Danish translation and cultural adaptation of the Psoriatic arthritis UnclutteRed screening Evaluation (PURE-4) scale.

OBJECTIVES: Screening tools are needed to help to identify psoriatic arthritis in patients with psoriasis. The Psoriatic arthritis UnclutteRed screening Evaluation (PURE-4) questionnaire was developed for this purpose and has been shown to perform very well. The aim of this study was to translate and culturally adapt the PURE-4 scale into the Danish language. METHOD: The translational process followed the guidelines provided by the Mapi Research Trust, which include the following steps: forward translation, backward translation, cognitive interviews, and proofreading. Following the guidelines helps to maintain the content validity of the questionnaire and secures a translation that is both literally and culturally appropriate for the target population. RESULTS: All four items were modified throughout the translation process, involving mainly minor changes such as the addition of more colloquial words in the Danish version. The new Danish version of PURE-4 was reviewed and approved by the original developers. CONCLUSIONS: A Danish version of the PURE-4 questionnaire was produced. The translation and cultural adaptation of PURE-4 constitute the first step in the validation of the questionnaire in Danish patients with psoriasis.

Carbon dioxide levels in neonates: what are safe parameters?

There is no consensus on the optimal pCO2 levels in the newborn. We reviewed the effects of hypercapnia and hypocapnia and existing carbon dioxide thresholds in neonates. A systematic review was conducted in accordance with the PRISMA statement and MOOSE guidelines. Two hundred and ninety-nine studies were screened and 37 studies included. Covidence online software was employed to streamline relevant articles. Hypocapnia was associated with predominantly neurological side effects while hypercapnia was linked with neurological, respiratory and gastrointestinal outcomes and Retinpathy of prematurity (ROP). Permissive hypercapnia did not decrease periventricular leukomalacia (PVL), ROP, hydrocephalus or air leaks. As safe pCO2 ranges were not explicitly concluded in the studies chosen, it was indirectly extrapolated with reference to pCO2 levels that were found to increase the risk of neonatal disease. Although PaCO2 ranges were reported from 2.6 to 8.7 kPa (19.5-64.3 mmHg) in both term and preterm infants, there are little data on the safety of these ranges. For permissive hypercapnia, parameters described for bronchopulmonary dysplasia (BPD; PaCO2 6.0-7.3 kPa: 45.0-54.8 mmHg) and congenital diaphragmatic hernia (CDH; PaCO2 ≤ 8.7 kPa: ≤65.3 mmHg) were identified. Contradictory findings on the effectiveness of permissive hypercapnia highlight the need for further data on appropriate CO2 parameters and correlation with outcomes. IMPACT: There is no consensus on the optimal pCO2 levels in the newborn. There is no consensus on the effectiveness of permissive hypercapnia in neonates. A safe range of pCO2 of 5-7 kPa was inferred following systematic review.

Imaging of adult intestinal failure.

Intestinal failure is the inability to maintain adequate nutrition or hydration through the gut. It is caused by a diverse range of benign and malignant aetiologies. Imaging takes a central role in the multidisciplinary assessment of patients with intestinal failure.

Imaging of intestinal transplantation.

Intestinal transplant is considered in a small number of patients with intestinal failure or locally invasive benign abdominal tumours to improve both quality of life and survival. The complexity of the underlying diseases and postoperative findings are reflected in the imaging undertaken to support this patient group. Increasing numbers of patients are undergoing these procedures. Radiologists are increasingly likely to encounter these patients before and after surgery. This article will discuss the imaging findings that may prompt referral for transplantation assessment. It will also describe surgical anatomy and postoperative complications.

Impact of Climate Change and Land Use on Groundwater Salinization in Southern Bangladesh-Implications for Other Asian Deltas.

Pervasive salinity in soil and water is affecting agricultural yield and the health of millions of delta dwellers in Asia. This is also being exacerbated by climate change through increases in sea level and tropical storm surges. One consequence of this has been a widespread introduction of salt water shrimp farming. Here, we show, using field data and modeling, how changes in climate and land use are likely to result in increased salinization of shallow groundwater in SE Asian mega-deltas. We also explore possible adaptation options. We find that possible future increase of episodic inundation events, combined with salt water shrimp farming, will cause rapid salinization of groundwater in the region making it less suitable for drinking water and irrigation. However, modified land use and water management practices can mitigate the impacts on groundwater, as well as the overlying soil, from future salinization. The study therefore provides guidance for adaptation planning to reduce future salinization in Asian deltas.

Do contamination of and exposure to chicken meat and water drive the temporal dynamics of Campylobacter cases?

Campylobacteriosis, the most frequent bacterial enteric disease, shows a clear yet unexplained seasonality. The study purpose was to explore the influence of seasonal fluctuation in the contamination of and in the behaviour exposures to two important sources of Campylobacter on the seasonality of campylobacteriosis. Time series analyses were applied to data collected through an integrated surveillance system in Canada in 2005-2010. Data included sporadic, domestically-acquired cases of Campylobacter jejuni infection, contamination of retail chicken meat and of surface water by C. jejuni, and exposure to each source through barbequing and swimming in natural waters. Seasonal patterns were evident for all variables with a peak in summer for human cases and for both exposures, in fall for chicken meat contamination, and in late fall for water contamination. Time series analyses showed that the observed campylobacteriosis summer peak could only be significantly linked to behaviour exposures rather than sources contamination (swimming rather than water contamination and barbequing rather than chicken meat contamination). The results indicate that the observed summer increase in human cases may be more the result of amplification through more frequent risky exposures rather than the result of an increase of the Campylobacter source contamination.

Videolaryngoscopy versus direct laryngoscopy for adult patients requiring tracheal intubation: a Cochrane Systematic Review.

Difficulties with tracheal intubation commonly arise and impact patient safety. This systematic review evaluates whether videolaryngoscopes reduce intubation failure and complications compared with direct laryngoscopy in adults. We searched CENTRAL, MEDLINE, Embase and clinicaltrials.gov up to February 2015, and conducted forward and backward citation tracking. We included randomized controlled trials that compared adult patients undergoing laryngoscopy with videolaryngoscopy or Macintosh laryngoscopy. We did not primarily intend to compare individual videolaryngoscopes. Sixty-four studies (7044 participants) were included. Moderate quality evidence showed that videolaryngoscopy reduced failed intubations (Odds Ratio (OR) 0.35, 95% Confidence Interval (CI) 0.19-0.65) including in participants with anticipated difficult airways (OR 0.28, 95% CI 0.15-0.55). There was no evidence of reduction in hypoxia or mortality, but few studies reported these outcomes. Videolaryngoscopes reduced laryngeal/airway trauma (OR 0.68, 95% CI 0.48-0.96) and hoarseness (OR 0.57, 95% CI 0.36-0.88). Videolaryngoscopy increased easy laryngeal views (OR 6.77, 95% CI 4.17-10.98) and reduced difficult views (OR 0.18, 95% CI 0.13-0.27) and intubation difficulty, typically using an 'intubation difficulty score' (OR 7.13, 95% CI 3.12-16.31). Failed intubations were reduced with experienced operators (OR 0.32, 95% CI 0.13-0.75) but not with inexperienced users. We identified no difference in number of first attempts and incidence of sore throat. Heterogeneity around time for intubation data prevented meta-analysis. We found evidence of differential performance between different videolaryngoscope designs. Lack of data prevented analysis of impact of obesity or clinical location on failed intubation rates. Videolaryngoscopes may reduce the number of failed intubations, particularly among patients presenting with a difficult airway. They improve the glottic view and may reduce laryngeal/airway trauma. Currently, no evidence indicates that use of a videolaryngoscope reduces the number of intubation attempts or the incidence of hypoxia or respiratory complications, and no evidence indicates that use of a videolaryngoscope affects time required for intubation.

Preimplant Normothermic Liver Perfusion of a Suboptimal Liver Donated After Circulatory Death.

Livers retrieved after circulatory death are associated with an increased incidence of primary nonfunction, early allograft dysfunction, and biliary strictures. The authors report a case of preimplant normothermic perfusion of a suboptimal liver from a 57-year-old donor after circulatory death who had been hospitalized for 9 days; predonation alanine transaminase level was 63 IU/L, and the period from withdrawal of life-supporting treatment to circulatory arrest was 150 minutes. After 5 hours of static cold storage, the liver was subject to normothermic machine perfusion with a plasma-free red cell-based perfusate. Perfusate lactate level fell from 7.2 to 0.3 mmol/L within 74 minutes of ex situ perfusion, at which point perfusate alanine transaminase level was 1152 IU/L and urea concentration was 9.4 mmol/L. After 132 minutes, normothermic perfusion was stopped and implantation begun. After transplantation, the patient made an uneventful recovery and was discharged on day 8; liver biochemistry was normal by day 19 and has remained normal thereafter. Donor common bile duct excised at implantation showed preservation of peribiliary glands, and cholangiography 6 months posttransplantation showed no evidence of cholangiopathy. Preimplant ex situ normothermic perfusion of the liver appears to be a promising way to evaluate a marginal liver before transplantation and may modify the response to ischemia.

Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2.

BACKGROUND: Somatic mutations in the Janus kinase 2 gene (JAK2) occur in many myeloproliferative neoplasms, but the molecular pathogenesis of myeloproliferative neoplasms with nonmutated JAK2 is obscure, and the diagnosis of these neoplasms remains a challenge. METHODS: We performed exome sequencing of samples obtained from 151 patients with myeloproliferative neoplasms. The mutation status of the gene encoding calreticulin (CALR) was assessed in an additional 1345 hematologic cancers, 1517 other cancers, and 550 controls. We established phylogenetic trees using hematopoietic colonies. We assessed calreticulin subcellular localization using immunofluorescence and flow cytometry. RESULTS: Exome sequencing identified 1498 mutations in 151 patients, with medians of 6.5, 6.5, and 13.0 mutations per patient in samples of polycythemia vera, essential thrombocythemia, and myelofibrosis, respectively. Somatic CALR mutations were found in 70 to 84% of samples of myeloproliferative neoplasms with nonmutated JAK2, in 8% of myelodysplasia samples, in occasional samples of other myeloid cancers, and in none of the other cancers. A total of 148 CALR mutations were identified with 19 distinct variants. Mutations were located in exon 9 and generated a +1 base-pair frameshift, which would result in a mutant protein with a novel C-terminal. Mutant calreticulin was observed in the endoplasmic reticulum without increased cell-surface or Golgi accumulation. Patients with myeloproliferative neoplasms carrying CALR mutations presented with higher platelet counts and lower hemoglobin levels than patients with mutated JAK2. Mutation of CALR was detected in hematopoietic stem and progenitor cells. Clonal analyses showed CALR mutations in the earliest phylogenetic node, a finding consistent with its role as an initiating mutation in some patients. CONCLUSIONS: Somatic mutations in the endoplasmic reticulum chaperone CALR were found in a majority of patients with myeloproliferative neoplasms with nonmutated JAK2. (Funded by the Kay Kendall Leukaemia Fund and others.).

Transport of ice into the stratosphere and the humidification of the stratosphere over the 21st century.

Climate models predict that tropical lower-stratospheric humidity will increase as the climate warms. We examine this trend in two state-of-the-art chemistry-climate models. Under high greenhouse gas emissions scenarios, the stratospheric entry value of water vapor increases by ~1 part per million by volume (ppmv) over this century in both models. We show with trajectory runs driven by model meteorological fields that the warming tropical tropopause layer (TTL) explains 50-80% of this increase. The remainder is a consequence of trends in evaporation of ice convectively lofted into the TTL and lower stratosphere. Our results further show that, within the models we examined, ice lofting is primarily important on long time scales - on interannual time scales, TTL temperature variations explain most of the variations in lower stratospheric humidity. Assessing the ability of models to realistically represent ice-lofting processes should be a high priority in the modeling community.

Differential gene expression in the duodenum, jejunum and ileum among crossbred beef steers with divergent gain and feed intake phenotypes.

Small intestine mass and cellularity were previously associated with cattle feed efficiency. The small intestine is responsible for the digestion of nutrients and absorption of fatty acids, amino acids and carbohydrates, and it contributes to the overall feed efficiency of cattle. The objective of this study was to evaluate transcriptome differences among the small intestine from cattle with divergent gain and feed intake. Animals most divergent from the bivariate mean in each of the four phenotypic Cartesian quadrants for gain × intake were selected, and the transcriptomes of duodenum, jejunum and ileum were evaluated. Gene expression analyses were performed comparing high gain vs. low gain animals, high intake vs. low intake animals and each of the phenotypic quadrants to all other groups. Genes differentially expressed within the high gain-low intake and low gain-high intake groups of animals included those involved in immune function and inflammation in all small intestine sections. The high gain-high intake group differed from the high gain-low intake group by immune response genes in all sections of the small intestine. In all sections of small intestine, animals with low gain-low intake displayed greater abundance of heat-shock genes compared to other groups. Several over-represented pathways were identified. These include the antigen-processing/presentation pathway in high gain animals and PPAR signaling, starch/sucrose metabolism, retinol metabolism and melatonin degradation pathways in the high intake animals. Genes with functions in immune response, inflammation, stress response, influenza pathogenesis and melatonin degradation pathways may have a relationship with gain and intake in beef steers.

Dedicated Orthogeriatric Service Saves the HSE a Million Euro.

Hip fracture is common in older adults and is associated with high morbidity, mortality and significant health care costs. A pilot orthogeriatrics service was established in an acute hospital. We aimed to establish the cost effectiveness of this service. Length of hospital stay, discharge destination and rehabilitation requirements were analysed for a one year period and compared to patients who received usual care prior to the service. We calculated the costs incurred and savings produced by the orthogeriatric service. Median length of stay was reduced by 3 days (p < 0.001) saving €266,976. There was a 19% reduction in rehabilitation requirements saving €192,600. Median rehabilitation length of stay was reduced by 6.5 days saving €171,093. Reductions in long term care requirements led to savings of €10,934 per week. Costs to establish such a service amount to €171,564. The introduction of this service led to improved patient outcomes in a cost effective manner.

Successful transplantation of kidneys from elderly circulatory death donors by using microscopic and macroscopic characteristics to guide single or dual implantation.

Most kidneys from potential elderly circulatory death (DCD) donors are declined. We report single center outcomes for kidneys transplanted from DCD donors over 70 years old, using preimplantation biopsy Remuzzi grading to inform implantation as single or dual transplants. Between 2009 and 2012, 43 single transplants and 12 dual transplants were performed from elderly DCD donors. Remuzzi scores were higher for dual than single implants (4.4 vs. 3.4, p < 0.001), indicating more severe baseline injury. Donor and recipient characteristics for both groups were otherwise similar. Early graft loss from renal vein thrombosis occurred in two singly implanted kidneys, and in one dual-implanted kidney; its pair continued to function satisfactorily. Death-censored graft survival at 3 years was comparable for the two groups (single 94%; dual 100%), as was 1 year eGFR. Delayed graft function occurred less frequently in the dual-implant group (25% vs. 65%, p = 0.010). Using this approach, we performed proportionally more kidney transplants from elderly DCD donors (23.4%) than the rest of the United Kingdom (7.3%, p < 0.001), with graft outcomes comparable to those achieved nationally for all deceased-donor kidney transplants. Preimplantation biopsy analysis is associated with acceptable transplant outcomes for elderly DCD kidneys and may increase transplant numbers from an underutilized donor pool.

When one becomes more: minimum renal artery length in laparoscopic live donor nephrectomy.

BACKGROUND: Laparoscopic donor nephrectomy may convert short main arteries into multiple arteries, increasing the technical challenge of implantation. We evaluated our experience to identify factors predictive of multiple arteries after laparoscopic nephrectomy. METHODS: All laparoscopic nephrectomies from the start of our program in November 2002 until June 2013 were studied, and preoperative imaging reviewed for donor artery length and multiplicity together with operative findings. RESULTS: A total of 287 consecutive laparoscopic live donor nephrectomies (64 right and 223 left nephrectomies) were studied. Renal artery length was measured from preoperative donor magnetic resonance or computed tomography angiogram and nephrectomy performed using a laparoscopic stapling device. Nine left kidneys with a single artery (6, 7, 9, 10, 11, 12, 13, 14, and 16 mm in length) and five right kidneys with a single artery (5, 13, 15, 20, and 26 mm) on imaging resulted in multiple renal arteries at implantation. Complex renal vein anatomy was associated with multiple arteries following retrieval. CONCLUSION: A main renal artery length of more than 16 mm on the left and 26 mm on the right is unlikely to result in multiple arteries to implant. The possibility of multiple arteries should be borne in mind when the donor renal artery is short.

Prevalence of human papillomavirus among oesophageal squamous cell carcinoma cases: systematic review and meta-analysis.

BACKGROUND: Oncogenic human papillomavirus (HPV) has been hypothesised as a risk factor for oesophageal squamous cell carcinoma (OSCC), but aetiological research has been limited by the varying methodology used for establishing HPV prevalence. The aims of this systematic review and meta-analysis were to estimate the prevalence of HPV DNA detected in OSCC tumours and the influence of study characteristics. METHODS: Study-level estimates of overall and type-specific HPV prevalence were meta-analysed to obtain random-effects summary estimates. RESULTS: This analysis included 124 studies with a total of 13 832 OSCC cases. The average HPV prevalence (95% confidence interval) among OSCC cases was 0.277 (0.234, 0.320) by polymerase chain reaction; 0.243 (0.159, 0.326) by in situ hybridisation; 0.304 (0.185, 0.423) by immunohistochemistry; 0.322 (0.154, 0.490) by L1 serology; and 0.176 (0.061, 0.292) by Southern/slot/dot blot. The highest HPV prevalence was found in Africa and Asia, notably among Chinese studies from provinces with high OSCC incidence rates. CONCLUSIONS: Future research should focus on quantifying HPV in OSCC cases using strict quality control measures, as well as determining the association between HPV and OSCC incidence by conducting large, population-based case-control studies. Such studies will provide a richer understanding of the role of HPV in OSCC aetiology.

In situ normothermic regional perfusion for controlled donation after circulatory death--the United Kingdom experience.

Organs recovered from donors after circulatory death (DCD) suffer warm ischemia before cold storage which may prejudice graft survival and result in a greater risk of complications after transplant. A period of normothermic regional perfusion (NRP) in the donor may reverse these effects and improve organ function. Twenty-one NRP retrievals from Maastricht category III DCD donors were performed at three UK centers. NRP was established postasystole via aortic and caval cannulation and maintained for 2 h. Blood gases and biochemistry were monitored to assess organ function. Sixty-three organs were recovered. Forty-nine patients were transplanted. The median time from asystole to NRP was 16 min (range 10-23 min). Thirty-two patients received a kidney transplant. The median cold ischemia time was 12 h 30 min (range 5 h 25 min-18 h 22 min). The median creatinine at 3 and 12 months was 107 µmol/L (range 72-222) and 121 µmol/L (range 63-157), respectively. Thirteen (40%) recipients had delayed graft function and four lost the grafts. Eleven patients received a liver transplant. The first week median peak ALT was 389 IU/L (range 58-3043). One patient had primary nonfunction. Two combined pancreas-kidney transplants, one islet transplant and three double lung transplants were performed with primary function. NRP in DCD donation facilitates organ recovery and may improve short-term outcomes.

Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts.

BACKGROUND: Myelodysplastic syndromes are a diverse and common group of chronic hematologic cancers. The identification of new genetic lesions could facilitate new diagnostic and therapeutic strategies. METHODS: We used massively parallel sequencing technology to identify somatically acquired point mutations across all protein-coding exons in the genome in 9 patients with low-grade myelodysplasia. Targeted resequencing of the gene encoding RNA splicing factor 3B, subunit 1 (SF3B1), was also performed in a cohort of 2087 patients with myeloid or other cancers. RESULTS: We identified 64 point mutations in the 9 patients. Recurrent somatically acquired mutations were identified in SF3B1. Follow-up revealed SF3B1 mutations in 72 of 354 patients (20%) with myelodysplastic syndromes, with particularly high frequency among patients whose disease was characterized by ring sideroblasts (53 of 82 [65%]). The gene was also mutated in 1 to 5% of patients with a variety of other tumor types. The observed mutations were less deleterious than was expected on the basis of chance, suggesting that the mutated protein retains structural integrity with altered function. SF3B1 mutations were associated with down-regulation of key gene networks, including core mitochondrial pathways. Clinically, patients with SF3B1 mutations had fewer cytopenias and longer event-free survival than patients without SF3B1 mutations. CONCLUSIONS: Mutations in SF3B1 implicate abnormalities of messenger RNA splicing in the pathogenesis of myelodysplastic syndromes. (Funded by the Wellcome Trust and others.).

Encapsulating peritoneal sclerosis--correlation of radiological findings at CT with underlying pathogenesis.

Encapsulating peritoneal sclerosis (EPS) is a rare entity most commonly associated with peritoneal dialysis (PD). Several imaging features at computed tomography (CT) are common to many diseases; however, appreciation of the features unique to this condition interpreted with the appropriate clinical findings is crucial to diagnosis.

Outcomes of allogeneic haemopoietic stem cell transplants at a small New Zealand centre: does size matter?

BACKGROUND: Reduced intensity conditioning (RIC) protocols for allogeneic haemopoietic cell transplants (HCT) have become commonplace treatments for patients with haematological disease, extending allogeneic HCT to older and less fit patients. There is a perception that centres treating larger numbers of patients have improved outcomes. AIMS: We wanted to examine whether outcomes for adult allogeneic HCT patients from our smaller centre were equivalent to those expected at larger centres internationally. METHODS: Clinical and laboratory data were collected on all patients who received allogeneic HCT during 2000-2012. Outcomes, including overall survival (OS) and progression-free survival, were compared between patients receiving myeloablative conditioning (MAC) and RIC protocols. RESULTS: One hundred and eighteen adult patients underwent allogeneic HCT with MAC (n = 51) or RIC (n = 67). The mean age of patients receiving MAC (35.8 years, range 18-56) was lower than those receiving RIC (48.4 years, range 19-64). Two-year OS was similar for MAC and RIC patients (66% vs 62%, P = 0.17), whereas 2-year progression-free survival was superior in MAC patients (63% vs 50%, P = 0.01) due to fewer relapses. OS was reduced in older patients irrespective of conditioning. Patients with chronic graft-versus-host disease had improved survival due to fewer relapses. OS was unaffected by HCT comorbidity index, donor, cell source or patient/donor cytomegalovirus status. CONCLUSION: RIC protocols have resulted in long-term survival in many patients ineligible for MAC protocols. In our smaller centre, patient age but not conditioning intensity influenced survival, which was equivalent to reports from larger centres.

Use of lean principals to improve flow of patients with fractured neck of femur--the HOPE study.

We describe the implementation of a care pathway for patients with fractured neck of femur (NOF) using Lean and Six Sigma principles. After introduction of the Lean pathway, 32 patients out a total of 86 (37%) with fractured NOF were admitted to the Trauma Ward within 4 hours of presentation to the hospital; prior to implementation this was 16 patients out of a total of 59 (27%). Post-Lean an earlier mean theatre start time of 8.40am was achieved, resulting in a 38 minute increase in daily theatre time. An additional 52 patients (12%) received surgery within 24 hours of admission, resulting in 1 night length of stay reduction. Lean methodology proved an effective method to guide change resulting in an improved journey for the patient and significant workflow gains.