Portal vein thrombosis (PVT) is a rare complication following percutaneous liver biopsy, with an incidence below 0.4% in large multicenter series. We report a 51-year-old male with common variable immunodeficiency (CVID), chronic liver enzyme elevation, and preoperative imaging consistent with cirrhotic morphology, who developed acute abdominal pain within minutes of ultrasound-guided liver biopsy. Notably, biopsy demonstrated only mild steatosis with portal chronic inflammation and no significant fibrosis-a discordance from imaging attributed to CVID-associated nodular regenerative hyperplasia and biopsy sampling error. Contrast-enhanced CT on the day of the procedure showed heterogeneous left lobe enhancement consistent with a transient hepatic attenuation difference (THAD) secondary to focal portal venous obstruction, with a subsegmental filling defect in segment 3 on portal venous phase imaging. Repeat CT on postprocedure day 1 demonstrated thrombus extension into the left main portal vein; MRCP excluded biliary complications and hemobilia. The patient was treated with intravenous heparin transitioned to oral apixaban, with symptomatic improvement and normalization of liver function tests. A formal hypercoagulable evaluation was not performed given the provoked clinical context and normal INR, and no postdischarge imaging was available to assess recanalization; both are acknowledged as limitations. This case illustrates the convergence of multiple risk factors-abnormal hepatic vascular architecture from CVID-related liver disease, endothelial injury from needle passage, and potential hemostatic agent migration-in the pathogenesis of postbiopsy PVT, and underscores the importance of prompt vascular imaging and anticoagulation in patients presenting with acute abdominal pain following liver biopsy.

NFKB2 encodes the precursor p100 which undergoes processing to generate the mature NF-κB2 transcription factor subunit p52. Most of the known pathogenic NFKB2 variants render p100 un-processable and are typically linked to immunodeficiency disorders with antibody deficiency, susceptibility to infections and often autoimmunity. We describe a heterozygous germline NFKB2 missense variant (c.781C>T; R261W) associated with antibody deficiency and recurrent respiratory tract infections in a German family with incomplete penetrance. Patient-derived cells had reduced p52 levels, indicating protein insufficiency as the primary defect. Characterization of the R261W variant in vitro employing overexpression of EGFP-fused wildtype and mutant p100/p52 in HEK293T cells revealed restricted levels of mutant p100, suggesting unsustainable protein expression while maintenance of mutant p52 was almost precluded, confirming a detrimental protein defect. Enforced p100-processing driven by constitutively active NF-κB inducing kinase (NIK) caused subnuclear aggregation of mutant EGFP-p52 while DNA-binding activity was undetectable. Although ectopically over-expressed EGFP-p52-R261W also formed intra-nuclear aggregates - a previously established diagnostic indicator of protein-decaying NFKB1 mutations - its DNA-binding ability was not abolished. In summary, the single amino acid substitution R261W in the N-terminal Rel-homology domain of p100/p52 causes protein loss, particularly of the mature subunit p52. This genetic condition is associated with an inheritable form of hypogammaglobulinemia with mild clinical symptoms. We therefore recommend genetic screening for NFKB2 loss-of-expression variants in mildly affected patients with recurrent respiratory tract infections.

Dolutegravir-based regimens are part of the preferred regimens in all populations living with HIV, but dolutegravir's pharmacokinetics can vary greatly with factors such as drug-drug interactions (DDIs) and age. For example, DDIs between dolutegravir and rifamycins in countries with a high burden of HIV/tuberculosis co-infection present a major challenge. Attaining therapeutic concentrations is crucial for virologic success and to prevent resistance. Understanding dolutegravir pharmacokinetics and its sources of variability is essential to ensure adequate exposure in all individuals. Population pharmacokinetic (PopPK) modeling is a powerful tool for characterizing medication disposition. In this review, we aim to synthesize existing dolutegravir PopPK models, highlighting key pharmacokinetic parameters and covariate effects. A literature search was done on Medline and Embase databases from inception to November 18th, 2025. This review included 23 studies: 15 in adults, 4 in pediatrics, 2 in pregnancy (mothers and their newborn), and 2 in term neonates. Almost all models included allometric scaling, with body weight especially, on apparent clearance (CL/F) and/or apparent volume of distribution (Vd/F) parameters. When considering differences in body size, CL/F and Vd/F were similar across populations. The absorption rate constant (ka) was higher in adults and presented high variability across populations. Other common covariates in adults and pediatrics were co-medications and background antiretrovirals. Data and tested covariates were limited in pregnant women and neonates. Study simulations and predefined target values indicated adequate recommended dolutegravir doses. Further characterization of dolutegravir PopPK in populations at risk of altered concentrations (e.g., preterm neonates, pediatrics, pregnancy, obesity, and older adults) is crucial to better understand dolutegravir pharmacokinetics in these populations as data are still limited.

Background: Hereditary angioedema (HAE) is a rare, potentially life-threatening bradykinin-mediated disorder with limited pediatric treatment options and little comparative evidence. Icatibant, a bradykinin B2 receptor antagonist, has demonstrated efficacy in adults and has emerging evidence in children. Objective: To evaluate and synthesize clinical evidence on the efficacy and safety of icatibant for acute HAE attacks in pediatric patients. Methods: A literature search was performed by using medical literature data bases, clinical trial and research registries, and key journals through January 2026. The primary outcome was the time to onset of symptom relief. Secondary outcomes included the time to minimum symptoms, pain scores, adverse events, and feasibility of self- or caregiver administration. All included studies were nonrandomized, single-arm trials with heterogeneous designs and outcomes definitions; therefore, a meta-analysis was not performed, and all studies were descriptively evaluated. Results: This systematic review identified three clinical studies of icatibant for acute HAE attacks in children ages 0 to 17 years. Three open-label, phase III studies, which included 43 pediatric patients were reviewed. Icatibant demonstrated rapid symptom relief, with a median onset at ∼1 hour and minimum symptoms within 2 hours, although repeated dosing showed variability. Icatibant was well tolerated, with injection-site reactions as the most common adverse events and no serious treatment-related events. Self- or caregiver administration was feasible and effective in adolescents. Conclusion: Icatibant was safe and effective in the pediatric studies, providing rapid symptoms relief and a favorable tolerability profile. Despite limitations from small sample sizes and lack of comparator trials, current evidence supports icatibant as a targeted, practical option for treating acute HAE attacks in children.