Prohepcidin Levels in Refractory Anaemia Caused by Lead Poisoning

Recent research evidence suggests a central role for hepcidin in iron homeostasis. Hepcidin is a hormone synthesized in the liver. Hepcidin is also thought to play a vital role in the pathogenic mechanism of anaemia in patients with inflammation or chronic disease. A 38-year-old female who presented with recurrent abdominal pain was found to have raised urinary porphyrins and a blood lead level of 779 μg/l. Her haemoglobin level was 8.3 g/dl. Her MCV was normal. Serum ferritin, B12 and folate were normal. Her serum prohepcidin level was 2,489 ng/ml (normal <450 ng/ml). To our knowledge, this is the first report of raised prohepcidin levels in a patient with anaemia of chronic disease resulting from lead poisoning

A novel albumin gene mutation (R222I) in familial dysalbuminemic hyperthyroxinemia.

CONTEXT: Familial dysalbuminemic hyperthyroxinemia, characterized by abnormal circulating albumin with increased T4 affinity, causes artefactual elevation of free T4 concentrations in euthyroid individuals. OBJECTIVE: Four unrelated index cases with discordant thyroid function tests in different assay platforms were investigated. DESIGN AND RESULTS: Laboratory biochemical assessment, radiolabeled T4 binding studies, and ALB sequencing were undertaken. (125)I-T4 binding to both serum and albumin in affected individuals was markedly increased, comparable with known familial dysalbuminemic hyperthyroxinemia cases. Sequencing showed heterozygosity for a novel ALB mutation (arginine to isoleucine at codon 222, R222I) in all four cases and segregation of the genetic defect with abnormal biochemical phenotype in one family. Molecular modeling indicates that arginine 222 is located within a high-affinity T4 binding site in albumin, with substitution by isoleucine, which has a smaller side chain predicted to reduce steric hindrance, thereby facilitating T4 and rT3 binding. When tested in current immunoassays, serum free T4 values from R222I heterozygotes were more measurably abnormal in one-step vs two-step assay architectures. Total rT3 measurements were also abnormally elevated. CONCLUSIONS: A novel mutation (R222I) in the ALB gene mediates dominantly inherited dysalbuminemic hyperthyroxinemia. Susceptibility of current free T4 immunoassays to interference by this mutant albumin suggests likely future identification of individuals with this variant binding protein.This work was supported by funding from the Wellcome Trust (Grant 100585/Z/12/Z, to N.S., Grant 095564/Z/11/Z, to K.C.) and National Institute for Health Research Cambridge Biomedical Research Centre (to C.M., and M.G.).This is the final published version of the article. It was originally published in The Journal of Clinical Endocrinology & Metabolism (Nadia Schoenmakers, Carla Moran, Irene Campi, Maura Agostini, Olivia Bacon, Odelia Rajanayagam, John Schwabe, Sonia Bradbury, Timothy Barrett, Frank Geoghegan, Maralyn Druce, Paolo Beck-Peccoz, Angela O'Toole, Penelope Clark, Michelle Bignell, Greta Lyons, David Halsall, Mark Gurnell, Krishna Chatterjee. J Clin Endocrinol Metab 2014 Jul 19;99(7):E1381-6. Epub 2014 Mar 19. http://dx.doi.org/10.1210/jc.2013-4077). A correction to this article was issued because the CC-BY licence was not present on the final published paper (http://dx.doi.org/10.1210/jc.2015-1656)

Is adhesion superficial? Silicon wafers as a model system to study van der Waals interactions

Adhesion is a key issue for researchers of various fields, it is therefore of uppermost importance to understand the parameters that are involved. Commonly, only surface parameters are employed to determine the adhesive forces between materials. Yet, van der Waals forces act not only between atoms in the vicinity of the surface, but also between atoms in the bulk material. In this review, we describe the principles of van der Waals interactions and outline experimental and theoretical studies investigating the influence of the subsurface material on adhesion. In addition, we present a collection of data indicating that silicon wafers with native oxide layers are a good model substrate to study van der Waals interactions with coated materials

Targeted temperature management in patients with intracerebral haemorrhage, subarachnoid haemorrhage, or acute ischaemic stroke: updated consensus guideline recommendations by the Neuroprotective Therapy Consensus Review (NTCR) group

Background: There is a lack of consistent, evidence-based guidelines for the management of patients with fever after brain injury. The aim was to update previously published consensus recommendations on targeted temperature management after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in patients who require admission to critical care. Methods: A modified Delphi consensus, the Neuroprotective Therapy Consensus Review (NTCR), included 19 international neuro-intensive care experts with a subspecialty interest in the acute management of intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke. An online, anonymised survey was completed ahead of the meeting before the group came together to consolidate consensus and finalise recommendations on targeted temperature management. A threshold of ≥80% for consensus was set for all statements. Results: Recommendations were formulated based on existing evidence, literature review, and consensus. After intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in patients who require critical care admission, core temperature should ideally be monitored continuously and maintained between 36.0°C and 37.5°C using automated feedback-controlled devices, where possible. Targeted temperature management should be commenced within 1 h of first fever identification with appropriate diagnosis and treatment of infection, maintained for as long as the brain remains at risk of secondary injury, and rewarming should be controlled. Shivering should be monitored and managed to limit risk of secondary injury. Following a single protocol for targeted temperature management across intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke is desirable. Conclusions: Based on a modified Delphi expert consensus process, these guidelines aim to improve the quality of targeted temperature management for patients after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in critical care, highlighting the need for further research to improve clinical guidelines in this setting

Fulminant Staphylococcus lugdunensis septicaemia following a pelvic varicella-zoster virus infection in an immune-deficient patient: a case report

<p>Abstract</p> <p>Introduction</p> <p>The deadly threat of systemic infections with coagulase negative <it>Staphylococcus lugdunensis </it>despite an appropriate antibiotic therapy has only recently been recognized. The predominant infectious focus observed so far is left-sided native heart valve endocarditis, but bone and soft tissue infections, septicaemia and vascular catheter-related bloodstream infections have also been reported. We present a patient with a fatal <it>Staphylococcus lugdunensis </it>septicaemia following zoster bacterial superinfection of the pelvic region.</p> <p>Case presentation</p> <p>A 71-year old male diagnosed with IgG kappa plasmocytoma presented with a conspicuous weight loss, a hypercalcaemic crisis and acute renal failure. After initiation of haemodialysis treatment his condition improved rapidly. However, he developed a varicella-zoster virus infection of the twelfth thoracic dermatome requiring intravenous acyclovir treatment. Four days later the patient presented with a fulminant septicaemia. Despite an early intravenous antibiotic therapy with ciprofloxacin, piperacillin/combactam and vancomycin the patient died within 48 hours, shortly before the infective isolate was identified as <it>Staphylococcus lugdunensis </it>by polymerase chain reaction.</p> <p>Conclusion</p> <p>Despite <it>S. lugdunensis </it>belonging to the family of coagulase-negative staphylococci with an usually low virulence, infections with <it>S. lugdunensis </it>may be associated with an aggressive course and high mortality. This is the first report on a <it>Staphylococcus lugdunensis </it>septicaemia following a zoster bacterial superinfection of the pelvic region.</p

Occurrence of genes of putative fibrinogen binding proteins and hemolysins, as well as of their phenotypic correlates in isolates of S. lugdunensis of different origins

<p>Abstract</p> <p>Background</p> <p><it>Staphylococcus lugdunensis </it>is an important human pathogen that causes potentially fatal endocarditis, osteomyelitis and skin and soft tissue infections similar to diseases caused by <it>Staphylococcus aureus</it>. Nevertheless, in contrast to <it>S. aureus</it>, data on pathogenicity factors of <it>S. lugdunensis </it>is scarce. Two adhesins, a fibrinogen and a von Willebrand factor binding protein, and a <it>S. lugdunensis </it>synergistic hemolysin (SLUSH) have been previously described. Moreover, the newly sequenced genome of <it>S. lugdunensis </it>revealed genes of other putative fibrinogen binding adhesins and hemolysins. The aim of this study was to gain more insight into the occurrence of genes likely coding for fibrinogen binding adhesins and hemolysins using clinical strains of <it>S. lugdunensis</it>.</p> <p>Findings</p> <p>Most of the putative adhesin genes and hemolysin genes investigated in this study were highly prevalent, except for the SLUSH gene cluster. In contrast to previous reports, binding to fibrinogen was detected in 29.3% of the <it>S. lugdunensis </it>strains. In most strains, hemolysis on blood agar plates was weak after 24 h and distinct after 48 h of incubation. The fibrinogen binding and hemolysis phenotypes were also independent of the type of clinical specimen, from which the isolates were obtained.</p> <p>Conclusion</p> <p>In this study we described a pyrrolidonyl arylamidase negative <it>S. lugdunensis </it>isolate. Our data indicate that a matrix-assisted laser desorption ionisation time-of-flight MS-based identification of <it>S. lugdunensis </it>or species-specific PCR's should be performed in favour of pyrrolidonyl arylamidase testing. In contrast to the high occurrence of putative fibrinogen binding protein genes, 29.3% of the <it>S. lugdunensis </it>strains bound to fibrinogen. Putative hemolysin genes were also prevalent in most of the <it>S. lugdunensis </it>strains, irrespective of their hemolysis activity on Columbia blood agar plates. Similar to a previous report, hemolysis after 48 h of incubation is also indicative for <it>S. lugdunensis</it>. The SLUSH gene cluster was detected in an estimated 50% of the strains, indicating that this locus is different or non-prevalent in many strains.</p

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Effect of extracellular polymeric substances on the mechanical properties of Rhodococcus

The mechanical properties of Rhodococcus RC291 were measured using force spectroscopy equipped with a bacterial cell probe. Rhodococcal cells in the late growth stage of development were found to have greater adhesion to a silicon oxide surface than those in the early growth stage. This is because there are more extracellular polymeric substances (EPS) that contain nonspecific binding sites available on the cells of late growth stage. It is found that EPS in the late exponential phase are less densely bound but consist of chains able to extend further into their local environment, while the denser EPS at the late stationary phase act more to sheath the cell. Contraction and extension of the EPS could change the density of the binding sites, and therefore affect the magnitude of the adhesion force between the EPS and the silicon oxide surface. By treating rhodococcal EPS as a surface-grafted polyelectrolyte layer and using scaling theory, the interaction between EPS and a solid substrate was modelled for the cell approaching the surface which revealed that EPS possess a large capacity to store charge. Changing the pH of the surrounding medium acts to change the conformation of EPS chains

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care