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Objective: To evaluate cardiopulmonary, arterial blood gas and propofol-sparing effects of magnesium sulfate (MgSO 4 ) constant rate infusion (CRI) in mechanically ventilated dogs maintained under total intravenous anesthesia with propofol., Study Design: Blinded, randomized, clinical trial., Animals: A total of 24 healthy adult dogs., Methods: Dogs were premedicated with intramuscular acepromazine (0.05 mg kg -1 ) and morphine (0.5 mg kg -1 ), followed by an intravenous (IV) bolus of saline or MgSO 4 (50 mg kg -1 over 15 minutes) and propofol (given to effect to induce anesthesia). Anesthesia was maintained with an IV propofol infusion (beginning at 0.3 mg kg -1 minute -1 , adjusted as necessary). Concurrently, one of three IV infusions were administered: GS (0.9% NaCl), GM30 (MgSO 4 , 30 mg kg -1 hour -1 ) or GM80 (MgSO 4 , 80 mg kg -1 hour -1 ). Propofol induction and maintenance doses were recorded. The following variables were recorded at baseline (T0), after bolus treatment (T1), after beginning mechanical ventilation (T5) and every 15 minutes until the end of the procedure (T15-T120): mean arterial pressure, heart rate, peripheral oxygen saturation, end-tidal partial pressure of CO 2 , temperature, blood gas variables, indirect calorimetry and extubation time. Values of p < 0.05 were considered significant., Results: Propofol induction bolus dose was lower in GM30 (31.2%, p = 0.04) and GM80 (38.9%, p = 0.003) than in GS. The maintenance propofol infusion rate in GM80 was 16.9% lower (p = 0.03), resulting in fewer propofol CRI rescues during the perioperative period. GM30 and GM80 exhibited faster extubation times than GS (46.2%, p = 0.002 and 48.9%, p = 0.001, respectively)., Conclusions and Clinical Relevance: Infusion of a 50 mg kg -1 bolus, followed by CRI of MgSO 4 (30 and 80 mg kg -1 hour -1 ), reduces the propofol induction and maintenance (CRI) requirement, maintaining cardiorespiratory stability and reducing the time required to extubation., (Copyright © 2024 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Approximately 10-20 % of individuals develop a recrudescent or persistent fever after intravenous immunoglobulin (IVIG) infusion for the initial treatment of Kawasaki disease. The aim of this study was to evaluate the efficacy and safety of the initial IVIG treatment of Kawasaki disease based on duration of infusion., Methods: This retrospective, single-center study included 53 patients with Kawasaki disease who were initially treated with 2 g/kg of IVIG by means of a single infusion from June 2018 to August 2019. We classified patients into two groups based on the duration of the infusion: the 12-h group and the 24-h group. We compared the treatment response of the primary IVIG and its adverse events using the Mann-Whitney U test and Fisher's exact or Chi-square tests., Results: There were no significant differences in the response to initial IVIG treatment between the two groups. The duration from treatment onset to defervescence was shorter in the 12-h group than the 24-h group (7 h vs. 12 h, respectively, p = 0.07); however, this was not significant. There were no significant between-group differences regarding adverse events., Conclusion: We concluded that the initial 12-h IVIG treatment was comparable to the 24-h treatment in terms of efficacy and safety. This will enable physicians to feel confident about pursuing a shorter course of treatment with similar results as conventional treatment and decide on administering additional therapy to their patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. None, (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Objective: To describe the use of total intravenous anaesthesia (TIVA) in dogs and cats by veterinary anaesthesiologists., Study Design: A cross-sectional online, voluntary, anonymous survey., Population: Data from 153 answered questionnaires., Methods: An anonymous questionnaire was sent via e-mail to diplomates, residents and residency-trained individuals from the American and European Colleges of Veterinary An(a)esthesia and Analgesia, to gather information on the use, perceived advantages, reasons for the use or not of TIVA and attitudes towards this technique in dogs and cats. Descriptive statistics and logistic regression analysis to detect significant associations were performed. The effect size was estimated using the odds ratio (OR) and 95% confidence interval (CI). A significance level of p < 0.05 was used., Results: We obtained 153/703 responses (66% diplomates, 34% residents; overall response rate of 21.7%). Although 99% and 94% of respondents used TIVA in dogs and cats, respectively, only 14% used it frequently (several times a week) in dogs, and < 1% in cats. Most respondents used propofol (97%, dogs) and alfaxalone (85%, cats), mostly combined with opioids. Reasons for not using TIVA more frequently included prolonged recovery (49%, dogs; 61%, cats), higher cost (46%, dogs) and concerns about drug accumulation (44%, cats). Frequent TIVA use was driven by clinical indications (100%) and greater haemodynamic stability (87%). A higher proportion of respondents using TIVA frequently reported the high stability of the anaesthetic plane (20%; OR = 5.0; 95% CI: 1.4-17.8; p = 0.013) and disagreed with using TIVA only when a specific clinical indication existed (OR = 3.3; 95% CI: 1.4-10.0; p = 0.013)., Conclusions and Clinical Relevance: Although occasional, TIVA use is reported among veterinary anaesthesiologists. Clinical indications for TIVA are the most likely reason for its use, whereas factors such as a prolonged recovery or higher cost might limit its use., (Copyright © 2024 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

The choice of maintenance anesthetic during cardiopulmonary bypass has been a subject of ongoing debate. Systematic reviews on the topic have so far failed to demonstrate a difference between volatile agents and total intravenous anesthesia (TIVA) in terms of mortality, myocardial injury, and neurological outcomes. Studies using animal models and noncardiac surgical populations suggest numerous mechanisms whereby TIVA has been associated with more favorable outcomes. However, even if the different anesthetic methods are assumed to equivalent in terms of patient outcomes in the context of cardiac surgery, additional factors, namely variables of occupational exposure and environmental impact, strongly support the preferred use of TIVA., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study investigates the impact of intravenous (IV) infusion protocols on the stability of Intravenous Immunoglobulin G (IVIG) and Rituximab, with a particular focus on subvisible particle generation. Infusion set based on peristaltic movement (Medifusion DI-2000 pump) was compared to a gravity-based infusion system (Accu-Drip) at different flow rates. The impacts of different diluents (0.9 % saline and 5.0 % dextrose) and plastic syringes with or without silicone oil (SO) were also investigated. The results from the aforementioned particular case demonstrated that peristaltic pumps generated high levels of subvisible particles (prominently < 25 µm), exacerbated by increasing flow rates, specifically in formulations lacking surfactants. Other factors, such as diluent type and syringe composition, also increased the number of subvisible particles. Strategies that can help overcome these complications include surfactant addition as well as the use of SO-free syringes and a gravity infusion system, which aid in reducing particle formation and preserving antibody monomer during administration. Altogether, these findings highlight the importance of the careful selection of formulations and infusion protocols to minimize particle generation during IV infusion both for patients' safety and treatment efficacy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Safe and efficient provision of intravenous lipid emulsion (ILE) requires a strategy to individualize infusion rates. Estimating the maximum acceptable infusion rate (MaxInfRate) of soybean oil-based ILE (SO-ILE) in individuals by using a triglyceride (TG) kinetic model was reported to be feasible. In this study, we aimed to externally validate and, if needed, update the MaxInfRate estimation., Methods: The maximum TG concentration (TG max ) in patients receiving SO-ILE at MaxInfRate was evaluated to determine if it met the definition of being <400 mg/dl for 90th percentile of patients. The TG kinetic model was evaluated through prediction performance checks and was subsequently updated using the data set of both the previous model development and present validation studies., Results: Out of 83 patients, 74 had TG max <400 mg/dl, corresponding to a probability of 89.2% (95% CI, 81.9%-95.2%), and the 90th percentile of TG max was 400 mg/dl (95% CI, 328-490 mg/dl), closely aligned with the theoretical values. However, the individual TG max values were biased by the infusion rate because the covariate effects were overestimated in the TG kinetic model, requiring a minor revision. The updated MaxInfRate with the combined data set showed unbiased and more accurate predictions., Conclusion: The MaxInfRate was validated in external inpatients and updated with all available data. MaxInfRate estimation for individuals could be an option for the safe and efficient provision of SO-ILE., (© 2024 The Authors. Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

Introduction: Pain related to injection of propofol during induction of anesthesia decreases from 66.8% without prevention, to 22-31% of cases when lidocaine is associated. Hypnoanalgesia of the hand is currently used for painful procedures in children but has never been evaluated in this indication. The primary aim of this prospective randomized single-blind study was to evaluate the efficacy of hypnoanalgesia of the hand for the prevention of moderate to severe pain during intravenous injection of propofol alone in comparison to lidocaine admixture. The secondary aim was to compare the global satisfaction of children in both methods., Patients and Methods: One hundred patients aged 7-14 years, ASA 1-2, admitted for scheduled surgery under general anesthesia were randomized into two groups. Group L received a mixture of 1% propofol (3 mg/kg) and 1% Lidocaine (0.3 mg/kg). Group H received 1% propofol (3 mg/kg) after hypnoanalgesia of the hand realized by a single experimented operator. A video was made in order to evaluate the pain related to propofol injection by a blinded observer using the 4-point score of Cameron (painful ≥ 2). The global satisfaction of children was evaluated in postanesthesia care unit and documented if visual analog score was <7/10., Results: Ninety-six patients were analyzed. The rate of painful patients did not differ significantly between groups (8.5% in group H [n = 47] vs 6.1% in group L [n = 49], OR= 0.70; 95% CI [0.13-3.35], p = 0.65), nor did the rate of nonsatisfied patients (10.6 in group H vs. 12.2% in group L, OR = 0.85; 95% CI [0.19-3.65], p = 1)., Conclusions: Our results suggest that hypnoanalgesia of the hand alone is effective to prevent the pain related to propofol injection in children. No significant difference was found in comparison with lidocaine admixture nor for pain or satisfaction., (© 2024 The Authors. Pediatric Anesthesia published by John Wiley & Sons Ltd.)

Purpose: The purpose of this study was to investigate the dynamic changes in serum (1-3)-β-D-glucan (BDG) caused by intravenous immunoglobulins (IVIG) infusion in adults., Methods: This study included patients who received IVIG infusion from October 2021 to October 2022 during hospitalization. We randomly examined two IVIG samples for every patient. Serum samples were collected at nine time points: before (Tpre), immediately (T1-0), 6h (T1-1) and 12h (T1-2) later on the first day; immediately (T2-0) and six hours later (T2-1) on the second day during IVIG infusion, and within three days after IVIG infusion (Ta1, Ta2, and Ta3, respectively). The Friedman test was used for statistical analysis., Results: A total of 159 serum BDG from 19 patients were included in the analysis. The BDG content of IVIG ranged from 249 pg/ml to 4812 pg/ml. Patients had significantly elevated serum BDG on T1-0 (176 (113, 291) pg/ml, p = 0.002) and Ta1 (310 (199, 470) pg/ml, p < 0.001), compared with Tpre (41 (38, 65) pg/ml). The increments of serum BDG (ΔBDG) were associated with BDG concentration of IVIG (Spearman r = 0.59, p = 0.02). Individuals with abnormal renal function indexes showed higher serum ΔBDG values at Ta1 (403 (207, 484) pg/ml) than patients with normal renal function (172 (85, 316) pg/ml, p = 0.036)., Conclusion: Patients who received IVIG had significantly higher serum BDG values. Elevated BDG levels correlate with BDG content of IVIG and abnormal renal function indexes., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To clarify the impact of intravenous infusion of gamma globulin (IVIg) on antinuclear antibodies (ANAs) in children., Methods: A retrospective analysis was performed on the data of children with nonspecific autoantibody-related diseases whose antinuclear antibody (ANA) and autoantibody profiles were detected in our hospital from January to March 2022. A total of 108 patients with a clear history of IVIg infusion within 28 days composed the IVIg group, and 1201 patients without a history of IVIg infusion composed the non-IVIg group., Results: All patients in the IVIg group had either positive ANAs or positive autoantibodies. Anti-SSA, anti-Ro52 and anti-AMA Mi2 were the top three autoantibodies in the IVIg group. The proportions of patients who were positive for either of these three autoantibodies in the IVIg group were significantly greater than those in the non-IVIg group (all P<0.5). Spearman correlation analysis revealed that the signal intensities of anti-SSA and anti-Ro52 were negatively correlated with the number of days of ANA detection after IVIg infusion (P<0.05). Multiple logistic analyses revealed that a greater total dosage of IVIg, greater IVIg per kilogram of body weight, and fewer ANA detection days after IVIg infusion were independent risk factors for positive anti-SSA and anti-Ro52 results., Conclusions: It is recommended that if rheumatic diseases are suspected, ANA detection should be carried out beforeIVIg infusion. But for patients who are positive for at least one of these three autoantibodies after IVIg infusion, doctors should first consider adoptive antibodies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Zhou, Zhang, Wang, Yan, Wang, Tang and Luo.)

Orthognathic surgery has a high incidence of postoperative nausea (PON) and vomiting (POV), delaying mobility initiation and postoperative recovery. Bleeding is another risk associated with this surgical procedure. We aimed to compare total intravenous anesthesia (TIVA) and volatile anesthesia in patients undergoing orthognathic surgery in terms of postoperative nausea and vomiting (PONV) incidence and hemodynamic changes. This retrospective study included 82 patients who underwent bilateral sagittal split ramus osteotomies at Saga University Hospital between April 2016 and April 2021. We compared the effects of TIVA and volatile anesthesia on PONV onset after surgery, acute postoperative hemodynamic changes (blood pressure and heart rate), and factors contributing to PONV. PON was significantly lower in the TIVA group than in the volatile anesthesia group. The total dose of fentanyl contributed to the onset of POV, while the onset of PON was associated with low volumes of fluid infusion and urine in the TIVA and volatile anesthesia groups, respectively. Furthermore, post-extubation hemodynamic change was significantly smaller in the TIVA group than in the volatile anesthesia group. Therefore, TIVA could have a reduced risk of PONV and hemodynamic changes in patients undergoing orthognathic surgery. Employing TIVA could mitigate perioperative complications and enhance patient safety., (© 2024. The Author(s).)

Background: When inhalant anesthetic equipment is not available or during upper airway surgery, intravenous infusion of one or more drugs are commonly used to induce and/or maintain general anesthesia. Total intravenous anesthesia (TIVA) does not require endotracheal intubation, which may be more difficult to achieve in rabbits. A range of different injectable drug combinations have been used as continuous infusion rate in animals. Recently, a combination of ketamine and propofol (ketofol) has been used for TIVA in both human patients and animals. The purpose of this prospective, blinded, randomized, crossover study was to evaluate anesthetic and cardiopulmonary effects of ketofol total intravenous anesthesia (TIVA) in combination with constant rate infusion (CRI) of midazolam, fentanyl or dexmedetomidine in eight New Zealand White rabbits. Following IV induction with ketofol and endotracheal intubation, anesthesia was maintained with ketofol infusion in combination with CRIs of midazolam (loading dose [LD]: 0.3 mg/kg; CRI: 0.3 mg/kg/hr; KPM), fentanyl (LD: 6 µg/kg; CRI: 6 µg/kg/hr; KPF) or dexmedetomidine (LD: 3 µg/kg; CRI: 3 µg/kg/hr; KPD). Rabbits in the control treatment (KPS) were administered the same volume of saline for LD and CRI. Ketofol infusion rate (initially 0.6 mg kg - 1 minute - 1 [0.3 mg kg - 1 minute - 1 of each drug]) was adjusted to suppress the pedal withdrawal reflex. Ketofol dose and physiologic variables were recorded every 5 min., Results: Ketofol induction doses were 14.9 ± 1.8 (KPM), 15.0 ± 1.9 (KPF), 15.5 ± 2.4 (KPD) and 14.7 ± 3.4 (KPS) mg kg - 1 and did not differ among treatments (p > 0.05). Ketofol infusion rate decreased significantly in rabbits in treatments KPM and KPD as compared with saline. Ketofol maintenance dose in rabbits in treatments KPM (1.0 ± 0.1 mg/kg/min) and KPD (1.0 ± 0.1 mg/kg/min) was significantly lower as compared to KPS (1.3 ± 0.1 mg/kg/min) treatment (p < 0.05). Ketofol maintenance dose did not differ significantly between treatments KPF (1.1 ± 0.3 mg/kg/min) and KPS (1.3 ± 0.1 mg/kg/min). Cardiovascular variables remained at clinically acceptable values but ketofol infusion in combination with fentanyl CRI was associated with severe respiratory depression., Conclusions: At the studied doses, CRIs of midazolam and dexmedetomidine, but not fentanyl, produced ketofol-sparing effect in rabbits. Mechanical ventilation should be considered during ketofol anesthesia, particularly when fentanyl CRI is used., (© 2024. The Author(s).)

Background: Post-ischemia reperfusion can lead to oxidative stress and an increase in oxidative markers. Employing preventive strategies and antioxidant agents may help mitigate ischemia-reperfusion injury (IRI). The use of a tourniquet in extremity surgery has been associated with IRI. This study aims to investigate the impact of three different approaches- brachial plexus block, total intravenous anesthesia (TIVA), and inhalation anesthesia-on IRI during upper extremity surgery using a tourniquet., Methods: Patients aged 18 to 45 with American Society of Anesthesiologists (ASA) I-II scores were randomly assigned to one of three groups: Group A received an axillary block with bupivacaine; Group I underwent inhalation anesthesia with sevoflurane; and Group T received TIVA with propofol and remifentanil infusion. Blood samples were collected to measure glucose, lactate, total anti-oxidant status (TAS), total oxidant status (TOS), and ischemia-modified albumin (IMA) levels at various time points: before anesthesia (t1), 1 minute before tourniquet release (t2), 20 minutes after tourniquet release (t3), and 4 hours after tourniquet release (t4)., Results: In Group I, lactate levels at t3, and glucose levels at t2 and t3, were higher compared to the other groups. Group A exhibited lower IMA levels at t2, t3, and t4 than the other groups. Additionally, Group I had lower IMA levels at t2, t3, and t4 compared to Group T. TAS levels were higher in Group I at t2, t3, and t4 compared to the other groups. TOS levels at t2 and t3 were lower in Group A than in Group I., Conclusion: Axillary anesthesia results in a sympathetic block, promoting better perfusion of the upper extremity. This study demonstrated lower levels of oxidative stress markers with axillary plexus block. Therefore, these results suggest that the axillary block has the potential to mitigate IRI.

Background and Objective: Systemic sclerosis (SSc) is a highly heterogeneous disease whose treatment is based mainly on immunosuppressants, antifibrotics, and vasodilators. Intravenous immunoglobulin (IVIG) have proved effective in other autoimmune diseases. The objective of this study is to evaluate the efficacy and safety of IVIG in SSc., Methods: The systematic review was conducted according to the PRISMA Statement. Medline, Embase and Cochrane Library databases were searched until March 2024. We assessed the quality of included studies using the Cochrane Risk of Bias 2.0 tool (RoB 2) for randomised clinical trials and the Cochrane Risk in non-randomized studies (ROBINS-I) tool for observational studies., Results: From 1242 studies identified, 15 studies were included, of which 14 were observational studies. In total, 361 patients with SSc were included, and 295 received treatment with IVIG. Most of the studies used a dose of 2 g/kg IVIG. Ten studies, including the clinical trial, showed high risk of bias, and five had a critical risk. Skin involvement was assessed using modified Rodnan skin score, in 11 studies and the authors reported cutaneous efficacy in 9 of them. The 6 studies that assessed muscle involvement reported an improvement. Six studies reported data on gastrointestinal efficacy. Other domains such as lung and joint involvement and steroid-sparing effect were evaluated. The most frequent adverse events were mild, including headache, abdominal pain, fever, and skin rash., Conclusion: Treatment with IVIG in SSc patients could be helpful and safe in patients with cutaneous, muscular, or digestive manifestations., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Transient positivity for hepatitis B core antibody (Anti-HBc) following intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin exposure is a well-described phenomenon. The aim of this study was to retrospectively review Hepatitis B viral screening practices in IVIG recipients in a hematology specific cohort at a single center., Methods: Electronic databases were analyzed to identify all hematology patients who received IVIG from September 2022 to March 2022 at a single Irish center (n = 43). The proportion of patients that had a baseline anti-HBc tested prior to IVIG receipt was assessed as well as the proportion of patients that developed a transiently positive anti-HBc following IVIG exposure. Data were also collected relating to signal cut-off ratios in patients with detectable anti-HBc post-IVIG., Results: 58.1% of patients had at least one serological hepatitis B viral test sent prior to IVIG exposure. Anti-HBc was the least common serological investigation performed prior to IVIG exposure (21% of recipients). A positive or equivocal "low level antibody" was identified in 15% of recipients and this was proven to be transient in all cases., Conclusion: The minority of hematology patients had a baseline anti-HBc assessed prior to IVIG exposure. All patients in this study had the potential to require further immunosuppressive therapies, which could be limited by a misleading anti-HBc result. We therefore advocate for baseline anti-HBc testing to be performed prior to IVIG exposure in hematology patients and for cautious interpretation of anti-HBc results taking into account signal cut-off ratios post-IVIG exposure., (© 2024 The Author(s). Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Intravenous immunoglobulin (IVIG) is frequently administered to patients with severe fever with thrombocytopenia syndrome (SFTS), particularly those with severe manifestations, although its efficacy remains controversial. The study retrospectively analyzed the effects of IVIG administration on SFTS patients in both mild and severe groups. The primary outcome measure was 28-day mortality. Inverse probability of treatment weighting (IPTW) with propensity score was used to account for baseline confounders. A total of SFTS patients with complete data enrolled from January 1, 2015, to August 1, 2023. Death at 28 days occurred for 68 (17.5%) patients. By unadjusted analysis, no difference was observed for 28-day mortality between the IVIG and non-IVIG groups in both the mild and severe groups. Similar results were found by propensity score matching and by IPTW analysis. Although IVIG is frequently used as adjuvant therapy for severe SFTS patients, no significant association was observed between IVIG treatment and reduced mortality in this patient population., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Objective: No clinical trials have been conducted to establish optimal and effective treatment in patients with immune-mediated necrotizing myopathy (IMNM), which can have a refractory course with increased morbidity from permanent muscle damage, especially in patients who experience delay in diagnosis and treatment. A subset of autoimmune necrotizing myopathy is associated with antibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Treatment involves withdrawing statins and using a combination of immunosuppressant and immunomodulatory treatment. Our study aims to provide longitudinally collected data on outcomes of early versus late initiation of intravenous Ig (IVIG) using our myositis center cohort of patients with anti-HMGCR IMNM., Methods: We conducted a retrospective chart review of 31 adult patients of the Oregon Health and Science University Myositis Center who were diagnosed with anti-HMGCR IMNM from September 2016 through October 2022 and reviewed physical examination, serologic laboratory data, and their treatment including prednisone reception as well as treatment response at 0 (the evaluation immediately before IVIG initiation), 3, 6, and 12 months on treatment. We divided this cohort into those who received IVIG at or before six months after receiving the diagnosis of anti-HMGCR IMNM and refer this as the cohort with nondelayed treatment, and those who received IVIG after six months following their diagnosis, which we referred to as the cohort with delayed treatment. Diagnosis of anti-HMGCR IMNM was defined as per the 2016 European Neuromuscular Centre criteria as having all three of elevated serum creatine kinase (CK), proximal muscle weakness, and anti-HMGCR antibodies. We evaluated the response to treatment by using a limited total improvement score (TIS) as per 2016 American College of Rheumatology/EULAR myositis response criteria., Results: Among the 31 total patients, 19 were included within the cohort with nondelayed treatment, and 12 within the cohort with delayed treatment. The two cohorts had a comparable amount of time between the onset of symptoms and diagnosis; however, the cohort with delayed treatment had a significantly longer time between diagnosis and IVIG treatment (P < 0.001). At disease onset, cohorts had a comparable serum CK (P > 0.999), but patients with delayed treatment had an expected lower serum CK (P = 0.016) at the 0-month time point. At the 0-month time point, nine of the patients with nondelayed treatment (47%) required the use of a walker or wheelchair, whereas eight of the cohort with delayed treatment (66%) did. Patients who received nondelayed treatment demonstrated significant improvement in manual muscle testing 8 at the 12-month intervals (P < 0.001). Average serum CK values of all patients measured at the 3, 6, and 12 months did not significantly differ between the groups with nondelayed and delayed treatment. TIS improved more in the group with nondelayed treatment than in the group with delayed treatment (P = 0.002 at 3 months, P = 0.019 at 6 months, and P = 0.001 at 12 months). Seven patients in the group with delayed treatment had permanent residual muscle weakness requiring walker or wheelchair use at 12 months, whereas none of the patients in the group with nondelayed treatment did., Conclusion: Though our results have limitations, they contribute to a growing body of evidence that suggests that IVIG may prove to be a valuable addition to an early and aggressive induction regimen in patients afflicted by anti-HMGCRIMNM, particularly those with moderate to severe weakness requiring the use of a wheelchair or walking aids. Delay in IVIG treatment may lead to the development of permanent residual weakness and long-term disability., (© 2024 American College of Rheumatology.)

Background and Objectives: Intravenous immunoglobulins (IVIgs) contain various autoantibodies, including those against glutamic acid decarboxylase (GADAb), a valuable biomarker of type 1 diabetes mellitus. Passive transfer of GADAb from IVIgs to patients poses a risk of misdiagnosis, and information on the specific titres of GADAb and their impact on diagnostic accuracy remains limited. This study aimed to provide further insights into the origin of GADAb detected in patient serum following IVIg infusion., Materials and Methods: GADAb titres in IVIg products from Japan and the United States were measured using enzyme-linked immunosorbent assay-based assays. For reliable quantification, GADAb titres in pooled plasma were quantified and compared with those in the IVIg products. The determined titres were used to estimate the likelihood of passively detecting acquired GADAb in individuals receiving IVIgs., Results: GADAbs were prevalent in IVIg products; however, the titres varied significantly among different lots and products. Importantly, IVIg-derived GADAb was estimated to remain detectable in patient serum for up to 100 days following a dosage of 2000 mg/kg., Conclusion: Clinicians should consider that IVIg preparations may contain GADAb, which can lead to false-positive results in serological assays. Careful interpretation of the assay results is key to the definitive diagnosis of type 1 diabetes mellitus., (© 2024 International Society of Blood Transfusion.)

Background: Transfusion-related acute lung injury (TRALI) is a rare life-threatening complication of blood product transfusion. Intravenous immunoglobulin (IVIG)-related TRALI is scarcely reported., Case Presentation: A 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., Conclusion: IVIG-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., (© 2024. The Author(s).)

Background: The effect of intraoperative anesthetic regimen on pulmonary outcome after minimally invasive esophagectomy for esophageal cancer is yet undetermined. The aim of this study was to determine the effect of volatile anesthesia (sevoflurane or desflurane) compared with propofol-based intravenous anesthesia on pulmonary complications after minimally invasive esophagectomy., Methods: Patients scheduled for minimally invasive esophagectomy were randomly assigned to 1 of 3 general anesthetic regimens (sevoflurane, desflurane, or propofol). The primary outcome was the incidence of pulmonary complications within the 7 days postoperatively, which was a collapsed composite end point, including respiratory infection, pleural effusion, pneumothorax, atelectasis, respiratory failure, bronchospasm, pulmonary embolism, and aspiration pneumonitis. The severity of pulmonary complications, surgery-related complications, and other secondary outcomes were also assessed., Results: Of 647 patients assessed for eligibility, 558 were randomized, and 553 were analyzed. A total of 185 patients were assigned to the sevoflurane group, 185 in the desflurane, and 183 in the propofol group. Patients receiving a volatile anesthetic (sevoflurane or desflurane) had a significantly lower incidence (36.5% vs 47.5%; odds ratio, 0.63; 95% confidence interval, 0.44-0.91; P = .013) and lower severity grade of pulmonary complications ( P = .035) compared to the patients receiving propofol. There were no statistically significant differences in other secondary outcomes between the 2 groups., Conclusions: In patients undergoing minimally invasive esophagectomy, the use of volatile anesthesia (sevoflurane or desflurane) resulted in the reduced risk and severity of pulmonary complications within the first 7 postoperative days as compared to propofol-based intravenous anesthesia., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

Introduction/aims: Intravenous immune globulin (IVIG) has been used as early treatment for autoimmune neuromuscular diseases, but due to cost and frequency, may be switched to rituximab. Rituximab and other B-cell-depleting medications require screening of hepatitis B virus (HBV) serologies given the risk of HBV reactivation (HBVr). We aimed to describe the incidence and characteristics of passively transferred antiviral serologies from IVIG and how to differentiate between passive antibody transfer and resolved HBV infection., Methods: This was a single-center descriptive study of neurology patients prescribed rituximab and IVIG. Retrospective medical record reviews were performed and patient-specific variables were collected., Results: Twelve patients had reactive anti-HBc results after starting IVIG, but only 9 were confirmed to have reactive anti-HBc from passive transfer. Whether reactive anti-HBc in the remaining three patients was from passive IVIG transfer could not be confirmed. Five patients with reactive anti-HBc results during rituximab screening did not have pre-IVIG anti-HBc results for comparison and were started on antiviral prophylaxis. Reactive anti-HBc serologies changed to nonreactive after IVIG discontinuation 44-321 days after the last IVIG infusion., Discussion: This study confirms IVIG can passively transfer anti-HBc serologies in a neurologic cohort. Ideally, HBV serologies would be checked before starting IVIG to help later determine if passive transfer occurred. With the increasing use of B-cell-depleting medications for neuromuscular conditions, it is important for providers to be knowledgeable on the interpretation of HBV serologies for patients on IVIG and to ensure implementation of an HBVr prophylaxis management strategy for patients when appropriate., (© 2024 Wiley Periodicals LLC.)

Background: 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., Methods: 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., Results: 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., Conclusion: Targeting the IL-6 pathway appears to offer therapeutic benefits in highly relapsing MOGAD patients who poorly respond to IVIG maintenance therapy., Competing Interests: Declaration of competing interest Kang YR, Kim KH, Hyun JW, and Kim SH report no potential conflicts of interest related to this study. HJK received a grant from the National Research Foundation of Korea and research support from Aprilbio and Eisai; received consultancy/speaker fees from Alexion, Aprilbio, Altos Biologics, Biogen, Celltrion, Daewoong, Eisai, GC Pharma, Handok, Horizon Therapeutics, Kaigene, Kolon Life Science, MDimune, Mitsubishi Tanabe Pharma, Merck Serono, Novartis, Roche, Sanofi Genzyme, Teva-Handok, and UCB; is a co-editor for the Multiple Sclerosis Journal and an associated editor for the Journal of Clinical Neurology., (Copyright © 2024 Elsevier B.V. All rights reserved.)

While it is known that immunoglobulin replacement therapy (IgRT) used in the treatment of primary immunodeficiency disorders (PIDs) can lead to the passive transfer of autoantibodies, there is no data indicating that these antibodies can cause clinical symptoms in patients. This study aimed to investigate the presence of autoantibodies and their clinical correlation in patients diagnosed with PIDs receiving IgRT. Paediatric patients who were diagnosed with PIDs, and administered IgRT at our immunology clinic between 1 January 2012 and 31 December 2021, were included in the study. The medical records of these patients were retrospectively analysed, and autoantibodies were screened. Autoantibody screening was conducted at least once in 48 cases. Among these cases, 29 cases (60.4%) demonstrated positivity for at least one of the autoantibodies screened in the study. Among these cases, 23 tested positive for anti-TPO, 9 for anti-TG and 2 for both anti-TPO and anti-TG. Only two of these patients were confirmed to have Hashimoto's thyroiditis. In 30 cases, autoantibodies related to Celiac disease (CD) were screened, with at least one being positive in five different cases; CD was not confirmed. The results of our study suggest that passive transfer of autoantibodies to patients with IgRT does not cause any significant clinical findings. In addition, in cases of PID, autoantibodies detected in the blood passed to patients with IgRT can lead to misdiagnosis. Screening for autoantibodies in patients with PID undergoing IgRT may not yield accurate results in terms of detecting autoimmune diseases., (© 2024 The Scandinavian Foundation for Immunology.)

Background: The incidence of refractory Mycoplasma pneumoniae pneumonia (RMPP) in children is increasing, posing a serious threat to life safety. Intravenous immunoglobulin (IVIG) has demonstrated the ability to modulate the immune system and has shown the potential to treat RMPP. This study evaluated the clinical efficacy and safety of azithromycin combined with IVIG in the treatment of RMPP in children through a meta-analysis., Methods: A comprehensive search was conducted in seven databases including PubMed and Cochrane Library, and the studies on the treatment of RMPP in children with azithromycin combined with IVIG were screened. After data extraction, meta-analysis and sensitivity analysis were performed to assess heterogeneity and stability., Results: Thirteen randomized controlled trials and two cohort studies were included, totaling 1,142 children. The results of meta-analysis showed a higher clinical efficacy rate (RR = 1.18, 95% CI: 1.11-1.25, P < 0.01) and shorter time to defervescence (MD = -2.12, 95% CI: -2.69--1.55), time to disappearance of pulmonary rales (MD = -2.90, 95% CI: -3.57--2.23), time to disappearance of cough (MD = -3.59, 95% CI: -4.51--2.67), and hospital length of stay (MD = -5.72, 95% CI: -8.80--2.64) in the experimental group receiving azithromycin combined with IVIG treatment compared to the control group treated with azithromycin alone. Additionally, there was no significant publication bias in this meta-analysis., Conclusion: Treatment with azithromycin combined with IVIG is more effective than treatment with azithromycin alone for children with RMPP., Clinical Trial Number: Not applicable., (© 2024. The Author(s).)

Background: Postoperative cognitive dysfunction (POCD) is one of the major complications after surgery, with devastating clinical outcomes. Although POCD is a condition with a multifactorial pathophysiology, blood-brain barrier (BBB) dysfunction and neuronal injury have been shown to play a critical role, especially in the elderly. Previous studies have demonstrated that the choice of anesthetics affect BBB permeability and neuroinflammation. However, most studies are carried out on animals, with limited research undertaken on humans. Therefore, we will compare the effect of intravenous anesthetics and inhaled anesthetics on BBB dysfunction and the change of inflammatory markers after surgery., Methods: One hundred and fifty-four patients who are 60 years of age or older undergoing major surgery for more than 2 h will be randomly allocated to two anesthetics groups (intravenous, inhaled) in a 1:1 ratio. In the intravenous anesthetics group (group P), propofol will be infused with a target-controlled infusion (TCI) system throughout the entire surgery. In the inhaled anesthetics group (group G), bolus injection of propofol will be administered for loss of consciousness, and simultaneously sevoflurane will be initiated for the maintenance of anesthesia. The primary outcome is the change in serum S100 calcium binding protein β (S100β) at four time points: before induction of anesthesia, at the end of surgery, 4 h after surgery, postoperative day 1. Secondary outcomes include changes in the inflammatory markers, serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and C-reactive protein; the incidence of delirium; and the change in the cognitive function between groups. In patients pre-scheduled for postoperative intensive care unit admission, the cerebrospinal fluid/serum albumin quotient (Qalb) between the two groups will be compared before and after surgery, and change in inflammatory markers in serum and CSF will be analyzed in relation to the Qalb., Discussion: The current study will compare the effect of intravenous versus inhaled anesthetics on blood-brain barrier permeability and, as a result, the difference in neuroinflammation in elderly patients. Also, the study results will provide additional information to develop intraoperative anesthetic strategies to reduce POCD., Trial Registration: The trial was prospectively registered at Clinical Trials protocol registration with identifier 2310-117-126 on April 9, 2024., (© 2024. The Author(s).)

Objective: This study aimed to investigate the outcomes associated with the administration of maternal intravenous immunoglobulin in high-risk red blood cell-alloimmunized pregnancies., Data Sources: Medline, Embase, and Cochrane Library were systematically searched until June 2023., Study Eligibility Criteria: This review included studies reporting on pregnancies with severe red blood cell alloimmunization, defined as either a previous fetal or neonatal death or the need for intrauterine transfusion before 24 weeks of gestation in the previous pregnancy as a result of hemolytic disease of the fetus and newborn., Methods: Cases were pregnancies that received intravenous immunoglobulin, whereas controls did not. Individual patient data meta-analysis was performed using the Bayesian framework., Results: Individual patient data analysis included 8 studies consisting of 97 cases and 97 controls. Intravenous immunoglobulin was associated with prolonged delta gestational age at the first intrauterine transfusion (gestational age of current pregnancy - gestational age at previous pregnancy) (mean difference, 3.19 weeks; 95% credible interval, 1.28-5.05), prolonged gestational age at the first intrauterine transfusion (mean difference, 1.32 weeks; 95% credible interval, 0.08-2.50), reduced risk of fetal hydrops at the time of first intrauterine transfusion (incidence rate ratio, 0.19; 95% credible interval, 0.07-0.45), reduced risk of fetal demise (incidence rate ratio, 0.23; 95% credible interval, 0.10-0.47), higher chances of live birth at ≥28 weeks (incidence rate ratio, 1.88; 95% credible interval, 1.31-2.69;), higher chances of live birth at ≥32 weeks (incidence rate ratio, 1.93; 95% credible interval, 1.32-2.83), and higher chances of survival at birth (incidence rate ratio, 1.82; 95% credible interval, 1.30-2.61). There was no substantial difference in the number of intrauterine transfusions, hemoglobin level at birth, bilirubin level at birth, or survival at hospital discharge for live births., Conclusion: Intravenous immunoglobulin treatment in pregnancies at risk of severe early hemolytic disease of the fetus and newborn seems to have a clinically relevant beneficial effect on the course and severity of the disease., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To compare the incidence of delirium and early (at 1 week) postoperative cognitive dysfunction (POCD) between propofol-based total intravenous anesthesia (TIVA) and volatile anesthesia with sevoflurane in adult patients undergoing elective coronary artery bypass graft surgery (CABG) with cardiopulmonary bypass (CPB)., Design: This was a prospective randomized single-blinded study., Setting: The study was conducted at a single institution, the Sree Chitra Tirunal Institute for Medical Sciences and Technology, a tertiary care institution and university-level teaching hospital., Participants: Seventy-two patients undergoing elective CABG under CPB participated in this study., Interventions: This study was conducted on 72 adult patients (>18 years) undergoing elective CABG under CPB who were randomized to receive propofol or sevoflurane. Anesthetic depth was monitored to maintain the bispectral index between 40 and 60. Delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit. Early POCD was diagnosed when there was a reduction of >2 points in the Montreal Cognitive Assessment score compared to baseline. Cerebral oximetry changes using near-infrared spectroscopy (NIRS), atheroma grades, and intraoperative variables were compared between the 2 groups., Measurements & Main Results: Seventy-two patients were randomized to receive propofol (n = 36) or sevoflurane (n = 36). The mean patient age was 59.4 ± 8.6 years. The baseline and intraoperative variables, including atheroma grades, NIRS values, hemoglobin, glycemic control, and oxygenation, were comparable in the 2 groups. Fifteen patients (21.7%) patients developed delirium, and 31 patients (44.9%) had early POCD. The incidence of delirium was higher with sevoflurane (n = 12; 34.2%) compared to propofol (n = 3; 8.8%) (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.13-2.62; p = 0.027)*. POCD was higher with sevoflurane (n = 20; 57.1%) compared to propofol (n = 11; 32.3%) (OR, 1.63; 95% CI, 1.01-2.62; p = 0.038)*. In patients aged >65 years, delirium was higher with sevoflurane (7/11; 63.6%) compared to propofol (1/7; 14.2%) (p = 0.03)*., Conclusions: Propofol-based TIVA was associated with a lower incidence of delirium and POCD compared to sevoflurane in this cohort of patients undergoing CABG under CPB. Large-scale, multicenter randomized trials with longer follow-up are needed to substantiate the clinical relevance of this observation., Competing Interests: Declaration of competing interest The authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To describe the short-term response, early prognostic markers, and survival after treatment of canine immune-mediated thrombocytopenia (ITP) with human intravenous immunoglobulin (hIVIG) and methylprednisolone., Design: Retrospective cohort study., Settings: Private referral veterinary medical center., Animals: Twenty-seven client-owned dogs with primary or secondary ITP., Interventions: All dogs received 2 mg/kg IV methylprednisolone once daily and a single infusion of 5% hIVIG administered over 6-12 hours., Measurements and Main Results: A substantial increase in platelet count within 60 ± 12 hours post-hIVIG infusion (T 60 ) was observed in 19 of the 27 (70%) dogs with ITP (responders). Thirty-four variables, including serum immunoglobulin (Ig) G concentration 24 ± 12 hours post-hIVIG infusion (T 24 IgG) and increase in serum IgG concentration 24 ± 12 hours post-hIVIG infusion (T 24 Δ IgG ), were compared between responders and nonresponders at 5 different time points. Mortality rates of responders and nonresponders were evaluated 14 days post-hIVIG infusion. Serum T 24 IgG and serum T 24 Δ IgG were both significantly higher at T 60 in responders. All responders were alive 14 days post-hIVIG infusion, and their mortality rate was significantly lower compared with nonresponders., Conclusions: Responder dogs had an excellent 14-day survival rate. Serum T 24 IgG and serum T 24 Δ IgG concentrations accurately predicted response status at 60 hours post-hIVIG infusion., (© Veterinary Emergency and Critical Care Society 2024.)

Delayed radiation myelopathy (DRM) is a rare yet severe complication of radiotherapy. This condition has a progressive pattern that is often irreversible. Several therapeutic strategies have been introduced to alleviate disease complications, including corticosteroids, hyperbaric oxygen, anticoagulants, and antivascular endothelial growth factor (VEGF) agents. However, despite their beneficial effect, they have not been the definitive treatments for DRM. Here we present the case of a 55-year-old woman with a history of multiple myeloma who developed neurological complications 11 months after radiation therapy. As her radiologic findings demonstrated transverse myelitis, based on the DRM diagnostic criteria, the diagnosis of delayed radiation myelitis was reached. Therefore, methylprednisolone pulse therapy was initiated, resulting in the complete resolution of her neurological symptoms. However, on her follow-up examination, although she did not have new neurological complications, magnetic resonance imaging (MRI) demonstrated a residual enhancement in the thoracic spinal cord area. Hence, due to the possibility of myelitis progression and spinal cord atrophy, intravenous immune globulin (IVIG) was administered, resulting in the resolution of lesion enhancement. Considering this outcome and the immunomodulatory properties of IVIG, it could be regarded as a potential therapeutic option in the case of DRM activity., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Rationale: This article presents a complex case of refractory Henoch-Schönlein purpura (HSP), initially manifesting with complex gastrointestinal (GI) symptoms, and discusses diagnostic and therapeutic challenges encountered. It aims to enhance understanding of the disease and provide evidence for the potential efficacy of intravenous immunoglobulin (IVIG) treatment in this condition., Patient Concerns: A 16-year-old male patient presented with persistent abdominal pain, nausea, vomiting, and constipation for 8 days, leading to hospital admission., Diagnoses: Establishing a definitive diagnosis was challenging initially due to the absence of typical petechiae. However, the appearance of characteristic petechiae subsequently confirmed the diagnosis of HSP., Interventions: Initial treatment with methylprednisolone sodium succinate for 3 days failed to elicit improvement. Subsequently, IVIG was introduced as a combination therapy., Outcomes: Following the combined administration of IVIG, the patient experienced complete resolution of abdominal pain, petechiae, and arthralgia within 4 days., Lessons: This case highlights the importance of considering HSP in the differential diagnosis of patients with complex GI symptoms. Furthermore, it suggests that IVIG may be a valuable therapeutic option for HSP patients with refractory GI symptoms. High-quality comparative trials are needed to establish more definitive evidence for the effectiveness of IVIG and to develop specific treatment guidelines., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Inadequate production of immunoglobulin G (IgG) antibodies renders patients with primary immunodeficiency susceptible to infection by numerous pathogens, some of which can lead to severe asthma exacerbation and possible death. These patients who are immunocompromised are often reliant on intravenous immunoglobulin (IVIG) therapies, which provide passive antibodies against various respiratory pathogens, including measles virus and encapsulated bacteria. Objective: We conducted a subanalysis of data from a multicenter, multinational, phase III, open-label bioequivalence study to compare protective concentrations of IgG antibodies provided by a 5% and a 10% IVIG product in patients with primary immunodeficiency. Methods: Patients on stable 21- or 28-day regimens of previous IVIG products were assigned to receive study treatment (adults: 5% IVIG and 10% IVIG; children: 10% IVIG) at doses of 300-800 mg/kg per infusion. Trough concentrations of total IgG, IgG subclasses, measles-neutralizing antibodies, and IgG against Haemophilus influenzae type b and Streptococcus pneumoniae serotypes were evaluated. Results: A total of 48 patients (33 adults ages 16-55 years; 15 children ages 2-15 years) were enrolled and received treatment. No statistically significant differences in trough concentrations of total IgG, IgG subclasses, measles-neutralizing antibodies, or IgG directed at encapsulated bacteria were observed between the 5% and 10% formulations in analyses by age (adult or pediatric) or infusion schedule (every 21 or 28 days). All evaluated patients had trough IgG concentrations above accepted thresholds for protection against disease. Conclusion: These findings support the conclusion that, at dose levels and infusion schedules prescribed in clinical practice, this 5% and 10% IVIG product provided consistent, predictable, and bioequivalent IgG concentrations for adult and pediatric patients with primary immunodeficiency disease. Both formulations delivered trough antibody concentrations of total IgG, measles-neutralizing antibodies, and antibodies against encapsulated bacteria that are above thresholds accepted as protective.Clinical trial NCT01963143, www.clinicaltrials.gov.

Introduction: We examined autoimmunity markers (AIM) and autonomic dysfunction in patients with chronic neurogastroenterological symptoms and their relationship to joint hypermobility/hypermobility spectrum disorder (JH/HSD)., Methods: AIM positivity was defined as a diagnosis of known autoimmune/autoinflammatory disorder with at least 1 positive seromarker of autoimmunity or at least 2 positive seromarkers by themselves. Three cohorts were studied: (i) retrospective (n = 300), (ii) prospective validation cohort (n = 133), and (iii) treatment cohort (n = 40), administered open-label intravenous immunoglobulin (IVIG)., Results: AIM positivity was found in 40% and 29% of the retrospective and prospective cohorts, the majority of whom (71% and 69%, respectively) had autoinflammatory disorder. Significantly more patients with AIM had elevations of C-reactive protein (31% vs 15%, P < 0.001) along with an increased proportion of cardiovascular autonomic dysfunction (48% vs 29%; P < 0.001), small fiber neuropathy (20% vs 9%; P = 0.002), and HLADQ8 positivity (24% vs 13%, P = 0.01). Patients with JH/HSD were more likely to have AIM (43% vs 15%, P = 0.001) along with more severe autonomic and gastrointestinal (GI) symptom scores. IVIG treatment was associated with robust improvement in pain, GI, and autonomic symptoms, but adverse events were experienced by 62% of patients., Discussion: Autoimmune markers and autonomic dysfunction are common in patients with unexplained GI symptoms, especially in those with JH/HSD. Many patients seem to respond to IVIG treatment, but this needs to be confirmed by controlled trials. These results highlight the need for vigilance for autoimmune and autonomic factors and JH/HSD in patients with neurogastroenterological disorders. Clinicaltrials.gov , NCT04859829., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Objective: The purpose of the present study was to evaluate whether intravenous immunoglobulin (IVIG) increases live birth rates and improves neonatal results in patients with antiphospholipid antibodies (aPL) at high-risk for miscarriage., Background: Positivity of aPL in pregnant women is a high-risk factor for miscarriage, and IVIG treatment has emerged as a potential intervention., Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was employed to search multiple electronic databases for articles published until August 20, 2023, including PubMed, Web of Science, Embase, Scopus and Medline. The inclusion criteria encompassed studies assessing the efficacy of IVIG in aPL-positive patients with a high risk of miscarriage. Relevant articles were assessed for the quality and data were extracted for analysis. Two independent reviewers performed study selection, data extraction, and quality assessments. The risk of bias was evaluated according to the Cochrane risk of bias tool. All analyses were conducted using Review Manager 5.3., Results: This systematic review included nine randomized controlled trials, with 366 aPL-positive women at high risk of miscarriage. These studies included in this review were randomized controlled trials. The primary outcome measures were successful pregnancy outcomes and live birth rates. The secondary outcomes included obstetric complications, and neonatal outcomes (such as birth weight and live-birth rate). The comparison between the intervention and control groups revealed no significant differences in terms of obstetric complications and neonatal outcomes. The group receiving IVIG treatment had a higher prevalence of preterm deliveries than controls (OR = 2.05, I 2 = 46%, 95% CI [0.58-5.24]), but also exhibited a partial improvement in live birth rates (OR = 2.86, I 2 = 52%, 95% CI [1.04-7.90]), because it reduced the number of miscarriages (OR = 0.35, I 2 = 52%, 95% CI [0.13-0.96])., Conclusion: Based on the available evidence, IVIG intervention appears to be a potentially effective approach for managing of aPL-positive pregnant women with high risk of miscarriage. While IVIG shows significant potential in tripling the chances of having a live-born child, further large-scale randomized controlled trials are necessary, preferably comparing IVIG with hydroxychloroquine or lifestyle and dietary interventions, to refine treatment protocols and ensure the most effective application., Competing Interests: The authors declare that they have no competing interests., (© 2024 Yuan et al.)

The association between granulomas and vaccine-derived rubella virus (VDRV) in people with primary immunodeficiencies has raised concerns about the ability of immunoglobulin preparations to neutralize VDRVs. We investigated the capacity of immunoglobulin to neutralize rubella vaccine virus and 4 VDRV strains. As expected, the rubella vaccine virus itself was potently neutralized by immunoglobulin preparations, but the VDRV isolates from patients after intrahost evolution, 2-6 times less so. Diagnosis of immune deficiencies before possible live-virus vaccination is thus of critical importance, while immunoglobulin replacement therapy can be expected to provide protection from rubella virus infection., Competing Interests: Potential conflicts of interest. C. L., M. R. F., M. K., and T. R. K. are employees of Takeda Manufacturing Austria AG, Vienna, Austria. M. R. F., M. K. and T. R. K. have Takeda stock interest. Other authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Purpose: Immunoglobulin replacement therapy remains a cornerstone of treatment in antibody deficiencies and other inborn errors of immunity. While patient preferences between subcutaneous and intravenous immunoglobulin have been studied through questionnaires, no study has yet explored patient perspectives in a free environment. Therefore, we aimed to conduct a sentiment analysis as well as a temporal and geographical analysis on public opinions obtained from social media to better understand patient satisfaction and public perception on immunoglobulin therapy., Methods: A dataset of 43,700 tweets spanning from the 1st of January of 2012 to the 31st of December of 2022 was obtained. A Valence Aware Dictionary for Sentiment Reasoning sentiment analysis was performed, followed by statistical, geographical and temporal analyses., Results: Mean polarity of intravenous immunoglobulin related tweets was 0.1295 (positive), while mean polarity for subcutaneous immunoglobulin was 0.2117 (positive). Temporal analysis through a statistical model demonstrated that the volume of tweets increased over time for both subcutaneous and intravenous treatment. Geographical analysis revealed that the majority of texts originated from the United States. The highest mean polarity was observed in Romania with a mean value of 0.2966, while the lowest polarity was documented in Norway with a mean of -0.0211., Conclusion: Tweets linked to subcutaneous immunoglobulin treatment had a higher average polarity, indicating a more positive public perception. The amount of tweets relating to both therapies showed a tendency to increase as the years progressed, implying an increase in public discussion on immunoglobulin treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tarango-García, Rodríguez-Narciso, Castañeda-Leyva, Prieto-Nevárez, Lugo Reyes, Espinosa-Rosales, Espinosa-Padilla, Staines-Boone, Torres-Bernal and Álvarez-Cardona.)

Considering its proven clinical usefulness and supportive evidence, intravenous immunoglobulin (IVIg) is used as first-line therapy for chronic inflammatory demyelinating polyneuropathy (CIDP) during the acute and chronic stages. However, the pathomechanism underlying IVIg administration for CIDP remains unclear. Autoantibodies, complement, inflammatory cytokines, chemokines, T cells, B cells, macrophages, and the blood-nerve barrier contribute to the onset and progress of CIDP. The mechanisms underlying the actions of IVIg in CIDP include the following: (1)neutralization of pathological autoantibodies by anti-idiotype antibodies, (2)inhibition of the neonatal Fc receptor (FcRn) with a consequent decrease in pathological autoantibodies, (3)neutralization of cytokines, chemokines, and complement, (4)activity modulation of T cells, B cells, and macrophages, and (5) recovery of blood-nerve barrier function. Compared with the management of typical CIDP, IVIg therapy is less effective for management of autoimmune nodopathy associated with anti-neurofascin-155 or contactin-1 IgG4 antibodies because (1)anti-idiotype antibodies associated with IVIg cannot effectively neutralize IgG4 owing to the strong antigen specificity of IgG4 autoantibodies, and (2)complement, T cells, and macrophages play an insignificant role in the pathomechanism of autoimmune nodopathy. Further understanding of the mechanisms underlying IVIg action and effectiveness of molecular targeted therapy, such as use of FcRn or complement inhibitors and the CD20 monoclonal antibody, is warranted to develop novel therapeutic strategies against CIDP.

Objective: Interstitial lung disease (ILD) resulting from connective tissue disease (CTD) greatly undermines people's health. Cyclophosphamide (CYC) is a widely used agent in treating CTD-ILD. We compared the efficacy and safety of oral and intravenous CYC in CTD-ILD treatment., Methods: The retrospectively enrolled CTD-ILD patients were divided into the oral and intravenous CYC groups. The chest high-resolution computed tomography examination, forced vital capacity (FVC), lung carbon monoxide diffusion capacity (Dlco) determinations, and 6 min walk test (6MWT) were performed pre-treatment and at the 3rd, 6th, and 12th months posttreatment. Radiographic ILD severity was assessed using the Warrick score. Krebs Von den Lungen-6, surfactant protein A (SP-A), SP-D, and erythrocyte sedimentation rate (ESR) before and at the 12th month post-treatment were determined. CYC cumulative dose and occurrence of adverse reactions during treatment were recorded., Results: CYC cumulative dose in the intravenous CYC group was reduced. Compared with oral CYC treatment, intravenous CYC caused decreased Warrick score and increased FVC and 6MWT at the 6th month, and elevated DLco at the 3rd and 6th months posttreatment. SP-A, SP-D and ESR levels in both groups were reduced 12 months posttreatment, with a more evident decrease in the intravenous CYC group. Intravenous CYC had lower total adverse reaction incidence., Conclusion: Compared with oral CYC, intravenous CYC decreases Warrick score and increases FVC and 6MWT at 6 months posttreatment, and reduces SP-A, SP-D, and ESR levels after 12 months of treatment, which shows low CYC cumulative dose and adverse reaction incidence in treating CTD-ILD., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)