[17-year study on the curative effect of treatment to prevent the recurrence of hepatitis B in different risk groups after liver transplantation].

Objective: To observe the recurrence condition of hepatitis B in different risk groups after liver transplantation in an attempt to provide useful information on whether to discontinue hepatitis B immunoglobulin (HBIG) in the future at an early stage. Methods: The patient population was divided into high, low-risk, and special groups [especially primary hepatocellular carcinoma (HCC)] according to the guidelines for the prevention and treatment of hepatitis B recurrence after liver transplantation. The recurrence condition and risk factors in this population were observed for hepatitis B. Measurement data were analyzed using a t-test and a rank-sum test. Count data were compared using a χ(2) test between groups. Results: This study finally included 532 hepatitis B-related liver transplant cases. A total of 35 cases had HBV recurrence after liver transplantation, including 34 cases that were HBsAg positive, one case that was HBsAg negative, and 10 cases that were hepatitis B virus (HBV) DNA positive. The overall HBV recurrence rate was 6.6%. The recurrence rate of HBV was 9.2% and 4.8% in the high- and low-risk HBV DNA positive and negative groups before surgery (P = 0.057). Among the 293 cases diagnosed with HCC before liver transplantation, 30 had hepatitis B recurrence after surgery, with a recurrence rate of 10.2%. The independent related factors for the recurrence of hepatitis B in patients with HCC after liver transplantation were HCC recurrence (HR =181.92, 95%CI 15.99~2 069.96, P < 0.001), a high postoperative dose of mycophenolate mofetil dispersible tablets (MMF) ( HR =5.190, 95%CI 1.289~20.889, P = 0.020), and a high dosage of HBIG (HR = 1.012, 95%CI 1.001~1.023, P = 0.035). Among the 239 cases who were non-HCC before liver transplantation, five cases (recurrence rate of 2.1%) arouse postoperative hepatitis B recurrence. Lamivudine was used in all cases, combined with on-demand HBIG prophylaxis after surgery. There was no hepatitis B recurrence in non-HCC patients who treated with entecavir combined with HBIG after surgery. Conclusion: High-barrier-to-resistance nucleotide analogues combined with long-term HBIG have a good effect on preventing the recurrence of hepatitis B after liver transplantation. The discontinuation of HBIG may be considered at an early stage after administration of a high-barrier-to-resistance nucleotide analogue in low-risk patients. Domestically, the HBV infection rate is high, so further research is still required to explore the timing of HBIG discontinuation for high-risk patients, especially those with HCC.

Facilitated subcutaneous immunoglobulin treatment patterns in pediatric patients with primary immunodeficiency diseases.

Aim: This retrospective study investigated real-world hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) treatment patterns in pediatric patients with primary immunodeficiency diseases (PIDs) in Poland. Methods: Clinical and demographic information, fSCIG treatment parameters and clinical outcomes were extracted from medical records of 28 participants (aged ≤18 years) with PIDs who received fSCIG. Results: 18 participants (64.3%) started fSCIG with a ramp-up (median duration: 35.5 days). 27 patients (96.4%) were administered fSCIG every 4 weeks and one patient every 3 weeks. 25 patients (89.3%) used one infusion site. No serious bacterial infections occurred. Conclusion: Data support the feasibility of administering fSCIG to children and adolescents with PIDs every 3-4 weeks using a single infusion site and indicate flexibility in modifying fSCIG infusion parameters. Clinical Trial Registration: NCT04636502 (ClinicalTrials.gov).

Antibodies, also known as immunoglobulins, are proteins that are made by the immune system to help fight infections. In primary immunodeficiency diseases (PIDs), part of the immune system may be missing or not working properly. This study looked at the use of an antibody treatment called hyaluronidase-facilitated subcutaneous immunoglobulin (or fSCIG) in Polish children aged 18 years or younger with PIDs. Information on patients, their disease, how fSCIG was being used and how patients responded to treatment was taken from medical records. Out of 28 patients, 18/28 (64.3%) had their fSCIG dose slowly increased, which took an average of 35.5 days. Overall, 27/28 patients were treated with fSCIG every 4 weeks (96.4%), and 25/28 patients used one place to inject fSCIG (89.3%). No serious infections caused by bacteria happened during the study. The study results suggest that children with PIDs could be treated every 3 to 4 weeks with fSCIG, and that flexibility in how fSCIG is injected may offer options suited to individual patients.

Efficacy evaluation of anti-DEC-IgY against antibiotic-resistant diarrhoeagenic Escherichia coli.

Introduction. The rise of multi-drug-resistant bacteria poses a global threat. In 2017, the World Health Organization identified 12 antibiotic-resistant 'priority pathogens', including Enterobacteriaceae, highlighting the menace of Gram-negative bacteria. Diarrhoeagenic Escherichia coli (DEC)-induced diarrhoea is particularly problematic for travellers and infants. In contrast to other antibiotic alternatives, passive immunotherapy is showing promise by providing immediate and precise protection. However, mammalian-sourced antibodies are costly, hindering large-scale production. Egg-laying chicken-derived IgY antibodies present a cost-effective, high-yield solution, revolutionizing antibody-based therapeutics compared to mammalian IgG.Hypothesis/Gap Statement. This study hypothesized that developing anti-DEC-IgY could combat DEC infections effectively.Aim. The primary aim was to develop anti-DEC-IgY and assess its potential in DEC-induced diarrhoeal management.Method. Chickens were immunized with DEC antigens to induce an immune response. IgY antibodies were extracted from immune eggs and purified using ion-exchange column chromatography. Anti-DEC-IgY's ability to inhibit DEC growth was evaluated through growth inhibition assays. Anti-DEC-IgY's capacity to prevent E. coli adhesion was assessed using mice intestinal mucosa. In vivo experiments measured pathogen colonization reduction and infection severity reduction. P values were calculated to confirm statistical significance.Result. The antibacterial efficacy of anti-DEC-IgY by growth inhibition assay demonstrated that 25 mg ml-1 of IgY could inhibit the DEC growth. The anti-adherence-property was tested using mice intestinal mucosa and found that anti-DEC-IgY could prevent the E. coli adhesion. In vivo results suggest that 12 mg ml-1 of IgY will reduce the pathogen colonization in intestine and reduce the severity of the infection. The P values between the experimental groups confirm the statistical significance of the findings.Conclusion. The study findings suggest that IgY-based passive immunotherapy could be a potential strategy for managing the risks associated with antibiotic-resistant bacterial infections. Additionally, this study paves the way for the development of IgY-related research and applications in India.

Use of Health Technology Assessment for the Continued Funding of Health Technologies: The Case of Immunoglobulins for the Management of Multifocal Motor Neuropathy.

INTRODUCTION: Funding decisions for many health technologies occur without undergoing health technology assessment (HTA), in particular, without assessment of cost effectiveness (CE). Immunoglobulins in Australia are an interesting case study because they have been used for a long time for various rare disorders and their price is publicly available. Undertaking an HTA enables us to assess CE for an intervention for which there is limited clinical and economic evidence. This study presents a post-market review to assess the CE of immunoglobulins for the treatment of multifocal motor neuropathy (MMN) compared with best supportive care. METHODS: A Markov model was used to estimate costs and quality-adjusted life-years (QALYs). Input sources included randomised controlled trials, single-arm studies, the Australian clinical criteria for MMN, clinical guidelines, previous Medical Services Advisory Committee (MSAC) reports and inputs from clinical experts. Sensitivity analyses were conducted to assess the uncertainty and robustness of the CE results. RESULTS: The cost per patient of treating MMN with immunoglobulin was AU$275,853 versus AU$26,191when no treatment was provided, with accrued QALYs of 6.83 versus 6.04, respectively. The latter translated into a high incremental cost-effectiveness ratio (ICER) of AU$317,552/QALY. The ICER was most sensitive to the utility weights and the price of immunoglobulins. MSAC advised to continue funding of immunoglobulins on the grounds of efficacy, despite the high and uncertain ICER. CONCLUSIONS: Beyond the ICER framework, other factors were acknowledged, including the high clinical need in a patient population for which there are no other active treatments available. This case study highlights the challenges of conducting HTA for already funded interventions, and the efficiency trade-offs required to fund effective high-cost therapies in rare conditions.

Benefits of Immunoglobulin (Ig) Replacement Therapy for Primary and Secondary Immunodeficiency in Chronic Rhinosinusitis.

This is the first study to examine chronic rhinosinusitis (CRS) outcomes after starting immunoglobulin (Ig) replacement therapy for patients with primary (PID) and secondary immunodeficiency (SID). This is a retrospective review of patients diagnosed with CRS from 2018 to 2022 prior to initiating Ig therapy for the treatment of PID or SID. Outcomes included medication use and Sinonasal Outcome Test (SNOT-22) scores. Ten patients met the inclusion criteria. PID and SID patients had a decrease in antibiotics (PID: 9.40 to 3.20, P = .05, SID: 8.20 to 2.00, P = .04) and steroids (PID: (5.40 to 0.60; P = .06; SID: 2.20 to 0.20, P = .047) prescribed in the year after Ig compared to the year prior. Patients with SID had a decrease in mean SNOT-22 scores by 12 months after Ig (47.50 to 20.50, P = 0.03). Patients receiving Ig for PID and SID showed decreased medication use and SID patients experienced subjective improvement in CRS symptoms in year-over-year comparison.

The role of HBIG in real life for patients undergoing liver transplantation due to HDV-related cirrhosis.

Recommended post-liver transplant (LT) prophylaxis in patients with hepatitis delta includes a nucleos(t)ide analogue (NA) and anti-hepatitis B immunoglobulin (HBIG) indefinitely. We analysed the use of HBIG in real-life clinical practice and its impact on HBV/HDV recurrence in 174 HDV-related LT patients from 10 Spanish liver transplant centres (1988-2018). Median post-LT follow-up was 7.8 (2.3-15.1) years and patient survival at 5 years was 90%. Most patients (97%) received HBIG in the immediate post-LT, but only 42% were on HBIG at the last control. Among those discontinuing HBIG, the median time on treatment was 18 (7-52) months. Post-LT HBsAg+ was detected in 16 (9%) patients and HBV-DNA in 12 (7%). Despite HBsAg positivity, HDV recurrence was reported only in three patients (1.7%), all of whom were not receiving NA and had discontinued HBIG. Our data suggest that a finite HBIG prophylaxis in HDV-LT is feasible, especially if high-barrier NAs are used.

Immune checkpoint inhibitors as potential therapy for reverting T-cell exhaustion and reverting HIV latency in people living with HIV.

The immune system of people living with HIV (PLWH) is persistently exposed to antigens leading to systemic inflammation despite combination antiretroviral treatment (cART). This inflammatory milieu promotes T-cell activation and exhaustion. Furthermore, it produces diminished effector functions including loss of cytokine production, cytotoxicity, and proliferation, leading to disease progression. Exhausted T cells show overexpression of immune checkpoint molecules (ICs) on the cell surface, including programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT), and lymphocyte activation gene-3 (LAG-3). The ICs also play a crucial role in T-cell exhaustion by reducing the immune response to cancer antigens. Immunotherapy based on immune checkpoint inhibitors (ICIs) has changed the management of a diversity of cancers. Additionally, the interest in exploring this approach in the setting of HIV infection has increased, including AIDS-defining cancers and non-AIDS-defining cancers in PLWH. To date, research on this topic suggests that ICI-based therapies in PLWH could be a safe and effective approach. In this review, we provide an overview of the current literature on the potential role of ICI-based immunotherapy not only in cancer remission in PLWH but also as a therapeutic intervention to restore immune response against HIV, revert HIV latency, and attain a functional cure for HIV infection.

Aptamer-Assisted Blockade of the Immune Suppressor Sialic Acid-Binding Immunoglobulin-Like Lectin-15 for Cancer Immunotherapy.

The percentage of low response and adaptive resistance to current antibody-based immune checkpoint blockade (ICB) therapy requires the development of novel immunotherapy strategies. Here, we developed an aptamer-assisted immune checkpoint blockade (Ap-ICB) against sialic acid-binding immunoglobulin-like lectin-15 (Siglec-15), a novel immune suppressor broadly upregulated on cancer cells and tumor infiltrating myeloid cells, which is mutually exclusive of programmed cell death ligand 1 (PD-L1). Using protein aptamer selection, we identified WXY3 aptamer with high affinity against Siglec-15 protein/Siglec-15 positive cells. We demonstrated that WXY3 aptamer rescued antigen-specific T cell responses in vitro and in vivo. Importantly, the WXY3 Ap-ICB against Siglec-15 amplified anti-tumor immunity in the tumor microenvironment and inhibited tumor growth/metastasis in syngeneic mouse model, which may result from enhanced macrophage and T cell functionality. In addition, by using aptamer-based spherical nucleic acids, we developed a synergetic ICB strategy of multivalent binding and steric hindrance, which further improves the in vivo anti-tumor effect. Taken together, our results support Ap-ICB targeted Siglec-15 as a potential strategy for normalization cancer immunotherapy.

Case of human rabies despite post-exposure prophylaxis (PEP) and complete recovery after intrathecal rabies immunoglobulin (RIG).

Rabies, a fatal viral zoonotic disease, has become a public health concern in Sarawak, Malaysia. Despite pre-exposure and post-exposure prophylaxis being available, there has been limited progress in developing treatments for rabies, emphasising the pressing need for productive solutions. We present a laboratory-confirmed human rabies case in which the patient survived without neurological sequelae after receiving intrathecal rabies immunoglobulin.

Comparison of SARS-CoV-2 Hyperimmune Immunoglobulins Following Infection Plus Vaccination vs Infection.

This cross-sectional study compares the neutralizing titers of convalescent plasma and hyperimmune anti­SARS-CoV-2 intravenous immunoglobulins against circulating Omicron subvariants.

Standardized Tapering off Subcutaneous Immunoglobulin in Chronic Inflammatory Demyelinating Polyneuropathy.

BACKGROUND: Attempting discontinuation of treatment in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) is recommended. However, there is no evidence based regimen for tapering off subcutaneous immunoglobulin (SCIG). This trial investigated stepwise tapering off SCIG to detect remission and the lowest effective dosage. During tapering off, frequent vs less frequent clinical evaluation was compared. METHODS: Patients with CIDP receiving a stable SCIG dosage followed a standardized tapering off regimen: 90%, 75%, 50%, 25% and 0% of the initial dose every 12th week, pending no deterioration occurred. In case of relapse during tapering off, the lowest effective dose was identified. Treatment with SCIG was registered for two years after participation. Disability score and grip strength were primary parameters. Participants were randomized to clinical evaluation every 6th week (frequent) or 12th week (less frequent). RESULTS: Fifty-five patients were included of which thirty-five relapsed. Twenty patients (36%) were able to discontinue treatment without relapse. In relapsing patients, median dosage could be reduced by 10% (range, 0-75). After two years, 18 of 20 patients were still in remission without treatment. Frequent clinical evaluation did not detect deterioration more frequently than less frequent evaluation; RR 0.5 (95% CI, 0.2-1.2) (p = 0.17). CONCLUSION: In stable CIDP patients, SCIG could be completely tapered off in 36% of the patients and only in 10% of these patients relapse occurred during the following two years. More frequent evaluation was not superior to detect deterioration.

Hyperimmune Globulins for the Management of Infectious Diseases.

This review is focused on the use of hyperimmune globulin therapy to treat some infectious diseases of viral or bacterial origin. Despite the introduction of antibiotics and vaccines, plasma immunoglobulin therapy from whole blood donation can still play a key role. These treatments provide passive transfer of high-titer antibodies that either reduces the risk or the severity of the infection and offer immediate but short-term protection against specific diseases. Antibody preparations derived from immunized human donors are commonly used for the prophylaxis and treatment of rabies, hepatitis A and B viruses, varicella-zoster virus, and pneumonia caused by respiratory syncytial virus, Clostridium tetani, Clostridium botulinum. The use of hyperimmune globulin therapy is a promising challenge, especially for the treatment of emerging viral infections for which there are no specific therapies or licensed vaccines.

Immunoglobulin Replacement Therapy During COVID-19 Pandemic: Practical and Psychological Impact in Patients with Antibody Deficiency.

PURPOSE: The COVID-19 pandemic has impacted on how health services deliver care and the mental health of the population. Due to their clinical vulnerability, to reduce in-hospital attendances during the COVID-19 pandemic, modifications in immunoglobulin treatment regimens were made for patients with antibody deficiency. These patients were also likely to experience social isolation due to shielding measure that were advised. We aimed to investigate the impact of modifying immunoglobulin treatment regimen on infection and mental health burden during shielding restrictions. METHOD: Patients on immunoglobulin replacement therapy (IGRT) responded to a standardised questionnaire examining self-reported infection frequency, anxiety (GAD-7), depression (PHQ-8), fatigue (FACIT), and quality of life during the pandemic. Infection frequency and immunoglobulin trough levels were compared to pre-pandemic levels. RESULTS: Patients who did not change treatment modality or those who received immunoglobulin replacement at home during the pandemic reported fewer infections. In patients who received less frequent hospital infusions, there was no significant increase in infections whilst immunoglobulin trough levels remained stable. There was no significant difference in anxiety, or depression scores between the treatment modality groups. Patients reported higher fatigue scores compared to the pre-COVID general population and in those discharged following hospitalisation for COVID. CONCLUSION: Changing immunoglobulin treatment regimen did not negatively impact infection rates or psychological wellbeing. However, psychological welfare should be prioritised for this group particularly given uncertainties around COVID-19 vaccination responsiveness and continued social isolation for many.

The Role of Antiviral Prophylaxis in Preventing HBV and HDV Recurrence in the Setting of Liver Transplantation.

Hepatitis B virus (HBV) is a prevalent underlying disease, leading to liver transplantation (LT) for both decompensated cirrhosis and hepatocellular carcinoma (HCC). The hepatitis delta virus (HDV) affects approximately 5-10% of HBsAg carriers, accelerating the progression of liver injury and HCC. The initial introduction of HBV immunoglobulins (HBIG), and then of nucleos(t)ide analogues (NUCs), considerably improved the survival of HBV/HDV patients post-transplantation, as they helped prevent re-infection of the graft and recurrence of liver disease. Combination therapy with HBIG and NUCs is the primary post-transplant prophylaxis strategy in patients transplanted for HBV- and HDV-related liver disease. However, monotherapy with high-barrier NUCs, such as entecavir and tenofovir, is safe and also effective in some individuals who are at low risk of HBV reactivation. To address the problems of organ shortage, last-generation NUCs have facilitated the use of anti-HBc and HBsAg-positive grafts to meet the ever-increasing demand for grafts.

Rabies postexposure prophylaxis: What the U.S. emergency medicine provider needs to know.

Approximately 55,000 patients per year in the United States are exposed to potentially rabid animals and receive rabies postexposure prophylaxis (PEP) and these patients commonly present to the emergency department (ED) for wound care and PEP. Despite the number of rabies exposures seen in EDs each year, there appears to be a knowledge gap among health care providers with regard to prescribing and administering rabies PEP. The following review aims to bridge that knowledge gap by discussing the importance of obtaining a comprehensive exposure history to determine the category of the encounter, the type of animal, and the location of the bite and of consulting outside expert resources to determine whether the rabies PEP series is indicated. In addition, this article will discuss dosing, administration, and schedule of the rabies vaccine and human rabies immune globulin to ensure patients are fully protected from developing rabies. Lastly, this article discusses the potential cost associated with rabies PEP and provides information on managing this barrier.

Amalgamation of nanotechnology with chicken IgY to enrich therapeutic and diagnostic applications: a systematic review.

Aim: The article explores the possibility of using nanoparticles and IgY technology together for biosensing and antibody delivery to fight mammalian infections. The use of IgG in passive immunotherapy has drawbacks; however, nanoparticles and IgY technology offer new opportunities for diagnostic and therapeutic applications. Methods: The primary selection of reports was based on the title and abstract, and potential studies were selected based on predefined inclusion criteria such as nanoparticle/nanomaterials and IgY, studies that have employed nanoparticles-IgY for diagnostic and therapeutic applications and animal experiments. Results: Nanoparticle-IgY conjugates have great potential in diagnostics and therapeutics, but translation of nanotechnology-based IgY technology from laboratory settings to clinical setup is still a challenge. As science advances, nanoimmunotherapy can be explored in modern-day medicine.

The human body makes proteins, called antibodies, that fight germs. Scientists use chickens and their eggs to make these proteins for treating diseases. If antibodies are used to treat diseases in the stomach, they can get damaged, but they can be protected with nanoparticles. They protect the proteins from degradation and deliver them safely to the target place. Thus, scientists use this combination to treat infections. The same combination also helps detect the germs.

Autoimmune glial fibrillary acidic protein astrocytopathy: clinical analysis and review of 15 cases.

BACKGROUND: To review clinical characteristics, auxiliary examination results, treatment effects, and outcomes of patients with autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). METHODS: We collated and retrospectively analyzed clinical data of 15 patients admitted with clinical characteristics of an autoimmune GFAP-A acute encephalitis or meningitis phenotype. RESULTS: All patients were diagnosed with acute-onset meningoencephalitis and meningoencephalomyelitis. Initial presentations included pyrexia and headache at onset; dual symptoms of prominent tremor with urinary and bowel dysfunction; ataxia, psychiatric and behavioral abnormalities, and impaired consciousness; neck resistance; reduced extremity muscle strength; blurred vision; epileptic seizures; and reduced basic blood pressure. Cerebrospinal fluid (CSF) examination showed that the degree of protein elevation was significantly higher than the degree of increase in white blood cells. Moreover, in the absence of obvious low chloride and glucose levels, CSF chloride levels decreased in 13 patients, accompanied by a CSF glucose level decrease in four. Brain abnormalities were found in magnetic resonance imaging of ten patients, with a linear radial perivascular enhancement present in the lateral ventricles of two patients and symmetric abnormalities in the splenium of the corpus callosum in three patients. CONCLUSIONS: Autoimmune GFAP-A may be a spectrum disorder, with acute- or subacute-onset meningitis, encephalitis, and myelitis being the main phenotypes. When used for acute stage treatment, combined hormone and immunoglobulin therapy was superior to hormone pulse therapy or immunoglobulin pulse therapy alone. However, hormone pulse therapy alone without immunoglobulin pulse therapy was associated with a greater number of remaining neurological deficits.

Successful clinical and virological outcomes of liver transplantation for HDV/HBV-related disease after long-term discontinuation of hepatitis B immunoglobulins.

BACKGROUND: Indefinite, long-term administration of hepatitis B immunoglobulins (HBIg), together with a third generation nucleos(t)ide analog (NA), is the currently recommended prophylactic strategy to prevent viral recurrence after liver transplantation (LT) for Hepatitis Delta virus (HDV)/Hepatitis B virus (HBV)-related disease. METHODS: We retrospectively analyzed the safety and long-term clinical and virological outcomes of a consecutive cohort of 16 patients (10 males, median age 64.5, range 41-75) transplanted for HDV/HBV-related cirrhosis at our Institution, who discontinued HBIg after a median of 24.5 months (range 15-116) after transplant. All patients continued prophylaxis with same NA used before LT. Recurrence of HDV/HBV infection was defined as reappearance of serum HDV-RNA with detectable serum HBsAg and/or HBV-DNA. RESULTS: The median follow-up after LT was 138 months (range 73-316) and 110 months (range 52-200) after HBIg withdrawal. All patients were HBsAg-positive, HBV-DNA negative, and anti-HDV positive at the time of LT and without coinfections with HCV or HIV. Patients were followed with biochemical and virological tests every 3-6 months after HBIg withdrawal. No recurrences of HDV/HBV infection or disease were observed during monoprophylaxis with NA. In addition, eight patients (50%) spontaneously developed anti-HBs titers above 10 IU/L at a median of 74 months (range 58-140) following HBIG discontinuation. CONCLUSIONS: HBIg withdrawal after LT is a safe and efficacious strategy in patients transplanted for HDV/HBV disease and is frequently associated with the spontaneous development of serological immunity against HBV. These data call for a revision of current prophylactic recommendations in this setting.