-Babesia microti antibody in commercial intravenous immunoglobulin (IVIG).

Babesiosis is a worldwide emerging protozoan infection that is associated with a spectrum of disease severity from asymptomatic infection to severe organ damage and death. While effective treatment strategies are available, some immunocompromised patients experience severe acute and prolonged/relapsing illness due in part to an impaired host antibody response. Intravenous immunoglobulin (IVIG) has been used as an adjunctive therapy in some immunocompromised babesiosis patients, but its therapeutic effect is uncertain. We evaluated the presence of Babesia microti antibodies in commercial samples of IVIG. The presence of B. microti antibodies in commercial samples of IVIG were tested using an immunofluorescence assay. A subset of samples was then tested for B. microti antibodies using an enzyme linked immunosorbent assay. Out of 57 commercial IVIG samples tested using IFA, and 52 samples tested using ELISA, none were positive for B. microti antibodies. Commercially available IVIG may not be of therapeutic benefit for babesiosis patients. Additional sampling of IVIG for B. microti antibody and a clinical trial of babesiosis patients given IVIG compared with controls would provide further insight into the use of IVIG for the treatment of babesiosis.

Long-Term Clinical Outcomes and B Cell Immune Reconstitution Following Allo-HCT With Prophylactic, Post-Transplant Rituximab

BackgroundChronic graft-versus-host disease (cGVHD) remains a significant source of morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). Post-transplant, prophylactic rituximab has successfully decreased cGHVD rates in clinical trials, but the durability of this strategy is uncertain. The long-terms effect of post-HCT B cell depletion on immune reconstitution, B cell function, and infectious complications are also unknown. ObjectiveIn this study, we provide 10 year follow-up and correlative analyses on patients given post-HCT, prophylactic rituximab. The objective of the study is to examine the durability of cGVHD protection as well as the long-term effect of rituximab prophylaxis on protective immune reconstitution, B cell function, and alloantibody formation. Study DesignWe analyzed 35 patients given prophylactic rituximab on phase II clinical trial. Clinical outcomes included cGVHD development, relapse and survival outcomes, and infectious outcomes. Correlative analyses included B cell subset analysis, development of antibodies to infectious antigens, and, for male patients receiving female donor grafts, development of antibodies to HY antigens. To further investigate the effect of rituximab on immune reconstitution and function, we also analyzed 43 similarly transplanted patients who did not receive post- or peri-HCT rituximab as a comparator group. ResultsFor patients who received rituximab, the 8-year cumulative incidence of cGHVD and freedom from immunosuppression were 20.0% and 76.2%, respectively. Importantly, no late incidences of cGVHD developed beyond 14 months post-HCT. Relative to patients who did not receive rituximab, post-HCT rituximab was associated with increased B cell aplasia at 1 year post-HCT (42.9% vs 11% of patients, p = 0.037); by 3 years post-HCT, this aplasia resolved. Patients who received rituximab also had a significantly lower proportion of IgD+/CD38+ transitional B cells at 3 years post-HCT (78.8% vs 89.9%, p = 0.039); at 10 years post-HCT, this percentage remained markedly decreased at 50.7%. Rituximab prophylaxis altered B cell function. In male patients receiving female donor grafts, fewer patients developed HY antibodies at 3 years post-HCT (20% vs 78%, p = 0.04). At 10 years post-HCT, HY antibody production remained decreased at 33%. Rituximab prophylaxis was also associated with significantly lower antibody response to tetanus and EBV infectious antigens as well as lower IgG levels. Despite these changes, post-HCT was not associated with increased infections, although patients who received rituximab required intravenous immunoglobulin (IVIG) supplementation more frequently than those who did not (62.9% vs 32.6% of patients, p = 0.01). ConclusionsPrior data on the efficacy and feasibility of rituximab prophylaxis are durable, with persistent reduction in cGVHD. Rituximab prophylaxis also results in lasting B cell immunologic changes, with altered B cell subset composition and decreased alloantibody formation. Associated infectious risks were not increased, perhaps mitigated by high IVIG use.

Exploring the diagnostic value of CLR and CPR in differentiating Kawasaki disease from other infectious diseases based on clinical predictive modeling.

Kawasaki disease (KD) is an important cause of acquired heart disease in children and adolescents worldwide. KD and infectious diseases can be easily confused when the clinical presentation is inadequate or atypical, leading to misdiagnosis or underdiagnosis of KD. In turn, misdiagnosis or underdiagnosis of KD can lead to delayed use of intravenous immunoglobulin (IVIG), increasing the risk of drug resistance and coronary artery lesions (CAL). The purpose of this study was to develop a predictive model for identifying KD and infectious diseases in children in the hope of helping pediatricians develop timely and accurate treatment plans. The data Patients diagnosed with KD from January 2018 to July 2022 in Shenzhen Longgang District Maternity & Child Healthcare Hospital, and children diagnosed with infectious diseases in the same period will be included in this study as controls. We collected demographic information, clinical presentation, and laboratory data on KD before receiving IVIG treatment. All statistical analyses were performed using R-4.2.1 (https://www.rproject.org/). Logistic regression and Least Absolute Shrinkage with Selection Operator (LASSO) regression analyses were used to build predictive models. Calibration curves and C-index were used to validate the accuracy of the prediction models. A total of 1,377 children were enrolled in this study, 187 patients with KD were included in the KD group and 1,190 children with infectious diseases were included in the infected group. We identified 15 variables as independent risk factors for KD by LASSO analysis. Then by logistic regression we identified 7 variables for the construction of nomogram including white blood cell (WBC), Monocyte (MO), erythrocyte sedimentation rate (ESR), alanine transaminase (ALT), albumin (ALB), C-reactive protein to procalcitonin ratio (CPR) and C-reactive protein to lymphocyte ratio (CLR). The calibration curve and C-index of 0.969 (95% confidence interval: 0.960-0.978) validated the model accuracy. Our predictive model can be used to discriminate KD from infectious diseases. Using this predictive model, it may be possible to provide an early determination of the use of IVIG and the application of antibiotics as soon as possible.

Implementation of a tier system for IVIG indications to address IVIG shortage at a tertiary care pediatric medical center.

Drug shortages are a common issue that healthcare systems face and can result in adverse health outcomes for patients requiring inferior alternate treatment. The United States recently experienced a national drug shortage of intravenous immunoglobulin (IVIG). Several reported strategies to address the IVIG and other drug shortages have been proposed; however, there is a lack of evidence-based methods for protocol development and implementation. To evaluate the efficacy of introducing a multidisciplinary task force and tier system of indications and to minimize adverse effects during a shortage of IVIG. Faculty members across disciplines with expertise in IVIG use were invited to participate in a task force to address the shortage and ensure adequate supply for emergent indications. A tier system of IVIG indications was established according to the severity of diagnosis, urgency of indication, and quality of supporting evidence. Based on inventory, indications in selected tiers were auto-approved. Orders that could not be automatically approved were escalated for task force review. Overall, there were 342 distinct requests for IVIG during the study period (August 1, 2019 to December 31, 2019). All Tier 1 indications were approved. Of all requests, only 2.6% (9) of requests were denied, none of which resulted in adverse effects based on retrospective chart review. Seven patients who regularly receive IVIG had possible adverse effects due to dose reduction or spacing of treatment; however, each complication was multifactorial and not attributed to the shortage or tier system implementation alone. Implementation of a multidisciplinary task force and tier system to appropriately triage high-priority indications for limited pharmaceutical agents should be considered in health institutions faced with a drug shortage.

Development, implementation and impact of an immunoglobulin stewardship programme in Saskatchewan, Canada.

Intravenous immunoglobulin (IVIG) is one of the most costly and limited-supply blood products. Judicious use of this therapy is important to ensure a continued supply is available for patients in need. The Saskatchewan IG Stewardship Program was initiated to monitor and reduce inappropriate IG use. The Program was developed and implemented through the collaborative efforts of a multidisciplinary, inter-organizational team. Funding was provided from provincial organizations to create new positions within the Program and to support stakeholder engagement throughout the process of implementation. Data were collected from local and national databases regarding the amount of IVIG used and appropriateness of orders based on published criteria. Over 20 months, the Program helped to reduce unnecessary IVIG use from pre-intervention levels by more than 20%. Interventions from nurse navigators alone reduced inappropriate IVIG use by 2.6%. During the 20-month period following Program initiation, more than 4 million CAD less was spent on IVIG compared with the previous 20 months. The Saskatchewan IG Stewardship Program has led to more appropriate IVIG use across the province, more effective preservation of this limited healthcare resource, and cost savings that more than cover the cost of administering the Program.

Fc-gamma receptor expression and cytokine responses to intravenous human immunoglobulin in whole blood from non-pregnant and pregnant women and newborns.

Intravenous immunoglobulin (IVIG) can suppress the inflammatory response in adults, but its role in pregnant women and newborns is poorly studied. While the adult immune system is considered mature, it is immature in neonates and suppressed in pregnancy. Since the immune response differs in these 3 groups, the use of IVIG could differentially modulate the immune response. We aimed to explore the effect of IVIG on myeloid blood cells from non-pregnant women, pregnant women and newborns. Whole blood from healthy donors was incubated with lipopolysaccharide (LPS) and/or IVIG. After 0 h, 24 h and 48 h of culture, Fc-gamma receptor (CD16, CD32 and CD64) expression, monocyte and neutrophil bacterial phagocytosis, and cytokine and chemokine concentrations were determined in the supernatant. The baseline expression of monocyte CD16 was higher in newborns than in adult women, but the expression of CD32 and CD64 was similar between groups. Furthermore, LPS and IVIG stimulation, together or separately, did not change Fc-gamma receptor expression in monocytes or neutrophils and did not modify their phagocytosis capacity. On the other hand, IVIG did not downregulate the proinflammatory cytokine response induced by LPS in any group. Interestingly, IVIG induced a strong interleukin 8 (IL-8) response in neonates but not in non-pregnant or pregnant women. Our results show that IVIG did not induce changes in Fc-gamma receptor expression, phagocytic ability, or the cytokine response to LPS in blood cells from neonates, non-pregnant or pregnant women. However, IVIG induced a strong IL-8 response in neonates that could improve immunity.

Intravenous immunoglobulin for treatment of hospitalized COVID-19 patients: an evidence mapping and meta-analysis.

The clinical efficacy and safety of intravenous immunoglobulin (IVIg) treatment for COVID-19 remain controversial. This study aimed to map the current status and gaps of available evidence, and conduct a meta-analysis to further investigate the benefit of IVIg in COVID-19 patients. Electronic databases were searched for systematic reviews/meta-analyses (SR/MAs), primary studies with control groups, reporting on the use of IVIg in patients with COVID-19. A random-effects meta-analysis with subgroup analyses regarding study design and patient disease severity was performed. Our outcomes of interest determined by the evidence mapping, were mortality, length of hospitalization (days), length of intensive care unit (ICU) stay (days), number of patients requiring mechanical ventilation, and adverse events. We included 34 studies (12 SR/MAs, 8 prospective and 14 retrospective studies). A total of 5571 hospitalized patients were involved in 22 primary studies. Random-effects meta-analyses of very low to moderate evidence showed that there was little or no difference between IVIg and standard care or placebo in reducing mortality (relative risk [RR] 0.91; 95% CI 0.78-1.06; risk difference [RD] 3.3% fewer), length of hospital (mean difference [MD] 0.37; 95% CI -2.56, 3.31) and ICU (MD 0.36; 95% CI -0.81, 1.53) stays, mechanical ventilation use (RR 0.92; 95% CI 0.68-1.24; RD 2.8% fewer), and adverse events (RR 0.98; 95% CI 0.84-1.14; RD 0.5% fewer) of patients with COVID-19. Sensitivity analysis using a fixed-effects model indicated that IVIg may reduce mortality (RR 0.76; 95% CI 0.60-0.97), and increase length of hospital stay (MD 0.68; 95% CI 0.09-1.28). Very low to moderate certainty of evidence indicated IVIg may not improve the clinical outcomes of hospitalized patients with COVID-19. Given the discrepancy between the random- and fixed-effects model results, further large-scale and well-designed RCTs are warranted.