Preexisting antibody assays for gene therapy: Considerations on patient selection cutoffs and companion diagnostic requirements.

Recombinant adeno-associated virus (AAV) vectors are the leading delivery vehicle used for gene therapies. Anti-AAV antibodies (AAV Abs) can interact with the viral capsid component of an AAV-based gene therapy (GT). Therefore, patients with preexisting AAV Abs (seropositive patients) are often excluded from GT trials to prevent treatment of patients who are unlikely to benefit or may have a higher risk for adverse events outweighing treatment benefits.

Membrane Proteome-Wide Screening of Autoantibodies in CIDP Using Human Cell Microarray Technology.

Background And Objectives: Autoantibody discovery in complex autoimmune diseases is challenging. Diverse successful antigen identification strategies are available, but, so far, have often been unsuccessful, especially in the discovery of protein antigens in which conformational and post-translational modification are critical. Our study assesses the utility of a human membrane and secreted protein microarray technology to detect autoantibodies in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

Psychological interventions to enhance positive outcomes in adult cancer caregivers: A systematic review.

This systematic review aims to examine the characteristics of psychological interventions that aim to enhance positive outcomes, such as wellbeing, post-traumatic growth, or hope in cancer caregivers. Studies published until December 2023 were searched on PubMed, Scopus, PsycINFO, WOS, PsycARTICLES and were included when examining interventions targeting positive outcomes with adult cancer caregivers. Of the 1424 articles retrieved through the databases, 16 studies were eligible for inclusion in this review, targeting 908 caregivers (70.

Isolated bulbar palsy and dysphagia in children with respiratory symptoms.

Oropharyngeal dysphagia can cause chronic aspiration leading to significant respiratory symptoms. When dysphagia is diagnosed, an underlying cause is sought. We present a case series of 15 children diagnosed aged 6 months to 5 years (mean 2y 5mo; 11 males, four females) over a 6-year period, who were found to have an isolated bulbar palsy on genioglossus electromyography, with no accompanying neurological or neurodevelopmental disorder.

Adenovirus cerebellitis in an immunocompetent 2-year-old girl.

Acute cerebellitis (AC) is a principal cause of acute cerebellar dysfunction in previously well children. Although the condition is usually benign, fatal complications include obstructive hydrocephalus and brainstem compression; therefore, prompt accurate diagnosis is vital. There are various pathogens reported in the literature as aetiological agents of AC; however, adenovirus is very rarely mentioned, with only one previous case report in the literature to the best of our knowledge.

Generation of two high affinity anti-mouse FcRn antibodies: Inhibition of IgG recycling in wild type mice and effect in a mouse model of immune thrombocytopenia.

Primary immune thrombocytopenia (ITP) is an autoimmune disease characterized by pathogenic immunoglobulin G (IgG) autoantibodies that bind to platelets, causing their phagocytic removal and leading to reductions in platelet number. The neonatal Fc receptor (FcRn) selectively salvages and recycles IgG, including pathogenic IgG, thereby extending the half-life of IgG in plasma. Two anti-mouse FcRn monoclonal antibodies (mAb) (4470 and 4464) were generated to evaluate the effect of inhibiting IgG recycling.

Prediction of natalizumab anti-drug antibodies persistency.

Background: Anti-drug antibodies (ADA) against natalizumab develop early during treatment. ADA persistency is defined by two consecutive positive results as performed by the current qualitative ELISA assay (positive/negative). Very little is known about the magnitude of the natalizumab ADA response and persistency.

Multivalent Fcγ-receptor engagement by a hexameric Fc-fusion protein triggers Fcγ-receptor internalisation and modulation of Fcγ-receptor functions.

Engagement of Fcγ-receptors triggers a range of downstream signalling events resulting in a diverse array of immune functions. As a result, blockade of Fc-mediated function is an important strategy for the control of several autoimmune and inflammatory conditions. We have generated a hexameric-Fc fusion protein (hexameric-Fc) and tested the consequences of multi-valent Fcγ-receptor engagement in in vitro and in vivo systems.

Fab-dsFv: A bispecific antibody format with extended serum half-life through albumin binding.

An antibody format, termed Fab-dsFv, has been designed for clinical indications that require monovalent target binding in the absence of direct Fc receptor (FcR) binding while retaining substantial serum presence. The variable fragment (Fv) domain of a humanized albumin-binding antibody was fused to the C-termini of Fab constant domains, such that the VL and VH domains were individually connected to the Cκ and CH1 domains by peptide linkers, respectively. The anti-albumin Fv was selected for properties thought to be desirable to ensure a durable serum half-life mediated via FcRn.

Metaphyseal dysplasia associated with chronic facial nerve palsy.

Introduction: Metaphyseal dysplasia (Pyle disease) is a rare autosomal recessive disease with impressive and characteristic radiological findings but relatively mild clinical features. It is usually incidentally diagnosed, despite the impressive radiological findings of gross metaphyseal widening and thinning of cortical bone.

Case Report: Herein, we report an exceptionally unusual case of metaphyseal dysplasia in association with chronic facial nerve palsy.

Characterizing the signature of flame flashback precursor through recurrence analysis.

In this paper, it is shown that prior to flashback, small dynamical changes appear in the system. These changes appear as a drift in the recurrence plots and are found to be associated with a gradual increase in the determinism and recurrence rate. Thus, this study indicates that precursors to flame flashback exist and can be detected in the multidimensional phase space reconstructed from pressure measurements acquired during flashback.

Bilateral reversible basal ganglia changes associated with dystonia and hemifacial spasms in central nervous system lupus.

We report a 40-year-old woman with systemic lupus erythematosus (SLE) and associated inflammatory polyarthritis who presented with acute facial dystonic spasms. Her speech was also affected. An MRI brain showed bilateral symmetrical basal ganglia signal change on T2.

Glow in the dark.

Objective: To highlight the importance of radiation safety and handling of radioactive secretions following 131I-meta iodobenzylguanidine (131I-mIBG) use in the treatment of neuroblastoma.

Methods: We report a 4-year-old girl with stage 4 neuroblastoma, on whom's single-photon emission computer tomography (SPECT) scan we demonstrate four extra-corporal areas of radioactivity confirming radiation uptake in the four corners of her 'comfort blanket' that had been used to cover her during the scan. It transpired that she had been sucking on the four corners of this blanket.

Kenny Caffey syndrome with severe respiratory and gastrointestinal involvement: expanding the clinical phenotype.

Kenny Caffey syndrome (KCS) is a rare syndrome reported almost exclusively in Middle Eastern populations. It is characterized by severe growth retardation-short stature, dysmorphic features, episodic hypocalcaemia, hypoparathyroidism, seizures, and medullary stenosis of long bones with thickened cortices. We report a 10-year-old boy with KCS with an unusually severe respiratory and gastrointestinal system involvement-features not previously described in the literature.

A mixture of functionally oligoclonal humanized monoclonal antibodies that neutralize Clostridium difficile TcdA and TcdB with high levels of in vitro potency shows in vivo protection in a hamster infection model.

Clostridium difficile infections are a major cause of antibiotic-associated diarrhea in hospital and care facility patients. In spite of the availability of effective antibiotic treatments, C. difficile infection (CDI) is still a major cause of patient suffering, death, and substantial health care costs.

An unusual case of suprascapular nerve neuropathy: a case report.

Introduction: Suprascapular nerve neuropathy constitutes an unusual cause of shoulder weakness, with the most common etiology being nerve compression from a ganglion cyst at the suprascapular or spinoglenoid notch. We present a puzzling case of a man with suprascapular nerve neuropathy that may have been associated with an appendectomy. The case was attributed to nerve injury as the most likely cause that may have occurred during improper post-operative patient mobilization.

Endoscopic ultrasound-guided fine needle aspiration cytology diagnosis of solid pseudopapillary tumor of the pancreas: a report of 3 cases.

Background: Solid pseudopapillary tumor of the pancreas (SPTP) is an exceedingly rare pancreatic tumor. We present the clinical, endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) cytologic features and immunohistochemical findings performed on cell blocks of 3 SPTPs.

Cases: Three females (17-32 years old) were admitted to our hospital due to unexplained episodic abdominal pain.

Internal fixation of scaphoid non-union: a comparative study of three methods.

In this study we compared the results of three methods of fixation for scaphoid non-union. The implants used were the AO 2 mm mini-fragment screw, the Herbert screw and the Kirschner (K) wires. Between 1990 and 1999, 132 patients underwent surgery for scaphoid fractures.

Functional outcome of high-pressure injection injuries of the hand.

Background: High-pressure injection (HPI) injury of the hand is a serious injury that can be potentially devastating. There have been a number of publications on the results of its treatment, but we are not aware of a report on the functional outcome of these hands.

Methods: We assessed the functional outcome of 15 patients with HPI injuries.

Proximal row transcarpal fracture from a punching injury.

We describe an unusual case of a 31-year-old woman who injured the right dominant wrist when she punched an assailant's shoulder. She described a mechanism of direct compression, with the wrist in hyperextension, radial deviation and the forearm in pronation. She sustained an oblique transverse fracture of the proximal pole of the scaphoid and a coronal plane fracture of the lunate and the triquetrum.