The Kampala Trauma Score has poor diagnostic accuracy for most emergency presentations

Publication date: Available online 7 August 2017
Source:Injury
Author(s): Stevan R Bruijns, Lee A Wallis




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Tumor- and class-specific patterns of immune-related adverse events of immune checkpoint inhibitors: a systematic review.

Abstract

Background:Immune checkpoint inhibitor (ICI) monoclonal antibodies (mAbs) targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1) or its ligand (PD-L1) produce unique toxicity profiles. The objective of this review was to identify patterns and incidence of immune related adverse events (irAE) based on tumor type and ICI class.Methods:MEDLINE, EMBASE and COCHRANE databases were searched to identify prospective monotherapy trials of ICIs from 2003 to November 2015. Paired reviewers selected studies for inclusion and extracted data. Odds ratio (OR), chi-squared tests and multivariable regression models were used to analyze for effect size and associations.Results:We identified 48 trials (6938 patients), including 26 CTLA-4, 17 PD-1, 2 PD-L1 trials, and 3 studies tested both CTLA-4 and PD-1. Grade 3/4 irAE were more common with CTLA-4 mAbs compared with PD-1 (31% vs 10%). All grades colitis (OR 8.7, CI 5.8-12.9), hypophysitis (6.5, 3.0-14.3) and rash (2.0, 1.8-2.3) were more frequent with CTLA-4 mAbs; whereas pneumonitis (6.4, 3.2-12.7), hypothyroidism (4.3, 2.9-6.3), arthralgia (3.5, 2.6-4.8) and vitiligo (3.5, 2.3-5.3) were more common with PD-1 mAbs. Comparison of irAE from the 3 most studied tumor types in PD-1 mAbs trials [melanoma (n = 2048), non-small cell lung cancer (n = 1030) and renal cell carcinoma (n = 573)] showed melanoma patients had a higher frequency of gastrointestinal and skin irAE and lower frequency of pneumonitis.Conclusions:CTLA-4 and PD-1 mAbs have distinct irAE profiles. Different immune microenvironments may drive histology-specific irAE patterns. Other tumor-dependent irAE profiles may be identified as data emerge from ICI trials.

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Response to: "Maternal infection can cause spontaneous abortion" [Letters]

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Canada needs a holistic First Nations health strategy [Commentary]

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Alcoholic versus aqueous chlorhexidine for skin antisepsis: the AVALANCHE trial [Research]

BACKGROUND:

Preoperative skin antisepsis is routine practice. We compared alcoholic chlorhexidine with aqueous chlorhexidine for skin antisepsis to prevent surgical site infection after minor skin excisions in general practice.

METHODS:

We conducted this prospective, multicentre, randomized controlled trial in 4 private general practices in North Queensland, Australia, from October 2015 to August 2016. Consecutive adult patients presenting for minor skin excisions were randomly assigned to undergo preoperative skin antisepsis with 0.5% chlorhexidine in 70% ethanol (intervention) or 0.5% chlorhexidine aqueous solution (control). Our primary outcome was surgical site infection within 30 days of excision. We also measured the incidence of adverse reactions.

RESULTS:

A total of 916 patients were included in the study: 454 underwent antisepsis with alcoholic chlorhexidine and 462 with aqueous chlorhexidine. Of these, 909 completed follow-up. In the intention-to-treat analysis of cases available at follow-up, there was no significant difference in the incidence of surgical site infection between the alcoholic chlorhexidine arm (5.8%, 95% confidence interval [CI] 3.6% to 7.9%) and the aqueous chlorhexidine arm (6.8%, 95% CI 4.5% to 9.1%). The attributable risk reduction was 0.010 (95% CI –0.021 to 0.042), the relative risk was 0.85 (95% CI 0.51 to 1.41), and the number needed to treat to benefit was 100. Per protocol and sensitivity analyses produced similar results. The incidence of adverse reactions was low, with no difference between groups (p = 0.6).

INTERPRETATION:

There was no significant difference in efficacy between alcoholic and aqueous chlorhexidine for the prevention of surgical site infection after minor skin excisions in general practice. Trial registration: http://ift.tt/1F0tq3G, no. ACTRN12615001045505

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New evidence of contaminants from fracking [News]

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Bariatric surgery [Practice]

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Maternal infection can cause spontaneous abortion [Letters]

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Severe allergic contact dermatitis due to Polysporin [Practice]

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Online pharmacy still open despite counterfeit allegations [News]

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The expert [Humanities]

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ParticiPAte CP: a protocol of a randomised waitlist controlled trial of a motivational and behaviour change therapy intervention to increase physical activity through meaningful participation in children with cerebral palsy

Introduction

Children with cerebral palsy (CP) participate in leisure-time physical activities (PA) less often, with less intensity and reduced diversity than their typically developing peers. Participation in leisure-time physical activities may be an important source of habitual physical activity (HPA) for children with CP, who as a group have lower levels of HPA and increased sedentary time compared with their typically developing peers. The proposed study aims to compare the efficacy of a participation focused therapy (ParticiPAte CP) to usual care in a pragmatic, randomised waitlist controlled trial.

Methods and analysis

Thirty-six children with CP (18 in each group), classified as Gross Motor Function Classification System levels I to III, aged between 8 and 12 years will be recruited across South East Queensland, Australia. Children will be randomised to receive either ParticiPAte CP or waitlist usual care using concealed allocation. ParticiPAte CP is an individually tailored, goal-directed intervention model of pragmatic participation-focused therapy using a toolbox of evidence-based strategies in the treatment of children with CP. This will include goal-setting; identification of barriers and facilitators to participation goals, strategy formation and planning and communication guided by principles of Self-Determination Theory using strategies of Motivational Interviewing. The intervention comprises 8 weekly sessions of 1 hour duration conducted by a physiotherapist in the child's home or community.

Trial registration number

ACTRN12615001064594.

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Reactions to international health care rankings [News]

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Answering medical questions at the point of care: a cross-sectional study comparing rapid decisions based on PubMed and Epistemonikos searches with evidence-based recommendations developed with the GRADE approach

Introduction

Using the best current evidence to inform clinical decisions remains a challenge for clinicians. Given the scarcity of trustworthy clinical practice guidelines providing recommendations to answer clinicians' daily questions, clinical decision support systems (ie, assistance in question identification and answering) emerge as an attractive alternative. The trustworthiness of the recommendations achieved by such systems is unknown.

Objective

To evaluate the trustworthiness of a question identification and answering system that delivers timely recommendations.

Design

Cross-sectional study.

Methods

We compared the responses to 100 clinical questions related to inpatient management provided by two rapid response methods with 'Gold Standard' recommendations. One of the rapid methods was based on PubMed and the other on Epistemonikos database. We defined our 'Gold Standard' as trustworthy published evidence-based recommendations or, when unavailable, recommendations developed locally by a panel of six clinicians following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Recommendations provided by the rapid strategies were classified as potentially misleading or reasonable. We also determined if the potentially misleading recommendations could have been avoided with the appropriate implementation of searching and evidence summary tools.

Results

We were able to answer all of the 100 questions with both rapid methods. Of the 200 recommendations obtained, 6.5% (95% CI 3% to 9.9%) were classified as potentially misleading and 93.5% (95% CI 90% to 96.9%) as reasonable. 6 of the 13 potentially misleading recommendations could have been avoided by the appropriate usage of the Epistemonikos matrix tool or by constructing summary of findings tables. No significant differences were observed between the evaluated rapid response methods.

Conclusion

A question answering service based on the GRADE approach proved feasible to implement and provided appropriate guidance for most identified questions. Our approach could help stakeholders in charge of managing resources and defining policies for patient care to improve evidence-based decision-making in an efficient and feasible manner.

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Associations between hyponatraemia, volume depletion and the risk of falls in US hospitalised patients: a case-control study

Objective

We aimed to determine if abnormal laboratory values which may indicate volume depletion are associated with increased odds of experiencing a hospital-acquired fall.

Design

Matched case–control study.

Setting

Four hospitals located in the Southeast USA.

Participants

Data from 699 adult fallers and 1189 matched controls (non-fallers) were collected via chart review from 2005 to 2010. Controls were matched to cases by nursing unit, time of fall and length of stay.

Outcome measures

The primary exposures included serum sodium, blood urea nitrogen (BUN), creatinine, BUN/creatinine ratio and haematocrit. Conditional logistic regression with m:n matching was used to determine adjusted and unadjusted ORs.

Results

Serum sodium levels were strongly associated with falls. In models controlling for demographic and other fall risk factors, patients with serum sodium levels of 125 mEq/L or less were associated with increased odds of experiencing a fall as compared with those with serum sodium levels of greater than 134 mEq/L (adjusted OR (aOR)=5.08, 95% CI 1.43 to 18.08). Conversely, elevated BUN, creatinine and elevated BUN/creatinine ratios were not associated with increased odds of experiencing a fall (aOR=0.64, 95% CI 0.49 to 0.84; aOR=0.70, 95% CI 0.54 to 0.92 and aOR=0.77, 95% CI 0.58 to 1.04, respectively.)

Conclusions

Laboratory indices that may indicate volume depletion appear to be unrelated to falls. However, hyponatraemia does appear to be a risk factor for falls, and those with serum sodium levels below 126 mEq/L are at especially high risk. It may be that other deficits associated with hyponatraemia, like altered mental status, are associated with risk of experiencing a hospital-acquired fall. These results indicate that abnormal laboratory values, like low sodium, can be useful for identifying hospitalised patients at risk of falling. Therefore, further investigation into abnormal laboratory values as predictors of hospital-acquired falls is warranted.

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Two tales of cardiovascular risks--middle-aged women living in Sweden and Scotland: a cross-sectional comparative study

Objectives

To compare cardiovascular risk factors as well as rates of cardiovascular diseases in middle-aged women from urban areas in Scotland and Sweden.

Design

Comparative cross-sectional study.

Setting

Data from the general population in urban areas of Scotland and the general population in two major Swedish cities in southeast Sweden, south of Stockholm.

Participants

Comparable data of middle-aged women (40–65 years) from the Scottish Health Survey (n=6250) and the Swedish QWIN study (n=741) were merged together into a new dataset (n=6991 participants).

Main outcome measure

We compared middle-aged women in urban areas in Sweden and Scotland regarding risk factors for cardiovascular disease (CVD), CVD diagnosis, anthropometrics, psychological distress and lifestyle.

Results

In almost all measurements, there were significant differences between the countries, favouring the Swedish women. Scottish women demonstrated a higher frequency of alcohol consumption, smoking, obesity, low vegetable consumption, a sedentary lifestyle and also more psychological distress. For doctor-diagnosed coronary heart disease, there were also significant differences, with a higher prevalence among the Scottish women.

Conclusions

This is one of the first studies that clearly shows that Scottish middle-aged women are particularly affected by a worse profile of CVD risks. The profound differences in CVD risk and outcome frequency in the two populations are likely to have arisen from differences in the two groups of women's social, cultural, political and economic environments.

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Multicentre randomised controlled trial to investigate the usefulness of continuous pneumatic regulation of tracheal cuff pressure for reducing ventilator-associated pneumonia in mechanically ventilated severe trauma patients: the AGATE study protocol

Introduction

Severe trauma represents the leading cause of mortality worldwide. While 80% of deaths occur within the first 24 hours after trauma, 20% occur later and are mainly due to healthcare-associated infections, including ventilator-associated pneumonia (VAP). Preventing underinflation of the tracheal cuff is recommended to reduce microaspiration, which plays a major role in the pathogenesis of VAP. Automatic devices facilitate the regulation of tracheal cuff pressure, and their implementation has the potential to reduce VAP. The objective of this work is to determine whether continuous regulation of tracheal cuff pressure using a pneumatic device reduces the incidence of VAP compared with intermittent control in severe trauma patients.

Methods and analysis

This multicentre randomised controlled and open-label trial will include patients suffering from severe trauma who are admitted within the first 24 hours, who require invasive mechanical ventilation to longer than 48 hours. Their tracheal cuff pressure will be monitored either once every 8 hours (control group) or continuously using a pneumatic device (intervention group). The primary end point is the proportion of patients that develop VAP in the intensive care unit (ICU) at day 28. The secondary end points include the proportion of patients that develop VAP in the ICU, early (≤7 days) or late (>7 days) VAP, time until the first VAP diagnosis, the number of ventilator-free days and antibiotic-free days, the length of stay in the ICU, the proportion of patients with ventilator-associated events and that die during their ICU stay.

Ethics and dissemination

This protocol has been approved by the ethics committee of Poitiers University Hospital, and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals.

Trial registration

Clinical Trials NCT02534974

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Impact of nutritional index on the association between phosphorus concentrations and mortality in haemodialysis patients: a cohort study from dialysis outcomes and practice pattern study in Japan

Objectives

While maintenance of both phosphorus concentration and nutritional status is a major concern in managing haemodialysis patients, the interaction between these parameters is not well understood. The aim of this study was to assess whether or not nutritional index influences the association between phosphorus concentration and all-cause mortality.

Design

A cohort study.

Setting

The Dialysis Outcomes and Practice Pattern Study, which included 99 representative dialysis facilities in Japan between 1997 and 2010.

Participants

A total of 6230 adult haemodialysis patients who had spent at least 6 months on haemodialysis.

Main predictors

Six categories based on time-averaged factors of the geriatric nutritional risk index (GNRI; the lowest two and highest tertiles) and phosphorus concentration (<3.5, 3.5 to <6 and ≥6 mg/dL).

Primary outcome measure

All-cause mortality rate.

Analysis

Time-dependent Cox regression adjusting for potential confounders.

Results

During the follow-up period (12 294 person-years), we noted 561 deaths (4.6 per 100 person-years), and both high phosphorus concentrations and low-middle GNRI were separately associated with all-cause mortality. The harmful effect of high phosphorus concentrations on all-cause mortality was stronger in patients with high GNRI than in those with low-middle GNRI. On the other hand, the harmful effect of low phosphorus concentrations was stronger in those with low-middle GNRI than in those with high GNRI. Relative excess risk due to interaction (RERI) between high phosphorus concentrations and low-middle GNRI was –0.57, indicating an antagonistic interaction. We also observed a significant statistical multiplicative interaction between phosphorus concentrations and GNRI (p=0.05 by likelihood ratio test).

Conclusions

The association between time-averaged serum phosphorus concentration and all-cause mortality differs across the nutritional index. Accordingly, nutritional index should be considered when the impact of phosphorus concentration on mortality in haemodialysis patients is evaluated.

http://ift.tt/2ujKuCZ

Access 3 project protocol: young people and health system navigation in the digital age: a multifaceted, mixed methods study

Background

The integration of digital technology into everyday lives of young people has become widespread. It is not known whether and how technology influences barriers and facilitators to healthcare, and whether and how young people navigate between face-to-face and virtual healthcare. To provide new knowledge essential to policy and practice, we designed a study that would explore health system access and navigation in the digital age. The study objectives are to: (1) describe experiences of young people accessing and navigating the health system in New South Wales (NSW), Australia; (2) identify barriers and facilitators to healthcare for young people and how these vary between groups; (3) describe health system inefficiencies, particularly for young people who are marginalised; (4) provide policy-relevant knowledge translation of the research data.

Methods and analysis

This mixed methods study has four parts, including: (1) a cross-sectional survey of young people (12–24 years) residing in NSW, Australia; (2) a longitudinal, qualitative study of a subsample of marginalised young people (defined as young people who: identify as Aboriginal and/or Torres Strait Islander; are experiencing homelessness; identify as sexuality and/or gender diverse; are of refugee or vulnerable migrant background; and/or live in rural or remote NSW); (3) interviews with professionals; (4) a knowledge translation forum.

Ethics and dissemination

Ethics approvals were sought and granted. Data collection commenced in March 2016 and will continue until June 2017. This study will gather practice and policy-relevant intelligence about contemporary experiences of young people and health services, with a unique focus on five different groups of marginalised young people, documenting their experiences over time. Access 3 will explore navigation around all levels of the health system, determine whether digital technology is integrated into this, and if so how, and will translate findings into policy-relevant recommendations.

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Identification and Characterization of Cadmium-Related Genes in Liver Carcinoma

Abstract

Evidence indicates that exposure to heavy trace element might be a risk factor for liver carcinoma. Cadmium has been supposed to be a carcinogen that has a correlation with the risk of a number of cancers, including liver cancer. However, the mechanisms underlying Cadmium-induced malignant transformation in liver cells are not fully understood. In the present study, we aimed to screen the differentially expressed genes (DEGs) that might play a role in both the Cadmium-related liver cell transformation and the development of liver cancer. Microarray-based gene expression profiles concerning liver carcinoma vs non-cancerous tissue (GSE64041) and Cadmium-treated liver cells vs controls (GSE8865 and GSE31286), respectively, were retrieved from Gene Expression Omnibus (GEO) database. Then, DEGs of each profile were calculated and screened. The intersection of each DEGs was obtained by Venn analysis. Afterwards, the possible roles of the selected genes in cancer development were evaluated by using Oncomine database and TCGA cohort analysis. Consequently, three DEGs, LRAT, SLC7A11, and ITGA2, were selected for further analysis. SLC7A11 and ITGA2, but not LRAT, were upregulated in liver cancer compared with those in normal tissues, respectively. After using a TCGA cohort analysis, results failed to show a significant correlation between SLC7A11 or ITGA2 expression and clinical parameters. However, the survival analysis showed that patients with high expression levels of SLC7A11 had a shorter overall survival time relative to those of the patients with low levels. In conclusion, SLC7A11 and ITGA2 might play a role in the Cadmium-induced liver cell damage or transformation, and the development of liver carcinoma. SLC7A11 might be a prognostic factor for patients with liver carcinoma. Future validation experiments are needed to verify the results.

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Application of bovine bone versus bovine DBM graft on bone healing of radial defect in rat

Abstract

Reconstruction of the fractured bone and bone healing biology is compound processes, and the effectiveness of osteosynthesis is determined by their success. Currently, autografts or allografts and mineral bone substitutes are used commonly for skeletal restoration. The aim of this study is to evaluate the effects of bovine demineralized bone matrix (DBM) and bovine bone (bovine xenografts) on the bone healing process in rat. Sixteen female Sprague-Dawley rats were used in separate four groups: autograft (positive control, n = 4), untreated defect (negative control, n = 4), bovine DBM (n = 4), and bovine bone graft (n = 4). Radiological, histopathological, and biomechanical evaluations were done during the study, and results were recorded and analyzed statistically. At the 56th postoperative day, there was no significant differences in different groups in the biomechanical and radiographical criteria (P > 0.05), but there were significant differences in the mode of union and cancellous bone formation between the groups in histopathological evaluation at the 56th postoperative day (P < 0.05); the present study showed that there was no difference in the radiological and biomechanical performances of the healing bones between the bovine DBM and bovine bone graft.

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Induced Cell Turnover: A Novel Therapeutic Modality for In Situ Tissue Regeneration

Human Gene Therapy , Vol. 0, No. 0.


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AICAR prevents fat gain following the cessation of voluntary physical activity

Abstract

The transition from physical activity to inactivity is associated with drastic increases in 'catch-up' fat that in turn foster the development of many obesity-associated maladies. We tested if 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) treatment would prevent gains in body fat following the sudden transition from a physically active state to an inactive state by locking a voluntary running wheel. Male, Wistar rats were either sedentary (SED), or given wheel access for 4 weeks, at which time rats with wheels continued running (RUN), either had their wheel locked (WL), or had WL with daily AICAR injection (WL + AICAR) for 1 week. RUN and WL + AICAR prevented gains in body fat compared to SED and WL (P < 0.001). Cyclin A1 mRNA, a marker of cell proliferation, was decreased in omental (OMAT), but not subcutaneous (SAT) adipose tissue, in RUN and WL + AICAR compared to SED and WL (P < 0.05). Both cyclin A1 mRNA and protein positively associated with gains in fat mass (P < 0.05). Cyclin A1 mRNA in OMAT, but not SAT, negatively correlated with p-AMPK levels (P < 0.05). Differences in fat gain and OMAT mRNA and protein levels were independent of changes in food intake and in differences in select hypothalamic mRNAs. These findings suggest that AICAR treatment prevents acute gains in adipose tissue following physical inactivity to levels of rats that continuously run, and that together continuous physical activity and AICAR could, at least initially under these conditions, exert similar inhibitory effects on adipogenesis in a depot-specific manner.

This article is protected by copyright. All rights reserved

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GSK2586184, a JAK1 selective inhibitor, in two patients with ulcerative colitis

Tofacitinib, a non-selective Janus kinase (JAK) inhibitor, is effective in inducing clinical and endoscopic remission in patients with active ulcerative colitis (UC). Tofacitinib inhibits cytokine signalling through blockade of JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2). Adverse events including neutropenia and anaemia resulting from JAK2 inhibition have been observed in actively treated patients. By selectively targeting JAK1, such adverse events could be expected to be avoided. This open label study was designed to enrol 15 patients with UC, however the trial was discontinued after two inclusions due to safety concerns with the agent in a parallel trial for systemic lupus erythematosus. GSK2586184 was administered in two patients with moderate-to-severe UC. The JAK1 selective inhibitor GSK2586184 was well tolerated and induced clinical and endoscopic response in two patients with moderate-to-severe UC. In addition, treatment with GSK2586184 decreased histology scores and faecal calprotectin levels at early withdrawal.

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Aggressive large-cell neuroendocrine carcinoma of the sigmoid colon in a patient with ulcerative colitis

Colonic inflammation seen in inflammatory bowel disease (IBD) predisposes to the development of colorectal adenocarcinoma. In contrast, colorectal neuroendocrine carcinomas (NECs) have rarely been reported in the setting of IBD, and no definitive relationship between these tumours and IBD has been established. Dysplasia from chronic inflammation leading to neuroendocrine cell differentiation may be responsible for NEC development, though this finding has not been seen consistently. We present a case of large-cell neuroendocrine carcinoma of the sigmoid colon in a 65-year-old woman with long-standing ulcerative colitis. Although she underwent regular endoscopic follow-ups and was receiving the tumour necrosis factor alpha inhibitor infliximab, her tumour was large and aggressive, with metastases to the liver discovered at time of diagnosis. This case highlights the aggressive nature and poor prognosis of NECs and stresses the need to identify patients at high risk of developing NECs and develop improved surveillance guidelines for detecting them.

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Rare combination of left-sided congenital diaphragmatic hernia and omphalocele

We reported a rare case of left-sided posterolateral congenital diaphragmatic hernia (CDH) and omphalocele, which is not associated with chromosomal abnormalities or other syndromes. Omphalocele was detected antenatally (CDH was not detected in antenatal ultrasound). The patient suffered from respiratory failure secondary to severe pulmonary hypertension. As the combination of CDH and omphalocele is rare and with the abdominal content herniating into the omphalocele instead of the thorax, antenatal diagnosis of such condition can be difficult. Unlike other reported cases in the literature, our patient's respiratory condition has been improving with time and is surviving beyond the infancy period. We believe this to be the first such survival case reported in the literature.

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Gallstone ileus of the duodenum: an unexpected presentation of Bouveret's syndrome

This report describes a patient who presented with a large gallstone obstructing the duodenal bulb, with the chief complaint of acute on chronic abdominal pain. Classically, this is known as Bouveret's syndrome or a gallstone ileus of the duodenum. Our patient's current health status presented a challenge, with the presence of several comorbidities, particularly a large abdominal aortic aneurism. We chose an open procedure for this reason. The stone was removed through a laparotomy, and the cholecystoduodenal fistula that the stone used to pass into the small bowel was repaired. With our patient's future medical needs in mind, only the necessary interventions were performed to regain functionality of the bowel. This came in the form of a diverting gastrojejunostomy, with a distal jejunostomy and feeding tube inserted. The patient tolerated the procedure well, only remaining intubated postoperative due to her chronic obstructive pulmonary disease (COPD). She achieved a complete recovery and transitioned home.

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Splenic rupture following synchronised direct current cardioversion

Atraumatic rupture of the normal spleen is a rare entity. Often, a triggering factor or minor physical event can be ascribed as the aetiology for rupture, including coughing, vomiting or minor medical procedures not involving the spleen. A 65-year-old man who was hospitalised for eosinophilic pneumonia developed haemodynamically unstable atrial flutter that necessitated urgent synchronised direct current cardioversion (DCCV). Two hours after successful cardioversion, he developed signs of an acute abdomen with free intraperitoneal fluid identified on bedside ultrasonography. Exploratory laparotomy revealed gross haemoperitoneum and splenic rupture requiring splenectomy. With exception of capsular defects and haemorrhage suggestive of organ rupture, the gross and histological examination of the spleen was otherwise unremarkable. The patient denied recent trauma. The cause of his spleen rupture was attributed to cardioversion and subsequent abdominal muscle contraction. This represents the first known case of splenic rupture associated with DCCV.

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Reduction en masse of inguinal hernia: a review of a rare and potential fatal complication following reduction of inguinal hernia

Reduction en masse is reduction of a hernial sac into the pre-peritoneal space with a loop of bowel remaining incarcerated at the neck of the sac, leading to early strangulation. This is a rare complication, usually encountered with inguinal hernias, with a false reassurance to the patient and the treating physician that complete reduction has been achieved. Unless early intervention is carried out, this condition will typically present with worsening pain and absence of an appreciable hernia bulge at the groin, and intestinal necrosis may be encountered on exploration. The outcome will depend on the severity of peritonitis/sepsis, and mortality remains high for late presentations. A case of early presentation of reduction en masse of an inguinal hernia is reported with a review of the existing literature.

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Orbital multiple myeloma: a diagnostic challenge

Orbital involvement in multiple myeloma is unusual. We describe the case of an 85-year-old woman who presented with right eye proptosis, reduced visual acuity and diplopia. Computed tomography showed a lobulated, enhancing soft tissue mass arising from the right greater wing of the sphenoid with intraconal, lacrimal gland and ocular muscle involvement. Histopathology revealed predominantly atypical plasma cells in a background of reactive lymphocytes, with monoclonality towards kappa light chain protein, suggestive of multiple myeloma. This case illustrates the diagnostic imaging challenge of orbital multiple myeloma.

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Paraneoplastic cerebellar degeneration secondary to ovarian carcinosarcoma: a cerebellar conundrum

We present a case of an elderly female patient who presented with a 6-month history of progressive slurred speech, vertigo, unsteadiness and falls. She underwent an extensive battery of neurological and cardiovascular investigations, none of which demonstrated a diagnostic cause for her symptoms. She was referred to the stroke and neurology teams and was started on treatment for presumed anxiety. As her symptoms continued to progress, she was referred to the falls service. Following a multidisciplinary team discussion, she was reviewed by the consultant geriatrician who felt this may be due to a malignancy so the consultant geriatrician arranged blood testsand CT scan of her chest, abdomen and pelvis. These demonstrated a large left adnexal mass and a raised Ca-125 level. The patient was diagnosed with an ovarian tumour, which was treated surgically. A provisional diagnosis of paraneoplastic cerebellar degeneration, secondary to ovarian carcinosarcoma, was made.

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Missed diaphragmatic injury after blunt trauma presenting with colonic strangulation: a rare scenario

Diaphragmatic rupture occurs in 4%–5% cases of thoracoabdominal injuries. It may present acutely, in a delayed fashion or as a complicated hernia. We are describing the case of a young male presenting in respiratory distress with history of chest trauma 1.5 years back. On investigation, he was found to have left side diaphragmatic hernia containing gangrenous colon with lung collapse. The patient underwent successful operative intervention and discharged after 25 days of hospital stay. Record review suggested that the above mentioned diaphragm injury was missed in his evaluation 1.5 years back. Diaphragmatic injury must always be suspected in thoracoabdominal injuries, as missed injury may cause devastating complications like the one narrated above in due course.

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An uncommon hip pain

Description

A 55-year-old man with a medical history of hypertension and dyslipidaemia, presented to our Hip clinic with non-traumatic left hip pain of five months duration. The pain was  insidious in onset and gradually progressive. The pain  aggravated on , prolonged sitting or squatting, and relieved with rest. There was no history of any constitutional symptoms. The gait of the patient was essentially normal. There was tenderness over the anterior joint line and mild pain on flexion and internal rotation of the hip. There was no limb length discrepancy or wasting of the adjacent muscles. Distal neurovascular examination was normal.

A plain X-ray of the pelvis showed an ill-defined expansile lytic lesion involving the left superior pubic ramus with sclerotic margins and few internal septations (figure 1). Further CT and MRI scans defined the extent of the lesion (figure 2A,B,C and 3A,B,C). Through a Pfannenstiel incision, the lesion in the...

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Abdominal aortic aneurysm in the setting of Clostridium perfringens pancreatitis

We report a case of a 56-year-old woman who presented with worsening abdominal pain located in the left upper quadrant together with abdominal distention, nausea and anorexia. One month prior to this admission, she had presented and had been diagnosed with concurrent acute pancreatitis and rapidly expanding abdominal aortic aneurysm. The aneurysm was prioritised over the pancreatitis and she underwent uncomplicated endovascular repair. Cross-sectional imaging was consistent with infected pancreatic necrosis and also revealed a large collection located in the anterior pararenal space with extensive gas formation. An image-guided fluid aspiration revealed Clostridium perfringens as the causative organism. She was treated by placement of large bore drains along with irrigation and targeted intravenous antibiotic for 6 weeks. The collections resolved completely and at 6 months follow-up she was well and symptom free.

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In this issue of Pharmacogenomics

Pharmacogenomics, Volume 18, Issue 12, Page 1117-1117, August 2017.


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Advance Care Planning in Palliative Care for People with Intellectual Disabilities: a Systematic Review

Advance care planning (ACP) is defined as a person-centred, ongoing process of communication that facilitates patients' understanding, reflection and discussion of goals, values and preferences for future care. There is evidence for the general palliative care population that ACP increases compliance with patients' end-of-life preferences and improves quality of care near the end of life.

http://ift.tt/2wCthWb

Neuropathic pain after breast cancer treatment: characterization and risk factors

Neuropathic pain (NP) may be an important contributor to the morbidity burden of breast cancer.

http://ift.tt/2vJEbNm

Development of Palliative Care (PC) in Armenia

In the last seven years, considerable progress has been made in palliative care in Armenia but many problems remain unresolved. Policies developed include completion of a national needs assessment, a recognized working group on palliative care formed, national standards approved, a concept paper on palliative care approved, resolutions on palliative care as a specialized service approved, palliative care became a subspecialty in medicine, palliative care qualifications developed, and a social assistance package approved.

http://ift.tt/2wCGcYn

Preventing early postoperative arm swelling and lymphedema manifestation by compression sleeves after axillary lymph node interventions in breast cancer patients: A randomized controlled trial.

Breast cancer related lymphedema (BCRL) remains one of the major long-term complications after surgery. Many reports showed the effectiveness of compression in BCRL treatment but randomized controlled trials evaluating compression garments for postoperative prevention are lacking.

http://ift.tt/2vJqmi0

European Association for Palliative Care: Forging a vision of excellence in palliative care in Central and Eastern European and former Sovjet Union countries (CEE/FSU)

The European Association for Palliative Care (EAPC) represents many thousands of health care workers and volunteers working in or with an interest in palliative care. In 2016, the EAPC has individual members from 48 nations across the world, and collective members from 57 national palliative care associations in 32 European Countries.Throughout its history, the EAPC has produced guidance on a range of palliative care issues. The biennial congresses and research congresses and the comprehensive website (www.eapcnet.eu) are renowned and well utilized platforms for dissemination and exchange of palliative care information.

http://ift.tt/2wCIaHY

Level of Care Preferences among Nursing Home Residents with Advanced Dementia

Delivering goal-directed care is a hallmark of high quality palliative care, but requires an understanding of preferences.

http://ift.tt/2vJHO6g

Palliative Care Development in Georgia

Georgia has established the foundational measures for a national palliative care program—policy, education, drug availability, and implementation. Amendments to legislation needed to develop palliative care have been approved. Palliative care has been recognized as a subspecialty in oncology, critical care, internal medicine and surgery. The National Plan for Palliative Care for 2011-2016 was approved. Opioids, especially oral morphine, are available on a limited basis for patients at home but oral morphine is not available for patients in the hospital.

http://ift.tt/2wCj2kD

Valuing attributes of home palliative care with service users: a pilot discrete choice experiment

Discrete choice experiment (DCE) is a quantitative method that helps determine which service attributes are most valued by people and consequently improve their well-being.

http://ift.tt/2vJE98c

Palliative Care Development In Mongolia

Since the year 2000, Mongolia has established the foundation measures for a national palliative care program and has made several significant achievements.

http://ift.tt/2wCQ0Se

Talking about death with terminally-ill cancer patients: What contributes to the regret of bereaved family members?

Talking about death is an important issue for terminally-ill cancer patients and their families. Little is known about how often and which bereaved families regret not having talked about death with their deceased loved one.

http://ift.tt/2vJqjmk

The Worldwide Hospice Palliative Care Alliance

The Worldwide Hospice Palliative Care Alliance (WHPCA) is an international non-governmental organization registered as a charity in England and Wales that was established in 2008 following a series of international gatherings that highlighted the important need for palliative care to be included in global policy and health planning. The vision of the WHPCA is a world with universal access to hospice and palliative care. Its mission is to foster, promote and influence the delivery of affordable, quality palliative care.

http://ift.tt/2wCtRTV

Neuropathic pain and Nerve Growth Factor in Chemotherapy-Induced Peripheral Neuropathy: prospective clinical-pathological study

Neuropathic pain can be present in patients developing chemotherapy-induced peripheral neuropathy (CIPN). Nerve growth factor (NGF) is trophic to small sensory fibers and regulates nociception.

http://ift.tt/2vJoTs5

Palliative Care for Tuberculosis

In 2014, 1.5 million people died of tuberculosis (TB) worldwide including 400,000 co-infected with HIV. TB remains a major cause of death and suffering globally, in spite of the fact that it is supposed to be a curable disease. Drug resistant forms of TB have developed as a result of poor treatment compliance including multi-drug and extreme drug resistant forms that take longer to treat and have higher likelihoods of treatment failure. In 2010, at the initiation of the TB community, a partnership was formed between the WHO Stop TB Program, the Worldwide Hospice Palliative Care Alliance, and the Open Society Foundation's International Palliative Care Initiative (OSF/IPCI) to explore how to improve the ability of TB professionals to deliver palliative care to their patients.

http://ift.tt/2wCHp1H

Palliative Care Rounds: Update on Spinal Cord Compression for the Palliative Care Clinician

Metastatic spinal cord compression (MSCC) is a devastating complication of cancer. Palliative care clinicians are often called to help manage the pain of such patients, and they can continue to assist the patient and family in choosing among treatment and rehabilitation options. The objectives of this case presentation are to alert palliative care providers to the subtle presentations of MSCC, the data on symptomatic therapy and the factors that enter into the decision for a recommendation of radiation therapy alone (RT) or surgery followed by RT, the newer RT and re-irradiation options, and the benefits of intensive rehabilitation therapy in select patients.

http://ift.tt/2vJNk8S

Why Computerized Adaptive Testing In Pediatric Brain Tumor Clinics

Monitoring of health-related quality of life (HRQOL) and symptoms of patients with brain tumors is needed yet not always feasible. This is partially due to lack of brief-yet-precise assessments with minimal administration burden that are easily incorporated into clinics. Dynamic computerized adaptive testing (CAT) or static fixed-length short-forms, derived from psychometrically-sound item banks, are designed to fill this void.

http://ift.tt/2wCnP5P

The International Association for Hospice and Palliative Care (IAHPC): Advancing Hospice and Palliative Care Worldwide

The International Association for Hospice and Palliative Care (IAHPC) is a membership based organization dedicated to the development and improvement of hospice and palliative care worldwide.The mission of IAHPC is to improve the quality of life of adults and children with life-threatening conditions and their families. The vision of IAHPC is universal access to high-quality palliative care, integrated into all levels of healthcare systems in a continuum of care with disease prevention, early diagnosis and treatment, to assure that any patient's or family caregiver's suffering is relieved to the greatest extent possible.

http://ift.tt/2vJNgpE

Comparative effectiveness of usual source of care approaches to improve end-of-life outcomes for children with intellectual disability

Children with intellectual disability (ID) are at risk for adverse end-of-life outcomes including high emergency room utilization and hospital readmissions, along with low hospice enrollment.

http://ift.tt/2vJFtIj

Exploring genetic attributions underlying radiotherapy-induced fatigue in prostate cancer patients

Despite numerous proposed mechanisms, no definitive pathophysiology underlying Radiotherapy-Induced Fatigue (RIF) has been established. However, the dysregulation of a set of 35 genes was recently validated to predict development of fatigue in prostate cancer patients (PCP's) receiving radiotherapy.

http://ift.tt/2wCtwRl

Cytokine Gene Polymorphisms Associated with Symptom Clusters in Oncology Patients Undergoing Radiation Therapy

Most of the reviews on the biological basis for symptom clusters suggest that inflammatory processes are involved in the development and maintenance of the symptom clusters. However, no studies have evaluated for associations between genetic polymorphisms and common symptom clusters (e.g., mood disturbance, sickness behavior).

http://ift.tt/2vJN49X

Association of inflammatory cytokines with the symptom cluster of pain, fatigue, depression, and sleep disturbance in Chinese patients with cancer

Pain, fatigue, depression, and sleep disturbance are common in patients with cancer and usually co-occur as a symptom cluster. However, the mechanism underlying this symptom cluster is unclear.

http://ift.tt/2wCFNVN

Gene Therapy

This issue of Hematology/Oncology Clinics of North America addresses the current status of gene therapy as it applies to hematologic diseases and hematopoietic stem cell–based treatments. It documents the exciting advances that have been accomplished in recent years to provide clinical benefits for patients suffering from a wide range of disorders. Improvements in methods for hematopoietic stem cell processing, ex vivo and in vivo gene transfer with viral vectors, and gene editing are described.

http://ift.tt/2ujG8Mo

A prospective evaluation of radiation-free direct solitary cholangioscopy for the management of choledocholithiasis

Endoscopy has replaced many radiological studies for the GI tract. However, ERCP remains a hybrid endoscopic-fluoroscopic procedure, which limits its portable delivery, creates delays due to fluoroscopy room unavailability and exposes patients/providers to radiation. We evaluated fluoroscopy/radiation-free management of patients with non-complex choledocholithiasis using direct solitary cholangioscopy (DSC).

http://ift.tt/2woHRRM

Three-year cytohistological correlation of salivary gland FNA cytology at a tertiary center with the application of the Milan system for risk stratification

BACKGROUND

Fine-needle aspiration (FNA) cytology of salivary glands is a well-established technique that plays a critical role in the preoperative diagnosis of lesions. A risk stratification of FNA diagnostic categories has been recently proposed to be useful in reporting. The aims of this study were to evaluate the diagnostic accuracy of salivary gland FNA and to apply the proposed Milan system for reporting salivary gland lesions.

METHODS

A retrospective audit of FNA specimens of salivary gland lesions reported from 2014 to 2016 was performed. A correlation with the follow-up histopathology, wherever it was available, was performed. The aspirates were then categorized according to the Milan system as follows: nondiagnostic, nonneoplastic, atypical, benign neoplasm, neoplasm of uncertain malignant potential (NUMP), suspicious for malignancy, or positive for malignancy. Furthermore, the risk of malignancy and the risk of high-grade malignancy were calculated for all diagnostic categories.

RESULTS

A total of 631 salivary gland aspirates were evaluated: 2.2% were nondiagnostic, 55.8% indicated nonneoplastic lesions, and 40.4% indicated neoplastic lesions. Histopathology was available for 94 cases (14.9%). FNA had a sensitivity of 79.4% and a specificity of 98.3% with an overall diagnostic accuracy of 91.4% for differentiating malignant tumors from benign tumors. The overall risk of malignancy was 17.4% for the nonneoplastic category, 100% for the atypical category, 7.3% for the benign neoplasm category, 50% for the NUMP category, and 96% for the positive-for-malignancy category.

CONCLUSIONS

Salivary gland FNA continues to have high diagnostic accuracy and is thus helpful for guiding management. Neoplasms with classic cytomorphology are easily diagnosed; however, in difficult cases showing overlapping features, the use of the Milan system could be beneficial. Cancer Cytopathol 2017. © 2017 American Cancer Society.

http://ift.tt/2vg2a3H

The fluorocycline TP-271 is efficacious in models of aerosolized Bacillus anthracis infection in BALB/c mice and cynomolgus macaques [PublishAheadOfPrint]

The fluorocycline TP-271 was evaluated in mouse and non-human (NHP) primate models of inhalational anthrax. BALB/c mice were exposed by nose-only aerosol to 18 - 88 LD₅₀Bacillus anthracis Ames spores. When 21 days of once-daily dosing was initiated at 24 hours post-challenge (post-exposure prophylaxis, PEP), survival for the 3, 6, 12 and 18 mg/kg TP-271 groups was 90%, 95%, 95%, and 84%, respectively. When 21 days of dosing was initiated at 48 hours post-challenge (treatment, Tx) survival for the 6, 12 and 18 mg/kg TP-271 groups was 100%, 91%, and 81%, respectively. No deaths of TP-271-treated mice occurred during the 39-day post-treatment observation period. In the NHP model, cynomolgus macaques received an average dose of 197 LD₅₀B. anthracis Ames spore equivalents using a head-only inhalation exposure chamber and once daily treatment of 1mg/kg TP-271, lasting for 14 or 21 days, was initiated within 3 hours of detection of protective antigen (PA) in the blood. No animals (0/8) survived in the vehicle control group, whereas all 8 infected macaques treated for 21 days, and 4 of 6 in the 14-day treatment group, survived to the end of study (56 days post-challenge). All survivors developed toxin-neutralizing antibody and anti-PA IgG titers, indicating an immunologic response. Based on results in mouse and NHP models, TP-271 shows promise as a countermeasure for the treatment of inhalational anthrax.

http://ift.tt/2vepO2i

N-acylated derivatives of sulfamethoxazole block Chlamydia fatty acid synthesis and interact with FabF [PublishAheadOfPrint]

The type II fatty acid synthesis (FASII) pathway is essential for bacterial lipid biosynthesis and continues to be a promising target for novel antibacterial compounds. Recently, it has been demonstrated that Chlamydia is capable of FASII and this pathway is indispensable for Chlamydia growth. Previously, a high-content-screen was performed with C. trachomatis infected cells and acylated sulfonamides were identified as potent growth inhibitors of the bacteria. C. trachomatis strains resistant to acylated sulfonamides were isolated by serial passaging a wild type strain in low compound concentrations. Results from whole genome sequencing of ten isolates from two independent drug resistant populations revealed that accumulated mutations in fabF were predominant. Protein-small molecule interaction studies showed that acylated sulfonamides directly bind to recombinant FabF in vitro and treatment of C. trachomatis infected HeLa cells with the compounds leads to a decrease in the synthesis of Chlamydia fatty acids. This work demonstrates the importance of FASII for Chlamydia development and may lead towards the development of new antimicrobials.

http://ift.tt/2woM08e

Pharmacokinetics of the protein microbicide 5P12-RANTES in sheep following single dose vaginal gel administration [PublishAheadOfPrint]

5P12-RANTES, a chemokine analogue that potently blocks the HIV CCR5 co-receptor, is being developed as both a vaginal and rectal microbicide for prevention of sexual transmission of HIV. Here, we report the first pharmacokinetic data for 5P12-RANTES, following single dose vaginal gel administration in sheep. Aqueous gel formulations containing low (1.24 mg/mL), intermediate (6.16 mg/mL) and high (32.0 mg/mL; suspension-type gel) concentrations of 5P12-RANTES were assessed via rheology, syringeability and in vitro release testing. Following vaginal gel administration in sheep, 5P12-RANTES concentrations were measured in vaginal fluid, vaginal tissue and serum over a 96-h period. All gels showed non-Newtonian pseudoplastic behaviour, with high concentration gels exhibiting greater viscosity and cohesive structure. In in vitro release testing, >90% 5P12-RANTES was released from the low and intermediate gels after 72 h. For the high concentration gel, ~50% 5P12-RANTES was detected, attributed to protein denaturation during lyophilisation and/or subsequent solvation of the protein within the gel matrix. In sheep, 5P12-RANTES concentrations in vaginal fluid, tissue and serum increased in a dose dependent manner. Highest concentrations were measured in fluid (10⁵–10⁷ ng/mL) followed by tissue (10⁴–10⁶ ng/mL) – both several orders of magnitude above reported half maximal inhibitory concentrations – and lowest in serum (< 10² ng/mL). The 5P12-RANTES pharmacokinetic data is similar to that reported previously for other candidate microbicides. These data, coupled with 5P12-RANTES's picomolar potency, its strong barrier to resistance, and full protection observed in a rhesus macaque vaginal challenge model, support the continued development of 5P12-RANTES as a microbicide.

http://ift.tt/2vecJpN

Pharmacokinetics of cefuroxime in synovial fluid [PublishAheadOfPrint]

Objectives: Cefuroxime is frequently used as preoperative antibiotic prophylaxis and may be used for treatment of septic arthritis. A prerequisite for successful treatment of septic arthritis is the ability of an antibiotic agent to penetrate into the target site. Therefore the concentration of cefuroxime in synovial fluid was evaluated.

Patients and Methods: Ten patients who underwent elective knee arthroscopy were included in this study. Patients were treated with a single dose of 1500 mg cefuroxime intravenously and subsequently concentrations were measured in plasma, interstitial fluid of muscle tissue and synovial fluid by using microdialysis. Pharmacokinetics / Pharmacodynamic calculations to predict bacterial killing were performed using epidemiologically defined MIC₉₀ of clinical isolates andCLSI breakpoints.

Results: Cefuroxime penetrated excellently into muscle tissue (AUC_muscle:AUC_{free plasma}: 1.79) and synovial fluid (AUC_synovia:AUC_{free plasma}: 1.94). Cefuroxime concentration was beyond the MIC₉₀ of S. aureus and S. epidermidis strains (≤ 2 mg/L) over the complete dosing interval (fT>MIC). CLSI defines staphylococci with MIC ≤ 8 mg/L as susceptible to cefuroxime. For staphylococci with MIC ≤ 8 mg/L, the fT>MIC of cefuroxime in plasma was 52.5% while in muscle tissue and synovial fluid fT>MIC was 93.6% and 96.3%, respectively.

Conclusion: Cefuroxime may be used to treat septic arthritis caused by susceptible bacterial strains (MIC ≤ 8 mg/L). The activity of cefuroxime in septic arthritis might be underestimated when relying exclusively on plasma concentrations.

http://ift.tt/2woUlJe

Pharmacokinetics of intravenous finafloxacin in healthy volunteers [PublishAheadOfPrint]

Background: Finafloxacin is a novel fluoroquinolone exhibiting enhanced activity under acidic conditions and a broad spectrum antibacterial profile. The present study assessed pharmacokinetic properties and safety/tolerability following intravenous infusions.

Methods: In this mixed parallel group/crossover study, healthy male and female volunteers received single (18 volunteers, 200 to 1000mg) or multiple (40 volunteers, 600 to 1000 mg) ascending doses of finafloxacin or placebo. Plasma and urine samples were collected by a dense sampling scheme to describe pharmacokinetics using a non-compartmental approach. Standard safety and tolerability data were documented.

Results: Finafloxacin had a volume of distribution of 90-127 L (range) at steady state and of 446-550 L at pseudo-equilibrium, indicating the elimination of a large fraction before reaching pseudo-equilibrium. Areas under the concentration-time curves and maximum plasma concentrations (geometric means) increased slightly more than proportionally (6.73 to 45.9 μg*h/mL, 2.56 to 20.2 μg/mL), t_1/2 increased (10.6 to 17.1 h) and urinary recovery decreased (44.2% to 31.7%) with increasing finafloxacin doses (single doses of 200 to 1000 mg). Pharmacokinetic profiles suggested multiphasic elimination by both glomerular filtration and saturable tubular secretion. Pharmacokinetic parameters were similar for single and multiple administrations. Between-subject variability of exposure ranged from 10% (≤600mg) to 38% (>600mg) (CV%). Adverse events were mild and non-specific, with no dependency on dose or treatment (including placebo).

Conclusions: Despite a relatively high inter-individual variability at higher doses, exposure following intravenous administration of finafloxacin appears to be predictable. Individual elimination processes should be evaluated in more detail. Finafloxacin exhibited a favorable safety/tolerability profile.

http://ift.tt/2veWxVf

Translocation of Carbapenemase Gene blaKPC-2 both Internal and External to Transposons Occurs via Novel Structures of Tn1721 and Exhibits Distinct Movement Patterns [PublishAheadOfPrint]

The bla_KPC-2 gene encodes a carbapenemase that hydrolyses almost all β-lactams, including carbapenems. The rapid emergence and international spread of this gene in Enterobacteriaceae seriously limits clinical treatment, posing an alarming threat for public health. Transposable elements often play a role in the dissemination of bla_KPC-2 gene, such as Tn4401, a proved transposon in Europe, USA etc. In eastern China, the bla_KPC-2 gene is frequently associated with several novel structures of Tn1721, but their transposition ability and mechanism remain unclear. Here we experimentally demonstrated that Tn1721-like transposons are capable of transferring the bla_KPC-2, both internal and external to the Tn1721 element, from one strain to another, and that distinct transposon structures exhibited different movement patterns and transposition frequencies. This process did not involve homologous recombination. Moreover, 5-bp duplication of target site, a characterized signature of transposition evens in Tn3-family, was confirmed. Tn1721-like transposons were found preferentially to insert into a 5-bp region exhibiting a degenerated degree of AT-rich from both sides to the middle gradually, and immediately flanked by GC-rich positions. The observation in clinical isolates, including the prevalence of Tn1721-like transposons, diverse sequences flanking the transposons and 5-bp duplication of target site, etc. also sustained our experiment results. This study gives evidences of the functional role of Tn1721-like transposons in transferring bla_KPC-2 gene firstly, and provides a new sight for the transposable element and the dissemination of antibiotic resistance in Enterobacteriaceae.

http://ift.tt/2wovSDZ

Monitoring Antifungal Resistance in a Global Collection of Invasive Yeasts and Moulds: Application of CLSI Epidemiological Cutoff Values and Whole Genome Sequencing Analysis for Detection of Azole Resistance in Candida albicans [PublishAheadOfPrint]

The activity of 7 antifungal agents was evaluated against 3,557 invasive yeasts and moulds collected in 29 countries worldwide during 2014-2015. Epidemiological cutoff values (ECVs) published in the CLSI M59 document were applied for species with no clinical breakpoints. Echinocandin susceptibility rates were 95.9% to 100.0% for the 5 most common Candida species except anidulafungin and C. parapsilosis (88.7% susceptible/100.0% wild-type). Fluconazole resistance ranged from 8.0% for C. glabrata to 0.4% for C. albicans. Seven Candida species displayed 100.0% wild-type amphotericin B and C. dubliniensis and C. lusitaniae exhibited wild-type echinocandin MIC results. The highest fluconazole, voriconazole, and posaconazole MIC values for Cryptococcus neoformans var. grubii were 8 μg/mL, 0.12 μg/mL, and 0.25 μg/mL, respectively. A. fumigatus were 100.0% wild-type for caspofungin and amphotericin B, but 3 (0.8%) of these isolates were non- wild-type to itraconazole (2 isolates) or voriconazole (1 isolate). Mutations on FKS hotspots (HS) were detected among 13/20 Candida isolates (16/20 were C. glabrata) displaying echinocandin MIC>ECV. Most isolates carrying FKS HS mutations were resistant to 2 or more echinocandins. Five fluconazole-nonsusceptible C. albicans were submitted to whole genome sequencing analysis. Gain of function, Erg11 heterozygous, and Erg3 homozygous mutations were observed in 1 isolate each. One isolate displayed MDR1 promoter allele alterations associated with azole resistance. Elevated expression of MDR1 or CDR2 was observed among 3 and 1 isolates, respectively. Echinocandin and azole resistance is still uncommon among contemporary fungal isolates; however, resistance mechanisms to antifungals were observed among Candida spp. showing that resistance can emerge and monitoring is warranted.

http://ift.tt/2vecH19

Pharmacokinetic-Pharmacodynamic Target Attainment Analyses to Determine Optimal Dosing of Ceftazidime-Avibactam for the Treatment of Acute Pulmonary Exacerbations in Cystic Fibrosis. [PublishAheadOfPrint]

Background: Acute pulmonary exacerbations (APE) involving Pseudomonas aeruginosa are associated with increased morbidity and mortality in CF. Drug resistance is a significant challenge to treatment. Ceftazidime-avibactam (CZA) demonstrates excellent in vitro activity against isolates recovered from CF; including drug-resistant strains. Altered pharmacokinetics (PK) of several beta-lactam antibiotics have been reported in CF. Therefore, this study sought to characterize the PK of CZA and perform target-attainment analyses to determine the optimal treatment regimen.

Methods: The PK of CZA was determined from 12 adult CF patients administered 3 intravenous doses of 2.5g q8h infused over 2h. Population modeling utilized the maximum-likelihood expectation method. Monte Carlo simulations determined the probability of target attainment (PTA). Exposure targets of free-ceftazidime (CAZ) above MIC (fT>MIC), and free-avibactam (AVI) above a 1 mg/L threshold concentration (fT>C_t) were evaluated. Published CAZ and CZA MIC distributions were incorporated to evaluate cumulative response probabilities.

Results: CAZ and AVI were best described by 1-compartment models. Total body clearances (CAZ CL_t: 7.53 ± 1.28 L/h, AVI CL_t: 12.30 ± 1.96 L/h) and volumes of distribution (CAZ V_d: 18.80 ± 6.54 L, AVI V_d: 25.30 ± 4.43 L) were broadly similar to published healthy adults. CAZ achieved a PTA (50% fT>MIC) > 0.9 for MICs ≤ 16 mg/L and AVI PTA (50% fT>C_t of 1.0) >0.99. The overall likelihood of treatment response was 0.82 with CZA vs. 0.42 for CAZ.

Conclusions: These data demonstrate improved pharmacodynamics of CZA in comparison with CAZ and provide guidance on optimal dosing of (CZA) for future studies.

http://ift.tt/2vyElql

Comparative Pharmacodynamics of Single-Dose Oritavancin and Daily High-Dose Daptomycin Regimens against Vancomycin-resistant Enterococcus faecium Isolates in an In Vitro PK/PD Model of Infection [PublishAheadOfPrint]

There are limited therapeutic options to treat infections caused by vancomycin-resistant Enterococcus faecium (VREfm). The lipoglycopeptide oritavancin exhibits in vitro activity against this pathogen although its utility against infections caused by VREfm has not been established clinically. In this study, the pharmacodynamic activity of free-drug levels associated with 12 mg/kg/day of daptomycin and a single 1200 mg dose of oritavancin were determined against three VanA VREfm isolates in an in vitro pharmacokinetic/pharmacodynamic model.

http://ift.tt/2vg4oQN

In vitro susceptibility to closthioamide among clinical and reference strains of Neisseria gonorrhoeae [PublishAheadOfPrint]

Neisseria gonorrhoeae is one of the leading antimicrobial resistance threats worldwide. This study determined the minimum inhibitory concentrations of closthioamide to be 0.008-0.5 mg/L for clinical N. gonorrhoeae strains and related species. Cross-resistance with existing antimicrobial resistance was not detected, indicating that closthioamide could be used to treat drug-resistant N. gonorrhoeae.

http://ift.tt/2vyXIj4

In Vitro Activities of Gepotidacin (GSK2140944) and Other Antimicrobial Agents Against Human Mycoplasmas and Ureaplasmas [PublishAheadOfPrint]

Gepotidacin, a novel, first in class, triazaacenaphthylene topoisomerase II inhibitor, was tested against 85 type strains and clinical isolates of Mycoplasma pneumoniae, Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma parvum, and Ureaplasma urealyticum in comparison to levofloxacin, moxifloxacin, azithromycin or clindamycin, and tetracycline. Gepotidacin MIC₉₀s (μg/ml) were: M. pneumoniae (0.125), M. genitalium (0.032), M. hominis (2), and Ureaplasma species (8). Gepotidacin activity was not affected by resistance to fluoroquinolones, tetracyclines, or macrolides in the strains tested. Gepotidacin merits further study for treating infections caused by these organisms.

http://ift.tt/2vg6xMm

Avibactam restores the susceptibility of aztreonam against clinical isolates of Stenotrophomonas maltophilia [PublishAheadOfPrint]

Stenotrophomonas maltophilia is an emerging opportunistic pathogen, classified by the World Health Organization as one of the leading multidrug resistant organisms in hospital settings. Discovery of novel compounds and/or combination therapies for S. maltophilia is urgent. We demonstrate the in-vitro efficacy of aztreonam-avibactam (ATM-AVI) against S. maltophilia, and kinetically characterize the inhibition of the L2 β-lactamase by avibactam. ATM-AVI overcomes aztreonam resistance in selected clinical strains of S. maltophilia, addressing an unmet medical need.

http://ift.tt/2vyQnjy

Antimicrobial Activity and Cell Selectivity of Synthetic and Biosynthetic Cationic Polymers [PublishAheadOfPrint]

The mammalian and microbial cell selectivity of synthetic and biosynthetic cationic polymers has been investigated. Among the polymers with peptide backbones, polymers containing amino side chains display greater antimicrobial activity than those with guanidine side chains whereas ethylenimines display superior activity over allylamines. The biosynthetic polymer -polylysine (PL) is non-cytotoxic to primary human dermal fibroblasts at concentrations up to 2000 μg/ml, suggesting that the presence of isopeptide backbone has greater cell selectivity than α-peptide backbones. Both PL and and linear polyethylenimine (LPEI) exhibit bactericidal properties by depolarizing the cytoplasmic membrane and disrupt the preformed biofilms. PL displays broad spectrum antimicrobial properties against antibiotic-resistant Gram-negative and Gram-positive strains and fungii. PL elicits rapid bactericidal activity against both Gram-negative and Gram-positive bacteria and its biocompatibility index is superior to cationic antiseptic agents and LPEI. PL does not interfere with the wound closure of injured rabbit cornea. In a rabbit model of bacterial keratitis, topical application of PL (0.3% w/v) decreases the bacterial burden and severity of the infections caused by P. aeruginosa and S. aureus strains. In vivo imaging studies confirm that PL treated cornea appeared transparent and non-edematous when compared to untreated infected cornea. Taken together, our results highlight the potential of PL in resolving topical microbial infections.

http://ift.tt/2vgkp9t

Identification of Plasmid-Mediated Quinolone Resistance in Salmonella Isolated from Swine Ceca and Retail Pork Chops in the United States [PublishAheadOfPrint]

Fluoroquinolones are important antimicrobial drugs used to treat human Salmonella infections, and resistance is rare in the United States for isolates from both human and animal sources. Recently, a number of Salmonella isolated from swine cecal contents and retail pork products from NARMS surveillance exhibited decreased susceptibility to ciprofloxacin. We identified two qnrB19 quinolone resistance plasmids as predominantly responsible for this phenomenon, and found them distributed among several Salmonella serotypes isolated throughout the United States.

http://ift.tt/2vz5Tw6

Impact of exposure of methicillin-resistant Staphylococcus aureus to polyhexanide in vitro and in vivo [PublishAheadOfPrint]

Staphylococcus aureus (MRSA) resistant to decolonization agents such as mupirocin and chlorhexidine increase the need to develop alternative decolonization molecules. The absence of reported adverse reactions and bacterial resistance to polyhexanide makes it an excellent choice as topical antiseptic. In the present study we evaluated the in vitro and in vivo capacity to generate strains with reduced polyhexanide susceptibility and cross-resistance with chlorhexidine and/or antibiotics currently used in clinic. Here we report the in vitro emergence of reduced-susceptibility to polyhexanide by prolonged-stepwise exposure to low concentrations in broth culture. Reduced susceptibility to polyhexanide was associated with genomic changes in the mprF and purR genes, and with concomitant decreased susceptibility to daptomycin and other cell-wall active antibiotics. However, the in vitro emergence of reduced-susceptibility to polyhexanide did not result in cross-resistance to chlorhexidine antiseptic. During in vivo polyhexanide clinical decolonization treatment, neither polyhexanide reduced-susceptibility nor chlorhexidine cross-resistance were observed. Together, these observations suggest that polyhexanide could be used safely for decolonisation of carriers of chlorhexidine-resistant S. aureus strains but highlight the need for careful use of polyhexanide at low antiseptic concentrations.

http://ift.tt/2vgqFxX

Irritable Bowel Syndrome (IBS)

http://ift.tt/2wovQMn

Double-blind, randomized phase 3 trial of low-dose 13-cis retinoic acid in the prevention of second primaries in head and neck cancer: Long-term follow-up of a trial of the Eastern Cooperative Oncology Group-ACRIN Cancer Research Group (C0590)

BACKGROUND

13-Cis retinoic acid (13-CRA) is a synthetic vitamin A derivative. High-dose 13-CRA in patients with squamous cell cancers of the head and neck (SCCHNs) reduces the incidence of second primary tumors (SPTs). The authors report long-term results from a phase 3 randomized trial that compared treatment with low-dose 13-CRA versus placebo for patients who had early stage SCCHN, with a focus on the development of SPTs and overall survival (OS).

METHODS

In total, 176 patients who received treatment for stage I/II SCCHN were randomized to receive either low-dose 13-CRA (weight-based dose of 7.5 mg or 10 mg) or placebo for 2 years. A competing-risk approach and the log-rank test were used to compare the time to SPT and OS, respectively, between groups.

RESULTS

13-CRA neither significantly reduced the cumulative incidence of SPT (P = .61) nor improved the time to SPT (hazard ratio [HR] for 13-CRA/placebo; 0.86; P = .61). Despite limited power, there was a trend toward improved OS for the 13-CRA arm (HR, 0.75; P = .14), particularly among patients whose index tumor was surgically excised (N = 26; HR, 0.50; P = .057) and among women (N = 39; HR, 0.44; P = .065) and never/former smokers (N = 129; HR, 0.61; P = .055), with a median follow-up of 16 years. The main 13-CRA related toxicities were dry skin and cheilitis.

CONCLUSIONS

Treatment with low-dose 13-CRA for 2 years did not decrease the incidence of SPT; subset analysis indicates a potential survival advantage among patients who are women and never/former smokers. More targeted interventions based on clinical risk factors and molecular characterization of tumors may yield greater success in future prevention trials. Cancer 2017. © 2017 American Cancer Society.

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Motor unit remodelling in multifocal motor neuropathy: the importance of axonal loss

To estimate the degree of axonal loss in patients diagnosed with multifocal motor neuropathy (MMN) using a novel assessment of motor unit numbers and size.

http://ift.tt/2ukj4RE

Rare Endobronchial Inflammatory Myofibroblastic Tumor in Pediatric Patient Detected on PET/CT Imaging

Abstract: Inflammatory myofibroblastic tumor (IMT) can be seen in all age groups, although it is more common in children and adolescents. We report the FDG PET/CT findings in an 8-year-old boy with endobronchial IMT. Endobronchial IMT is more commonly seen in young adults.

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Dual Isotope SPECT Study With Epilepsy Patients Using Semiconductor SPECT System

Purpose: We developed a prototype CdTe SPECT system with 4-pixel matched collimator for brain study. This system provides high-energy-resolution (6.6%), high-sensitivity (220 cps/MBq/head), and high-spatial-resolution images. The aim of this study was to evaluate dual-isotope study of CBF and central benzodiazepine receptor (BZR) images using 99mTc-ECD and 123I-IMZ with the new SPECT system in patients with epilepsy comparing with single-isotope study using the conventional scintillation gamma camera. Methods: This study included 13 patients with partial epilepsy. The BZR images were acquired at 3 hours after 123I-IMZ injection for 20 minutes. The images of IMZ were acquired with a conventional 3-head scintillation gamma camera. After BZR image acquisition with the conventional camera, 99mTc-ECD was injected, and CBF and BZR images were acquired simultaneously 5 minutes after ECD injection with the new SPECT system. The CBF images were also acquired with the conventional camera on separate days. The findings were visually analyzed, and 3D-SSP maximum Z scores of lesions were compared between the 2 studies. Results: There were 47 abnormal lesions on BZR images and 60 abnormal lesions on CBF images in the single-isotope study with the conventional camera. Dual-isotope study with the new system showed concordant abnormal findings of 46 of 47 lesions on BZR and 54 of 60 lesions on CBF images with the single-isotope study with the conventional camera. There was high agreement between the 2 studies in both BZR and CBF findings (Cohen κ values = 0.96 for BZR and 0.78 for CBF). In semiquantitative analysis, maximum Z scores of dual-isotope study with the new system strongly correlated with those of single-isotope study with the conventional camera (BZR: r = 0.82, P

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Oligometastatic Stomach Carcinoma From Lung Squamous Cell Carcinoma Detected by 18F-FDG PET/CT

Abstract: Metastasis from squamous cell carcinoma of the lung to the stomach is extremely rare. 18F-FDG PET/CT demonstrated intense 18F-FDG uptake in the lower lobe of the left lung, stomach, and mediastinal lymph node in a 61-year-old man. Lower lobe of the left lung resection, mediastinal lymphadenectomy, partial gastrectomy, and esophagogastric anastomosis was performed. Immunohistochemical studies revealed squamous cell lung carcinoma in the left lung and metastatic carcinoma of gastric and lymph nodes. The present case further demonstrated the value of 18F-FDG PET/CT in the staging of malignant disease.

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Whole-Body 68Ga-DOTANOC PET/MRI Versus 68Ga-DOTANOC PET/CT in Patients With Neuroendocrine Tumors: A Prospective Study in 28 Patients

Purpose: The aim of this study was to assess the diagnostic performance of simultaneous whole-body 68Ga-DOTANOC PET/MRI compared with 68Ga-DOTANOC PET/CT for detection of distant metastatic disease in patients with well-differentiated neuroendocrine tumors (NETs). Methods: Patients with histologically proven, well-differentiated NET (G1 or G2) were included in this prospective, institutional review board–approved study. Patients underwent 68Ga-DOTANOC PET/CT and subsequent 68Ga-DOTANOC PET/MRI after a single tracer injection on the same day for staging or restaging purposes. Images were evaluated for the presence of NET lesions by 2 rater teams, each consisting of a nuclear medicine physician and a radiologist, in an observer-blinded fashion. Overall agreement, accuracy, sensitivity, and specificity, relative to a composite reference standard (consensus review including follow-up data), were calculated. Results: Between July 2014 and June 2016, 28 patients were enrolled. Overall agreement and accuracy between the 2 rater teams were 91.7% (95% confidence interval [CI], 87.5%–95.9%) and 97% (95% CI, 94.4%–99.6%) for PET/MRI and 92.3% (95% CI, 88.3%–96.3%) and 94.6% (95% CI, 91.2%–98.1%) for PET/CT, respectively (P = 1.00). Overall, PET/MRI reached 89.8% sensitivity (95% CI, 77.8%–96.6%) and 100% specificity (95% CI, 97%–100%); PET/CT showed 81.6% sensitivity (95% CI, 68%–91.2%) and 100% specificity (95% CI, 97%–100%) for the detection of metastatic disease in NETs. Conclusions: Whole-body 68Ga-DOTANOC PET/MRI appears to be comparable to 68Ga-DOTANOC PET/CT for lesion detection in patients with well-differentiated NETs.

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Pancreatic Ductal Adenocarcinoma With High Radiotracer Uptake in 68Ga–Prostate-Specific Membrane Antigen PET/CT

Abstract: Prostate-specific membrane antigen imaging with PET/CT is increasingly used in prostate cancer and was shown to have a high diagnostic performance. We report a clinical case of a 67-year-old man with previous history of operated prostate cancer and increasing prostate-specific antigen blood level. 68Ga-HBED-CC prostate-specific membrane antigen PET/CT imaging was indicated for the assessment of local recurrence and lymph node metastases of prostate cancer. In addition, a soft tissue mass in the body of the pancreas with high radiotracer uptake was detected. Histopathology confirmed a pancreatic ductal adenocarcinoma.

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Serum Ceruloplasmin and Striatal Dopamine Transporter Density in Parkinson Disease: Comparison With 123I-FP-CIT SPECT

Purpose: In patients with Parkinson disease (PD), decreased serum ceruloplasmin levels have been observed. This study investigated a correlation between serum ceruloplasmin—along with its related serum markers— and striatal presynaptic dopaminergic denervation measured with 123I-FP-CIT SPECT. Methods: We analyzed a total of 141 de novo patients divided into 2 groups: the PD group (107 patients with PD) and the disease control group (34 patients with vascular pseudoparkinsonism, essential tremor, or drug-induced parkinsonism). Serum ceruloplasmin and related serum markers, such as copper, iron, total iron-binding capacity, and ferritin, were measured. Specific binding ratios of the striatum, caudate nucleus, putamen, and posterior putamen were obtained by 123I-FP-CIT SPECT. Results: There was no difference in the serum markers, except for ceruloplasmin, between the 2 groups. Ceruloplasmin level was significantly lower in PD patients with longer symptom duration (>2 years) than in the disease control group (21.4 ± 3.4 vs 24.0 ± 3.8, P = 0.03). Serum ceruloplasmin had a significant correlation with specific binding ratios of the striatum, caudate nucleus, and putamen in a subgroup with longer symptom duration (P = 0.01, P = 0.02, P = 0.02, respectively, for the subgroup with symptom duration >1 year, and P 2 years). Conclusions: Decrease in serum ceruloplasmin had a positive correlation with a decrease in dopamine transporter density in PD patients with symptom duration of more than 1 year.

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Diagnostic and Prognostic Implications of Exercise Treadmill and Rest First-Pass Radionuclide Angiography in Patients With Pulmonary Hypertension

Purpose: Pulmonary hypertension (PH) is characterized by abnormally increased pulmonary vascular pressure, leading to deteriorated right ventricular function and premature death. Pulmonary mean transit time (PMTT) and biventricular function response to exercise in first-pass radionuclide angiography (FP-RNA) may provide early detection and timely disease monitoring of PH. This study aimed to investigate the diagnostic and prognostic values of this imaging modality in PH patients. Methods: Left and right ventricular ejection fraction (LVEF/RVEF) and PMTT at rest and immediately after exercise treadmill test were measured by FP-RNA in 77 consecutive patients with clinical presentations suggestive of PH (aged 46 ± 15 years, 33 men), mostly with symptoms of unexplained progressive dyspnea. These parameters, along with other clinical variables, were correlated with right-sided heart catheterization data and clinical outcomes. Results: Fifty patients (64.9%) were diagnosed as having definite PH. Besides higher N-terminal pro–B-type natriuretic peptide levels, right atrial pressure, and pulmonary vascular resistance, PH patients had significantly longer PMTT, lower LVEF after exercise and rest, and lower poststress RVEF (all P

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Quality and Safety in Health Care, Part XXVI: The Adult Cardiac Surgery Database

Abstract: The Adult Cardiac Surgery Database of the Society of Thoracic Surgeons has provided highly useful information in quality and safety in general thoracic surgery, including ratings of the surgeons and institutions participating in this type of surgery. The Adult Cardiac Surgery Database information is very helpful for writing guidelines and determining optimal protocols and for many research projects. This article discusses the history and current status of this database.

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Impressive Paget Disease of the Lumbar Spine Masks the Coexisting Multiple Myeloma

Abstract: Multimodality imaging, including MRI, bone scintigraphy, and FDG PET/CT, was performed to evaluate a 49-year-old man who had right hip and lower limb pain for 4 months because possible malignancy was suspected. All 3 modalities showed obvious Paget disease of the lumbar spine. However, less impressive increased activity was also noted on FDG PET/CT images. Subsequent laboratory tests and pathology examination leads to diagnosis of multiple myeloma. Our case further confirms the notion that it is insufficient to focus on the most obvious and unintentionally overlook the less impressive findings in interpreting nuclear medicine images.

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Quality and Safety in Health Care, Part XXVII: Research and Future Directions of the Adult Cardiac Surgery Database

Abstract: This article discusses some of the most recent research and future directions of the Adult Cardiac Surgery Database of the Society of Thoracic Surgeons. In addition to numerous articles on short-term outcomes from cardiac surgery on adults, there are new initiatives of the Adult Cardiac Surgery Database which will allow long-term outcome analysis and better estimation for each patient on the likely value of the procedure to that individual.

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Incidental Papillary Bladder Carcinoma on 18F-Fluoromethylcholine PET/CT Undertaken to Evaluate Prostate Malignancy

Abstract: FDG PET is known to have a low sensitivity for the detection of prostate and bladder tumors because of high levels of urinary excretion, which potentially obscures sites of disease. Fluoromethylcholine PET has a higher sensitivity for the detection of metastatic prostate cancer compared with 18F-FDG PET, partly because of lower levels of urinary excretion. We present a case of a patient who underwent 18F-fluoromethylcholine PET for possible recurrent prostate cancer. The study identified an incidental, avid metachronous bladder tumor. We discuss the potential use of fluoromethylcholine PET in the detection of bladder tumors.

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A Pediatric Case of Well-Functioning Supernumerary Kidney: Relative Renal Function Assessment Using Radionuclide Imaging

Abstract: We present an interesting image of a well-functioning supernumerary kidney evaluated with DMSA (dimercaptosuccinic acid) renal scintigraphy in a 14-year-old girl. At 2 years of age, the patient had a diagnosis of supernumerary kidney. She remained asymptomatic up to childhood age, and then a DMSA study was required to guide the following adequate surveillance strategy. DMSA study provided a clear imaging of supernumerary kidney in the left side of the abdomen showing a regular uptake and a normal function in relation to its own size.

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Tophaceous Gout of the Lumbar Spine Mimicking Malignancy on FDG PET/CT

Abstract: A 46-year-old man with over a 10-year history of gout complained of progressive bilateral buttock pain with numbness of legs for 4 months. Serum uric acid level was elevated. Lumbar radiographs showed decreased density of the bilateral L4–L5 facet joints. CT showed lytic lesions of the facet joints with hyperdense periarticular lesions. Enhanced MRI showed marked enhancement of these lesions. FDG PET/CT showed avid FDG uptake of the bony and periarticular lesions with SUVmax of 16.8. A decompressive posterior lumbar laminectomy with periarticular lesion resection was performed. Histopathologic findings of the periarticular lesions were consistent with tophaceous gout.

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Aggressive Imaging Features in a Malignant Pheochromocytoma With a Novel Mutation of the SDHB Gene

Abstract: We describe a 15-year-old boy with a huge bilateral adrenal pheochromocytoma that had a de novo germline mutation in the succinate dehydrogenase subunit B (SDHB) gene. 18F-FDG PET/CT revealed bilateral metabolically active large masses in the adrenal glands and the activated brown adipose tissues. The 123I-MIBG scintigraphic findings revealed only a mild accumulation of MIBG in the right adrenal mass, but a high uptake in the left adrenal mass. Thus, 18F-FDG PET/CT imaging may be more effective than 123I-MIBG scintigraphy for the evaluation of pheochromocytomas that are associated with highly malignant characteristics resulting from mutations of the SDHB gene.

http://ift.tt/2fnWH75

Endotracheal Leiomyoma Mimicking Malignancy on 18F-FDG PET/CT in a Patient With Papillary Thyroid Carcinoma

Abstract: Endotracheal leiomyoma is a rare benign lesion, accounting for approximately 1% of tracheal tumors, and generally occurs in the lower respiratory tract. Because its growth causes airway obstruction symptom, surgical treatment is generally suggested after detection. We report a case with leiomyoma of the cervical endotracheal space showing intense FDG uptake on 18F-FDG PET/CT mimicking malignancy in a 79-year-old woman with papillary thyroid carcinoma.

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Diffuse Thyroid Metastasis From Lung Cancer Mimicking Thyroiditis on 99mTc-Pertechnetate Scintigraphy

Abstract: Possible thyroiditis was suspected in a 56-year-old man who initially presented sore throat because laboratory examinations revealed decreased serum thyroid hormone and the 99mTc-pertechnetate scintigraphy showed no tracer uptake by the thyroid gland. However, subsequent examination demonstrated that the absence of pertechnetate activity in the thyroid was due to complete replacement of thyroid gland by the metastasis from lung adenocarcinoma, which was unknown at the initial presentation.

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False Positive Uptake in Bilateral Gynecomastia on 68Ga-PSMA PET/CT Scan

Abstract: A 66-year-old man on hormonal therapy with prostate cancer was referred for 68Ga-PSMA PET/CT scan for biochemical recurrence. 68Ga-PSMA PET/CT scan detected moderate heterogeneous tracer concentration in bilateral breast parenchyma, in addition to the abnormal tracer concentration in enlarged prostate gland, right external iliac lymph node, and sclerotic lesion in L4 vertebra. On clinical examination, he was found to have bilateral gynecomastia. Abnormal concentration of 68Ga-PSMA in breast cancer is now well known, and in this context, it is important to know that tracer localization can occur in gynecomastia as well, as evidenced in this case.

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Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome Combined With Adrenocortical Carcinoma on 18F-FDG PET/CT

Abstract: Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is a recognized distinct phenotypic variant of multiple cutaneous and uterine leiomyomatosis. The present case reports an extremely rare case of HLRCC syndrome combined with adrenocortical carcinoma. The case suggests that HLRCC should be considered in any young patient with bulky uterine leiomyomas and renal cell cancer, and 18F-FDG PET/CT can help detect unexpected additional primary malignancy in a patient with known cancer.

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Pretreatment Primary Tumor SUVmax on 18F-FDG PET/CT Images Predicts Outcomes in Patients With Salivary Gland Carcinoma Treated With Definitive Intensity-Modulated Radiation Therapy

Purpose: The aim of this study was to investigate the prognostic significance of 18F-FDG uptake in salivary gland carcinoma (SGC) patients treated with definitive intensity-modulated radiation therapy (IMRT). Methods: We retrospectively examined 46 SGC patients who received pretreatment 18F-FDG PET/CT and definitive IMRT between 2007 and 2014. Most tumors were located in the minor salivary glands (n = 35 [76%]). Forty-six percent (n = 21) of the participants had unresectable disease. The median radiation dose was 72 Gy. Treatment outcomes were examined in relation to clinicopathologic parameters and pretreatment primary tumor SUVmax on 18F-FDG PET/CT. Results: After a median follow-up of 54 months, the 5-year locoregional progression-free survival (LRPFS), distant metastasis-free survival, progression-free survival (PFS), and overall survival (OS) rates were 77%, 75%, 63%, and 61%, respectively. The median primary tumor SUVmax was 7.4 (range, 2.3–23.6), and the optimal cutoff value that maximized the prognostic significance for 5-year PFS was 7.4 (P = 0.006). Patients with a high SUVmax (≥7.4) had significantly lower 5-year LRPFS (P = 0.007), distant metastasis-free survival (P = 0.046), and OS (P = 0.013) rates than those with a low SUVmax (

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Infection of Ventricular Assist Device Detected and Monitored by 18F-FDG PET/CT

Abstract: We report a case of a 59-year-old man who presented with fever, sepsis, and left cervicothoracic cutaneous inflammation 13 months after implantation of Jarvik 2000 device. Device infection was suspected and 18F-FDG PET/CT showed an intense and homogeneous uptake along driveline cable. Bacteriological local sample showed Staphylococcus aureus. After adapted antibiotherapy, control 18F-FDG PET/CT displays treatment efficacy with no residual uptake in driveline. 18F-FDG PET/CT could be an important tool for early noninvasive detection of left ventricular assist device infection and monitoring antibiotherapy response.

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Pulmonary oxidative stress in diabetic rats exposed to hyperoxia

Abstract Purpose: To evaluate the pulmonary oxidative stress in diabetic rats exposed to hyperoxia for 90 minutes. Methods: Forty male Wistar rats were divided into four groups, each one containing 10 animals, according to the oxygen concentration to which they were exposed: 21%, 50%, 75% and 100% (hyperoxia). In each group five animals were randomly induced to diabetes by means of at a dose of 55 mg/kg of streptozotocin (STZ). Results: Seventy two hours after diabetes induction, a significant difference was seen in blood glucose in the experimental groups in comparison with the control. In the experimental groups a significant difference was observed in the concentration of malondialdehyde (MDA) in lung tissue and blood plasma (p<0.05), except the 50% group. In the control group, significant differences in the MDA concentration in plasma and lung tissue were also observed (p<0.05), except the 75% group. The MDA concentration in lung tissue in comparison with the diabetic and non-diabetic groups showed a significant difference in the 21% group; however, no difference was seen in the 75 and 100% groups. Conclusion: In diabetic animals high oxygen concentrations (75 and 100%) do not appear to exert deleterious effects on lipid peroxidation in lung tissue.

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Does mesenchymal stem cell improve the liver regeneration after the 70% hepatectomy?

Abstract Purpose: To evaluate the effects of mesenchymal stem cells on liver regeneration in rats following a 70% hepatectomy. Methods: Forty rats were subjected to 70% hepatectomy and then ~106 mesenchymal stem cells (test group), or saline solution (control group), were infused into their livers via the portal vein. Each treatment group was divided into early and late subgroups (euthanized 3 d and 5 d following the operation, respectively). Group comparisons of Albumin, aminotransaminases (AST, ALT), and Alcaline Phosphatase (AP) levels, proliferative index (ki-67+ straining), and mitotic cell counts were conducted. Results: No significant differences in liver regeneration rate, number of mitoses, proliferative index, or serum levels of albumin, AST, or AP were observed. ALT levels were higher in the test group than in the control group (p<.05). Conclusions: Mesenchymal stem-cell therapy did not improve liver regeneration rate 3 d or 5 d after 70% hepatectomy in rats. Likewise, the therapy appeared not to affect liver function, proliferative index, or number of mitoses significantly.

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Effect of mild hypothermia on renal ischemia/reperfusion injury after cardiopulmonary resuscitation in a swine model

Abstract Purpose: To investigate the effect of intravascular cooling on renal function after resuscitation. Methods: Twenty four pigs were randomized into three groups (n=8 in each group): therapeutic hypothermia group (TH group), normothermia group (NH group) and sham operation group (SHAM group). After 6 minutes of untreated VF, CPR was performed. Upon ROSC, the TH group received the intravascular cooling. The NH and SHAM group did not undergo therapeutic hypothermia. Haemodynamic parameters were recorded. The bloods were analyzed for serum creatinine (sCr), CysC and NGAL. The kidney was surgically removed observe pathologic changes under a light microscope. Results: The sCr increased in both TH and NH groups after ROSC, compared to baseline. Between two groups, the sCr and creatinine clearance (Cc) showed lower level in the TH group. The urine volume per hour in the TH group were higher during cooling. After resuscitation, NGAL and CysC in the NH group were higher than in the TH group. Under the light microscope, compared with the TH group, the renal injury was prominent in the NH group. Conclusion: Mild hypothermia had a protection to renal ischemia reperfusion injury after resuscitation.

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Impact of propofol on renal ischemia/reperfusion endoplasmic reticulum stress

Abstract Purpose: To investigate the protective mechanisms of propofol (Pro) on renal ischemia/reperfusion (I/R) injury by studying its impact on renal I/R endoplasmic reticulum stress. Methods: Eighteen male Sprague-Dawley rats (SD rats) were randomly divided into three groups: the I/R group, the Pro pretreatment group, and the control group, and corresponding treatments were performed. The levels of serum creatinine (Cr) and blood urea nitrogen (BUN) of each group were detected. The expression levels of CCAAT-enhancer-binding protein (C/EBP) homology protein (CHOP) and caspase-12 protein within renal tissue samples were detected by western blot. Results: The periodic acid-Schiff (PAS) staining was performed to observe the morphological changes within the renal tissues, and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay was performed to detect the presence of renal apoptosis. The Pro pretreatment significantly reduced the serum Cr and BUN levels, as well as the expressions levels of CHOP and caspase-12 protein inside the kidney of I/R rats, improving renal pathological injury and reducing the I/R-induced renal apoptosis. Conclusion: Propofol could downregulate the expression of stress-apoptotic proteins CHOP and caspase-12 in the endoplasmic reticulum, thus reducing renal I/R injury.

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Transplantation of human immature dental pulp stem cell in dogs with chronic spinal cord injury

Abstract Purpose: To investigate the therapeutic potential of human immature dental pulp stem cells in the treatment of chronic spinal cord injury in dogs. Methods: Three dogs of different breeds with chronic SCI were presented as animal clinical cases. Human immature dental pulp stem cells were injected at three points into the spinal cord, and the animals were evaluated by limb function and magnetic resonance imaging (MRI) pre and post-operative. Results: There was significant improvement from the limb function evaluated by Olby Scale, though it was not supported by the imaging data provided by MRI and clinical sign and evaluation. Conclusion: Human dental pulp stem cell therapy presents promising clinical results in dogs with chronic spinal cord injuries, if used in association with physical therapy.

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Low-energy shock wave preconditioning reduces renal ischemic reperfusion injury caused by renal artery occlusion

Abstract Purpose: To evaluate whether low energy shock wave preconditioning could reduce renal ischemic reperfusion injury caused by renal artery occlusion. Methods: The right kidneys of 64 male Sprague Dawley rats were removed to establish an isolated kidney model. The rats were then divided into four treatment groups: Group 1 was the sham treatment group; Group 2, received only low-energy (12 kv, 1 Hz, 200 times) shock wave preconditioning; Group 3 received the same low-energy shock wave preconditioning as Group 2, and then the left renal artery was occluded for 45 minutes; and Group 4 had the left renal artery occluded for 45 minutes. At 24 hours and one-week time points after reperfusion, serum inducible nitric oxide synthase (iNOS), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), creatinine (Cr), and cystatin C (Cys C) levels were measured, malondialdehyde (MDA) in kidney tissue was detected, and changes in nephric morphology were evaluated by light and electron microscopy. Results: Twenty-four hours after reperfusion, serum iNOS, NGAL, Cr, Cys C, and MDA levels in Group 3 were significantly lower than those in Group 4; light and electron microscopy showed that the renal tissue injury in Group 3 was significantly lighter than that in Group 4. One week after reperfusion, serum NGAL, KIM-1, and Cys C levels in Group 3 were significantly lower than those in Group 4. Conclusion: Low-energy shock wave preconditioning can reduce renal ischemic reperfusion injury caused by renal artery occlusion in an isolated kidney rat model.

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The role of ischemic preconditioning and pentoxifylline in intestinal ischemia/reperfusion injury of rats

Abstract Purpose: To investigate the role of ischemic preconditioning (IPC) and pentoxifylline (PTX) in intestinal mucosa ischemia/reperfusion injury (IR). Methods: Thirty rats were assigned to 5 groups (N=6): (CG): no clamping of the superior mesenteric artery (90 min.); (IR-SS): saline + ischemia (30 min.) + reperfusion (60 min.); (IR-PTX): PTX + ischemia (30min.) + reperfusion (60 min.); (IPC-IR-SS): 5 min. of ischemia + 5 minutes of reperfusion (IPC) + saline + ischemia (30 min.) + reperfusion (60 min.); (IPC-IR-PTX ): 5 min. of ischemia + 5 min. of reperfusion (IPC) + PTX + 30 min. of I + 60 minutes of R. Results: The IR-PTX, IPC-IR-SS and IPC-IR-PTX groups had significantly lower scores of mucosa damage than the IR-SS group. IR-PTX group showed higher scores than the IPC-IR-PTX group, in accordance with the hypothesis of a favorable effect of IPC alone or in association with PTX. Additionally, IPC-IR-SS had a higher damage score than the IPC-IR-PTX. The villi height and crypt depth were similar in all groups. The villi height in the IR-SS was significantly lower. Conclusion: Ischemic preconditioning or pentoxifylline alone protect the intestinal mucosa from ischemia/reperfusion injury. However, they do not have a synergistic effect when applied together.

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Experimental study of peripheral-blood pro-surfactant protein B for screening non-small cell lung cancer

Abstract Purpose: To evaluate the possibility of using peripheral-blood presurfactant protein B (Pro-SFTPB) for screening non-small cell lung cancer (NSCLC). Methods: A total of 873 healthy volunteers and 165 lung cancer patients hospitalized in the Fifth People's Hospital of Dalian were tested Pro-SFTPB once every half year from January 2014 to September 2015. The healthy volunteers were also conducted spiral computed tomography (CT) examination once every year. The data were then com-pared and statistically analyzed. Results: The positive expression rate of Pro-SFTPB in NSCLC was significantly higher than that in healthy volunteers, and significantly higher in lung adenocarcinoma than in squamous cell carcinoma; additionally, the expression rate was increased with the in-crease of smoking index, and the intergroup differences showed statistical signifi-cance (p≤0.05). The positive rate of newly diagnosed lung cancer was 29.55%, higher than healthy volunteers (22.34%), but there was no significant difference (p>0.05). Conclusion: Pro-SFTPB is over expressed in non-small cell lung cancer, especially in lung adeno-carcinoma, but it can't be used as a clinical screening tool for lung cancer.

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A prospective randomized study of the inflammatory responses to multiport and singleport laparoscopic hysterectomies

Abstract Purpose: To evaluate the inflammatory responses induced by laparoscopic hysterectomies with multiport and singleport approaches. Methods: This was a pilot prospective randomized study that included 42 women candidates for hysterectomy at School of Medicine, Hospital das Clínicas, USP. The patients were randomized to two groups: MP-TLH (total laparoscopic hysterectomy with 3 abdominal incisions), and SP-TLH (total laparoscopic hysterectomy with a single umbilical incision).We evaluated the inflammatory response (via CRP, IL-6, IL-10, TNFα, VEGF and leukogram assessments), surgical time, postoperative pain, blood loss and surgical complications in both groups. Results: Both techniques were similar regarding C-reactive protein (p=.666), IL-6 (p=.833), IL-10 (p=.420), TNF-α(p=.098), VEGF (p=.092) and the leukogram (p=.712) measures. The operative time was significantly longer in the SP-TLH group than in the MP-TLH group (p=.001). The pain evaluation was similar in both groups (p=.170). Hemoglobin variation and the aspirated blood volume were similar in both groups (p=.493 and p=.347). There were no major complications. Conclusions: Multiport and singleport laparoscopic approaches are both safe methods for hysterectomy. Although SP-TLH resulted in a significantly longer operative time than MP-TLH, no differences were observed between the groups in inflammatory responses, blood loss and postoperative pain.

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Unintentional pediatric injuries in São Paulo. How often is it severe?

Abstract Purpose: To evaluate severity and built a pilot of a national databank about pediatric trauma and to determine its severity. Methods: Prospective study of unintentional pediatric trauma in five hospitals in the city of São Paulo, Brazil. Results: 916 patients in 4 months. 61.5% of traumatized children were male, average 6.5 years. 48. 4% were falls. Most families had an average monthly income less than three minimum wages. 42% of accidents occurred at home. 18.9% of children were alone. 59,8% of parents thought it could be prevented. 26.5% of children had previous accidents. GCS was severe: 5 patients, moderate: 8 patients. 21 patients were intubated (2.4%), RTS <7 in 10.2%, PTS<8 in 3.6%. 8.5% patients were considered severe, which was related to falls (p=0.001); sports (p=0.045); pedestrian (p=0.006); child education (p=0.015) and cared by male (p=0.007). Conclusions: Severity occurred in 8.5% and was associated to falls, sports, traffic, child education, and cared by male. Simple preventive measures could have prevented most of the accidents. The tested tool for details was successful and can be used throughout the country.

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Pathophysiology and immunological profile of myasthenia gravis and its subgroups

Fredrik Romi | Yu Hong | Nils Erik Gilhus

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Known unknowns: how might the persistent herpesvirome shape immunity and aging?

Janko Nikolich-Zugich | Felicia Goodrum | Kenneth Knox | Megan J Smithey

http://ift.tt/2vdNi7v