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Disaster planning is a core facet of modern health care practice. Owing to complex infrastructure requirements, radiology departments are vulnerable to system failures that may occur in isolation or during a disaster event when the urgency for and volume of imaging examinations increases. Planning for systems failures helps ensure continuity of service provision and patient care during an adverse event. Hazards to which a radiology department is vulnerable can be identified by applying a systematic approach with recognized tools such as the Hazard, Risk, and Vulnerability Analysis. Potential critical weaknesses within the department are highlighted by the Failure Mode and Effects Analysis tool. Recognizing the potential latent conditions and active failures that may impact systems allows implementation of strategies to prevent failure or to build resilience and mitigate the effects if they happen. Inherent system resilience to an adverse event can be estimated, and the ability of a department to operate during a disaster and the subsequent recovery can be predicted. The main systems at risk in a radiology department are staff, structure, stuff (supplies and/or equipment), and software, although individual issues and solutions within these are department specific. When medical imaging or examination interpretation needs cannot be met in the radiology department, the use of portable imaging modalities and teleradiology can augment the disaster response. All phases of disaster response planning should consider both sustaining operations and the transition back to normal function.

OBJECTIVE To describe the development and implementation of a Peer Curbside Consult Service (PCCS) for a pediatric hospital medicine (PHM) division. METHODS We developed a pilot intervention with hospitalists at a freestanding children’s hospital to provide peer consultation services for challenging clinical cases. Postconsultation surveys collected from both the requesting and consulting hospitalists provided feedback about the program. The 12-point Template for Intervention Description and Replication (TIDieR) checklist is used to describe the process for program creation and implementation. RESULTS The PCCS has provided 60 consultations in the first 2 years since implementation in April 2020 and supports a large PHM division with >75 members who practice at a tertiary care, freestanding children’s hospital and 7 affiliate sites. Hospitalists request peer consultation for challenging clinical cases. The consultations were typically conducted in person or via telephone. Currently, 11 PHM faculty members within the division volunteer as consultants, with 2 assigned per week. Electronic postconsultation experience surveys were received from 70% of requesting and 89% of consultant hospitalists. We also provide preliminary data from this pilot intervention in the Supplemental Information. CONCLUSIONS We successfully established a peer consult service that provided just-in-time clinical decision support across the various practice sites. Through transparent reporting using the TIDieR checklist, other divisions may be able to replicate and adapt their own peer consult program.

Background Recent evidence suggests a role for lung microbiome in occurrence of chronic lung allograft dysfunction (CLAD). However, the mechanisms linking the microbiome to CLAD are poorly delineated. We investigated a possible mechanism involved in microbial modulation of mucosal response leading to CLAD with the hypothesis that a Proteobacteria dominant lung microbiome would inhibit N-myc-interactor (NMI) expression and induce epithelial to mesenchymal transition (EMT). Methods Explant CLAD, non-CLAD, and healthy nontransplant lung tissue were collected, as well as bronchoalveolar lavage from 14 CLAD and matched non-CLAD subjects, which were followed by 16S rRNA amplicon sequencing and quantitative polymerase chain reaction (PCR) analysis. Pseudomonas aeruginosa (PsA) or PsA-lipopolysaccharide was cocultured with primary human bronchial epithelial cells (PBEC). Western blot analysis and quantitative reverse transcription (qRT) PCR was performed to evaluate NMI expression and EMT in explants and in PsA-exposed PBECs. These experiments were repeated after siRNA silencing and upregulation (plasmid vector) of EMT regulator NMI. Results 16S rRNA amplicon analyses revealed that CLAD patients have a higher abundance of phyla Proteobacteria and reduced abundance of the phyla Bacteroidetes . At the genera level, CLAD subjects had an increased abundance of genera Pseudomonas and reduced Prevotella . Human CLAD airway cells showed a downregulation of the N-myc-interactor gene and presence of EMT. Furthermore, exposure of human primary bronchial epithelial cells to PsA resulted in downregulation of NMI and induction of an EMT phenotype while NMI upregulation resulted in attenuation of this PsA-induced EMT response. Conclusions CLAD is associated with increased bacterial biomass and a Proteobacteria enriched airway microbiome and EMT. Proteobacteria such as PsA induces EMT in human bronchial epithelial cells via NMI, demonstrating a newly uncovered mechanism by which the microbiome induces cellular metaplasia .

Objectives We present a full autopsy with a focused radiology and pathologic review of the coronary arteries. We hope that the results described in this article will help create better diagnostic measures and prevent future coronary artery vasculitis misdiagnosis. Methods A full autopsy was performed on the body of Dr Myung Choong Yoon, with full consent from the family, within the department of pathology and laboratory medicine at Vancouver General Hospital. Tissue samples from the heart, brain, lungs, and spinal cord were submitted to specialist pathologists for histologic processing. Results Cardiac gated computed tomography coronary angiography suggested periarteritis. Coexistent calcified coronary atherosclerosis with linear calcifications was present along the luminal wall, along with coronary artery ectasia. Histologic assessment confirmed features of dense adventitial fibrosis around the coronary arteries, with an exuberant lymphoplasmacytic infiltrate and numerous plasma cells consistent with IgG4-related disease. The media of the coronary arteries was markedly attenuated or completely absent, which likely contributed to the coronary arterial ectasia noted microscopically. These findings confirmed IgG4-related coronary arteritis. Conclusions Coronary periarteritis is an uncommon manifestation of IgG4-related disease established radiographically and later by autopsy.

In the current cultural climate, gender disparity is a topical and contentious issue. In academic medicine, there is an underrepresentation of female faculty in leadership positions with lower research output and fewer grant awards. We study the gender differences in faculty rank, leadership positions, and research output among chest radiologists in North America.A list of clinical faculty at radiology programs in North America was obtained using the FREIDA database and program websites. Demographic information and data pertaining to academic rank, peer-reviewed publications, and research productivity of each chest radiologist was obtained from Doximity and SCOPUS databases.Four hundred ten (281 male:129 female) academic chest radiologists were included. Females were underrepresented at senior faculty level accounting for 18.8% (n = 21) of full, 29.2% (n = 21) of associate and 40.7% (n = 61) of assistant professors. 23.1% (n = 14) of department chiefs were women. Women were more likely to occupy a faculty position in chest radiology in Canada than in US (P 0.05). The median H-index, and numbers of publications and citations were lower for females than male faculty (P 0.05). Male faculty had more years of experience - median of 19 years, 16.5 years for females (P 0.05).Gender disparity exists in chest radiology with similar male predominance in terms of senior faculty rank, leadership roles, and research productivity to other medical specialties. The observed deficiency of research and scholarly output among female chest radiologists and the paucity of aspirational female radiologists in senior academic/leadership positions are factors which perpetuate this gender disparity and contribute to persistence of the gender pay gap.

Since the advent of multidetecter computed tomography (CT), radiologist sensitivity in detection of traumatic bowel and mesenteric abnormalities has significantly improved. Although several CT signs have been described to identify intestinal injury, accurate interpretation of these findings can remain challenging. Early detection of bowel and mesenteric injury is important as it alters patient management, disposition, and follow-up. This article reviews the common imaging findings of traumatic small bowel and mesenteric injury.

A mass casualty incident (MCI) is an event that generates more patients at one time than locally available resources can manage using routine procedures. By their nature, many of these incidents have no prior notice but result in large numbers of casualties with injuries that range in severity. They can happen anywhere and at any time and regional hospitals and health-care providers have to mount a response quickly and effectively to save as many lives as possible. Radiologists must go from passenger to pilot when it comes to MCI planning. When involved at the hospital-wide planning stage, they can offer valuable expertise on how radiology can improve triage accuracy and at what cost in terms of time and resources and thereby contribute a pragmatic understanding of radiology’s role and value during MCIs. By taking ownership of MCI planning in their own departments, radiologists can ensure that the radiology department can respond quickly and effectively to unforeseen emergencies. Well-designed radiology protocols will save lives in an MCI setting.

Tuberculosis (TB), caused byIn many environments, bacteria live together in structures called biofilms. Cells in biofilms coordinate with each other to protect the group and allow it to survive difficult conditions.

Aim This study evaluated the use of Lumbar Puncture (LP) in a general paediatric unit over a 3-year period. Methods Index patients, who had a successful LP, were identified from the microbiology database and failed LP procedures were identified from a chart review of the serum PCR database. Data abstracted included 1) patient age, 2) LP indication, 3) LP procedure outcome; classified as atraumatic, traumatic or failed, 4) grade of doctor undertaking the procedure and 5) the final diagnosis. Results We identified 104 paediatric patients, of whom 29(27.9%) were neonates. LP was indicated for the evaluation of acute undifferentiated illnesses, with 33 (31.7%) patients having fever without source beyond the neonatal period and 16 (15.4%) being neonates with fever. A CSF sample was obtained in 96 (92.4%) patients, with 71 (73.9%) being atraumatic. Successful LP was undertaken by Consultants in 4 (4.1%), Registrars in 83 (86.5%) and SHOs in 9 (9.4%) patients. 14 (14.6%) patients had positive CSF cultures with an additional 23 having positive cultures or serology (9 blood cultures, 11 urine cultures and 3 positive serum PCR). Conclusion Skill in LP performance is still required, to evaluate acute undifferentiated illness, in general paediatric units and ancillary methods to aid SHOs with LP skill development is desirable.

Purpose Prospective radiology fellows often rely on the internet to obtain information with regard to the application process for and the unique qualities of different fellowship programs. The aim of this study was to analyze the content of websites of the United States' and Canadian cardiothoracic radiology fellowships. Methods All active Cardiothoracic Radiology fellowship websites as of July 2019 were evaluated and compared using 25 criteria in the following domains: Application, Recruitment, Clinical Training, Education/Research, and Incentives. Program website information availability was compared by geographic region. Results There were 60 active cardiothoracic radiology fellowships, and 59 of these fellowships had a dedicated fellowship website. Websites, on average, had 9.3 of the 25 criteria (37.2%). The mean number of schools that satisfied the criterion in the "Incentives" domain ([7.75/59] 10.5%±2.8%) was significantly lower than that for the "Application Process" domain ([40.50/59]; 68.7%±40.6%) (P=0.01). There was no significant difference in the information content of programs in different geographic regions (P=0.246). Conclusion Most cardiothoracic radiology fellowship websites were lacking content relevant to prospective fellows. Provision of more relevant and easily accessible online content may support programs to better inform and recruit residents and to promote the specialty of cardiothoracic radiology.

Objectives Experienced physicians must rapidly identify ill pediatric patients. We evaluated the ability of an illness rating score (IRS) to predict admission to a pediatric hospital and explored the underlying clinical reasoning of the gestalt assessment of illness. Methods We used mixed-methods to study pediatric emergency medicine physicians at an academic children’s hospital emergency department (ED). Physicians rated patients’ illness severity with the IRS, anchored by 0 (totally well) and 10 (critically ill), and shared their rationale with concurrent think-aloud responses. The association between IRS and need for hospitalization, respiratory support, parenteral antibiotics, and resuscitative intravenous (IV) fluids were analyzed with mixed effects linear regression. Area under the curve (AUC) receiver operator characteristic (ROC) curve and test characteristics at different cut-points were calculated for IRS as a predictor of admission. Think-aloud responses were qualitatively analyzed via inductive process. Results A total of 141 IRS were analyzed (mean 3.56, SD 2.30, range 0–9). Mean IRS were significantly higher for patients requiring admission (4.32 vs. 3.13, p Conclusions Rapid assessments as captured by the IRS differentiated pediatric patients who required admission and medical interventions. Think-aloud responses for the rationale for rapid assessments may form the basis for teaching the skill of identifying ill pediatric patients.

Introduction We assessed management of patients with de novo metastatic rectal cancer, referred for radiotherapy to the rectum, who were candidates for short-course radiotherapy (SCRT) and chemotherapy, followed by resection of all disease. We assessed surgical outcomes, overall survival (OS) and progression-free survival (PFS). Methods Retrospective review of patients meeting criteria: (i) treatment with SCRT to rectum; (ii) locally advanced primary rectal cancer; and (iii) resectable distant metastases at diagnosis. Data were collected from charts, correspondence and electronic patient records. OS and PFS were calculated using the Kaplan-Meier method. Results Between 2016 and 2020, 48 patients with stage IV rectal cancer at diagnosis were treated with SCRT. Only 15 patients (31%) had resectable metastatic disease and were intended for SCRT (25 Gy/5#), then chemotherapy, followed by resection of all sites of disease and are included in our study. 12 of the 15 surgical candidates (80%) had rectal surgery as planned, and 11 of the 15 (73%) had resection of the rectal primary and all metastatic disease. One patient had a pathological complete response (pCR), and 50% of surgical patients had a Mandard TRG of 1 or 2. Median PFS and OS for the 15 surgical candidates were 12.6 and 25.2 months, respectively, with a median FU of 21.2 months. Conclusion For this cohort of patients, our treatment paradigm is pragmatic and results in excellent pathological response. However, the effectiveness of this approach should be the subject of future prospective studies.

Postgraduate medical training incorporates education, both formal and informal, combined with clinical service. This study explored the early training experience of pediatricians in Ireland and its potential impact on patient safety.We sought to identify factors that contribute to the patient safety experience of new entrant pediatric trainees.Trainees, or senior house officers (SHOs), in their first year of postgraduate training, participated in an interview conducted using a critical interview technique (CIT). They described an adverse event where the medical care delivered to the patient was not ideal. Thematic analysis identified themes that influenced the described event.Thirteen trainees participated in the interviews. This study identified influences on the relationship between the SHO and patient safety, including the SHO themselves, teamwork and communication. Colleagues within the workplace, including consultants, registrars, and nurses, also affect this relationship. The registrar is described as a central figure holding an active role in clinical care in 11 of the 13 stories told. In the participants' experience, the registrar was the senior decision-maker, teacher, team builder, and communication intermediary within the teams' hierarchical structure. The registrars' previous clinical experience, communication style, along with their ability to supervise and provide feedback shaped the SHO experience.Through a process designed to focus on exploring patient safety, it emerged that the registrar plays a crucial role in the working experience of their junior colleagues. The influence of the registrar needs to be recognized within clinical teams and by postgraduate training bodies.

Mass casualty incidents, by nature of their scale and unpredictability, can rapidly overwhelm health infrastructure. Preparation is the key to managing these crises with the lowest risk to emergency and health personnel, while providing maximal life saving measures. We present an overview of the multitiered planning that should go into forming a well set out emergency response plan and one that is capable of being adapted to a wide range of mass casualty scenarios. We highlight the ethical implications that a healthcare team faces while making challenging decisions rapidly in a high-pressure environment. Radiology trainees should be aware of the response systems in place at their institutions and the role that is expected of them in mass casualty incidents.

Background/objectives Little research has compared clinician acne severity assessment with either adolescent- or parent-rated scales of acne severity or impact on quality of life (QOL). We sought to assess how adolescents and their parents perceive the severity and impact of acne on the adolescent's QOL and correlate this with clinical severity. Methods Each adolescent and a parent completed a validated QOL survey regarding the adolescent's acne and rated the adolescent's acne severity and QOL impact using a Likert scale. Clinicians assessed the adolescent's acne using a standardized acne severity scale. Statistical analysis compared adolescent scores with respective parent scores or with clinician assessment using a paired t test or Spearman rank-order correlation test. Results The Likert impact score more accurately reflected acne impact on QOL for adolescents than for parents when considering the validated QOL survey as the gold standard (r2 = .56 vs r2 = .36). Likert scores for adolescents and parents were weakly correlated for acne severity but not for acne QOL impact (r2 = .36 vs r2 = .18). Correlations of acne severity scores between clinician and either adolescent or parent were weak. Conclusions Parents and adolescents are in relative agreement regarding acne severity and QOL impact. However, parent and adolescent perceptions are disparate from clinician acne assessment. It is important that physicians identify and consider adolescent and parent perceptions in addition to clinical assessment to better inform the approach to acne management.

KEY POINTS A 76-year-old man presented to a quaternary care hospital with a 6-day history of respiratory symptoms, fatigue and a fainting episode. The patient had a resolving postinfectious dry cough from an upper respiratory infection that occurred 3 months before presentation. He had hypertension

Preoperative radiotherapy or combined chemoradiotherapy for locally advanced rectal cancer (LARC) can cause acute and late gastrointestinal (GI) side-effects. There is thought to be a dose-volume relationship between small bowel irradiation and the development of these effects. A planning study was undertaken to compare small bowel sparing for a range of 3D conformal and dynamic arc planning solutions. A planning study was carried out for 20 LARC patients. Organs at risk (OAR) contoured included bowel loops and peritoneal space (PS). For each of the 20 patients, 5 plans were created: (1) standard 3D conformal plan; (2) standard dual dynamic arc plan; (3) dual dynamic arc plan with 90° avoidance sector through the anterior portion of the patient; (4) dual dynamic arc plan with an anterior avoidance structure in the optimizer; (5) dual dynamic arc plan with both an anterior avoidance structure and an avoidance sector. The prescription was 50.4 Gy in 28 fractions to the planning target volume (PTV). Five Dose Volume Levels (DVLs; V15 Gy, V20 Gy, V25 Gy, V35 Gy, V40 Gy, and V50.4 Gy) for bowel and PS were selected. The DVLs were compared between the plans using Friedman Tests and Wilcoxon Signed Rank Tests. Comparison of the 5 plans revealed that a dual dynamic arc plan containing both an anterior avoidance sector and structure significantly improved the dose to the bowel compared to a standard 3D conformal plan and to a standard dual dynamic arc plan. This improvement was achieved while maintaining PTV coverage. This novel dual dynamic arc planning technique that uses both an avoidance sector and structure reduces the dose to the bowel and PS, which may lead to a reduction in GI toxicity.

This review aims to examine the challenges facing radiologists interpreting trauma computed tomography (CT) images in this era of a changing approach to management of solid organ trauma. After reviewing the pearls and pitfalls of CT imaging protocols for detection of traumatic solid organ injuries, we describe the key changes in the 2018 American Association for the Surgery of Trauma Organ Injury Scales for liver, spleen, and kidney and their implications for management strategies. We then focus on the important imaging findings in observed in patients who undergo nonoperative management and patients who are imaged post damage control surgery.

Pediatric emergency visits for behavioral health complaints have been increasing for more than a decade. There are currently no best practices or ideal models of care. However, the evidence base for existing emergency department operational concepts can be used to implement modifications to workflow, care model, staffing, and physical environment to address patient needs. Rapid assessment, split flow, blended care model, multidisciplinary team development, mental health nursing triage, and staff training can all positively affect length of stay, staff safety, and patient satisfaction.

Objectives Our goal was to ascertain the quality of health information related to CT radiation exposure using a simulated Internet search and from incident information that may be available during day-to-day Internet usage. Methods We entered 14 terms relating to information on CT dose into the most commonly used Internet search engine and analyzed the first 100 web page results for each. A Rich Search Site (RSS) feed search was also used to evaluate incidental information over a 12-week period in 2014. Each web page was classified as being "completely accurate," "somewhat accurate," or "inaccurate." Results Of 1,400 web pages, 290 were relevant and accessible. We deemed 12.8% of these pages as inaccurate and 67.2% of pages as completely accurate. The highest proportion of web pages was from media sources, which, along with discussion forums, commercial websites, and blogs, were found to have proportionally the largest amount of inaccurate information. Of 1,943 posts, 136 (7.0%) identified by the RSS were relevant, 9.6% were deemed inaccurate, and only 29.9% were deemed completely accurate. The results of our simulated query highlight the importance of public education regarding Internet usage when researching topics relating to radiation exposure associated with CT.

This study is an evaluation of the emergency department (ED) satisfaction with the current radiologic reporting system used at a major Northeastern academic medical center. The radiology reports are the main form of communication and usually the final product of any radiological investigation delivered to clinicians. The aim of this study was to improve current radiology reporting practices and to better tailor reports to match the needs and expectations of ED clinicians.A 9-question online survey was sent to ED residents, fellows, faculty, and nurse practitioners/advanced practice providers at a major Northeastern academic medical center in the United States. For the open-ended section, coding and emergent theme categorization was conducted for quantification of responses. The survey was designed to evaluate the attitudes toward the structure, style, form, and wording used in reports.The response rate was 48.6% (68/140). The ED respondents were generally satisfied with radiology reports, their language, vocabulary, and clarity. They preferred the impression section to be before the findings in simple examinations and to stratify the reports according to emergency status for complex examinations. They did not like extended differential, hedge terms, and delayed reporting. Additionally, ED respondents recommended focused, fast reporting with considerable changes toward a more standardized report.This evaluation delivered a list of actionable recommendations. The top recommendation is to standardize reporting structure, style, and lexicon, in addition to being focused, timely, and brief.

Significance African trypanosomes, Trypanosoma brucei spp., are transmitted by the bite of infected tsetse flies. Mammalian vaccines are not available, and diagnosis and treatment remain difficult in the affected remote areas. The transcriptomic analysis of individual parasites from infected tsetse salivary glands provides insight into the developmental processes that give rise to infective metacyclic parasites transmitted to the host bite site. We describe proteins associated with the different parasite developmental stages in salivary glands and specifically highlight a family of nonvariant surface proteins associated with metacyclic parasites. Immunization with one member of this family reduced parasitemia early in the infection in mice, promising to be a potential candidate antigen for a transmission blocking vaccine approach., Tsetse-transmitted African trypanosomes must develop into mammalian-infectious metacyclic cells in the fly’s salivary glands (SGs) before transmission to a new host. The molecular mechanisms that underlie this developmental process, known as metacyclogenesis, are poorly understood. Blocking the few metacyclic parasites deposited in saliva from further development in the mammal could prevent disease. To obtain an in-depth perspective of metacyclogenesis, we performed single-cell RNA sequencing (scRNA-seq) from a pool of 2,045 parasites collected from infected tsetse SGs. Our data revealed three major cell clusters that represent the epimastigote, and pre- and mature metacyclic trypanosome developmental stages. Individual cell level data also confirm that the metacyclic pool is diverse, and that each parasite expresses only one of the unique metacyclic variant surface glycoprotein (mVSG) coat protein transcripts identified. Further clustering of cells revealed a dynamic transcriptomic and metabolic landscape reflective of a developmental program leading to infectious metacyclic forms preadapted to survive in the mammalian host environment. We describe the expression profile of proteins that regulate gene expression and that potentially play a role in metacyclogenesis. We also report on a family of nonvariant surface proteins (Fam10) and demonstrate surface localization of one member (named SGM1.7) on mature metacyclic parasites. Vaccination of mice with recombinant SGM1.7 reduced parasitemia early in the infection. Future studies are warranted to investigate Fam10 family proteins as potential trypanosome transmission blocking vaccine antigens. Our experimental approach is translationally relevant for developing strategies to prevent other insect saliva-transmitted parasites from infecting and causing disease in mammalian hosts.

Summary Esophageal cancer stenting offers symptomatic relief for patients suffering from dysphagia. There are limited data to support their use to relieve dysphagia and improve nutrition during neoadjuvant therapy with some concern that they may negatively impact oncological outcomes. The aim of this systematic review was to quantify the impact of esophageal stents on outcomes prior to resection with curative intent. A literature search was performed using Embase, Medline, PubMed, PubMed Central, the Cochrane library for articles pertaining to esophageal stent use prior to or during neoadjuvant chemotherapy or chemoradiotherapy in patients planned for curative esophagectomy. Data extracted included basic demographics, clinical, nutritional and oncologic outcomes. A total of 9 studies involving 465 patients were included. Esophageal stent use resulted in a significant improvement in mean dysphagia scores in the immediate post stent period but failed to demonstrate any positive changes in weight, body mass index (BMI) or albumin. Only 33% of stented patients ultimately progressed to potential curative surgical resection and stents were associated with reduced R0 resection rates and lower overall survival. This systematic review shows that, although esophageal stenting is associated with improvements in dysphagia during neoadjuvant therapy, their effect on improving patient nutritional status is less clear and they may be associated with poorer long-term oncological outcomes. Stents should be used with caution in patients who are being considered for potentially curative resection of esophageal malignancies and other strategies of nutritional supplementation should be considered.

We report a case of primary pulmonary cryptococcosis in a 59-year-old female patient with a history of systemic lupus erythematosus, interstitial lung disease and glaucoma. She presented with a cough, severe fatigue, unintentional weight loss, shortness of breath (increase in home oxygen use from baseline) and pleuritic chest pain of 2 months duration. During these 2 months, her symptoms had worsened despite multiple hospital visits, empirical antibiotics and empirical increase of her steroid dosage. Cytopathology of the bronchoalveolar lavage fluid showed yeast cells with narrow-based budding and grew Cryptococcus neoformans on fungal culture. She was treated with oral fluconazole 400 mg/day for 6 months with an improvement in cough, decrease in shortness of breath (return to baseline oxygen use) and resolution of pleuritic chest pain.

Selective pressures imposed by pathogens have varied among human populations throughout their evolution, leading to marked inter-population differences at some genes mediating susceptibility to infectious and immune-related diseases. Here, we investigated the evolutionary history of a common polymorphism resulting in a Y529 versus C529 change in the cadherin related family member 3 (CDHR3) receptor which underlies variable susceptibility to rhinovirus-C infection and is associated with severe childhood asthma. The protective variant is the derived allele and is found at high frequency worldwide (69–95%). We detected genome-wide significant signatures of natural selection consistent with a rapid increase of the haplotypes carrying the allele, suggesting that non-neutral processes have acted on this locus across all human populations. However, the allele has not fixed in any population despite multiple lines of evidence suggesting that the mutation predates human migrations out of Africa. Using an approximate Bayesian computation method, we estimate the age of the mutation while explicitly accounting for past demography and positive or frequency-dependent balancing selection. Our analyses indicate a single emergence of the mutation in anatomically modern humans ~150 000 years ago and indicate that balancing selection has maintained the beneficial allele at high equilibrium frequencies worldwide. Apart from the well-known cases of the MHC and ABO genes, this study provides the first evidence that negative frequency-dependent selection plausibly acted on a human disease susceptibility locus, a form of balancing selection compatible with typical transmission dynamics of communicable respiratory viruses that might exploit CDHR3.

Blastomycosis is a potentially life-threatening infection caused by the fungus Blastomyces dermatitidis. As with related fungal diseases, blastomycosis is noted to affect some populations more than others. These patterns of illness are often not related to predisposing conditions or exposure risks; thus, genetic differences are thought to underlie these health disparities. People of Hmong ancestry in Wisconsin are at elevated risk of blastomycosis compared to the general population. We studied the genetic codes of Hmong blastomycosis patients and identified candidate sites in their genomes that may explain their susceptibility to this infection. We further studied one particular region of the genome that is involved with the immune processes that fight B. dermatitidis. Our work revealed population differences in the response to fungi. A better understanding of the genetic underpinnings of susceptibility to infectious diseases has broader implications for community health, especially in the paradigm of personalized medicine., Genetic differences are hypothesized to underlie ethnic disparities in incidence rates of the endemic systemic mycoses, including blastomycosis. Individuals of Hmong ancestry display elevated risk for this serious fungal infection. Here, we interrogated the genomes of Wisconsin (WI) Hmong blastomycosis patients using homozygosity mapping to uncover regions of the genome that are likely shared among the greater Hmong population and filtered for variants with high potential to affect disease susceptibility. This approach uncovered 113 candidate susceptibility variants, and among the most promising are those in genes involved in the interleukin-17 (IL-17) response. In particular, we identified 25 linked variants near the gene encoding IL-6 (IL6). We validated differences in cytokine production between Hmong and European volunteers and formally demonstrated a critical role for IL-6 in the development of adaptive immunity to Blastomyces dermatitidis. Our findings suggest that the dysregulation of IL-17 responses underlies a recently reported and poorly understood ethnic health disparity.

Introduction The authors propose that tablet computers could benefit patients with acute stroke in the remote care setting, where time to and accuracy of CT interpretation greatly influences patient outcome. Methods One hundred and fifty consecutive patients who presented to the Emergency Department of a tertiary referral neurosciences centre within a time window suitable for intravenous thrombolytic therapy were included. Images were wirelessly transmitted to a tablet computer (iPad 3rd Generation, model = A1430, Apple, Cupertino, CA) and were reviewed by radiologists with three levels of experience for signs of intracranial haemorrhage, large vessel occlusion and parenchymal infarction. Reference standard interpretation was performed by two neuroradiologists using a diagnostic monochrome display. Results Consensus neuroradiologist review on the tablet display found and correctly classified all of the 23 cases of intracranial haemorrhage including 21 cases of parenchymal haematoma, two cases of petechial haemorrhage and one patient with an acute subdural haematoma. Less experienced readers missed cases of petechial and subdural haematomas. There was excellent agreement between the tablet and diagnostic monochrome display in cases with no infarct or extensive parenchymal infarction. Conclusions Tablet computers can be used to facilitate rapid preliminary CT interpretation in patients with acute stroke in the remote setting.

Methylmalonic acid (MMA) is a by-product of propionic acid metabolism through the vitamin B12 (cobalamin)-dependent enzyme methylmalonyl CoA mutase. Elevated MMA concentrations are a hallmark of several inborn errors of metabolism and indicators of cobalamin deficiency in older persons. In a genome-wide analysis of 2,210 healthy young Irish adults (median age 22 years) we identified a strong association of plasma MMA with SNPs in 3-hydroxyisobutyryl-CoA hydrolase (HIBCH, p = 8.42 × 10(-89)) and acyl-CoA synthetase family member 3 (ACSF3, p = 3.48 × 10(-19)). These loci accounted for 12% of the variance in MMA concentration. The most strongly associated SNP (HIBCH rs291466; c:2TC) causes a missense change of the initiator methionine codon (minor-allele frequency = 0.43) to threonine. Surprisingly, the resulting variant, p.Met1?, is associated with increased expression of HIBCH mRNA and encoded protein. These homozygotes had, on average, 46% higher MMA concentrations than methionine-encoding homozygotes in young adults with generally low MMA concentrations (0.17 [0.14-0.21] μmol/L; median [25(th)-75(th) quartile]). The association between MMA levels and HIBCH rs291466 was highly significant in a replication cohort of 1,481 older individuals (median age 79 years) with elevated plasma MMA concentrations (0.34 [0.24-0.51] μmol/L; p = 4.0 × 10(-26)). In a longitudinal study of 185 pregnant women and their newborns, the association of this SNP remained significant across the gestational trimesters and in newborns. HIBCH is unique to valine catabolism. Studies evaluating flux through the valine catabolic pathway in humans should account for these variants. Furthermore, this SNP could help resolve equivocal clinical tests where plasma MMA values have been used to diagnose cobalamin deficiency.

Introduction Preoperative radiation combined with mesorectal excision has reduced local recurrence rates in rectal cancer. The role for neoadjuvant therapy in upper third rectal cancer remains unclear. The current study aimed to use meta-analytical techniques to compare outcomes of upper third rectal tumors relative to those of the middle and lower rectum. Materials and Methods Meta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases were searched for studies comparing outcomes between patients with upper third and more distal rectal cancer undergoing primary resection. Patients receiving neoadjuvant treatment were excluded. Results were reported as odds ratios (ORs) with 95% confidence intervals (95% CIs). Results A total of 174 citations were reviewed; 5 studies comprising 3381 patients were included in the analysis. There was no difference in the rate of T3/4 tumors (OR, 1.303; 95% CI, 0.920-1.847; P = .137), lymph node positivity (OR, 1.004; 95% CI, 0.865-1.165; P = .961), and circumferential resection margin positivity (OR, 0.898; 95% CI, 0.556-1.450; P = .660) between upper third and more distal rectal cancers. However local recurrence (OR, 0.495; 95% CI, 0.302-0.811; P = .005) and distant recurrence (OR, 0.613; 95% CI, 0.511-0.734; P Conclusions These data suggest that upper third rectal cancer has reduced local and distant recurrence rates despite similarity in disease stage and margin positivity. Further studies examining effects of neoadjuvant radiation in rectal cancer should consider upper rectal tumors as a distinct entity to middle and lower rectal tumors.

Repeated emergence, not international dissemination, is behind the rise of multidrug-resistant lineage 4 tuberculosis., On the basis of population genomic and phylogeographic analyses of 1669 Mycobacterium tuberculosis lineage 4 (L4) genomes, we find that dispersal of L4 has been completely dominated by historical migrations out of Europe. We demonstrate an intimate temporal relationship between European colonial expansion into Africa and the Americas and the spread of L4 tuberculosis (TB). Markedly, in the age of antibiotics, mutations conferring antimicrobial resistance overwhelmingly emerged locally (at the level of nations), with minimal cross-border transmission of resistance. The latter finding was found to reflect the relatively recent emergence of these mutations, as a similar degree of local restriction was observed for susceptible variants emerging on comparable time scales. The restricted international transmission of drug-resistant TB suggests that containment efforts at the level of individual countries could be successful.

This study was undertaken to evaluate uncertainty from the Basic Specialist Trainee perspective. The survey of trainees explored 1) factors in decision making, 2) the personal impact of uncertainty, 3) the responses to both clinical errors and challenges to their decision making and 4) the potential strategies to address uncertainty. Forty-one (93%) of trainees surveyed responded. Important factors in decision making were clinical knowledge and senior colleague's opinion. Sixty percent experienced significant anxiety post call as a consequence of their uncertainty. When errors are made by colleagues, the trainee's response is acceptance (52.5%), and sympathy (32%).Trainees are strongly influenced by the opinions of senior colleagues often changing their opinions having made confident decisions. Solutions to address uncertainty include enhanced knowledge translation, and to a lesser extent, enhanced personal awareness and resilience awareness. To enhance the training experience for BST and lessen the uncertainty experienced these strategies need to be enacted within the training milieu.

Background Neoadjuvant therapy is increasingly the standard of care in the management of locally advanced adenocarcinoma of the oesophagus and junction (AEG). In randomised controlled trials (RCTs), the MAGIC regimen of pre- and postoperative chemotherapy, and the CROSS regimen of preoperative chemotherapy combined with radiation, were superior to surgery only in RCTs that included AEG but were not powered on this cohort. No completed RCT has directly compared neoadjuvant or perioperative chemotherapy and neoadjuvant chemoradiation. The Neo-AEGIS trial, uniquely powered on AEG, and including comprehensive modern staging, compares both these regimens. Methods This open label, multicentre, phase III RCT randomises patients (cT2-3, N0-3, M0) in a 1:1 fashion to receive CROSS protocol (Carboplatin and Paclitaxel with concurrent radiotherapy, 41.4Gy/23Fr, over 5 weeks). The power calculation is a 10% difference in favour of CROSS, powered at 80%, two-sided alpha level of 0.05, requiring 540 patients to be evaluable, 594 to be recruited if a 10% dropout is included (297 in each group). The primary endpoint is overall survival, with a minimum 3-year follow up. Secondary endpoints include: disease free survival, recurrence rates, clinical and pathological response rates, toxicities of induction regimens, post-operative pathology and tumour regression grade, operative in-hospital complications, and health-related quality of life. The trial also affords opportunities for establishing a bio-resource of pre-treatment and resected tumour, and translational research. Discussion This RCT directly compares two established treatment regimens, and addresses whether radiation therapy positively impacts on overall survival compared with a standard perioperative chemotherapy regimen Sponsor: Irish Clinical Research Group (ICORG). Trial registration NCT01726452. Protocol 10-14. Date of registration 06/11/2012. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3386-2) contains supplementary material, which is available to authorized users.

The term functional gastrointestinal disorders (FGID) describes various aggregations of chronic gastrointestinal (GI) symptoms not explained by identifiable organic pathology; accordingly, their diagnosis rests on symptom-based criteria and a process of exclusion. Evidence is lacking on the appropriate use of abdominal imaging studies (AIS) in FGIDs. We investigated the utilisation of AIS (site, modality, diagnostic yield/significance) at a tertiary FGID clinic over an 11-year period. Of 1,621 patients, 507 (31 %; 67.5 % women, mean age 43.9 ± 17.37 years) referred from primary care had 997 AIS (1.7 per patient): ultrasonography (US) 36.1 %, fluoroscopy (FLS) 28.8 %, computed tomography (CT) 19.6 %, plain radiography (PR) 13.5 %, nuclear medicine (NM) 1 %). Of the 997 AIS, 55.6 % (554/997) were normal. Of the AIS with positive findings, 9.9 % (62/625) were deemed ‘probably significant’ and 14.7 % (92/625) ‘significant’. Of the CT and FLS studies, 12.3 % and 13.6 %, respectively, yielded ‘significant’ abnormalities compared to 2.2 % of the US studies and 2.1 % of the PR studies. CT identified five of seven neoplasms, associated with male sex, increasing age and symptom onset after age 50 years. This study confirmed low use of AIS in tertiary FGID clinics and a high proportion of normal studies. Barium swallow/meal and CT were more likely to identify ‘probably significant’ or ‘significant’ findings, including neoplasms. • Imaging referral rates from a specialist functional gastrointestinal disorder clinic are low • Despite this, normal studies are still frequent in those who are imaged • Ultrasonography was the most frequent investigation, yet yielded significant findings infrequently • Abdominal radiographs accounted for 13.5 % of investigations yet were normal in 71.8 % • CT and fluoroscopy were more likely to yield positive findings

This study investigated demographic factors, experience of burn/care and first aid course attendance as factors influencing burn first aid knowledge.A cross-sectional study was undertaken using convenience sampling of members of sporting and recreation clubs. The main outcome measure was the proportion of correct responses to multiple-choice questions relating to four burn scenarios: (1) scald, (2) contact burn, (3) ignited clothing, and (4) chemical burn.A total of 2602 responses were obtained. Large gaps (30-50% incorrect answers) were identified in burn first aid knowledge across all scenarios. 15% more individuals gave correct answers if they had attended a first aid course compared to those who had not (p0.0001); this proportion increased if the course was undertaken within the previous five years (p0.0001) or contained a burns-specific component (p0.0001). Males and younger (≤25 years) and older (≥65 years) age-groups had relatively lower levels of burn first aid knowledge. Gender and age were significant predictors of first aid course attendance, with males and younger (≤25 years) and older (≥65 years) age-groups less likely to have attended a first aid course.In this sample, first aid training undertaken within the last 5 years with a specific burns component was associated with enhanced burn first aid knowledge.

Severe burn injury significantly affects cardiovascular function for up to 3 years. However, whether this leads to long-term pathology is unknown. The impact of non-severe burn injury, which accounts for over 80% of admissions in developed countries, has not been investigated. Using a rodent model of non-severe burn injury with subsequent echocardiography we showed significantly increased left ventricular end systolic diameter (LVESD) and ventricular wall thickness at up to 3 months post-injury. Use of propranolol abrogated the changes in cardiac measures observed. Subsequently we investigated changes in a patient cohort with non-severe injury. Echocardiography measured at baseline and at 3 months post-injury showed increased LVESD at 3 months and significantly decreased posterior wall diameter. Finally, 32 years of Western Australian hospital records were used to investigate the incidence of cardiovascular disease admissions after burn injury. People who had experienced a burn had increased hospital admissions and length of stay for cardiovascular diseases when compared to a matched uninjured cohort. This study presents animal, patient and population data that strongly suggest non-severe burn injury has significant effects on cardiovascular function and long-term morbidity in some burn patients. Identification of patients at risk will promote better intervention and outcomes for burn patients.

Background Results of previous studies have shown that repeated abdominopelvic computed tomography (CT) examinations can lead to substantial cumulative diagnostic radiation exposure in patients with Crohn's disease (CD). Improved selection of patients referred for CT will reduce unnecessary radiation exposure. This study examines if serum C-reactive protein (CRP) concentration predicts which symptomatic patients with CD are likely to have significant disease activity or disease complications (such as abscess) detected on abdominopelvic CT. Methods All abdominopelvic CTs performed on patients with CD at a tertiary referral centre during the period June 2003 to June 2008 were identified. CT findings were coded by a pair of independent blinded senior radiologists for (i) small bowel luminal disease, (ii) large bowel luminal disease, (iii) mesenteric inflammatory changes, (iv) penetrating disease (fistulas, abscess, or phlegmon), (v) acute disease complications (obstruction or perforation), and (vi) acute non-CD findings. Imaging findings were correlated with serum CRP checked within 14 days before imaging. The reference range for CRP was defined as 0–5 mg/L. Results A total of 147 patients with symptomatic CD had a CRP assay performed within 14 days before undergoing abdominopelvic CT. The median time from CRP assay to imaging was 2 days (interquartile range, 0-6 days). Median CRP before imaging was 24 mg/L (interquartile range, 6-88 mg/L). CT was normal in 34 of 147 case (23.1%). Patients with normal CRP (n = 36) were significantly less likely to have penetrating disease (odds ratio [OR], 0.04 [95% confidence interval {CI}, 0.01-0.7]; P < .001) or large bowel luminal disease (OR, 0.3 [95% CI, 0.1-0.8]; P < .05). Normal CRP excluded penetrating disease with a sensitivity of 1.0 (95% CI, 0.87-1.0). CRP levels did not correlate with the presence of small bowel luminal disease (n = 82), mesenteric inflammatory changes (n = 68), or acute disease complications (n = 10). Conclusion Symptomatic patients with CD and normal serum CRP are unlikely to have evidence of abscess, fistulating disease, or large bowel luminal disease detected on abdominopelvic CT. However, abdominopelvic CT may demonstrate evidence of clinically significant non-penetrating CD or complications, including perforation and acute obstruction, regardless of serum CRP concentration.

Aim To determine the diagnostic yield and clinical value of plain film of the abdomen (PFA) in Crohn's disease (CD) patients and to determine whether performance of PFA yields definitive diagnostic information or whether additional imaging examinations are required. Materials and methods One hundred and seventy-seven CD patients underwent 643 PFAs during the period September 1992 to August 2008. Two radiologists blinded to the clinical details independently evaluated individual PFAs and/or their reports for abnormal findings using the following criteria: normal, small bowel (SB) findings; colonic findings, acute CD complications, extra-colonic findings; global assessment/impression. The results of additional imaging studies performed within 5 days of PFA were recorded and findings were analysed. Results A mean of 3.6 (range 1–22) PFAs was performed per patient during the study period. Almost 70% of films were normal ( n = 449). SB abnormalities were detected in 21.8% ( n = 140) PFAs; most commonly dilated loops (18.8%, n = 121) and mucosal oedema (5%, n = 32). Colonic abnormalities were present in 11.4% ( n = 73); most commonly mucosal oedema (7.5%, n = 48) and dilated loops (5%, n = 32). Four cases of pneumoperitoneum were detected. There was no case of toxic megacolon. There was one case in which intra-abdominal abscess/collection was suspected and two cases of obstruction/ileus. Extracolonic findings (renal calculi, sacro-iliitis, etc.) were identified in 7.5% ( n = 48). PFAs were followed by additional abdominal imaging within 5 days of PFA in 273/643 (42.5%) of cases. Conclusion Despite the high rates of utilization of PFA in CD patients, there is a low incidence of abnormal findings (32.5%). Many of the findings are non-specific and clinically irrelevant and PFA is frequently followed by additional abdominal imaging examinations.

Four employees at a chemical plant sustained extensive chemical burns following the explosion of a pipeline containing 100% sulphuric acid. We describe the management of these patients from the initial ED triage through to discharge from hospital in life and limb threatening chemical burns.Four patients who sustained chemical burns to the torso and extremities are reviewed. Data was retrieved from patient case notes and operating theatre logbooks.Four patients sustained chemical burns during the blast and were immediately transferred to a local ED where a prompt referral was made to the burns service. All patients were male aged 25-59 years (mean 46.5). Burn size was 2-50% BSA (mean 22.5). Following RFDS transfer to the state burns service two patients required immediate excisional surgery. In these patients the chemical burn involved full thickness skin loss with extensive underlying muscle and neurovascular damage. One patient required immediate above knee amputation of one leg and fascial burn excision of the other. The other patient required fascial burn excision of both legs followed by Integra placement 24h later. Both patients had prolonged hospital stays due to the complex nature of their injuries requiring multiple trips to theatre and lengthy rehabilitation. The two patients with smaller burns had straightforward surgery and an unremarkable recovery.Early communication following this mass casualty incident allowed for organisation of tertiary services and early radical surgery which was life saving. Management lessons were learnt following this mass casualty chemical burn incident.

Introduction With increasing numbers of illicit drug users in both urban and rural communities, users and producers are becoming increasingly enterprising in their sourcing of mind altering drugs. An example of this is the ‘amateur’ production of methamphetamine in domestic dwellings. We describe the mechanism of burn seen in methamphetamine production, the pattern of clinical injury, and the difficulties in treating these patients. Methods A 12 month retrospective study of five patient groups presenting to our burn service with injuries following methamphetamine laboratory explosion. Results Out of five patient groups we have treated 9 individual patients (with one patient presenting on two different occasions) with burns following methamphetamine laboratory explosion. All patients were male and required hospital admission. The cause of the explosive injury was initially reported as barbeque or oven related, assault, or accident in all patients. Two patients (in separate events) required intubation for associated inhalation injury. Burn size varied from 1% to 40% BSA. 7 patients required surgical debridement and skin grafting. Injury type was thermal and chemical. All patients had difficult follow-up due to low levels of clinic attendance. Conclusion Methamphetamine laboratory explosion burns are difficult injuries from the start. Invariably the true circumstances surrounding the injury are not clear, and clinicians should be suspicious of a meth lab explosion in suspect individuals with burns plus airway injury. Patient management is complex and often requires substantial analgesic and anxiolytic medication in conjunction with clinical psychology and psychiatry as an inpatient.

Prevention of bacterial colonization and consequent biofilm formation remains a major challenge in implantable medical devices. Implant-associated infections are not only a major cause of implant failures but also their conventional treatment with antibiotics brings further complications due to the escalation in multidrug resistance to a variety of bacterial species. Owing to their unique properties, antimicrobial peptides (AMPs) have gained significant attention as effective agents to combat colonization of microorganisms. These peptides have been shown to exhibit a wide spectrum of activities with specificity to a target cell while having a low tendency for developing bacterial resistance. Engineering biomaterial surfaces that feature AMP properties, therefore, offer a promising approach to prevent implant infections. Here, we engineered a chimeric peptide with bifunctionality that both forms a robust solid-surface coating while presenting antimicrobial property. The individual domains of the chimeric peptides were evaluated for their solid-binding kinetics to titanium substrate as well as for their antimicrobial properties in solution. The antimicrobial efficacy of the chimeric peptide on the implant material was evaluated in vitro against infection by a variety of bacteria, including Streptococcus mutans, Staphylococcus. epidermidis, and Escherichia coli, which are commonly found in oral and orthopedic implant related surgeries. Our results demonstrate significant improvement in reducing bacterial colonization onto titanium surfaces below the detectable limit. Engineered chimeric peptides with freely displayed antimicrobial domains could be a potential solution for developing infection-free surfaces by engineering implant interfaces with highly reduced bacterial colonization property.

Body composition assessment is an integral feature of elite sport as optimization facilitates successful performance. This study aims to refine the use of B-mode ultrasound in the assessment of athlete body composition by determining suitable sites for measurement. 67 elite athletes recruited from the Human Performance Laboratory, University College Cork, Ireland, underwent dual measurement of body composition. Subcutaneous adipose tissue thickness at 7 anatomical sites were measured using ultrasound and compared to percentage body fat values determined using Dual-Energy X-ray Absorptiometry. Multiple linear regressions were performed and an equation to predict percentage body fat was derived. The present study found subcutaneous adipose tissue depths at the triceps, biceps, anterior thigh and supraspinale sites correlated significantly with percentage body fat by X-ray absorptiometry (all p

To explore the community integration of individuals who had suffered a Traumatic Brain Injury (TBI) and compare this to members of the general public.An independent groups design explored differences in three groups' levels of community integration. These groups consisted of ten survivors of TBI, ten male and ten female controls and were measured using The Community Integration Measure (CIM). All participants were resident in Northern Ireland (NI). The brain injured participants were drawn from a Belfast-based social skills programme.Mann-Whitney U tests showed a statistically significant difference between female controls and brain-injured individuals (U = 26.50, N(1) = 10, N(2) = 10, p = 0.037, one-tailed).Females were more integrated into their communities than males, who were, in turn, more integrated than brain injured individuals. It would appear that brain injury survivors are doubly disadvantaged. Their gender (mainly male), and the injury itself, conspire to reduce their integration within the wider community.

Summary: Purpose: When seizures do not respond to medications, video-EEG monitoring is the best available diagnostic tool and is the principal activity of epilepsy centers. The purpose of this study was to analyze the eventual disposition of patients who undergo video-EEG monitoring at a typical referral epilepsy center. Methods: We reviewed the diagnoses and dispositions of all patients (adults and children) who underwent inpatient video-EEG monitoring (≥24 h) at our center (University of South Florida–Tampa General Hospital) over a 1-year period (2002). Results: In total, 251 inpatient video-EEG monitoring sessions were performed. Nonepileptic seizures were diagnosed in 75 (30%); 58 (23%) were found to be surgical candidates; seven were implanted with the vagus nerve stimulator. In 47 (19%) patients, seizures were recorded, and the diagnosis of epilepsy was confirmed and clarified (symptomatic/cryptogenic generalized epilepsy, seven; localization-related epilepsy, 35; idiopathic generalized epilepsy, five). Conclusions: The eventual outcome of video-EEG monitoring is diverse. The largest groups, as expected, are psychogenic nonepileptic seizures (30%), and surgery (23%).

To establish patients' perception of the effect of sport on rehabilitation.Single investigator telephone questionnaire survey.Spinal Cord Injuries Unit, Musgrave Park Hospital, Belfast, Northern Ireland, UK.A telephone questionnaire was administered to patients admitted over a 12-month period. Information on patient demographics, sports participation before and after injury and patients' perception of the impact of sports on rehabilitation was recorded.In all, 33 (84.6%) of the 39 patients could be contacted and all completed the questionnaire. Of the respondents 27 (81.8%) had a diagnosis of spinal cord injury. Six (18.2%) were female and 20 (60.6%) were below 45 years.A total of 15 (45.5%) patients previously participated in regular sporting activity. At least 24 (72.7%) tried one sport during admission. In all, 14 reported taking part in regular sporting activity after discharge, although 23 expressed a desire to do so. Of those 60% who had regularly exercised continued to do so and 27% of those who reported no regular sport, before injury, commenced regular active exercise. A general benefit of sporting activity was recognised by 78.8% and a rehabilitation benefit by 69.7%. Self-reported benefits included increase in fitness, quality of life, confidence and social contact.A high proportion of patients perceived sporting activity as beneficial. Patients exercising before injury were more likely to exercise after injury. All inpatients were introduced to sport by staff, emphasising the importance of this rehabilitation opportunity in planning in-patient care.

The morphometric oxygen diffusive conductance ( D p ) of the placenta provides a measure of the efficiency of oxygen transfer between the mother and the developing fetus. Any change in the D p may point towards possible adaptation in the light of altered oxygen transfer. Placentae from normal ( n =40) and small for gestational age SGA ( n =24) pregnancies were analysed using stereological techniques. Each placenta was uniform randomly sampled and tissue samples processed to wax infiltration and embedding using conventional histological preparatory methods. A combination of stereological techniques and physiological constants were used to estimate the partial conductances across the five major tissue compartments involved in oxygen transfer. There was a significant reduction in both fetal birthweight and placental weight in the SGA group when compared with controls. A decrease in both chorionic ( S cv ) and fetal capillary ( S fc ) surface area was also observed in SGA placentae when compared with controls ( P >0.001). Villous membrane harmonic thickness ( T vm ) was reduced in the SGA placentae (2.33 μm) when compared with controls (2.67 μm P =0.019). This resulted in a reduction in the minimum D p in SGA placentae when compared with controls ( P =0.023). Adjusting for fetal weight resulted in no difference in the specific diffusive conductance. Changes in T vm in SGA placentae combined with changes in basic surface areas were insufficient to maintain overall D p values comparable with control placentae.

Background: The purpose of this study was to further delineate the outcome of arthroscopically assisted anterior cruciate ligament reconstruction in 125 patients who had previously been followed for two to five years. One of the original 125 patients was excluded from the present study because of insufficient follow-up, and an additional group of 101 patients was added. All 225 patients in the present study were followed for a minimum of six years. Methods: Patients were randomly assigned to reconstruction with a double-stranded semitendinosus-gracilis graft with use of a two‐incision technique (group I), reconstruction with a patellar ligament graft with use of a two‐incision technique (group II), or reconstruction with a patellar ligament graft with use of a single‐incision endoscopic technique (group III). The groups were compared with regard to the rate of graft failure, the amount of instability, knee strength, radiographic signs of degenerative changes, and functional outcome. Results: There was no significant difference among the three groups with regard to the rate of graft failure, the amount of knee instability, or the functional outcome. A normal or nearly normal functional outcome was recorded for 208 (92%) of the 225 patients. There were significant differences among the groups with regard to quadriceps muscle-strength deficits: group I had fewer patients with deficits than group III, and groups I and III both had fewer patients with deficits than group II (p = 0.04). There also were significant differences among the groups with regard to hamstring muscle-strength deficits: group III had fewer patients with deficits than group II, and group II had fewer patients with deficits than group I (p < 0.01). Twelve knees (16%) in group I, six knees (8%) in group II, and eight knees (11%) in group III showed radiographic evidence of progressive degenerative changes, but the differences among the three groups were not significant. Conclusion: Although 11.6% of the 225 knees had radiographic evidence of degenerative arthritis at a minimum of six years after arthroscopically assisted reconstruction of the anterior cruciate ligament, the choice of graft and the technique of reconstruction did not seem to affect the rate of development of these changes.

Acute pancreatitis is an uncommon cause of abdominal pain during pregnancy, and rarely progresses to the necrotizing from of the disease in this clinical setting. Hyperlipidemia is an infrequent cause of acute pancreatitis. Whereas only 100 cases of hyperlipidemia-induced necrotizing pancreatitis have been reported in the literature to date, all of the cases were mild in severity and responsive to conservative medical management. Herein we present a case of life-threatening necrotizing pancreatitis, which developed in a hyperlipidemic pregnant woman and required multiple peripartum pancreatic necrosectomies. Additionally, we review the evaluation of pregnant patients with abdominal pain, the pathophysiology of hyperlipidemia-induced necrotizing pancreatitis, and the operative care of this challenging group of patients, revisiting an innovative technique for management of the retroperitoneum.

Summary Early diagnosis of malaria followed by appropriate treatment can help reduce related morbidity and mortality as well as interrupt transmission. Previous studies of household responses to malaria have tended to focus on endemic areas where the burden of this disease is greatest. With the apparent increasing frequency of epidemics in African highlands, a better understanding of treatment behaviours in areas of unstable transmission may be important to future public health interventions. This study was undertaken following a serious epidemic of malaria in the highlands of south-western Uganda. Our objectives were to characterize actions taken by both adults and caretakers of children ≤5 years old during their most recent episode of self-diagnosed malaria, and to identify factors that were associated with prompt treatment at a health facility. A survey of 300 households selected in a 2-stage cluster sampling procedure produced 453 adult respondents and 133 caretakers of children ≤5 years old. We found that almost 65% of adults and 62% of children who had experienced an episode of malaria in the last year (most during the epidemic) had sought treatment from a health facility first as opposed to self-treatment. Most of these people had visited the health facility within 1 day of symptom onset. By the end of their malaria episode, over 87% of adults and 80% of children had visited a health facility at least once. Factors associated with prompt presentation at a health facility included severity of illness, household proximity to a health facility, and knowledge of malaria prevention methods. Our results indicate that there is an important role for the formal health care system in mitigating morbidity and mortality and reducing transmission during malaria epidemics in Uganda.

Given the genetically heterogeneous nature of many dominantly inherited disorders, it will be imperative to design mutation-independent therapeutic strategies to circumvent such heterogeneity. Intragenic polymorphism represents a genomic resource that may be harnessed in the development of allele-specific mutation-independent therapeutics. A hammerhead ribozyme, Rzpol1a1, selectively cleaves a common single-nucleotide polymorphism (SNP) of the human COL1A1 transcript (heterozygosity frequency of 2 pq = 0.4032, from Hardy-Weinberg equilibrium). One SNP variant contains a hammerhead ribozyme cleavage site, and the other does not. Kinetic evaluation shows Rzpol1a1 to be both specific and extremely efficient in vitro. Thus, a single efficient ribozyme has been characterized that should be valuable in the development of a gene therapy suitable for up to 1 in 5 dominant-negative osteogenesis imperfecta (OI) patients, where over 150 different mutations have been identified to date. Given the increasing characterization of intragenic SNP, it is predicted that such a mutation-independent strategy, based on selective silencing of mutant alleles at SNP, may become increasingly important in future genomics-driven drug development for many heterogeneous dominant disorders and complex traits.

CONTEXT AND QUESTION ASKED: In patients with metastatic cancer, chemotherapy may provide symptom control, prevent complications, prolong life, or improve quality of life. Except in rare cases, however, patients with metastatic disease will not be cured. In older patients with metastatic cancer, hospitalization for treatment toxicity may reduce the quality of an already limited life expectancy. We evaluated the association between chemotherapy for metastatic cancer and risk of hospitalization. MAIN CONCLUSION: Hospitalizations are common in patients with incurable advanced malignancies and are more likely among those who receive chemotherapy. APPROACH: In the linked SEER-Medicare dataset, we identified Medicare beneficiaries aged 66 years or older with a primary diagnosis of metastatic breast, colorectal, ovarian, bladder, lung, pancreas, esophageal, stomach, or prostate cancer between 2001 and 2009 who died by the end of 2010. Chemotherapy recipients and nonrecipients were pair-matched by age, sex, race, comorbidity, geographic region and survival duration. The primary endpoint was hospital admission, identified in inpatient claims between cancer diagnosis and the first of hospice admission or death. We also identified the subset of admissions associated with a primary or secondary diagnosis code suggestive of an adverse effect of chemotherapy. The association between chemotherapy and hospitalization was estimated in separate multivariable Cox proportional-hazards regression models for each cancer site, accounting for the matched-pairs design and controlling for unmatched demographic and disease characteristics. RESULTS: Of 18,486 patients who received chemotherapy for metastatic cancer, 92% were hospitalized at least once for any reason, including 51% hospitalized for a likely toxicity. The corresponding rates among matched non-recipients were 83% and 34% (Figure). In nearly all cancers, chemotherapy recipients had a greater risk of hospitalization for a likely toxicity or for any cause. Chemotherapy recipients had substantially higher hospitalization for infection or fever (21% v 15%), hematologic complications (11% v 3%), dehydration (13% v 6%), and PE or DVT (9% v 4%) compared with nonrecepients. Chemotherapy was associated with a significantly increased risk of likely toxicity-related hospitalization in nearly all cancers, controlling for sociodemographic characteristics and other treatment. The association was greatest in patients with metastatic esophageal cancer (adjusted hazard ratio, 2.00; 95% CI, 1.11 to 3.60) and smallest in patients with metastatic prostate cancer (adjusted hazard ratio, 1.22; 95% CI, 1.01 to 1.47). INTERPRETATION: Older patients receiving chemotherapy for incurable advanced cancers are at high risk of hospitalization, of which a non-negligible proportion is likely attributable to adverse effects of treatment. Infection, fever, dehydration, and hematologic complications constitute a large proportion of these events, some of which may be preventable through evidence-based patient management, prophylactic interventions, and effective outpatient care. Our findings might be limited to older patients with advanced cancer who have a generally poor prognosis or limited expected survival. SIGNIFICANCE OF FINDINGS: Understanding the common reasons for hospital admissions and developing toxicity management programs and educational resources may help patients and their families make informed treatment decisions, minimize adverse effects and reduce hospitalizations in this population with limited life expectancy. [Figure: see text]