Cyclosporine,prednisone,and high-dose immunoglobulin treatment of angioimmunoblastic T-cell lymphoma refractory to prior CHOP or CHOP-like regimen

Angioimmunoblastic T-cell lymphoma(AITL) is a rare,distinct subtype of peripheral T-cell lymphoma,possessing an aggressive course and poor prognosis with no standard therapy.Twelve patients who have failed at least two initial CHOP or CHOP-like regimens were enrolled in this study and treated with individualized cyclosporine(CsA),prednisone(PDN),and monthly,high-dose intravenous immunoglobulin(HDIVIG).The dose of CsA was adjusted individually based on the blood trough concentration of CsA and renal function.All patients were examined for response,toxicity and survival.The most significant toxicities(≥ grade 2) were infection(16.7%),renal insufficiency(8.3%),hypertension(8.3%),diabetes(8.3%) and insomnia(16.7%).Discontinuation of treatment occurred in one patient(8.3%) due to grade 3 renal toxicity and subsequent grade 4 pulmonary infection.Treatment-related death was not observed.The overall response rate was 75.0%(complete response,33.3%;partial response,41.7%).With a median follow-up of 25.5 months,the median duration of response was 20 months(range,12 to 49 months) and the median progression-free survival(PFS) was 25.5 months(range,10 to 56 months).The 2-year PFS rate was 81.5%.Our findings indicate the combination of CsA,PDN and HDIVIG is an effective salvage regimen for refractory or relapsed AITL with predictable and manageable toxicity.

Effects of high-dose glucose-insulin-potassium on acute coronary syndrome patients receiving reperfusion therapy:a meta-analysis

BACKGROUND:This meta-analysis aimed to assess the efficacy of high-dose glucose-insulinpotassium(GIK) therapy on clinical outcomes in acute coronary syndrome(ACS) patients receiving reperfusion therapy.METHODS:We searched the PubMed,Web of Science,MEDLINE,Embase,and Cochrane Library databases from inception to April 26,2022,for randomized controlled trials(RCTs) that compared high-dose GIK and placebos in ACS patients receiving reperfusion therapy.The primary endpoint was major adverse cardiovascular events(MACEs).RESULTS:Eleven RCTs with 884 patients were ultimately included.Compared with placebos,high-dose GIK markedly reduced MACEs(risk ratio [RR] 0.57,95% confidence interval [95% CI]:0.35 to 0.94,P=0.03) and the risk of heart failure(RR 0.48,95% CI:0.25 to 0.95,P=0.04) and improved the left ventricular ejection fraction(LVEF)(mean difference [MD] 2.12,95% CI:0.40 to 3.92,P=0.02) at 6 months.However,no difference was observed in all-cause mortality at 30 d or 1 year.Additionally,high-dose GIK was significantly associated with increased incidences of phlebitis(RR 4.78,95% CI:1.36 to 16.76,P=0.01),hyperglycemia(RR 9.06,95% CI:1.74 to 47.29,P=0.009) and hypoglycemia(RR 6.50,95% CI:1.28 to 33.01,P=0.02) but not reinfarction,hyperkalemia or secondary reperfusion.In terms of oxidative stress-lowering function,high-dose GIK markedly reduced superoxide dismutase(SOD) activity but not glutathione peroxidase(GSH-Px) or catalase(CAT) activity.CONCLUSION:Patients with ACS receiving reperfusion therapy exhibited a reduction in MACEs and good oxidative stress-lowering eflcacy in response to high-dose GIK.Moreover,with a higher incidence of complications such as phlebitis,hyperglycemia,and hypoglycemia.Furthermore,there were no observed survival benefits associated with high-dose GIK.More trials with long-term follow-up are still needed.

Intravenous immunoglobulin accompanied with high-dose methylprednisolone therapy for 17 children with anti-N-methyl-D-aspartate receptor encephalitis:Clinic and nursing

Objective:An increasing number of pediatric patients are being diagnosed with anti-N-methyl-Daspartate receptor(NMDAR)encephalitis,whose treatment requires immunotherapy through nursing interventions.This study aimed to analyze the clinical features and long-term prognosis of pediatric anti-NMDAR encephalitis and to gather nursing experiences of immunotherapy.Methods:Seventeen children diagnosed with anti-NMDAR encephalitis were admitted to the pediatric department.They were subjected to a therapy of intravenous immunoglobulin(IVIG)accompanied with high-dose methylprednisolone(HDMP).Multidisciplinary cooperation and intensive care were used to manage them.The effects of nursing intervention and therapy were repeatedly assessed and analyzed throughout the course of treatment and recovery.Results:None of the patients manifested adverse drug reaction(ADR)during IVIG administration.At the first administration of HDMP,ADRs were promptly and efficiently treated in four patients(24%;i.e.,one case each of hyperglycosemia,hypertension,aggravated symptoms,and gastrointestinal bleed).Two patients underwent rehabilitation,and six patients received hyperbaric oxygenation during hospitalization.Nine patients with indwelling gastric tubes experienced four times of unplanned extubation.Hospital stay ranged from 11 days to 59 days,with the mean duration of 26 days.Discharge evaluation revealed that 16 patients who scored 0e2 on the modified Rankin scale presented obvious remission,and one patient who had a mRS score of 4 exhibited less improvement.The mRS scores of hospitalization,discharge,and six-month follow-up displayed statistically significant differences.Conclusions:Nursing interventions of immunotherapy ensures the security of IVIG administration.Multidisciplinary cooperation promotes remission.Our findings can serve as reference for healthcare teams.

Clinical value of high-dose VitC + immunoglobulin for the treatment of viral myocarditis in children

Objective: To study the clinical value of high-dose VitC + immunoglobulin for the treatment of viral myocarditis in children. Methods: Children who were diagnosed with viral myocarditis in the hospital between May 2014 and March 2017 were selected as the research subjects and divided into two groups by random number table, observation group received high-dose VitC+ immunoglobulin combined with conventional symptomatic and supportive treatment and control group received conventional symptomatic and supportive treatment. The serum levels of myocardial injury indexes, myocardial remodeling indexes and inflammatory response indexes were measured before treatment as well as at 1 week and 2 weeks after treatment. Results: 1 week and 2 weeks after treatment, serum CK-MB, cTnI, MDA, BNP, PINP, ICTP, MMP2, MMP9, TGFβ1, TNF-α, ICAM-1, MIP-1α and IL-17 levels of both groups of patients were significantly lower than those before treatment, and serum CK-MB, cTnI, MDA, BNP, PINP, ICTP, MMP2, MMP9, TGFβ1, TNF-α, ICAM-1, MIP-1α and IL-17 levels of observation group were lower than those of control group. Conclusion: High-dose VitC +immunoglobulin can reduce the myocardial damage and inhibit the myocardial remodeling and inflammatory response in children with viral myocarditis.

High-dose vs low-dose proton pump inhibitors for upper gastrointestinal bleeding:A meta-analysis

AIM:To evaluate the efficacy of high-dose proton pump inhibitors(PPIs)vs low-dose PPIs for patients with upper gastrointestinal bleeding.METHODS:PubMed,Embase,the Cochrane Library,and Web of Science were searched to identify relevant randomized controlled trials(RCTs).Eligible trials were RCTs that compared high-dose PPI with low-dose PPI following endoscopic hemostasis.The primary endpoint was rebleeding;secondary endpoints were patient numbers that needed surgery,and mortality.The meta-analysis was performed with a fixed effects model or random effects model.RESULTS:Nine eligible RCTs including 1342 patients were retrieved.The results showed that high-dose intravenous PPI was not superior to low-dose intra-venous PPI in reducing rebleeding[odds ratio(OR)= 1.091,95%confidential interval(CI):0.777-1.532],need for surgery(OR=1.522,95%CI:0.643-3.605) and mortality(OR=1.022,95%CI:0.476-2.196).Subgroup analysis according to different region revealed no difference in rebleeding rate between Asian patients(OR=0.831,95%CI,0.467-1.480)and European patients(OR=1.263,95%CI:0.827-1.929).CONCLUSION:Low-dose intravenous PPI can achieve the same efficacy as high-dose PPI following endoscopic hemostasis.

Predictors of post-treatment stenosis in cervical esophageal cancer undergoing high-dose radiotherapy

AIM To evaluate toxicity and treatment outcome of highdose radiotherapy(RT) for cervical esophageal cancer(CEC).METHODS We reviewed a total of 62 consecutive patients who received definitive RT for stage Ⅰ to Ⅲ cervical esophageal cancer between 2001 and 2015. Patients who received < 45 Gy, treated for lesions below sternal notch, treated with palliative aim, treated with subsequent surgical resection, or diagnosed with synchronous hypopharyngeal cancer were excluded. Treatment failures were divided into local(occurring within the RT field), outfield-esophageal, and regional [occurring in regional lymph node(s)] failures. Factors predictive of esophageal stenosis requiring endoscopic dilation were analyzed.RESULTS Grade 1, 2, and 3 esophagitis occurred in 19(30.6%), 39(62.9%), and 4 patients(6.5%), respectively, without grade ≥ 4 toxicities. Sixteen patients(25.8%) developed post-RT stenosis, of which 7 cases(43.8%) were malignant. Four patients(6.5%) developed tracheoesophageal fistula(TEF), of which 3(75%) cases were malignant. Factors significantly correlated with post-RT stenosis were stage T3/4(P = 0.001), complete circumference involvement(P < 0.0001), stenosis at diagnosis(P = 0.024), and endoscopic complete response(P = 0.017) in univariate analysis, while complete circumference involvement was significant in multivariate analysis(P = 0.003). A higher dose(≥ 60 Gy) was not associated with occurrence of postRT stenosis or TEF. With a median follow-up of 24.3(range, 3.4-152) mo, the 2 y local control, outfield esophageal control, progression-free survival, and overall survival(OS) rates were 78.9%, 90.2%, 49.6%, and 57.3%, respectively. Factors significantly correlated with OS were complete circumference involvement(P = 0.023), stenosis at diagnosis(P < 0.0001), and occurrence of post-RT stenosis or TEF(P < 0.001) in univariate analysis, while stenosis at diagnosis(P = 0.004) and occurrence of post-RT stenosis or TEF(P = 0.023) were significant in multivariate analysis. CONCLUSION Chemoradiation for CEC was well tolerated, and a higher dose was not associated with stenosis. Patients with complete circumferential involvement require close follow-up.

High-dose interferon-α2b induction therapy in combination with ribavirin for treatment of chronic hepatitis C in patients with non-response or relapse after interferon-a monotherapy

AIM： To evaluate the daily high-dose induction therapy with interferon-α2b （IFN-α2b） in combination with ribavirin for the treatment of patients who failed with interferon monotherapy and had a relapse, based on the assumption that the viral burden would decline faster, thus increasing the likelihood of higher response rates in this difficult-totreat patient group. METHODS： Seventy patients were enrolled in this study. Treatment was started with 10 NU IFN-α2b daily for 3 wk, followed by IFN-α2b 5 NU/TIW in combination with ribavirin （1 000-1 200 mg/d） for 21 wk. In case of a negative HCV RNA PCR, treatment was continued until wk 48 （IFN-α2b 3MU/TIW＋1000-1200 mg ribavirin/daily）. RESULTS： The dose of IFN-α2b or ribavirin was reduced in 16% of patients because of hematologic side effects, and treatment was discontinued in 7% of patients. An early viral response （EVR） was achieved in 60% of patients. Fifty percent of all patients achieved an end-oftreatment response （EOT） and d0% obtained a sustained viral response （SVR）. Patients with no response had a significantly lower response rate than those with a former relapse （SVR 30% vs 53%; P=0.049）. Furthermore, lower response rates were observed in patients infected with genotype la/b than in patients with non-1-genotype （SVR 28% vs7d%; P=0.001）. As a significant predictive factor for a sustained response, a rapid initial decline of HCV RNA could be identified. No patient achieving a negative HCV-RNA PCR at wk 18 or later eventually eliminated the virus. CONCLUSION： Daily high-dose induction therapy with interferon-α2b is well tolerated and effective for the treatment of non-responders and relapsers, when interferon monotherapy fails. A fast decline of viral load during the first 12 wk is strongly associated with a sustained viral response.

Dose-individualization Efficiently Maintains Sufficient Exposure to Methotrexate without Additional Toxicity in High-dose Methotrexate Regimens for Pediatric Acute Lymphoblastic Leukemia

Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities.Methods:We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol(clinical trial number:ChiCTR-IPR-14005706)and analyzed the data of actual MTX dosage,MTX concentration,toxicity,and prognosis.We compared data between the dose-adjustment Program 1(fixed 20%reduction in dose)and the dose-adjustment Program 2(dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h),which were applied if the MTX clearance was delayed in the previous cycle.Results:The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1(P<0.001).No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2(P<0.001).No significant correlations were observed between the MTX dose,dose-adjustment programs,or MTX concentrations and relapse-free survival.Conclusion:Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.

The Experience of Pain and Anxiety in Cervical Cancer Patients Undergoing Multiple Fraction High-Dose Rate Brachytherapy: A Prospective Observational Study

Purpose: To evaluate the anxiety and pain levels of cervical cancer patients undergoing intracavitary multifraction high-dose rate (HDR) brachytherapy, as part of a process to develop guidelines for quality patient-centered care. Methods: Cervical cancer patients (n = 31) undergoingmultiple fraction HDR brachytherapy treatment at the National Institute of Oncology in Rabat (Morocco) completed ratings of pain and anxiety intensity using 11-point verbal analog scales, at 6 key time points over 2 brachytherapy insertion procedures and 4 brachytherapy fractions. Women were evaluated for psychological status at baseline before starting the brachytherapy process using the Hospital Anxiety and Depression Scale (HADS). Scores were grouped as follows: 0 - 7 = normal, 8 - 10 = borderline, 11 - 21 = abnormal. Factors that could affect anxiety levels such as education level, relationship status, number of pregnancies and prior surgical history were documented. Results: Between July and August 2020, 31 women with a median age of 49.6 years were evaluated (range: 27 - 70). The HADS score identified depression in 5 patients (16.1%) and anxiety in 12 patients (38.7%). Throughout both treatment procedures, anticipatory anxiety was reported, with a maximum intensity in the operating room during spinal anesthesia (3.23 ± 1.7) and during applicator insertion (2.97 ± 2.4). Moderate-to-severe anxiety scores were reported in 25.8% and 22.6% of patients respectively. Level of education showed a significant correlation with anxiety scores (p = 0.027). Pain increased significantly during the procedure (p ± 1.4) and applicator removal (4.74 ± 1.5) turned out to be the most painful parts of the procedure. No correlation was found between pain and anxiety levels. Conclusion: Intracavitary multifraction high-dose rate brachytherapy is associated with mild to moderate levels of pain and anxiety, although a subset of patients reported more severe symptoms and may require additional medical and psychological support, with particular emphasis on bed-rest duration and applicator removal. The development of effective interventions (both pharmacological and non-pharmacological) is needed to improve women’s experiences of brachytherapy for locally advanced cervical cancer.

Very-high-dose olanzapine for treatment-resistant schizophrenia

Treatment-resistant schizophrenia has an extremely negative impact on mental health and social life. If clozapine, the gold standard treatment, fails, there are very few options left. The literature suggests that high-dose olanzapine (20 - 60 mg/day) is a possible alternative. We report two cases in which very high doses of olanzapine were administered, with significant clinical improvements above 60 mg/day. Clinical, metabolic and cardiac tolerance was good. This report highlights the usefulness of very-high-dose olanzapine in treatment-resistant schizophrenia. The main hypotheses concerning the psychopharmacological mechanisms of very-high-dose olanzapine are discussed.

Comparison of High-Dose Dexamethasone and Prednisone for Initial Treatment of Adult Primary Immune Thrombocytopenia

Prednisone is the most common first-line treatment for adult primary immune thrombocytopenia (ITP). However, the best initial therapeutic approach is still a matter of debate. Prior studies have shown that high-dose dexamethasone (HD-DXM) produces a high sustained efficacy not achieved by conventional prednisone therapy. However, the definition of response widely differs between individual reports, and this heterogeneity makes comparison of the efficacy difficult. The aim of our study was to compare the therapeutic outcomes of a conventional dose of prednisone with HD-DXM for adult ITP patients as initial therapy. Thirty patients treated with prednisone and 22 patients treated HD-DXM were retrospectively analyzed. No significant differences between the HD-DXM and prednisone groups were observed for the rates of complete response (68% vs. 70%) and response (18% vs. 17%). However, 1 year probability of sustained response was significantly greater in the HD-DXM group than in the prednisone group (78% vs. 38%;P = 0.008). No adverse events necessitating discontinuation of treatment were observed in either group. Our retrospective analysis showed that initial treatment with HD-DXM produced longer response duration compared to a conventional dose of prednisone. Randomized clinical trials are warranted to establish the optimal initial steroid therapy for adult ITP.

A New Variant of Combined Pulmonary Fibrosis and Emphysema from Long-Term High-Dose of Glucocorticoid Therapy: A Case Report

Recent studies have described the combination of both pulmonary emphysema and idiopathic interstitial lung disease (ILDs) by means of high-resolution computed axial tomography (HRCT). Definition of this syndrome was first named by Cottin as combined pulmonary fibrosis and emphysema (CPFE). Functional and radiological findings have showed that these patients are suffering from severe breathlessness, but whose pulmonary functional tests revealed no signs of obstruction, normal static lung volumes, and depressed DLco, most with a history of smoking [1] [2]. The radiological and endoscopic studies especially show that these patients have both areas of upper-lobe predominant emphysema and lesions compatible with fibrosis in both lung bases [3]. No prior research has reported any cases of such condition in person with no prior history of smoking as well as long-term high-dose of glucocorticoid therapy. In this case report, we discuss the presentation, diagnosis, and management of a 53-year-old non-smoker with increasing shortness of breath with a long-term high-dose of glucocorticoid therapy discovered to have an abnormal variant or presentation of CPFE. The cause of disease was attributed to a certain history of smoking in most studies;other potential risk factors have yet to be properly analyzed. This clinical report features a special case about the problem and solution surrounding this issue.

Can serum immunoglobulin G4 levels and age serve as reliable predictors of relapse in autoimmune pancreatitis?

We are writing in response to the paper published in the World Journal of Gastroenterology by Zhou et al.The authors identified higher serum immunoglobulin(Ig)G4 levels and age over 55 years as independent risk factors for disease relapse.Despite notable strengths,it is crucial to address potential biases.Firstly,the cohort study included 189 patients with autoimmune pancreatitis(AIP)type 1(with higher IgG4 seropositivity and higher relapse)and 24 with type 2(with lower IgG4 seropositivity and lower relapse).Consequently,most,if not all,AIP type 2 patients were assigned to the normal group,possibly inflating the association of higher serum IgG4 levels with relapse and potentially exaggerating the association of older age with relapse.Secondly,the authors did not provide sufficient details regarding AIP diagnosis,such as the ratio of definitive vs probable cases and the proportion of biopsies.In cases where histological evidence is unavailable or indeterminate,AIP type 2 may be misdiagnosed as definitive type 1,and type 1 may also be misdiagnosed as probable type 2,particularly in cases with normal or mildly elevated serum IgG4 levels.Lastly,in this retrospective study,approximately one-third of the consecutive patients initially collected were excluded for various reasons.Accordingly,the impact of nonrandom exclusion on relapse outcomes should be carefully considered.In conclusion,the paper by Zhou et al offers plausible,though not entirely compelling,evidence suggesting a predictive role of elevated serum IgG4 levels and advanced age in AIP relapse.The foundation for future investigations lies in ensuring a reliable diagnosis and accurate disease subtyping,heavily dependent on obtaining histological specimens.In this regard,endoscopic ultrasound-guided fine-needle biopsy emerges as a pivotal component of the diagnostic process,contributing to mitigating biases in future explorations of the disease.

Immunoglobulin G4-related spinal pachymeningitis:A case report

BACKGROUND Immunoglobulin G4-related disease(IgG4-RD)is a complex immune-mediated condition that causes fibrotic inflammation in several organs.A significant clinical feature of IgG4-RD is hypertrophic pachymeningitis,which manifests as inflammation of the dura mater in intracranial or spinal regions.Although IgG4-RD can affect multiple areas,the spine is a relatively rare site compared to the more frequent involvement of intracranial structures.CASE SUMMARY A 70-year-old male presented to our hospital with a two-day history of fever,altered mental status,and generalized weakness.The initial brain magnetic resonance imaging(MRI)revealed multiple small infarcts across various cerebral regions.On the second day after admission,a physical examination revealed motor weakness in both lower extremities and diminished sensation in the right lower extremity.Electromyographic evaluation revealed findings consistent with acute motor sensory neuropathy.Despite initial management with intravenous immunoglobulin for presumed Guillain-Barrésyndrome,the patient exhibited progressive worsening of motor deficits.On the 45th day of hospitalization,an enhanced MRI of the entire spine,focusing specifically on the thoracic 9 to lumbar 1 vertebral level,raised the suspicion of IgG4-related spinal pachymeningitis.Subsequently,the patient was administered oral prednisolone and participated in a comprehensive rehabilitation program that included gait training and lower extremity strengthening exercises.CONCLUSION IgG4-related spinal pachymeningitis,diagnosed on MRI,was treated with corticosteroids and a structured rehabilitation regimen,leading to significant improvement.

Serum Immunoglobulin Concentrations in Juvenile Idiopathic Arthritis Cases during Active and Inactive Disease States

Background: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. Both the humoral and cell mediated immunities are involved in the pathogenesis of JIA. It is reported that overall immunoglobulin levels in JIA patients are significantly higher than their control during the active state of disease. Methodology: This prospective observational study was conducted over a period of 18 months All the newly diagnosed oligo-articular and poly-articular JIA patients having active disease were included by purposive sampling. Data were collected by a semi-structured predesigned questionnaire. Result: Most of the study subjects (57.6%) belonged to age group > 3 - 9 years. Oligo JIA was diagnosed in 66.7% and poly JIA in 33.3% of JIA children. The difference in mean (±SD) ESR (33.52 ± 21.29 and 15.09 ± 7.71 mm in 1st hour) at active and inactive states was highly significant. Mean (±SD) difference of IgG, IgM and IgA in active and inactive states of disease were highly significant. Conclusion: Higher and abnormal levels of immunoglobulin (IgG, IgM, and IgA) were present among JIA patients in active disease state which became normal during inactive disease state after treatment.

Immunoglobulin A glomerulonephropathy:A review

In this editorial,we comment on the article by Meng et al published in the World Journal of Clinical Cases.We comprehensively review immunoglobulin A nephro-pathy(IgAN),including epidemiology,clinical presentation,diagnosis,and management.IgAN,also known as Berger's disease,is the most frequent type of primary glomerulonephritis(GN)globally.It is mostly found among the Asian population.The presentation can be variable,from microscopic hematuria to a rapidly progressive GN.Around 50%of patients present with single or recurring episodes of gross hematuria.An upper respiratory infection and tonsillitis often precede these episodes.Around 30%of patients present microscopic hematuria with or without proteinuria,usually detected on routine examination.The diagnosis relies on having a renal biopsy for pathology and immunofluorescence microscopy.We focus on risk stratification and management of IgAN.We provide a review of all the landmark studies to date.According to the 2021 KDIGO(kidney disease:Improving Global Outcomes)guidelines,patients with non-variant form IgAN are first treated conservatively for three to six months.This approach consists of adequate blood pressure control,reduction of proteinuria with renin-angiotensin system blockade,treatment of dyslipidemia,and lifestyle modifications(weight loss,exercise,smoking cessation,and dietary sodium restrictions).Following three to six months of conservative therapy,patients are further classified as high or low risk for disease progression.High-risk patients have proteinuria≥1 g/d or<1 g/d with significant microscopic hematuria and active inflammation on kidney biopsy.Some experts consider proteinuria≥2 g/d to be very high risk.Patients with high and very high-risk profiles are treated with immunosuppressive therapy.A proteinuria level of<1 g/d and stable/im-proved renal function indicates a good treatment response for patients on immu-nosuppressive therapy.

STAT3-Dependent Effects of Polymeric Immunoglobulin Receptor in Regulating Interleukin-17 Signaling and Preventing Autoimmune Hepatitis

One-third of patients with autoimmune hepatitis(AIH)have cirrhosis at the time of diagnosis.The relevance of these variables,although unknown,is believed to be critical in AIH because of suspected interactions between the gut microbiome and genetic factors.Dysbiosis of the gut flora and elevated polymeric immunoglobulin receptor(pIgR)levels have been observed in both patients and mouse models.Moreover,there is a direct relationship between pIgR expression and transaminase levels in patients with AIH.In this study,we aimed to explore how pIgR influences the secretion of regenerating islet-derived 3 beta(Reg3b)and the flora composition in AIH using in vivo experiments involving patients with AIH and a concanavalin A-induced mouse model of AIH.Reg3b expression was reduced in pIgR gene(Pigr)-knockout mice compared to that in wild-type mice,leading to increased microbiota disruption.Conversely,exogenous pIgR supplementation increased Reg3b expression and maintained microbiota homeostasis.RNA sequencing revealed the participation of the interleukin(IL)-17 signaling pathway in the regulation of Reg3b through pIgR.Furthermore,the introduction of external pIgR could not restore the imbalance in gut microbiota in AIH,and the decrease in Reg3b expression was not apparent following the inhibition of signal transducer and activator of transcription 3(STAT3).In this study,pIgR facilitated the upregulation of Reg3b via the STAT3 pathway,which plays a crucial role in preserving the balance of the intestinal microbiota in AIH.Through this research,we discovered new molecular targets that can be used for the diagnosis and treatment of AIH.

Airway management of a patient with linear immunoglobulin A bullous dermatosis:A case report

BACKGROUND There is limited literature on managing the airway of patients with linear immunoglobulin A(IgA)bullous dermatosis,a rare mucocutaneous disorder that leads to the development of friable bullae.Careful clinical decision making is necessary when there is a risk of bleeding into the airway,and a multidisciplinary team approach may lead to decreased patient morbidity during these high-risk scenarios,especially when confronted with an unusual cause for bleeding.CASE SUMMARY A 45-year-old African American female presented to our ambulatory surgical center for right corneal transplantation due to corneal perforation after blunt trauma in the setting of cicatricial conjunctivitis and diffuse corneal neovascularization from linear IgA bullous dermatosis.The diagnosis of IgA dermatosis was recent,and the patient had been lost to follow-up.The severity of the disease and extent of airway involvement was unknown at the time of the surgery.Significant airway bleeding was noticed upon intubation and the otorhinolaryngology team had to be called to the operating room.The patient required transfer to the intensive care unit where a multidisciplinary team was involved in her case.The patient was extubated on postoperative day 4.CONCLUSION A multidisciplinary approach to treating this disease is the best course of action before a surgical procedure.In our case,key communication between the surgery,anesthesia,and dermatology teams led to the quick and safe treatment of our patient’s disease.Ambulatory surgery should not be considered for these cases unless they are in full remission and there is no mucous membrane involvement.

Impact of hepatitis B immunoglobulin mode of administration on treatment experiences of patients after liver transplantation: Results from an online survey

BACKGROUND Hepatitis B immunoglobulin(HBIG)in combination with a potent nucleos(t)ide analog is considered the standard of care for prophylaxis against hepatitis B virus(HBV)reinfection after liver transplantation for HBV-associated disease.AIM To evaluate patients’satisfaction,preferences,and requirements for subcutaneous(SC),intramuscular(IM),and intravenous(IV)HBIG treatments.METHODS A self-completion,cross-sectional,online,22-question survey was conducted to examine perceptions and satisfaction with current HBIG treatment in adults receiving HBIG treatment following liver transplantation for HBV-associated disease in France,Italy,and Turkey.Hypothetical HBIG products with different administration modes were evaluated using target product profile assessment and a conjoint(trade-off)exercise.RESULTS Ninety patients were enrolled;32%,17%,and 51%were SC,IM,and IV HBIG users,respectively.Mean duration of treatment was 36.2 months.SC HBIG had the least negative impact on emotional well-being and social life and was perceived as the most convenient,easiest to administer,least painful,and had the highest self-rating of treatment compliance.More IM HBIG users than SC or IV HBIG users reported that administration frequency was excessive(67%,28%,and 28%,respectively).In the target product profile assessment,76%of patients were likely to use hypothetical SC HBIG.In the conjoint exercise,administration route,frequency,and duration were key drivers of treatment preferences.CONCLUSION Ease,frequency,duration,and side effects of HBIG treatment administration were key drivers of treatment preferences,and SC HBIG appeared advantageous over IM and IV HBIG for administration ease,convenience,and pain.A hypothetical SC HBIG product elicited a favorable response.Patient demographics,personal preferences,and satisfaction with HBIG treatment modalities may influence long-term treatment compliance.

Exploring the impact of hepatitis B immunoglobulin and antiviral interventions to reduce vertical transmission of hepatitis B virus

Hepatitis B virus(HBV)infection is a major public health burden.In HBV endemic regions,high prevalence is also correlated with the infections acquired in infancy through perinatal transmission or early childhood exposure to HBV,the socalled mother-to-child transmission(MTCT).Children who are infected with HBV at a young age are at higher risk of developing chronic HBV infection than those infected as adults,which may lead to worse clinical outcome.To reduce the incidence of HBV MTCT,several interventions for the infants or the mothers,or both,are already carried out.This review explores the newest information and approaches available in literature regarding HBV MTCT prevalence and its challenges,especially in high HBV endemic countries.This covers HBV screening in pregnant women,prenatal intervention,infant immunoprophylaxis,and postvaccination serological testing for children.