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.

Commercial Immunoglobulin Products Contain Neutralizing Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein.

Background: Patients with antibody deficiency respond poorly to coronavirus disease 2019 (COVID-19) vaccination and are at risk of severe or prolonged infection. They are given long-term immunoglobulin replacement therapy (IRT) prepared from healthy donor plasma to confer passive immunity against infection. Following widespread COVID-19 vaccination alongside natural exposure, we hypothesized that immunoglobulin preparations will now contain neutralizing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antibodies, which confer protection against COVID-19 disease and may help to treat chronic infection.

Activation of the cGAS-STING innate immune response in cells with deficient mitochondrial topoisomerase TOP1MT.

The recognition that cytosolic mitochondrial DNA (mtDNA) activates cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) innate immune signaling has unlocked novel disease mechanisms. Here, an uncharacterized variant predicted to affect TOP1MT function, P193L, was discovered in a family with multiple early onset autoimmune diseases, including Systemic Lupus Erythematosus (SLE). Although there was no previous genetic association between TOP1MT and autoimmune disease, the role of TOP1MT as a regulator of mtDNA led us to investigate whether TOP1MT could mediate the release of mtDNA to the cytosol, where it could then activate the cGAS-STING innate immune pathway known to be activated in SLE and other autoimmune diseases.

Functional characterization of two variants of mitochondrial topoisomerase TOP1MT that impact regulation of the mitochondrial genome.

TOP1MT encodes a mitochondrial topoisomerase that is important for mtDNA regulation and is involved in mitochondrial replication, transcription, and translation. Two variants predicted to affect TOP1MT function (V1 - R198C and V2 - V338L) were identified by exome sequencing of a newborn with hypertrophic cardiomyopathy. As no pathogenic TOP1MT variants had been confirmed previously, we characterized these variants for their ability to rescue several TOP1MT functions in KO cells.

Bowel Histology of CVID Patients Reveals Distinct Patterns of Mucosal Inflammation.

Diarrhea is the commonest gastrointestinal symptom in patients with common variable immunodeficiency (CVID). Different pathologies in patients' bowel biopsies have been described and links with infections have been demonstrated. The aim of this study was to analyze the bowel histology of CVID patients in the Royal-Free-Hospital (RFH) London CVID cohort.

Altered Microbiota, Impaired Quality of Life, Malabsorption, Infection, and Inflammation in CVID Patients With Diarrhoea.

Diarrhoea is the commonest gastrointestinal symptom in patients with common variable immunodeficiency (CVID). The aim of this study was to describe the prevalence and clinical presentation of chronic and recurrent diarrhoea in the Royal-Free-Hospital (RFH) London CVID cohort, including symptoms, infections, level of inflammation, and microbial diversity. A cross-sectional study of adult CVID patients (139 out of 172 diagnosed with CVID completed the screening questionnaire).

A rare and unusual complication of the STING procedure.

Unlabelled: An 8-year-old boy underwent a STING procedure for vesicoureteric reflux. 11 years later, at 19-years-old he presented with the passage of sediment per urethra every 7 weeks. CT scan demonstrated a lesion at the right VUJ.

Absence of Persistent Hepatitis E Virus Infection in Antibody-Deficient Patients Is Associated With Transfer of Antigen-Neutralizing Antibodies From Immunoglobulin Products.

Background: Persistent hepatitis E virus (HEV) infection is described in a number of immunosuppressive conditions. We aimed to determine the risk of persistent HEV infection in patients with primary or secondary antibody deficiency.

Methods: Two hundred forty-five antibody-deficient patients receiving regular immunoglobulin replacement therapy were tested for HEV RNA and anti-HEV immunoglobulin G (IgG).

Investigating the Effectiveness, Acceptability and Impact on Healthcare Usage of Providing a Cognitive-Behavioural Based Psychological Therapy Service for Patients with Primary Antibody Deficiency.

Purpose: Patients with primary antibody deficiency report poorer quality of life and higher rates of anxiety and depression than the general population. Cognitive-behavioral therapy has been shown to be a valuable treatment for patients with other long-term physical health conditions, improving well-being and enabling them to manage their symptoms more effectively. The aim of this project was to establish the feasibility and effectiveness of providing cognitive-behavioral based therapy to patients with primary antibody deficiency.

Successful outcome following allogeneic hematopoietic stem cell transplantation in adults with primary immunodeficiency.

The primary immunodeficiencies (PIDs), rare inherited diseases characterized by severe dysfunction of immunity, have been successfully treated by allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in childhood. Controversy exists regarding optimal timing and use of Allo-HSCT in adults, due to lack of experience and previous poor outcomes. Twenty-nine consecutive adult patients, with a mean age at transplant of 24 years (range, 17-50 years), underwent Allo-HSCT.

Transmission of Hepatitis B Core Antibody and Galactomannan Enzyme Immunoassay Positivity via Immunoglobulin Products: A Comprehensive Analysis.

Background: Therapeutic immunoglobulins are used as replacement or immunomodulatory therapy, but can transmit clinically important molecules. We investigated hepatitis B virus (HBV) antibodies and galactomannan enzyme immunoassay (GM-EIA) positivity. Detection of HBV core antibody may prompt antiviral prophylaxis when commencing therapy such as rituximab; a positive GM-EIA result prompts investigation or treatment for invasive fungal disease.

'A reservoir within a reservoir' - An unusual complication associated with a defunctioned inflatable penile prosthesis reservoir.

Introduction: Inflatable penile prostheses (IPP) have been a successful method of treating men with erectile dysfunction since the early 1970s. IPP are comprised of two intracorporal cylinders, a scrotal pump and a fluid reservoir.

Presentation Of Case: We present a case of a retained reservoir in a sixty eight year old gentlemen presenting with a cystic abdominal mass and bothersome LUTS, 15 years after the removal of the penile components of a three-piece penile prosthesis.

Prognostic value of inflammation or granuloma after intravesival BCG in non-muscle-invasive bladder cancer.

Objective: To evaluate the prognostic value of inflammation or granuloma after intravesical bacille Calmette-Guérin (BCG) treatment in non-muscle-invasive bladder cancer (NMIBC).

Materials And Methods: Patients with NMIBC treated with intravesical BCG over a 5-year period were identified. The correlations between histopathological results and disease recurrence and progression were assessed, with survival analysis performed using the Kaplan-Meier method.

Quantitative analysis of BTF3, HINT1, NDRG1 and ODC1 protein over-expression in human prostate cancer tissue.

Prostate carcinoma is the most common cancer in men with few, quantifiable, biomarkers. Prostate cancer biomarker discovery has been hampered due to subjective analysis of protein expression in tissue sections. An unbiased, quantitative immunohistochemical approach provided here, for the diagnosis and stratification of prostate cancer could overcome this problem.

Haemophagocytic syndrome after intravesical bacille Calmette-Guérin instillation.

Abstract Intravesical bacille Calmette-Guérin (BCG) is used to treat high-risk superficial bladder cancer. This article reports a case of secondary haemophagocytosis after intravesical BCG instillation in a 70-year-old man with bladder cancer and presents a literature review of this very rare but potentially fatal complication of intravesical BCG treatment.

Systemic BCG-Osis as a Rare Side Effect of Intravesical BCG Treatment for Superficial Bladder Cancer.

Intravesical Bacilli Calmette-Guérin (BCG) immunotherapy is a commonly used treatment for superficial bladder cancer. Although the treatment is well tolerated in 95% of cases, life-threatening side effects including BCG sepsis can occur. This report describes the case of an 82-year-old man with a background of lung disease.

Urological applications of single-site laparoscopic surgery.

Single-port, single-incision laparoscopy is part of the natural development of minimally invasive surgery. Refinement and modification of laparoscopic instrumentation has resulted in a substantial increase in the use of laparoendoscopic single-site surgery (LESS) in urology over the past 2 years. Since the initial report of single-port nephrectomy in 2007, the majority of laparoscopic procedures in urology have been described with a single-site approach.

The impact of conservation on the status of the world's vertebrates.

Using data for 25,780 species categorized on the International Union for Conservation of Nature Red List, we present an assessment of the status of the world's vertebrates. One-fifth of species are classified as Threatened, and we show that this figure is increasing: On average, 52 species of mammals, birds, and amphibians move one category closer to extinction each year. However, this overall pattern conceals the impact of conservation successes, and we show that the rate of deterioration would have been at least one-fifth again as much in the absence of these.

A novel role for Wnt/Ca2+ signaling in actin cytoskeleton remodeling and cell motility in prostate cancer.

Wnt signaling is a critical regulatory pathway in development and disease. Very little is known about the mechanisms of Wnt signaling in prostate cancer, a leading cause of death in men. A quantitative analysis of the expression of Wnt5A protein in human tissue arrays, containing 600 prostate tissue cores, showed >50% increase in malignant compared to benign cores (p<0.

Spatiotemporal dynamics in the cortical microcircuit: a modelling study of primary visual cortex layer 2/3.

The plexus of long and short range lateral connections is a prominent feature of the layer 2/3 microcircuit in the primary visual cortex. Despite the scope for possible functionality, the interdependence of local and long range circuits is still unclear. Spatiotemporal patterns of activity appear to be shaped by the underlying connectivity architecture and strong inhibition.

Surgical excision of isolated renal-bed recurrence after radical nephrectomy for renal cell carcinoma.

Objective: To present our results on managing loco-regional recurrence of renal cell carcinoma (RCC) with surgical excision, as local recurrence at the site of a previous nephrectomy is resistant to both systemic therapy and radiotherapy.

Patients And Methods: In all, 16 patients were operated on between 1994 and 2003 for local recurrence of RCC. The median (mean, range) age at the time of local recurrence was 57.

Percutaneous versus open tendo achillis repair.

A retrospective analysis was conducted comparing open and percutaneous repair of ruptured Achilles tendon, over a 14-year period. One hundred and eight patients were identified; 70 underwent traditional open repair and 38 had a modified Ma & Griffith repair. The mean operating time with percutaneous repair was 28.