Concurrent immunomodulator therapy is associated with higher adalimumab trough levels during scheduled maintenance therapy.

Introduction: Combination therapy with infliximab and immunomodulators is superior to monotherapy, resulting in better outcomes and higher trough levels of infliximab. The role of concurrent immunomodulatory therapy on adalimumab trough levels has not been adequately investigated. We evaluated the impact of concomitant immunomodulation on adalimumab trough levels in patients on scheduled maintenance therapy.

New-Generation High-Definition Colonoscopes Increase Adenoma Detection when Screening a Moderate-Risk Population for Colorectal Cancer.

Background And Aim: Adenoma detection rate (ADR) is the most important quality indicator for screening colonoscopy, due to its association with colorectal cancer outcomes. As a result, a number of techniques and technologies have been proposed that have the potential to improve ADR. The aim of this study was to assess the potential impact of new-generation high-definition (HD) colonoscopy on ADR within the Bowel Cancer Screening Programme (BCSP).

A Founder Effect for the HGD G360R Mutation in Italy: Implications for a Regional Screening of Alkaptonuria.

We sought to establish rapid and specific genotyping methods for G360R mutation and for seven tightly linked markers in the homogentisate dioxygenase gene to address the question of whether G360R is a mutational hot spot or the result of a founder effect, as it has been repeatedly found in alkaptonuric patients from a geographic isolate in Italy.For G360R and single nucleotide polymorphism genotyping, high-resolution melting analysis was performed. Microsatellites were analysed by multiplex PCR and capillary electrophoresis.

Pneumococcal Colonization Rates in Patients Admitted to a United Kingdom Hospital with Lower Respiratory Tract Infection: a Prospective Case-Control Study.

Current diagnostic tests are ineffective for identifying the etiological pathogen in hospitalized adults with lower respiratory tract infections (LRTIs). The association of pneumococcal colonization with disease has been suggested as a means to increase the diagnostic precision. We compared the pneumococcal colonization rates and the densities of nasal pneumococcal colonization by (i) classical culture and (ii) quantitative real-time PCR (qPCR) targetinglytAin patients with LRTIs admitted to a hospital in the United Kingdom and control patients.

UK Lung Cancer RCT Pilot Screening Trial: baseline findings from the screening arm provide evidence for the potential implementation of lung cancer screening.

Background: Lung cancer screening using low-dose CT (LDCT) was shown to reduce lung cancer mortality by 20% in the National Lung Screening Trial.

Methods: The pilot UK Lung Cancer Screening (UKLS) is a randomised controlled trial of LDCT screening for lung cancer versus usual care. A population-based questionnaire was used to identify high-risk individuals.

New technologies and techniques to improve adenoma detection in colonoscopy.

Adenoma detection rate (ADR) is a key component of colonoscopy quality assessment, with a direct link between itself and future mortality from colorectal cancer. There are a number of potential factors, both modifiable and non-modifiable that can impact upon ADR. As methods, understanding and technologies advance, so should our ability to improve ADRs, and thus, reduce colorectal cancer mortality.

Concordant chromosome 3 results in paired choroidal melanoma biopsies and subsequent tumour resection specimens.

Background/aim: The study's aim was to compare chromosome 3 aberrations of choroidal melanoma (CM) as determined by multiplex ligation dependent probe amplification (MLPA) or microsatellite analysis (MSA) in intraocular tumour biopsies with those results obtained from subsequent endoresection/enucleation of the same CM.

Methods: A retrospective cohort of 28 patients with CM seen between 2007 and 2014 at the Liverpool Ocular Oncology Centre was analysed. Prognostic genetic testing, for chromosome 3 status, was performed on all tumour specimens, either by MLPA or MSA, depending on DNA yield.

First human challenge testing of a pneumococcal vaccine. Double-blind randomized controlled trial.

Rationale: New vaccines are urgently needed to protect the vulnerable from bacterial pneumonia. Clinical trials of pneumonia vaccines are slow and costly, requiring tens of thousands of patients. Studies of pneumococcal vaccine efficacy against colonization have been proposed as a novel method to down-select between vaccine candidates.

CD56+ T cells are increased in kidney transplant patients following cytomegalovirus infection.

Background: CD56+ T cells previously have been identified as potentially cytotoxic lymphocytes, and relative numbers are increased in some infectious diseases.

Patients And Methods: Relative proportions of CD56+ T cells were measured by flow cytometry in groups of renal transplant patients differing in cytomegalovirus (CMV) status of donor (D) and recipient (R). These measurements were related to episodes of CMV viremia.

A rare case of cutaneous collagenous vasculopathy.

Cutaneous collagenous vasculopathy is a rare microangiopathy first described by Salama and Rosenthal in 2000. Several cases have been reported to date, describing distinct histological findings of thick hyaline collagenous blood vessel walls in the superficial dermis. Clinical confusion can arise with generalised essential telangiectasia.

Analysis of HGD Gene Mutations in Patients with Alkaptonuria from the United Kingdom: Identification of Novel Mutations.

Alkaptonuria (AKU) is a rare autosomal recessive disorder with incidence ranging from 1:100,000 to 1:250,000. The disorder is caused by a deficiency of the enzyme homogentisate 1,2-dioxygenase (HGD), which results from defects in the HGD gene. This enzyme converts homogentisic acid to maleylacetoacetate and has a major role in the catabolism of phenylalanine and tyrosine.

Serum markers in alkaptonuria: simultaneous analysis of homogentisic acid, tyrosine and nitisinone by liquid chromatography tandem mass spectrometry.

Background: Alkaptonuria is a rare debilitating autosomal recessive disorder of tyrosine metabolism, where deficiency of homogentisate 1,2-dioxygenase results in increased homogentisic acid. Homogentisic acid is deposited as an ochronotic pigment in connective tissues, especially cartilage, leading to a severe early onset form of osteoarthritis, increased renal and prostatic stone formation and hardening of heart vessels. Treatment with the orphan drug, nitisinone, an inhibitor of 4-hydroxyphenylpyruvate dioxygenase has been shown to reduce urinary excretion of homogentisic acid.

Calprotectin and lactoferrin faecal levels in patients with Clostridium difficile infection (CDI): a prospective cohort study.

Measurement of both calprotectin and lactoferrin in faeces has successfully been used to discriminate between functional and inflammatory bowel conditions, but evidence is limited for Clostridium difficile infection (CDI). We prospectively recruited a cohort of 164 CDI cases and 52 controls with antibiotic-associated diarrhoea (AAD). Information on disease severity, duration of symptoms, 30-day mortality and 90-day recurrence as markers of complicated CDI were recorded.

Kikuchi-Fujimoto Disease: part of the differential diagnosis of cervical lymphadenopathy in an HIV-positive patient.

A 38-year-old HIV-positive Nigerian woman presented with a three-week history of cervical lymphadenopathy, night sweats, weight loss and fever. Provisional diagnoses of tuberculosis and lymphoma were considered; however, a histological diagnosis of Kikuchi-Fujimoto Disease was reached. This rare benign disease has presenting features that mimic more serious conditions commonly occurring in HIV-positive patients.

Urine homogentisic acid and tyrosine: simultaneous analysis by liquid chromatography tandem mass spectrometry.

Alkaptonuria (AKU) is a rare debilitating autosomal recessive disorder of tyrosine metabolism. Deficiency of homogentisate 1,2-dioxygenase results in increased homogentisic acid (HGA) which although excreted in gram quantities in the urine, is deposited as an ochronotic pigment in connective tissues, especially cartilage. Ochronosis leads to a severe, early-onset form of osteoarthritis, increased renal and prostatic stone formation and hardening of heart vessels.

Bronchoalveolar lavage (BAL) for research; obtaining adequate sample yield.

We describe a research technique for fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) using manual hand held suction in order to remove nonadherent cells and lung lining fluid from the mucosal surface. In research environments, BAL allows sampling of innate (lung macrophage), cellular (B- and T- cells), and humoral (immunoglobulin) responses within the lung. BAL is internationally accepted for research purposes and since 1999 the technique has been performed in > 1,000 subjects in the UK and Malawi by our group.

Feasibility study for early supported discharge in adults with respiratory infection in the UK.

Background: Many patients with pneumonia and lower respiratory tract infection that could be treated as outpatients according to their clinical severity score, are in fact admitted to hospital. We investigated whether, with medical and social input, these patients could be discharged early and treated at home.

Objectives: (1) To assess the feasibility of providing an early supported discharge scheme for patients with pneumonia and lower respiratory tract infection (2) To assess the patient acceptability of a study comprising of randomisation to standard hospital care or early supported discharge scheme.

Isolated pharyngeal Neisseria gonorrhoeae in heterosexual male contacts.

Pharyngeal infection with Neisseria gonorrhoeae (NG) in heterosexual men is thought to be of low prevalence and the value of routinely testing this group of patients is uncertain. We present two cases of NG, isolated only in the pharynx, in asymptomatic heterosexual male contacts. The presence of pharyngeal NG was found irrespective of direct oropharyngeal sexual exposure.