Are we missing the Staphylococcus aureus bacteraemia forest for the MRSA trees?

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Trends in incidence and resistance patterns of Staphylococcus aureus bacteremia

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Immune Response and Protective Efficacy of a Heterologous DNA-Protein Immunization with Leishmania Superoxide Dismutase B1

Growing evidence shows that antioxidant proteins of Leishmania could be used as vaccine candidates. In this study, we report the efficacy of Leishmania donovani iron superoxide dismutase B1 (LdFeSODB1) as a vaccine antigen in BALB/c mice in a DNA-protein prime-boost immunization regimen in the presence or absence of murine granulocyte macrophage colony stimulating factor (mGMCSF) DNA adjuvant. The expression study confirmed that LdFeSODB1 is expressed in mammalian cells and mGMCSF fusion mediates the secretion of the recombinant protein. Heterologous immunization with LdFeSODB1 induced a strong antibody- and cell-mediated immune response in mice. Immunization triggered a mixed Th1/Th2 response as evidenced by the ratio of IgG2a to IgG1. Antigen-stimulated spleen cells from the immunized mice produced high level IFN-γ. Multiparametric flow cytometry data showed that immunization with LdFeSODB1 induced significantly higher expression of TNF-α or IL-2 by antigen-stimulated T cells. Eight weeks after L. major infection, immunization with the antigen shifted the immune response to a more Th1 type than the controls as demonstrated by IgG2a/IgG1 ratio. Moreover, IFN-γ production by antigen-stimulated spleen cells from immunized mice remained high. The footpad swelling experiment showed that immunization with LdFeSODB1 resulted in partial protection of mice from a high dose L. major infection.

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Ischaemic pituitary tumour apoplexy and concurrent meningitis: a diagnostic dilemma

Pituitary tumour apoplexy is a rare but potentially life threatening clinical syndrome that mostly results from haemorrhage in the pre-existent tumour. Pure ischaemic subtype of apoplexy is even rarer. The presentation can be hard to differentiate clinically from bacterial meningitis. Moreover, the presence of one does not necessarily exclude the other and early diagnosis of both conditions is imperative for timely management. We report a case of ischaemic pituitary tumour apoplexy that may have precipitated in the setting of bacterial meningitis.

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Hyperacute leucopenia associated with furosemide

A 72-year-old man presented to the hospital with exacerbation of congestive heart failure. He was given furosemide 40 mg intravenously twice at 4 hours apart. At 4 hours after the second dose of furosemide, his white blood cells (WBC) dropped acutely from 9.8 to 2.4x10⁹/L (reference range 4.1 to 9.3x10⁹/L). With the discontinuation of furosemide, the WBC trended up to 7.1x10⁹/L about 13 hours after the second dose of intravenous furosemide and remained in normal range for the next 3 days. However, when the oral furosemide was started on hospital day 4, there was a mild drop in WBC count, which returned to and maintained at baseline since the next day. The dynamic changes in the patient's WBC were coincident with the use of furosemide. The possible mechanisms of furosemide-associated transient hyperacute leucopenia were discussed.

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Giant insulinoma: an unusual cause of hypoglycaemia

Description 

A 70-year-old non-diabetic man presented to the accident and emergency department with convulsions and symptoms of hunger, anxiety and blurred vision. A non-tender epigastric mass was identified, and he was found to be hypoglycaemic, with plasma glucose levels of 1.5 mmol/L (4.4–6.1 mmol/L). C-peptide and insulin levels were both inappropriately elevated.

After stabilisation with glucose, the patient was investigated with CT, which revealed a 154 mm mass in the pancreas that displaced the stomach and encased the coeliac trunk, the superior mesenteric vein and the splenic vein (figure 1). Collaterals were found at the level of the hepatic hilum, the gastro-oesophageal junction and adjacent to the mass itself. Calcifications typical of insulinomas were evident (figure 2). No metastases were seen. Fine-needle aspiration was then performed, confirming the diagnosis (figure 3).

Figure 1

Multiplanar reconstruction identifying the 154 mm insulinoma.

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Severe panniculitis and polyarthritis caused by acinar cell carcinoma arising from an ectopic pancreas

The pancreatitis, panniculitis and polyarthritis (PPP) syndrome is a rare condition caused by pancreatic diseases, such as acute or chronic pancreatitis or pancreatic carcinoma. We report the first case of PPP syndrome caused by metastatic acinar cell carcinoma from an ectopic pancreas. The symptoms were successfully managed by the treatment of the metastatic carcinoma. Pancreatic cytosteatonecrosis should be always considered in a patient who is showing symptoms of panniculitis and polyarthritis.

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Retrobulbar heavy liquid discovered 5 years postvitrectomy

Description

This report of a mass in the upper eyelid resulting from long-term complications of heavy liquid tamponade therapy of retinal detachment is a good example of learning from rare cases.

Retinal detachments may be repaired by scleral buckling, vitrectomy surgery or by a combination of both techniques. Retinal detachments repaired by vitrectomy are typically tamponaded by either gas or silicone oil. In certain complex cases, heavy liquid (perfluorohexyloctane/polydimethylsiloxane) is used as a short-term tamponading agent that is subsequently replaced with gas or silicone oil.1 2

A 16-year-old woman presented with bilateral retinal detachments secondary to giant tears. The patient had no relevant ocular history and denied trauma. The left eye had a macula-sparing detachment and the right eye had a macula-off retinal detachment. Both retinas were reattached sequentially with a combination of scleral buckling and vitrectomy with heavy liquid tamponade. The heavy...

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Comparing safety information of biosimilars with their originators: a cross-sectional analysis of European Risk Management Plans

Abstract

Background

Biosimilars have been available in the European Union since 2006. However, their uptake in routine care is heterogeneous across countries.

Aims

To compare the safety information of biosimilars and their originators based on the information in the EU risk management plan (RMP).

Methods

A cross-sectional analysis on publicly available regulatory documents (RMPs and Summaries of Product Characteristics) of biosimilars and corresponding originators until 1 November 2015 was performed. The safety concerns were extracted and merged into General Safety Concerns and clinical relevancy was assessed. The frequency of safety concerns and the representation of these safety concerns per general safety concern were assessed either comparing RMPs of biosimilars and originators (if available for both) or comparing RMPs with the Summary of Product Characteristics of the originator.

Results

Nineteen biosimilars and 6 originators were included. Overall, 55 general safety concerns (12 low, 21 medium and 22 highly clinically relevant) were identified. For all active substances, except for infliximab, no or only one difference was found in the listed general safety concerns. Comparison of regulatory documents for infliximab identified 3 medium clinically relevant general safety concerns more for infliximab biosimilars and 2 general safety concerns more for its originator.

Conclusion

Based on publicly available information filed for regulatory purposes, no substantial differences were observed in the reporting of safety information for biosimilars and related originators. A direct comparison between biosimilars and related originators through formal post-marketing studies is needed to evaluate specific safety issues emerging during the products' life cycle.

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Spatializing Emotion: No Evidence for a Domain-General Magnitude System

Abstract

People implicitly associate different emotions with different locations in left-right space. Which aspects of emotion do they spatialize, and why? Across many studies people spatialize emotional valence, mapping positive emotions onto their dominant side of space and negative emotions onto their non-dominant side, consistent with theories of metaphorical mental representation. Yet other results suggest a conflicting mapping of emotional intensity (a.k.a., emotional magnitude), according to which people associate more intense emotions with the right and less intense emotions with the left — regardless of their valence; this pattern has been interpreted as support for a domain-general system for representing magnitudes. To resolve the apparent contradiction between these mappings, we first tested whether people implicitly map either valence or intensity onto left-right space, depending on which dimension of emotion they attend to (Experiments 1a, b). When asked to judge emotional valence, participants showed the predicted valence mapping. However, when asked to judge emotional intensity, participants showed no systematic intensity mapping. We then tested an alternative explanation of findings previously interpreted as evidence for an intensity mapping (Experiments 2a, b). These results suggest that previous findings may reflect a left-right mapping of spatial magnitude (i.e., the size of a salient feature of the stimuli) rather than emotion. People implicitly spatialize emotional valence, but, at present, there is no clear evidence for an implicit lateral mapping of emotional intensity. These findings support metaphor theory and challenge the proposal that mental magnitudes are represented by a domain-general metric that extends to the domain of emotion.

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Detection of Hepatitis C antibodies without viral transmission in Hepatitis C negative recipients receiving kidneys from Hepatitis C positive donors treated with Direct Acting Anti-Viral Therapy

No abstract available

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Use of organs from hepatitis C virus positive donors for uninfected recipients: a potential cost-effective approach to save lives?

Background Organs from hepatitis C virus (HCV) seropositive (HCVpos) individuals are seldom used for transplantation because of the risk of disease transmission. Because transmitted HCV is now amenable to effective treatment we estimated the potential impact of using HCVpos deceased donor organs for transplantation. Methods The Potential Donor Audit (PDA) of patients (

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Analysis of biomarkers within the initial 2 years posttransplant and 5-year kidney transplant outcomes: results from Clinical Trials in Organ Transplantation-17

ABSTRACT Background An early posttransplant biomarker/surrogate marker for kidney allograft loss has the potential to guide targeted interventions. Previously published findings, including results from the Clinical Trials in Organ Transplantation (CTOT)-01 study, showed that elevated urinary chemokine CXCL9 levels and elevated frequencies of donor-reactive interferon gamma-(IFNγ)-producing T cells by enzyme linked immunosorbent spot (ELISPOT) assay associated with acute cellular rejection within the first year and with lower 1-year posttransplant estimated glomerular filtration rate (eGFR). How well these biomarkers correlate with late outcomes, including graft loss, is unclear. Methods In CTOT-17, we obtained 5-year outcomes in the CTOT-01 cohort and correlated them with a) biomarker results and b) changes in eGFR (Chronic Kidney Disease Epidemiology Collaboration formula) over the initial 2 years posttransplant using univariable analysis and multivariable logistic regression. Results Graft loss occurred in 14/184 subjects (7.6%) 2 to 5 years posttransplant. Neither IFNγ ELISPOTs nor urinary CXCL9 were informative. In contrast, a ≥40% decline in eGFR from 6 months to 2 years posttransplant independently correlated with thirteen-fold odds of 5-year graft loss [adjusted odds ratio (aOR) 13.1; 95% CI 3.0-56.6], a result that was validated in the independent Genomics of Chronic Allograft Rejection cohort (n=165, aOR: 11.2). Conclusions We conclude that while pre and early posttransplant ELISPOT and chemokine measurements associate with outcomes within 2-years posttransplant, changes in eGFR between 3 months or 6 months and 24 months are better surrogates for 5-year outcomes, including graft loss. Corresponding author: Peter S Heeger, MD, Translational Transplant Research Center, Icahn School of Medicine at Mount Sinai, New York, USA, Email: peter.heeger@mssm.edu, Phone: 212 241 6324, Fax: 212 987 0389 Authorship Geovani Faddoul, M.D. Participated in data analysis and writing/editing of the manuscript Girish N Nadkarni, M.D. Participated in data analysis and writing/editing of the manuscript Nancy D. Bridges, M.D. Participated in study design and writing/editing of the manuscript Jens Goebel, M.D. Participated in writing/editing of the manuscript Donald E. Hricik, M.D. Participated in study design, data analysis and writing/editing of the manuscript Richard Formica, M.D. Participated in study design and writing/editing of the manuscript Madhav C Menon, M.D. Participated in study design, data analysis and writing/editing of the manuscript Yvonne Morrison, Participated in study design and writing/editing of the manuscript Barbara Murphy, M.D. Participated in study design and writing/editing of the manuscript Kenneth Newell, M.D. Participated in study design and writing/editing of the manuscript Peter Nickerson, M.D. Participated in study design and writing/editing of the manuscript Emilio D. Poggio, M.D. Participated in study design and writing/editing of the manuscript David Rush, M.D. Participated in study design and writing/editing of the manuscript Peter S. Heeger, M.D. Participated in study design, data analysis and writing/editing of the manuscript Disclosure The authors of this manuscript have no conflicts of interest to disclose. Funding The study was supported by National Institutes of Health U01 grant AI63594 awarded to P Heeger and K23DK107908 to G Nadkarni Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Heme Oxygenase 1 Attenuates Hypoxia-Reoxygenation Injury in Mice Liver Sinusoidal Endothelial Cells

ABSTRACT Background Heme oxygenase 1 (HO-1), a heat shock protein, can be involved in the resolution of inflammation by modulating cytokine expression and apoptotic cell death. Based on recent evidence that liver sinusoidal endothelial cells (LSECs) is the critical target in early period of liver ischemia-reperfusion injury (IRI), this study aims to clarify whether overexpression of HO-1 gene provides a protective effect on mice LSECs. Method LSECs were transfected with adenovirus vectors encoding mice HO-1 gene (Ad-HO-1) or green fluorescent protein (Ad-EGFP). Controls were not infected with any vector. LSECs were then treated with hypoxic or normoxic culture. We used low serum culture medium and hypoxia-reoxygenation (H-R) conditions to cause IRI in vitro. The transfection efficiency of HO-1 gene in LSECs, after 48 hours of transfection, and the effect of HO-1 on the model of H-R injury in LSECs were observed. Results Transfection of LSECs with Ad-HO-1 was at an optimal dose (MOI=80) to markedly express HO-1 mRNA and protein. Groups of overexpressed HO-1 showed lower levels of inflammatory factor mediators IL-6 and TNF-α. Survival rate of the cells after H-R injury was higher and attributed to overexpressed HO-1. In contrast, the control adenovirus expressing the EGFP failed to induce HO-1 expression, and stimulated cell apoptosis. HO-1 expression was down-regulated in all H-R groups compared to normoxia groups, which may be related to the disruption of the LSEC structure. Conclusion Up-regulation of HO-1 can attenuate H-R injury in LSECs by inhibiting proinflammatory cytokine release and diminishing apoptotic cell death. Corresponding author: Zhong Zeng, MD, PhD, Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical College, 295 Xichang Road, Kunming 650032, Yunnan Province, China. Telephone: +86-871-65359202; Fax: +86-871-65359202; Email: zzong@medmail.com.cn Authorship: Siming Qu, Bo Yuan, and Zhong Zeng contributed equally to this work; Siming Qu and Bo Yuan performed the majority of experiments; Hongbin Zhang participated in the performance of the research; Hanfei Huang participated in data analysis; Shikun Yang, Jie Lin, Li Jin, and Pu Wu participated in the writing of the paper. Disclosure: The authors declare no conflicts of interest. Funding: National Nature Science Foundation of China, No. 81660113 Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Comparison of BQ123, Epoprostenol, and Verapamil as Vasodilators During Normothermic Ex Vivo Liver Machine Perfusion

Background The optimal vasodilator to avoid hepatic artery (HA) vasospasm during normothermic ex vivo liver perfusion (NEVLP) is yet to be determined. We compared safety and efficacy of BQ123 (endothelin1 antagonist), Epoprostenol (prostacyclin analogue), and Verapamil (calcium channel antagonist). Methods Livers from porcine heart beating donors were perfused for 3 hours and transplanted into recipient pigs. Four groups were compared: Group 1: livers perfused with a dose of 1.25 mg of BQ123 at baseline and at 2 hours of perfusion, Group 2: Epoprostenol at a continuous infusion of 4mg/hr, Group 3: Verapamil 2.5mg at baseline and at 2 hours of perfusion, Group 4: No vasodilator used during ex vivo perfusion. Liver injury and function were assessed during perfusion, and daily post transplantation until postoperative day 3. All groups were compared to a cold storage group for post operative graft function. Results Hepatic artery flow during NEVLP was significantly higher in BQ123 compared to Verapamil, Epopostenol, and no vasodilator treated livers. AST levels were significantly lower with BQ123 and Verapamil compared to Epoprostenol and control group during perfusion. Peak AST levels were lower in pigs receiving BQ123 and Verapamil perfused grafts compared to Epoprostenol and control group. INR, alkaline phosphatase, and total bilirubin levels were lower in the BQ123 and Verapamil groups compared to Epoprostenol group. Cold storage group had increased markers of ischemia reperfusion injury and slower graft function recovery compared to machine perfused grafts. Conclusion The use of BQ123, Epoprostenol, and Verapamil during NEVLP is safe. Livers perfused with BQ123 and Verapamil have higher HA flow and reduced hepatocyte injury during perfusion compared to Epoprostenol. Hepatic artery flow is significantly reduced in the absence of vasodilators during NEVLP. Authors Contributions. Juan Echeverri: Conception and design of the study, completion of experiments, acquisition of data, data analysis and interpretation, drafted manuscript, final approval for publication, and agreement to be accountable for all aspects of the work. Nicolas Goldaracena: Completion of experiments, acquisition of data, data analysis and interpretation, revised manuscript critically for important intellectual content, final approval for publication, and agreement to be accountable for all aspects of the work. Johan Moritz Kaths: Completion of experiments, acquisition of data, data analysis and interpretation, revised manuscript critically for important intellectual content, final approval for publication, and agreement to be accountable for all aspects of the work. Ivan Linares: Completion of experiments, acquisition of data, data analysis and interpretation final approval for publication, and agreement to be accountable for all aspects of the work. Roizar Rosales: Completion of experiments, acquisition of data, data analysis and interpretation final approval for publication, and agreement to be accountable for all aspects of the work. Dagmar Kollmann: Completion of experiments, acquisition of data, data analysis and interpretation final approval for publication, and agreement to be accountable for all aspects of the work. Matyas Hamar: Acquisition of data, data analysis and interpretation final approval for publication, and agreement to be accountable for all aspects of the work. Peter Urbanellis: Analysis and interpretation of data, revised manuscript critically for important intellectual content, final approval for publication, and agreement to be accountable for all aspects of the work. Sujani Ganesh: Acquisition of data, analysis and interpretation of data, revised manuscript critically for important intellectual content, final approval for publication, and agreement to be accountable for all aspects of the work. Oyedele Adeyi: Analysis and interpretation of data, revised manuscript critically for important intellectual content, final approval for publication, and agreement to be accountable for all aspects of the work. Mahmood Tazari: Statistical analysis and interpretation of data, revised manuscript critically, final approval for publication, and agreement to be accountable for all aspects of the work. Markus Selzner: Conception and design of the study, completion of experiments, acquisition of data, data analysis and interpretation, drafted manuscript, final approval for publication, and agreement to be accountable for all aspects of the work. Nazia Selzner: Conception and design of the study, acquisition of data, data analysis and interpretation, drafted manuscript, final approval for publication, and agreement to be accountable for all aspects of the work. Disclosure: The authors declare no conflicts of interest. Correspondence: Nazia Selzner, MD, PhD, Toronto General Hospital, NCSB 11C-1244, 585 University Avenue, Toronto, ON M5G2N2, Phone: 1-416-340-5230, Fax: 1-416-340-5242, e-mail: nazia.selzner@uhn Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Myeloid-Derived Suppressor Cells and their Potential Application in Transplantation

Abstract Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immunosuppressive cells of the myeloid lineage upregulated by mediators of inflammation such as IL-2, GCSF, and S100A8/A9. These cells have been studied extensively by tumor biologists. Because of their robust immunosuppressive potential, MDSCs have stirred recent interest among transplant immunologists as well. MDSCs inhibit T cell responses through, among other mechanisms, the activity of arginase-1 and iNOS, and the expansion of T regulatory (Treg) cells. In the context of transplantation, MDSCs have been studied in several animal models, and to a lesser degree in humans. Here, we will review the immunosuppressive qualities of this important cell type and discuss the relevant studies of MDSCs in transplantation. It may be possible to exploit the immunosuppressive capacity of MDSCs for the benefit of transplant patients. Disclosure: The authors have no financial disclosures. Grant support: This work was supported by a grant (to JRS) from the American Surgical Association Foundation and by the Living Legacy Foundation of Maryland. Author contributions: JRS – read the literature, developed the concept/hypotheses, wrote the manuscript, lead the project, revised the paper YSL – read the literature, contributed to hypotheses, edited the paper ED – read the literature, edited the paper, contributed to manuscript's structure JSB – read the literature, edited the paper, contributed to manuscript's structure, mentored the project Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Association of Cardiac Abnormalities to the Frail Phenotype in Cirrhotic Patients on the Waitlist: From the Functional Assessment in Liver Transplantation (FrAILT) Study.

ABSTRACT Background Frailty is a syndrome of decreased physiologic reserve that results from compromise of multiple physiologic systems including cardiovascular. We aimed to determine the association between the frail phenotype and cardiac abnormalities in liver transplant (LT) candidates through evaluation of transthoracic echocardiography (TTE) indices. Methods Included were consecutive outpatients listed for LT who underwent a frailty assessment from 1/1/14-6/30/16 (using the Liver Frailty Index) and a 2-dimensional/doppler TTE exam. Patients were categorized as robust, intermediate frail, or frail by the Liver Frailty Index based on scores of 34cc/m2 (p= 0.001). In linear regression adjusted for age, sex, hypertension and diabetes, the Liver Frailty Index was positively associated with LA dimension (coeff 0.20, 95%CI 0.07-0.34), LAVIcc/m2 (coeff 0.01, 95%CI 0.005-0.02), ejection fraction (coeff 1.59, 95%CI 0.32-2.85) and pulmonary artery systolic pressure (coeff 0.01, 95%CI 0.003-0.02) and negatively associated with LV hypertrophy (coeff -0.22, 95%CI -0.37, -0.06). Conclusion In LT candidates, frailty is associated with cardiac structural and functional changes, independent of known risk factors. Our study provides evidence to support that measures of frailty in cirrhotic patients encompass abnormalities of the cardiovascular system and may inform assessments of cardiovascular reserve in this population. CORRESPONDENCE INFORMATION: Jennifer C. Lai, MD, MBA, Department of Medicine, Division of Gastroenterology and Hepatology, University of California-San Francisco, San Francisco, CA, 513 Parnassus Avenue, UCSF Box 0538, San Francisco, CA 94143, Email: Jennifer.lai@ucsf.edu, Academic office: (415) 476-2777 AUTHORSHIP Puchades:Study concept and design; acquisition of data; analysis and interpretation of data; drafting of manuscript; critical revision of the manuscript for important intellectual content. Chau: Study design; acquisition of data, interpretation of data; critical revision of the manuscript for important intellectual content. Dodson: Study design; interpretation of data; drafting of manuscript; critical revision of the manuscript for important intellectual content. Mohamad: Study design; interpretation of data; critical revision of the manuscript for important intellectual content. Mustain: Study design; interpretation of data; critical revision of the manuscript for important intellectual content. Lebsack: Study design; analysis and interpretation of data; critical revision of the manuscript for important intellectual content. Aguilera: Study design; interpretation of data; critical revision of the manuscript for important intellectual content. Prieto: Study design; interpretation of data; critical revision of the manuscript for important intellectual content. Lai: Study concept and design; analysis and interpretation of data; drafting of manuscript; critical revision of the manuscript for important intellectual content; statistical analysis and study supervision. DISCLOSURE: The authors of this manuscript have no conflicts of interest to disclose. FUNDING: This study was funded by the Spanish Transplantation Society (Puchades), an American College of Gastroenterology Junior Faculty Development Award (Lai), P30AG044281 (UCSF Older Americans Independence Center; Lai), and K23AG048337 (Paul B. Beeson Career Development Award in Aging Research; Lai). These funding agencies played no role in the analysis of the data or the preparation of this manuscript. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Rituximab and Therapeutic Plasma Exchange in Recurrent Focal Segmental Glomerulosclerosis Postkidney Transplantation

Background Focal segmental glomerulosclerosis (FSGS) is a common cause of end stage renal disease (ESRD) with a high rate of recurrence after kidney transplantation. Several factors such as white race, rapid progression, and previous allograft failure due to recurrence were found to be risks of recurrence. Data are limited on the benefits of rituximab and/or therapeutic plasma exchange (TPE) in preventing recurrence. In this study, we sought to assess the efficacy of rituximab and TPE for the prevention and treatment of recurrent FSGS post kidney transplantation. Methods We enrolled 66 patients with FSGS in this prospective observational study and followed their outcomes. Patients with high risk for recurrence received preventative therapy with TPE and/or rituximab. Results Twenty three of the thirty seven (62%) who received preventative therapy developed recurrence compared to fourteen recurrences out of the twenty seven (51%) who did not receive any therapy (p=0.21). There was a trend for less relapse when rituximab was used as a therapy for recurrent FSGS, (6/22 versus 9/18, p=0.066). We utilized a clinical score of 5 values to assess the prediction of FSGS recurrence. A score of 3 or more had a predictive Receiver Operating Characteristic (ROC) curve of 0.72. Treatment with TPE and/or rituximab resulted in better allograft survival than historical studies. Allograft failure due to recurrent FSGS occurred in only 6 patients (9%). Conclusion Preventative therapies do not decrease the recurrence rate of recurrent FSGS. However, prompt treatment of recurrence with these therapies may result in improved outcomes. Corresponding Author: Nada Alachkar, MD, 600 Wolfe St. Brady 502, Baltimore, MD. Email: nalachk1@jhmi.edu Authorship Page: Sami Alasfar: data collection, data analysis and interpretation, drafting the article Dany Matar: data collection Robert A Montgomery: critical revision of the article Niraj Desai: critical revision of the article Bonnie Lonze: critical revision of the article Vikas Vujjini: data collection Michelle M. Estrella: critical revision of the article John Manllo Dieck: data collection, critical revision of the article Gebran Khneizer: data collection Sanja Sever: critical revision of the article Jochen Reiser: critical revision of the article Nada Alachkar: design of the work, data collection, data analysis and interpretation, drafting the article, final approval of the version to be published Disclosures: JR and SS are cofounders and stock holders of Trisaq, a biotechnological company developing novel therapeutics for chronic kidney diseases and FSGS, and have pending and issued patents in the therapeutic and diagnostic space regarding kidney diseases. Sources of support: NIH R01DK101350-04, Nada Alachkar Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Valganciclovir prophylaxis versus preemptive therapy in cytomegalovirus-positive renal allograft recipients: Long-term results after 7 years of a randomized clinical trial

Background The VIPP study compared valganciclovir prophylaxis with preemptive treatment regarding efficacy, safety and long-term graft outcome in CMV-positive (R+) renal transplant recipients. Methods Multicenter, open-label, randomized clinical study with a 12-month study phase and a follow-up of up to 84 months. Patients in the prophylaxis group received 2x450 mg/day oral valganciclovir for 100 days adjusted to renal function. Preemptive treatment with 2x900 mg/day valganciclovir was initiated at a viral load of ≥400 CMV copies/mL (PCR) and maintained over ≥14 days, followed by secondary prophylaxis. Patients were stratified by donor CMV IgG serostatus (D+/R+, D-/R+). Results The 12-month-results were reported previously (Witzke et al Transplantation 2012). The intent-to-treat/safety population comprised 148 patients in the prophylaxis (61.5% D+/R+) and 151 patients in the preemptive group (52.3% D+/R+). Overall, 47% patients completed the follow-up. Significantly fewer patients in the prophylaxis compared to preemptive group experienced a CMV infection or disease up to month 84 (11.5% [95% CI: 6.8%,17.8%] vs. 39.7% [31.9%,48.0%], p

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Interaction between alcohol consumption and metabolic syndrome in predicting severe liver disease in the general population

ABSTRACT

The metabolic syndrome and alcohol risk use are both associated with high prevalence of hepatic steatosis, but only a minority develop liver failure or liver cancer. Few general population studies have analyzed metabolic predictors of such severe liver complications. We studied which metabolic factors best predict severe liver complications, stratified by alcohol consumption. 6732 individuals without baseline liver disease who participated in the Finnish population-based Health 2000 Study (2000-2001), a nationally representative cohort. Follow-up data from national registers until 2013 were analyzed for liver-related admissions, mortality, and liver cancer. Baseline alcohol use and metabolic factors were analyzed by backward stepwise Cox regression analysis. 84 subjects experienced a severe liver event during follow-up. In the final multivariate model, factors predictive of liver events were age (HR 1.02, 95%CI 1.004-1.04), gender (women HR 0.55, 0.34-0.91), alcohol use (HR 1.002, 1.001-1.002), diabetes (HR 2.73, 1.55-4.81), LDL cholesterol (HR 0.74, 0.58-0.93), and HOMA-IR (HR 1.01, 1.004-1.02). Among alcohol risk users (average alcohol use ≥210 g/week for men, ≥140 g/week for women), diabetes (HR 6.79, 95%CI 3.18-14.5) was the only significant predictor. Among non-risk drinkers, age, alcohol use, smoking, waist circumference, low LDL cholesterol and HOMA-IR were significant independent predictors. The total cholesterol-to-LDL cholesterol-ratio and waist circumference-to-BMI-ratio emerged as additional independent predictors.

Conclusion: Multiple components of the metabolic syndrome independently affected the risk for severe liver disease. Alcohol was significant even when average alcohol consumption was within the limits currently defining non-alcoholic fatty liver disease. This article is protected by copyright. All rights reserved.

http://ift.tt/2BczTOb

Accuracy of Invasive and Noninvasive Parameters for Diagnosing Ventilatory Overassistance During Pressure Support Ventilation

Objective: Evaluate the accuracy of criteria for diagnosing pressure overassistance during pressure support ventilation. Design: Prospective clinical study. Setting: Medical-surgical ICU. Patients: Adults under mechanical ventilation for 48 hours or more using pressure support ventilation and without any sedative for 6 hours or more. Overassistance was defined as the occurrence of work of breathing less than 0.3 J/L or 10% or more of ineffective inspiratory effort. Two alternative overassistance definitions were based on the occurrence of inspiratory esophageal pressure-time product of less than 50 cm H2O s/min or esophageal occlusion pressure of less than 1.5 cm H2O. Interventions: The pressure support was set to 20 cm H2O and decreased in 3-cm H2O steps down to 2 cm H2O. Measurements and Main results: The following parameters were evaluated to diagnose overassistance: respiratory rate, tidal volume, minute ventilation, peripheral arterial oxygen saturation, rapid shallow breathing index, heart rate, mean arterial pressure, change in esophageal pressure during inspiration, and esophageal and airway occlusion pressure. In all definitions, the respiratory rate had the greatest accuracy for diagnosing overassistance (receiver operating characteristic area = 0.92; 0.91 and 0.76 for work of breathing, pressure-time product and esophageal occlusion pressure in definition, respectively) and always with a cutoff of 17 incursions per minute. In all definitions, a respiratory rate of less than or equal to 12 confirmed overassistance (100% specificity), whereas a respiratory rate of greater than or equal to 30 excluded overassistance (100% sensitivity). Conclusion: A respiratory rate of 17 breaths/min is the parameter with the greatest accuracy for diagnosing overassistance. Respiratory rates of less than or equal to 12 or greater than or equal to 30 are useful clinical references to confirm or exclude pressure support overassistance. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/29S62lw). Work was performed at the Heart Institute (InCor), Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. Supported and funded by Fundação de Amparo a Pesquisa do Estado de São Paulo (Fapesp) (2012/09170-3 and 2010/08947-9), a governmental nonprofit agency. No restrictions were placed on authors regarding the statements made in the manuscript. Dr. de Albuquerque received support for article research from FAPESP - Fundação de Amparo à Pesquisa do Estado de São Paulo, and he disclosed government work. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: pedro.caruso@hc.fm.usp.br Copyright © by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

http://ift.tt/2zYhW7G

Initial Antifungal Strategy Reduces Mortality in Critically Ill Patients With Candidemia: A Propensity Score–Adjusted Analysis of a Multicenter Study

Objective: The objective of this study was to evaluate the impact of the empirical therapy with fluconazole or an echinocandin on 30- and 90-day mortality in critically ill patients with candidemia. The outcome of patients in whom the empirical echinocandin was deescalated to fluconazole was also assessed. Design: Retrospective, observational multicenter study. Setting: Medical and surgical ICUs in nine Spanish hospitals. Patients: Adult patients (≥ 18 yr) with an episode of Candida bloodstream infection during ICU admission from January 2011 to April 2016. Interventions: Patient characteristics, infection-related variables, therapeutic interventions, and metastatic complications were reviewed. A propensity score–adjusted multivariable analysis was performed to identify the risk factors significantly associated with 30-day and 90-day mortality. Measurements and Main Results: A total of 294 patients were diagnosed of candidemia in the participant ICUs. Sixty patients were excluded (other antifungals in the primary therapy or the patient died without empirical antifungal therapy). The study group comprised 115 patients who received fluconazole (30-day mortality, 37.4%) and 119 patients treated empirically with an echinocandin (30-day mortality, 31.9%). The use of an echinocandin in the empirical therapy was a protective factor for 30-day (odds ratio, 0.32; 95% CI, 0.16–0.66; p = 0.002) and 90-day mortality (odds ratio, 0.50; 95% CI, 0.27–0.93; p = 0.014) in the propensity score– adjusted multivariable analysis. Deescalation of the empirical echinocandin to fluconazole was not associated with a higher mortality or the occurrence of long-term complications. Conclusions: Empirical use of an echinocandin in critically ill patients with documented candidemia reduces mortality at 30 and 90 days significantly. Deescalation of the empirical echinocandin to fluconazole is safe and effective in fluconazole-susceptible infections. Dr. Garnacho-Montero has served as speaker for Merck, Sharp & Dohme (MSD) and Astellas; and received an educational grant from Astellas. Dr. Ramirez has served as speaker for Pfizer, MSD, and Astellas. Dr. Rodriguez-Delgado has served as speaker for Merck, Sharp, and Dohme de España S.A. Dr. Garcia-Garmendia received an educational grant from MSD in 2015. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: jgarnachom@gmail.com Copyright © by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

http://ift.tt/2hI0SIR

Impact of Quality Bundle Enforcement by a Critical Care Pharmacist on Patient Outcome and Costs

Objectives: Surgical and medical ICU patients are at high risk of mortality and provide a significant cost to the healthcare system. The aim of this study is to describe the effect of pharmacist-led interventions on drug therapy and clinical strategies on ICU patient outcome and hospital costs. Design: Before and after study in two French ICUs (16 and 10 beds). Patients: ICU patients. Intervention: From January 1, 2013, to June 30, 2015, a pharmacist observation period was compared with an intervention period in which a critical care pharmacist provided recommendations to clinicians regarding sedative drugs and doses, choice of mechanical ventilation mode and related settings, antimicrobial de-escalation, and central venous and urinary catheters removal. Differences in ICU and hospital length of stay, duration of mechanical ventilation, mortality rate, and hospital costs per patient were quantified between groups with patients matched for severity of illness (Simplified Acute Physiology Score II) at admission. Measurements and Main Results: From the 1,519 and 1,268 admitted patients during the observation and intervention periods, respectively, 1,164 patients were evaluable in both groups after matching for Simplified Acute Physiology Score II score. The intervention period was associated with mean (95% CI) reductions in patient hospital length of stay (3.7 d [5.2–2.3 d]; p

http://ift.tt/2zWVzQg

The Glucagon-Like Peptide-1 Analog Exenatide Increases Blood Glucose Clearance, Lactate Clearance, and Heart Rate in Comatose Patients After Out-of-Hospital Cardiac Arrest

Objectives: To investigate the effects of the glucagon-like peptide-1 analog exenatide on blood glucose, lactate clearance, and hemodynamic variables in comatose, resuscitated out-of-hospital cardiac arrest patients. Design: Predefined post hoc analyzes from a double-blind, randomized clinical trial. Setting: The ICU of a tertiary heart center. Patients: Consecutive sample of adult, comatose patients undergoing targeted temperature management after out-of-hospital cardiac arrest from a presumed cardiac cause, irrespective of the initial cardiac rhythm. Interventions: Patients were randomized 1:1 to receive 6 hours and 15 minutes of infusion of either 17.4 μg of the glucagon-like peptide-1 analog exenatide (Byetta; Lilly) or placebo within 4 hours from sustained return of spontaneous circulation. The effects of exenatide were examined on the following prespecified covariates within the first 6 hours from study drug initiation: lactate level, blood glucose level, heart rate, mean arterial pressure, and combined dosage of norepinephrine and dopamine. Measurements and Main Results: The population consisted of 106 patients receiving either exenatide or placebo. During the first 6 hours from study drug initiation, the levels of blood glucose and lactate decreased 17% (95% CI, 8.9–25%; p = 0.0004) and 21% (95% CI, 6.0–33%; p = 0.02) faster in patients receiving exenatide versus placebo, respectively. Exenatide increased heart rate by approximately 10 beats per minute compared to placebo (p

http://ift.tt/2hIUwcf

Should Transfusion Trigger Thresholds Differ for Critical Care Versus Perioperative Patients? A Meta-Analysis of Randomized Trials

Objective: To address the significant uncertainty as to whether transfusion thresholds for critical care versus surgical patients should differ. Design: Meta-analysis of randomized controlled trials. Setting: Medline, EMBASE, and Cochrane Library searches were performed up to 15 June 2016. Patients: Trials had to enroll adult surgical or critically ill patients for inclusion. Interventions: Studies had to compare a liberal versus restrictive threshold for the transfusion of allogeneic packed RBCs. Measurements and Main Results: The primary outcome was 30-day all-cause mortality, sub-grouped by surgical and critical care patients. Secondary outcomes included myocardial infarction, stroke, renal failure, allogeneic blood exposure, and length of stay. Odds ratios and weighted mean differences were calculated using random effects meta-analysis. To assess whether subgroups were significantly different, tests for subgroup interaction were used. Subgroup analysis by trials enrolling critically ill versus surgical patients was performed. Twenty-seven randomized controlled trials (10,797 patients) were included. In critical care patients, restrictive transfusion resulted in significantly reduced 30-day mortality compared with liberal transfusion (odds ratio, 0.82; 95% CI, 0.70–0.97). In surgical patients, a restrictive transfusion strategy led to the opposite direction of effect for mortality (odds ratio, 1.31; 95% CI, 0.94–1.82). The subgroup interaction test was significant (p = 0.04), suggesting that the effect of restrictive transfusion on mortality is statistically different for critical care (decreased risk) versus surgical patients (potentially increased risk or no difference). Regarding secondary outcomes, for critically ill patients, a restrictive strategy resulted in reduced risk of stroke/transient ischemic attack, packed RBC exposure, transfusion reactions, and hospital length of stay. In surgical patients, restrictive transfusion resulted in reduced packed RBC exposure. Conclusions: The safety of restrictive transfusion strategies likely differs for critically ill patients versus perioperative patients. Further trials investigating transfusion strategies in the perioperative setting are necessary. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Dr. Chong extracted the data, performed the data analysis, created the figures/tables, and prepared the article. Contribution: Dr. Krishnan extracted the data, performed the data analysis, created the figures/tables, and revised the article. Dr. Cheng provided resource support in this study, guidance with article preparation, and revised the final article. Dr. Martin conceived the idea of performing a meta-analysis of transfusion triggers, provided guidance with article preparation and data analysis, and revised the final article. All authors attest to the integrity of the original data and analysis, as well as approved the final article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/29S62lw). The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: janet.martin@lhsc.on.ca Copyright © by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

http://ift.tt/2zYhNRG

Kinetics of Urinary Cell Cycle Arrest Markers for Acute Kidney Injury Following Exposure to Potential Renal Insults

Objectives: Urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 predict the development of acute kidney injury following renal insults of varied aetiology. To aid clinical interpretation, we describe the kinetics of biomarker elevations around an exposure. Design: In an ancillary analysis of the multicenter SAPPHIRE study, we examined the kinetics of the urinary [tissue inhibitor of metalloproteinase-2]•[insulin-like growth factor binding protein 7] in association with exposure to common renal insults (major surgery, IV radiocontrast, vancomycin, nonsteroidal anti-inflammatory drugs, and piperacillin/tazobactam). Setting: Thirty-five sites in North America and Europe between September 2010 and June 2012. Patients: Seven hundred twenty-three critically ill adult patients admitted to the ICU. Interventions: None. Measurements and Main Results: We compared the urinary [tissue metalloproteinase-2]•[insulin growth factor binding protein 7] kinetics from the day prior to exposure up to 5 days after exposure in patients developing acute kidney injury stage 2–3, stage 1, or no acute kidney injury by Kidney Disease Improving Global Outcome criteria. Among the 723 patients, 679 (94%) had at least one, 70% had more than one, and 35% had three or more exposures to a known renal insult. There was a significant association between cumulative number of exposures up to study day 3 and risk of acute kidney injury (p = 0.02) but no association between the specific type of exposure and acute kidney injury (p = 0.22). With the exception of radiocontrast, patients who developed acute kidney injury stage 2–3 after one of the five exposures, had a clear rise and fall of urinary [tissue inhibitor of metalloproteinase-2]•[insulin-like growth factor binding protein 7] from the day of exposure to 24–48 hours later. In patients without acute kidney injury, there was no significant elevation in urinary [tissue inhibitor of metalloproteinase-2]•[insulin-like growth factor binding protein 7]. Conclusions: Exposure to potential renal insults is common. In patients developing acute kidney injury stage 2–3, the kinetics of urinary [tissue inhibitor of metalloproteinase-2]•[insulin-like growth factor binding protein 7] matched the exposure except in the case of radiocontrast. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. For a full list of the SAPPHIRE Investigators, see the supplemental data (Supplemental Digital Content 1, http://ift.tt/2zWVtrS). Supported by Astute Medical, San Diego, CA. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/29S62lw). Dr. Ostermann disclosed that the original Sapphire study was funded by Astute Medical. She received grant support from Fresenius Medical Care. Dr. Forni received funding from Astute Medical and Orthodox Clinical Diagnostic (lecture fees). Dr. Bagshaw received funding from Baxter Healthcare. He was also supported by a Canada Research Chair in Critical Care Nephrology. Dr. Joannidis received speaker´s fees from Astute Medical. Dr. Shi received funding from Astute Medical and disclosed that her husband also consults for Astute Medical. Dr. Kashani's institution received funding from Astute Medical. Dr. Honore's institution received funding from Baxter. Dr. Chawla disclosed that he is an employee of La Jolla Pharmaceutical. He also disclosed that he and his institution received funding from Astute Medical. Dr. Kellum and his institution received funding from Astute Medical. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: Marlies.Ostermann@gstt.nhs.uk Copyright © by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

http://ift.tt/2hIUtx5

Rapid Gene Family Evolution of a Nematode Sperm Protein Despite Sequence Hyper-conservation

Reproductive proteins are often observed to be the most rapidly evolving elements within eukaryotic genomes. The major sperm protein (MSP) is unique to the phylum Nematoda and is required for proper sperm locomotion and fertilization. Here we annotate the MSP gene family and analyze their molecular evolution in ten representative species across Nematoda. We show that across the phylum, MSPs are hyper-conserved having maintained an amino acid sequence identity of 83.5% to 97.7% for over 500 million years. This extremely slow rate of evolution makes MSPs some of the most highly conserved genes yet identified. At the gene family level, however, we show hyper-variability in both gene copy number and genomic position within species, suggesting rapid, lineage-specific gene family evolution. Additionally, we find evidence that extensive gene conversion contributes to the maintenance of sequence identity within chromosome-level clusters of MSP genes. Thus, while not conforming to the standard expectation for the evolution of reproductive proteins, our analysis of the molecular evolution of the MSP gene family is nonetheless consistent with the widely repeatable observation that reproductive proteins evolve rapidly, in this case in terms of the genomic properties of gene structure, copy number, and genomic organization. This unusual evolutionary pattern is likely generated by strong pleiotropic constraints acting on these genes at the sequence-level balanced against expansion at the level of the whole gene family.

http://ift.tt/2zaBmmG

Caenorhabditis elegans DBL-1/BMP Regulates Lipid Accumulation via Interaction with Insulin Signaling

Metabolic homeostasis is coordinately controlled by diverse inputs. Understanding these regulatory networks is vital to combating metabolic disorders. The nematode Caenorhabditis elegans has emerged as a powerful, genetically tractable model system for the discovery of lipid regulatory mechanisms. Here we introduce DBL-1, the C. elegans homolog of bone morphogenetic protein 2/4 (BMP2/4), as a significant regulator of lipid homeostasis. We used neutral lipid staining and a lipid droplet marker to demonstrate that both increases and decreases in DBL-1/BMP signaling result in reduced lipid stores and lipid droplet count. We find that lipid droplet size, however, correlates positively with the level of DBL 1/BMP signaling. Regulation of lipid accumulation in the intestine occurs through non-cell-autonomous signaling, since expression of SMA-3, a Smad signal transducer, in the epidermis (hypodermis) is sufficient to rescue the loss of lipid accumulation. Finally, genetic evidence indicates that DBL-1/BMP functions upstream of Insulin/IGF-1 Signaling in lipid metabolism. We conclude that BMP signaling regulates lipid metabolism in C. elegans through inter-organ signaling to the Insulin pathway, shedding light on a less well-studied regulatory mechanism for metabolic homeostasis.

http://ift.tt/2BdhDnO

Rice TSV3 Encoding Obg-Like GTPase Protein Is Essential for Chloroplast Development During the Early Leaf Stage Under Cold Stress

The Spo0B-associated GTP-binding (Obg) proteins are essential for the viability of nearly all bacteria. However, detailed roles of Obg proteins in higher plants have not yet been elucidated. In this study, we identified a novel rice (Oryza sativa L.) thermo-sensitive virescent mutant, tsv3 that displayed albino phenotype at 20°C before the 3-leaf stage while being normal green at 32°C or even at 20°C after the 4-leaf stage. The mutant phenotype was consistent with altered chlorophyll content and chloroplast structure in leaves. Map-based cloning and complementation experiments showed that TSV3 encoded a small GTP-binding protein. Subcellular localization studies revealed that TSV3 was localized to the chloroplasts. Expression of TSV3 was high in leaves and weak or undetectable in other tissues, suggesting a tissue-specific expression of TSV3. In the tsv3 mutant, expression levels of genes associated with the biogenesis of the chloroplast ribosome 50S subunit were severely decreased at the 3-leaf-stage under cold stress (20°C), but could be recovered to normal levels at a higher temperature (32°C). These observations suggest that the rice nuclear-encoded TSV3 plays important roles in chloroplast development at early leaf stage under cold stress.

http://ift.tt/2zccnzn

Cognitive rehabilitation and mindfulness in multiple sclerosis (REMIND-MS): a study protocol for a randomised controlled trial

Cognitive problems frequently occur in patients with multiple sclerosis (MS) and profoundly affect their quality of life. So far, the best cognitive treatment options for MS patients are a matter of debate. Th...

http://ift.tt/2BcvXgv

The Biology of Cancer Exosomes: Insights and New Perspectives

Exosomes are a subclass of extracellular vesicles involved in intercellular communication that are released by all cell types, including cancer cells. Cancer exosomes carry malignant information in the form of proteins, lipids, and nucleic acids that can reprogram recipient cells. Exosomes have emerged as putative biological mediators in cancer contributing to major steps of disease progression. A leading role exists for cancer exosomes in specific aspects of tumor progression: modulation of immune response, tumor microenvironment reprogramming, and metastasis. This review will address the functions attributed to cancer exosomes in these three aspects of cancer biology, highlighting recent advances and potential limitations. Finally, we explore alternative strategies to develop better models to study cancer exosomes biology. Cancer Res; 77(23); 1–9. ©2017 AACR.

http://ift.tt/2jcEHLr

Precision Oncology: Between Vaguely Right and Precisely Wrong

Precision Oncology seeks to identify and target the mutation that drives a tumor. Despite its straightforward rationale, concerns about its effectiveness are mounting. What is the biological explanation for the "imprecision?" First, Precision Oncology relies on indiscriminate sequencing of genomes in biopsies that barely represent the heterogeneous mix of tumor cells. Second, findings that defy the orthodoxy of oncogenic "driver mutations" are now accumulating: the ubiquitous presence of oncogenic mutations in silent premalignancies or the dynamic switching without mutations between various cell phenotypes that promote progression. Most troublesome is the observation that cancer cells that survive treatment still will have suffered cytotoxic stress and thereby enter a stem cell–like state, the seeds for recurrence. The benefit of "precision targeting" of mutations is inherently limited by this counterproductive effect. These findings confirm that there is no precise linear causal relationship between tumor genotype and phenotype, a reminder of logician Carveth Read's caution that being vaguely right may be preferable to being precisely wrong. An open-minded embrace of the latest inconvenient findings indicating nongenetic and "imprecise" phenotype dynamics of tumors as summarized in this review will be paramount if Precision Oncology is ultimately to lead to clinical benefits. Cancer Res; 77(23); 1–7. ©2017 AACR.

http://ift.tt/2A2aCpT

Poziotinib Shows Promise for Rare Lung Cancer [News in Brief]

Good responses seen in patients with exon 20 mutations, for which approved EGFR inhibitors are largely ineffective.

http://ift.tt/2jcjBwH

FOXF1 defines the core-regulatory circuitry in gastrointestinal stromal tumor (GIST) [Research Articles]

The cellular context that integrates upstream signaling and downstream nuclear response dictates the oncogenic behaviour and shapes treatment responses in distinct cancer types. Here, we uncover that in GIST, the forkhead family member, FOXF1, directly controls the transcription of two master regulators, KIT and ETV1, both required for GIST precursor-interstitial cells of Cajal (ICC) lineage-specification and GIST tumorigenesis. Further, FOXF1 co-localizes with ETV1 at enhancers and functions as a pioneer factor that regulates the ETV1-dependent GIST-lineage specific transcriptome through modulation of the local chromatin context, including chromatin accessibility, enhancer maintenance and ETV1 binding. Functionally, FOXF1 is required for human GIST cell growth in vitro and murine GIST tumor growth and maintenance in vivo. The simultaneous control of the upstream signaling and nuclear response sets up a unique regulatory paradigm and highlights the critical role of FOXF1 in enforcing the GIST cellular context for highly lineage-restricted clinical behaviour and treatment response.

http://ift.tt/2A049eR

NKG2D-dependent anti-tumor effects of chemotherapy and radiotherapy against glioblastoma

Purpose: NKG2D is a potent activating immune cell receptor and glioma cells express the cognate ligands (NKG2DL). These ligands are inducible by cellular stress and temozolomide (TMZ) or irradiation (IR), the standard treatment of glioblastoma, could affect their expression. However, a role of NKG2DL for the efficacy of TMZ and IR has never been addressed. Experimental Design:We assessed the effect of TMZ and IR on NKG2DL in vitro and in vivo in a variety of murine and human glioblastoma models including glioma-initiating cells and a cohort of paired glioblastoma samples from patients before and after therapy. Functional effects were studied with immune cell assays. The relevance of the NKG2D system for the efficacy of TMZ and IR was assessed in vivo in syngeneic orthotopic glioblastoma models with blocking antibodies and NKG2D knockout mice. Results:TMZ or IR induced NKG2DL in vitro and in vivo in all glioblastoma models and glioblastoma patient samples had increased levels of NKG2DL after therapy with TMZ and IR. This enhanced the immunogenicity of glioma cells in a NGK2D-dependent manner, was independent from cytotoxic or growth inhibitory effects, attenuated by O6-methylguanine-DNA-methyltransferase (MGMT) and required the DNA damage response. The survival benefit afforded by TMZ or IR relied on an intact NKG2D system and was decreased upon inhibition of the NKG2D pathway. Conclusions: The immune system may influence the activity of convential cancer treatments with particular importance of the NKG2D pathway in glioblastoma. Our data provide a rationale to combine NKG2D-based immunotherapies with TMZ and IR.

http://ift.tt/2zayhD6

Doctors perception of support and the processes involved in complaints investigations and how these relate to welfare and defensive practice: a cross-sectional survey of the UK physicians

Objective

How adverse outcomes and complaints are managed may significantly impact on physician well-being and practice. We aimed to investigate how depression, anxiety and defensive medical practice are associated with doctors actual and perceived support, behaviour of colleagues and process issues regarding how complaints investigations are carried out.

Design

A survey study. Respondents were classified into three groups: no complaint, recent/current complaint (within 6 months) or past complaint. Each group completed specific surveys.

Setting

British Medical Association (BMA) members were invited to complete an online survey.

Participants

95 636 members of the BMA were asked to participate. 7926 (8.3%) completed the survey, of whom 1780 (22.5%) had no complaint, 3889 (49.1%) had a past complaint and 2257 (28.5%) had a recent/current complaint. We excluded those with no complaints leaving 6144 in the final sample.

Primary outcomes measures

We measured anxiety and depression using the Generalised Anxiety Disorder Scale 7 and Physical Health Questionnaire 9. Defensive practice was assessed using a new measure for avoidance and hedging.

Results

Most felt supported by colleagues (61%), only 31% felt supported by management. Not following process (56%), protracted timescales (78%), vexatious complaints (49%), feeling bullied (39%) or victimised for whistleblowing (20%), and using complaints to undermine (31%) were reported. Perceived support by management (relative risk (RR) depression: 0.77, 95% CI 0.71 to 0.83; RR anxiety: 0.80, 95% CI 0.74 to 0.87), speaking to colleagues (RR depression: 0.64, 95% CI 0.48 to 0.84 and RR anxiety: 0.69, 95% CI 0.51 to 0.94, respectively), fair/accurate documentation (RR depression: 0.80, 95% CI 0.75 to 0.86; RR anxiety: 0.81, 95% CI 0.75 to 0.87), and being informed about rights (RR depression 0.96 (0.89 to 1.03) and anxiety 0.94 (0.87 to 1.02), correlated positively with well-being and reduced defensive practice. Doctors worried most about professional humiliation following a complaint investigation (80%).

Conclusion

Poor process, prolonged timescales and vexatious use of complaints systems are associated with decreased psychological welfare and increased defensive practice. In contrast, perceived support from colleagues and management is associated with a reduction in these effects.

http://ift.tt/2BbuE18

Alkaline peptone water enrichment with a dipstick test to quickly detect and monitor cholera outbreaks

Detection, confirmation and monitoring of cholera outbreaks in many developing countries including Uganda is a big challenge due to lack of the required resources and the time the test takes. Culture method wh...

http://ift.tt/2jN5txJ

ICU-treated influenza A(H1N1) pdm09 infections more severe post pandemic than during 2009 pandemic: a retrospective analysis

We compared in a single mixed intensive care unit (ICU) patients with influenza A(H1N1) pdm09 between pandemic and postpandemic periods.

http://ift.tt/2hTRXYN

Antifungal susceptibility testing of Candida species isolated from the immunocompromised patients admitted to ten university hospitals in Iran: comparison of colonizing and infecting isolates

Antifungal susceptibility testing is a subject of interest in the field of medical mycology. The aim of the present study were the distributions and antifungal susceptibility patterns of various Candida species i...

http://ift.tt/2jPtvIE

Absence of nuclease activity in commonly used oxygen-scavenging systems

Oxygen scavenging systems are routinely used during single-molecule imaging experiments to improve fluorescent dye stability. Previous work has shown nuclease contamination in the commonly used oxygen scavengi...

http://ift.tt/2zqWp8R

High-throughput SuperSAGE for gene expression analysis of Nicotiana tabacum–Rhizoctonia solani interaction

The ubiquitous soil pathogen Rhizoctonia solani causes serious diseases in different plant species. Despite the importance of this disease, little is known regarding the molecular basis of susceptibility. SuperSA...

http://ift.tt/2mQtR2J

No long-term effect of a 2-days intervention on how to prepare homemade food, on toddlers’ skepticism for new food and intake of fruits and vegetables and sweet beverages: a randomized, controlled trial

Optimal nutrition from early age reduces the risk of developing non-communicable diseases later in life. The aim of this study was to examine the long-term effect on toddlers' fruit and vegetable intake and sw...

http://ift.tt/2zrfGqs

Calpain-5 gene expression in the mouse eye and brain

Our objective was to characterize CAPN5 gene expression in the mouse central nervous system. Mouse brain and eye sections were probed with two high-affinity RNA oligonucleotide analogs designed to bind CAPN5 RNA ...

http://ift.tt/2mTJsyC

A preliminary study of cross-amplified microsatellite loci using molted feathers from a near-threatened Painted Stork (Mycteria leucocephala) population of north India as a DNA source

In continuation of an earlier study in which we reported the cross-amplification of Wood stork microsatellites on the DNA obtained from molted feathers of Painted stork (Mycteria leucocephala), here we investigat...

http://ift.tt/2zrf0Bq

The usefulness of chief complaints to predict severity, ventilator dependence, treatment option, and short-term outcome of patients with Guillain-Barré syndrome: a retrospective study

It remains an urgent need for early recognition of disease severity, treatment option and outcome of Guillain-Barré syndrome (GBS). The chief complaint may be quickly obtained in clinic and is one of the candi...

http://ift.tt/2BcmBBo

The Conduct and Reporting of Child Health Research: An Analysis of Randomized Controlled Trials Published in 2012 and Evaluation of Change over 5 Years

For child health randomized controlled trials (RCTs) published in 2012, we aimed to describe design and reporting characteristics and evaluate changes since 2007; assess the association between trial design and registration and risk of bias (RoB); and assess the association between RoB and effect size.

http://ift.tt/2hSQDW0

Characteristics and Progression of Hearing Loss in Children with Down Syndrome

To evaluate hearing impairment in children with Down syndrome, and to describe the factors that influence the severity of hearing loss or changes in hearing over time.

http://ift.tt/2jMD0bq

Laryngeal Mask Airway for Surfactant Administration in Neonates: A Randomized, Controlled Trial

To determine if preterm infants with moderate respiratory distress syndrome on continuous positive airway pressure (CPAP) who received surfactant via a laryngeal mask airway (LMA) would have a decreased rate of intubation and mechanical ventilation compared with those on CPAP who did not receive surfactant.

http://ift.tt/2jJDwH7

Acute Pancreatitis Admission Trends: A National Estimate through the Kids' Inpatient Database

To evaluate national health care use and costs for pediatric acute pancreatitis.

http://ift.tt/2hT98tl

Patterns of Care at the End of Life for Children and Young Adults with Life-Threatening Complex Chronic Conditions

To characterize patterns of care at the end of life for children and young adults with life-threatening complex chronic conditions (LT-CCCs) and to compare them by LT-CCC type.

http://ift.tt/2hQRW7K

The combined activation of KCa3.1 and inhibition of Kv11.1/hERG1 currents contribute to overcome Cisplatin resistance in colorectal cancer cells

The combined activation of K_Ca3.1 and inhibition of K_v11.1/hERG1 currents contribute to overcome Cisplatin resistance in colorectal cancer cells

The combined activation of K_Ca3.1 and inhibition of K_v11.1/hERG1 currents contribute to overcome Cisplatin resistance in colorectal cancer cells, Published online: 21 November 2017; doi:10.1038/bjc.2017.392

http://ift.tt/2A2or7H

The impact of folate intake on the risk of head and neck cancer in the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO) cohort

The impact of folate intake on the risk of head and neck cancer in the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO) cohort

The impact of folate intake on the risk of head and neck cancer in the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO) cohort, Published online: 21 November 2017; doi:10.1038/bjc.2017.383

http://ift.tt/2A2omAV

Rapid nodal staging of head and neck cancer surgical specimens with flow cytometric analysis

Rapid nodal staging of head and neck cancer surgical specimens with flow cytometric analysis

Rapid nodal staging of head and neck cancer surgical specimens with flow cytometric analysis, Published online: 21 November 2017; doi:10.1038/bjc.2017.408

http://ift.tt/2A2osZj

Cadherin-1 and cadherin-3 cooperation determines the aggressiveness of pancreatic ductal adenocarcinoma

Cadherin-1 and cadherin-3 cooperation determines the aggressiveness of pancreatic ductal adenocarcinoma

Cadherin-1 and cadherin-3 cooperation determines the aggressiveness of pancreatic ductal adenocarcinoma, Published online: 21 November 2017; doi:10.1038/bjc.2017.411

http://ift.tt/2A2oujT

Determination of an optimal response cut-off able to predict progression-free survival in patients with well-differentiated advanced pancreatic neuroendocrine tumours treated with sunitinib: an alternative to the current RECIST-defined response

Determination of an optimal response cut-off able to predict progression-free survival in patients with well-differentiated advanced pancreatic neuroendocrine tumours treated with sunitinib: an alternative to the current RECIST-defined response

Determination of an optimal response cut-off able to predict progression-free survival in patients with well-differentiated advanced pancreatic neuroendocrine tumours treated with sunitinib: an alternative to the current RECIST-defined response, Published online: 21 November 2017; doi:10.1038/bjc.2017.402

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Factors to improve the interobserver agreement for gastric atrophy and intestinal metaplasia: Consensus of definition and criteria

Abstract

Aims

Intestinal metaplasia and atrophy of the gastric mucosa are associated with Helicobacter pylori infection and are considered premalignant lesions. The updated Sydney system is used to these parameters but experienced pathologists and consensus processes are required for interobserver agreement. We sought to determine the influence of consensus process on assessment of intestinal metaplasia and atrophy.

Methods and results

Two study sets were used; consensus set and validation set. The consensus set was circulated and 5 gastrointestinal pathologists independently evaluated them using the updated Sydney system. After then the consensus of the definitions was determined in the first consensus meeting. The same set was recirculated to determine the effect of the consensus. The second consensus meeting was held to standardize the grading criteria and the validation set was circulated to determine the influence. Two additional circulations were performed to assess the maintainance of consensus and intraobserver variability. Interobserver agreement of intestinal metaplasia and atrophy was improved through consensus process (intestinal metaplasia: baseline κ=0.52 vs. final κ=0.68, p=0.006; atrophy: baseline κ=0.19 vs. final κ=0.43, p<0.001). Higher interobserver agreement in atrophy was observed after consensus of definition (pre-consensus: κ=0.19 vs. post-consensus: κ=0.34, p=0.001). There was improved interobserver agreement in intestinal metaplasia after standardization of the grading criteria (pre-standardization: κ=0.56 vs. post-standardization: κ=0.71, p=0.010).

Conclusions

This study suggests that interobserver variability regarding intestinal metaplasia and atrophy may result from lack of a precise definition and fine criteria, and can be reduced by consensus of definition and standardization of grading criteria.

This article is protected by copyright. All rights reserved.

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The Root Membrane Technique: Human Histologic Evidence after Five Years of Function

Background. The "root membrane" (RM) is a technique that has become popular among implantologists for placement of immediate implants in the anterior maxilla. Purpose. To present histologic evidence of an immediate implant placed in the human anterior maxilla, according to the RM technique, and retrieved after five years. Methods. A fixture, along with the surrounding tissues, was retrieved from the anterior maxilla of a 68-year-old patient, who had been treated five years earlier with immediate implant placement and RM technique. The specimen was processed for histologic/histomorphometric evaluation. Results. The buccal bone plate was maintained without any resorption; a healthy periodontal ligament was evidenced. The implant showed osseointegration, with a high percentage of bone-to-implant contact (BIC = 76.2%). With regard to the space between the RM and the implant, the apical and medial thirds were filled with compact, mature bone; the coronal third was colonized by noninfiltrated connective tissue. Conclusions. The RM technique appears to be effective in preventing bone resorption of the buccal bone plate of the human anterior maxilla, five years after the placement of an immediate implant.

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Fatigue in Inflammatory Bowel Disease Reflects Mood and Symptom-reporting Behavior Rather than Biochemical Activity or Anemia

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Lugol Chromoendoscopy Detects Esophageal Dysplasia With Low Levels Of Sensitivity In A High-Risk Region Of China

Chromoendoscopy with Lugol dye is used to screen for early-stage esophageal squamous dysplasia (ESD) and esophageal cancer. However, the sensitivity with which Lugol chromoendoscopy detects ESD or esophageal cancer has not been fully assessed in large populations in China.

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Microarray analysis of gene expression in the cyclooxygenase (COX) knockout mice - a connection to Autism Spectrum Disorder

Abstract

The cellular and molecular events that take place during brain development play an important role in governing function of the mature brain. Lipid signalling molecules such as prostaglandin E₂ (PGE₂) play an important role in healthy brain development. Abnormalities along the COX/PGE₂ signalling pathway due to genetic or environmental causes have been linked to Autism Spectrum Disorders (ASDs). This study aims to evaluate the effect of altered COX/PGE₂ signalling on development and function of the prenatal brain using male mice lacking cyclooxygenase-1 and -2 (COX-1^-/- and COX-2^-/-) as potential model systems of ASD. Microarray analysis was used to determine global changes in gene expression during embryonic days 16 (E16) and 19 (E19). Gene Ontology: Biological Process (GO:BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were implemented to identify affected developmental genes and cellular processes. We found that in both knockouts the brain at E16 had nearly twice as many differentially expressed genes and affected biological pathways containing various ASD associated genes important in neuronal function. Interestingly, using GeneMANIA and Cytoscape we also show that the ASD-risk genes identified in both COX-1^-/-and COX-2^-/- models belong to protein-interaction networks important for brain development despite of different cellular localization of these enzymes. Lastly, we identified 8 genes that belong to the Wnt signalling pathways exclusively in the COX-2^-/- mice at E16. The level of PKA-phosphorylated β-catenin (S552), a major activator of the Wnt pathway, was increased in this model, suggesting cross-talk between the COX-2/PGE₂ and Wnt pathways during early brain development. Overall, these results provide further molecular insight into the contribution of the COX/PGE₂ pathways to ASD and demonstrate that COX-1^-/- and COX-2^-/- animals might be suitable new model systems for studying the disorders.

This article is protected by copyright. All rights reserved.

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Predatory journals: a serious complication in the scholarly publishing landscape

Your daily routine probably involves wading through numerous emails that invite you to submit your work, attend a conference, or become an editorial board member for one journal after another, some of which sound vaguely familiar. This is a great honor, right? Not necessarily.

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miR-335 inhibited cell proliferation of lung cancer cells by target Tra2β

Abstract

Accumulating evidence has suggested that the dysregulation of miRNAs is an important factor in the pathogenesis of lung cancer. Here, we demonstrate that miR-335 expression is reduced in non-small cell lung cancer (NSCLC) tumors relative to non-cancerous adjacent tissues, whilst the expression of Tra2β is increased. In addition, clinical data revealed that the increased Tra2β and decreased miR-335 expression observed in NSCLC cells was associated with poor patient survival rates. In-vitro experimentation showed that the overexpression of miR-335 inhibited the growth, invasion and migration capabilities of A459 lung cancer cells, by targeting Tra2β. In contrast, inhibition of miR-335 or overexpression of the Tra2β target gene stimulated the growth, invasion and migratory capabilities of A459 lung cancer cells in vitro. Furthermore, overexpression of miR-335 or inhibition of Tra2β decreased the phosphorylation of Rb-S780 and Rb-AKT. Overall, these findings suggest that the downregulation of miR-335 in A459 lung cancer cells promoted cell proliferation by upregulation of Tra2β, mediated via activation of the AKT/mTOR signaling pathway, and suggest that miR-335 may have potential as a novel therapeutic target for NSCLC.

This article is protected by copyright. All rights reserved.

http://ift.tt/2zbHuLx

Difficulties in pain management using oxycodone and fentanyl in enzalutamide-treated patients with advanced prostate cancer

Pain treatment in patients with bone metastasized advanced prostate cancer is often challenging. A range of treatment modalities are available to control prostate cancer-specific pain, such as androgen deprivation therapies, taxane-based chemotherapy, radionuclide therapy with radium-223 or palliative radiotherapy. In addition, analgesics are commonly used for direct symptom management.

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Determination of an optimal response cut-off able to predict progression-free survival in patients with well-differentiated advanced pancreatic neuroendocrine tumours treated with sunitinib: an alternative to the current RECIST-defined response

http://ift.tt/2jOkLm5

Rapid nodal staging of head and neck cancer surgical specimens with flow cytometric analysis

http://ift.tt/2hSPT35

Cadherin-1 and cadherin-3 cooperation determines the aggressiveness of pancreatic ductal adenocarcinoma

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The combined activation of KCa3.1 and inhibition of Kv11.1/hERG1 currents contribute to overcome Cisplatin resistance in colorectal cancer cells

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The impact of folate intake on the risk of head and neck cancer in the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO) cohort

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Imaging characteristics of subcutaneous amyloid deposits in diabetic patients: the “insulin ball”

Abstract

Objective

The purpose of this study was to describe the imaging characteristics of subcutaneous amyloid deposits occurring at sites of insulin injection, commonly known as "insulin balls," in diabetic patients on ultrasound, CT, and MRI with pathologic correlation.

Materials and methods

We retrospectively reviewed the radiographic findings of 14 lesions in 9 patients diagnosed with subcutaneous amyloid deposits at our institution between 2005–2015. Three board-certified radiologists analyzed the following: (1) the shape, size, margin, morphologic characteristics, and blood flow on US using the color Doppler signal, (2) shape, size, margin, attenuation, and presence or absence of contrast enhancement on CT, and (3) shape, size, margin, signal intensity, and presence or absence of contrast enhancement on MRI.

Results

All lesions showed ill-defined hypovascular subcutaneous nodules with irregular margins. The median diameter of lesions was 50.4 mm on US, 46.8 mm on CT, and 51.4 mm on MRI. The internal echogenicity of subcutaneous amyloid deposits was hypoechoic and heterogeneous on US. All lesions showed isodensity compared to muscle with irregular margins and minimal contrast enhancement on CT. Both T1- and T2-weighted MR images showed low signal intensity compared with subcutaneous fat. Normal diffusion and minimal contrast enhancement were seen.

Conclusions

Subcutaneous amyloid deposits which cause insulin resistance are typically ill-defined and heterogeneous hypovascular subcutaneous nodules with irregular margins on imaging that correspond to insulin injection sites. It is also characteristic that T2WI shows low intensity compared with fat on MRI, reflective of the amyloid content.

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Slowly growing mass on the left shoulder

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Browser’s notes

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Conservatively treated knee injury is associated with knee cartilage matrix degeneration measured with MRI-based T2 relaxation times: data from the osteoarthritis initiative

Abstract

Objective

To investigate the association of cartilage degeneration with previous knee injuries not undergoing surgery, determined by morphologic and quantitative 3-T magnetic resonance imaging (MRI).

Materials and methods

We performed a nested cross-sectional study of right knee MRIs from participants in the Osteoarthritis Initiative (OAI) aged 45–79 with baseline Kellgren-Lawrence score of 0–2. Cases were 142 right knees of patients with self-reported history of injury limiting the ability to walk for at least 2 days. Controls were 426 right knees without history of injury, frequency-matched to cases on age, BMI, gender, KL scores and race (1:3 ratio). Cases and controls were compared using covariate-adjusted linear regression analysis, with the outcomes of region-specific T2 mean, laminar analysis and heterogeneity measured by texture analysis to investigate early cartilage matrix abnormalities and the Whole-Organ Magnetic Resonance Imaging Score (WORMS) to investigate morphologic knee lesions.

Results

Compared to control subjects, we found significantly higher mean T2 values in the injury [lateral tibia (28.10 ms vs. 29.11 ms, p = 0.001), medial tibia (29.70 ms vs. 30.40 ms, p = 0.014) and global knee cartilage (32.73 ms vs. 33.29 ms, p = 0.005)]. Injury subjects also had more heterogeneous cartilage as measured by GLCM texture contrast, variance and entropy (p < 0.05 in 14 out of 18 texture parameters). WORMS gradings were not significantly different between the two groups (p > 0.05).

Conclusion

A history of knee injury not treated surgically is associated with higher and more heterogeneous T2 values, but not with morphologic knee abnormalities. Our findings suggest that significant, conservatively treated knee injuries are associated with permanent cartilage matrix abnormalities.

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Correction to: Highlights of the annual scientific meeting of the 24th congress of the European Society of Musculoskeletal Radiology (ESSR) 2017

Abstract

The original version of this article unfortunately contained mistakes. The name and affiliations of Luca Maria Sconfienza are already corrected on this article.

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Southwick angle measurements and SCFE slip severity classifications are affected by frog-lateral positioning

Abstract

Objective

Slipped capital femoral epiphysis (SCFE) is a hip disorder where the femoral head slips relative to the neck at the physis. Appropriate treatment of SCFE depends on the severity of the slip, commonly categorised using the Southwick (SW) angle. The SW angle is measured in the frog-lateral leg position, which can be painful and potentially unattainable for patients. The purpose of this study is to determine how errors in frog-lateral radiograph positioning affect measured SW angles and slip classifications.

Methods

Models of SCFE hips were produced from one CT scan of a normal hip; 360 deformities were created. SW angles were measured from a simulated frog-lateral position. Femoral lateral head-neck angles (LHNA; equivalent to SW in incorrect frog-lateral plane) were measured over a range of 837 incorrect frog-lateral leg positions with positioning errors in flexion and/or internal/external rotation.

Results

Seventy-six per cent of all imaging position-deformity combinations had error in the reported angle (>1° difference between LHNA and SW). Of those, 70% had <5°, 24% had 5° to 10°, and 6% had >10° of error from the actual SW angle. Three per cent of LHNAs that had >10° error resulted from <10° of positioning error.

Conclusions

If the patient is limited in flexion or external rotation, more diagnostic testing should be considered if error in the reported slip measurement would affect treatment decisions or if accurate severity classification is needed for research. Small positioning errors in moderate and severe slips can cause a > 10° LHNA error; additional three-dimensional imaging should be considered.

http://ift.tt/2zWvkd1

Undifferentiated pleomorphic sarcoma: indolent, tail-like recurrence of a high-grade tumor

Abstract

Recurrence of a soft tissue sarcoma typically manifests as a round or oval mass at imaging, and recurrent high-grade soft tissue sarcomas generally enlarge relatively rapidly. We present a case of high-grade undifferentiated pleomorphic sarcoma in the calf of a 48-year-old male that recurred as a thin, curvilinear "tail" of enhancing tissue at magnetic resonance imaging (MRI), with extremely indolent growth over a 7-year period. The unusual imaging finding of a slowly enlarging "tail" should not be dismissed as postoperative changes, even for a high-grade soft tissue sarcoma.

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Is lead shielding of patients necessary during fluoroscopic procedures? A study based on kyphoplasty

Abstract

Objective

To determine the benefits, risks, and limitations associated with wrapping a patient with lead shielding during fluoroscopy-guided kyphoplasty procedures as a way to reduce operator radiation exposure.

Materials and methods

An anthropomorphic phantom was used to mimic a patient undergoing a kyphoplasty procedure under fluoroscopic guidance. Radiation measurements of the air kerma rate (AKR) were made at several locations and under various experimental conditions. First, AKR was measured at various angles along the horizontal plane of the phantom and at varying distances from the phantom, both with and without a lead apron wrapped around the lower portion of the phantom (referred to here as phantom shielding). Second, the effect of an operator's apron was simulated by suspending a lead apron between the phantom and the measurement device. AKR was measured for the four shielding conditions—phantom shielding only, operator apron only, both phantom shielding and operator apron, and no shielding. Third, AKR measurements were made at various heights and with varying C-arm angle.

Results

At all locations, the phantom shielding provided no substantial protection beyond that provided by an operator's own lead apron. Phantom shielding did not reduce AKR at a height comparable to that of an operator's head.

Conclusions

Previous reports of using patient shielding to reduce operator exposure fail to consider the role of an operator's own lead apron in radiation protection. For an operator wearing appropriate personal lead apparel, patient shielding provides no substantial reduction in operator dose.

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Spontaneous shrinkage of solitary osteochondromas

Abstract

Objective

Osteochondromas are the most common benign bone tumors, and thus far, their spontaneous shrinkage is considered a rare phenomenon. This study was designed to investigate the exact ratio of remission to progressive or stable cases and analyze the mechanism of tumor regression on the basis of existing theories.

Materials and methods

We retrospectively collected images of solitary osteochondromas in patients from 1992 to 2013, excluding cases involving short-term follow-up periods and follow-up periods that ended before growth plate closure. A total of 121 patients were diagnosed and screened for study inclusion. Tumor shrinkage was measured by assessing three points on tumor contours to determine if they had regressed or vanished. Patterns of shrinkage were further divided on the basis of mechanisms described as incorporation, absorption, and fracture.

Results

Seventeen patients (mean age at initial diagnosis 13.1 years) met the study inclusion criteria. Tumor morphological classifications were pedunculated (10 cases) and sessile (7 cases). Osteochondroma shrinkage was the most common outcome (8 cases), followed by stable osteochondromas (6 cases), and osteochondromas that had progressed (3 cases). Tumors with sessile morphology were more prone to shrinkage (6 of 7 cases) compared with those of pedunculated morphology (2 of 10 cases; p = 0.015). Among pedunculated cases, tumor shrinkage was via absorption. The timing of tumor growth cessation was related to the pattern of tumor shrinkage. Absorption mostly followed tumor growth cessation, whereas incorporation mostly preceded tumor growth cessation.

Conclusion

The shrinkage of osteochondromas appears less rare than was originally thought.

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Slowly growing mass on the left shoulder

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Assessment of hindfoot alignment using MRI and standing hindfoot alignment radiographs (Saltzman view)

Abstract

Objective

To compare the hindfoot alignment measured on standing HAV radiographs (Saltzman view) and on non-weight-bearing coronal MR images.

Materials and methods

The apparent moment arm was measured on weight-bearing conventional radiographs (Saltzman views) and on MRIs of the ankle in 50 consecutive patients (mean age, 54 years; age range, 18–77 years). The evaluation was performed independently by three readers using analogous reference points for both methods. Positive values were assigned when the deepest point of the calcaneus was lateral to the tibial axis as valgus, negative values as varus. The intertechnique agreement and correlation for the measurements performed with HAV radiographs and MRI were assessed for each reader using the Bland-Altman method and the Pearson correlation coefficient, respectively. The interobserver agreement was assessed using the intraclass correlation coefficient.

Results

The means of apparent moment arms, with the standard deviation (SD) in parentheses, of three readers were +2.0 (±8.4) mm, +1.5 (±6.6) mm and −1.4 (±8.2) mm on HAV radiographs and +4.6 (±7.4) mm, +6.3 (±5.3) mm and +5.4 (±6.4) mm on MRI. The Bland-Altman analysis found a systematic bias for all three readers, corresponding to an overestimation of measurements with MRI (systematic bias ranging from 2.6 to 4.8 mm). The intertechnique correlation was found moderate to high. The Pearson coefficients for the three readers were 0.75, 0.64 and 0.65. The interobserver agreement among the three readers was 0.72, 0.77 and 0.68 for HAV, MRI and both modalities together, respectively.

Conclusion

Hindfoot alignment can be estimated on MRI but the correlation between the values on HAV radiographs and MR images is only moderate with a tendency to increased positive values (valgization) on MR images.

http://ift.tt/2zVZBsp

Highlights of the annual scientific meeting of the 24th congress of the European Society of Musculoskeletal Radiology (ESSR) 2017

Abstract

This paper summarizes the main aspects of the 24th Annual Scientific Meeting of the European Society of Musculoskeletal Radiology (ESSR), which was hosted in Bari (Italy) in June 2017.

http://ift.tt/2AkBRyC

Intraosseous migration of tendinous calcifications: two case reports

Abstract

Calcific tendinopathy of the rotator cuff is a common cause of shoulder pain. Inflammation of the rotator cuff tendons may be complicated by adjacent bone erosion and subsequent migration of calcific deposits within the bone resulting in marrow inflammation. Bone marrow involvement is not readily visible using X-ray and ultrasound (US) and further testing is necessary. Magnetic resonance imaging (MRI) is a highly sensitive technique that can detect a focal bone T1 and T2-weighted hypointensity with bone marrow edema-like signal and cortical erosion. These findings can mislead the radiologist by suggesting an infectious or neoplastic lesion, often requiring further evaluation with computed tomography (CT) and biopsy. We report two cases of patients with shoulder pain in which different radiological approaches were used with pathological confirmation in one of them. In the first case, MRI revealed significant bone involvement in the head of the humerus and cortical erosion of the greater tuberosity. A CT examination and a biopsy was necessary for a final diagnosis of inflammatory bone reaction from intraosseous migration of tendinous calcifications. In the second case, similar MRI findings prompted re-evaluation of imaging to make a diagnosis of intraosseous migration of tendinous calcifications, obviating the need to perform CT and biopsy. We illustrate MRI signs of this complication that we think would allow to narrow the differential diagnosis potentially avoiding biopsy and additional CT examinations.

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Subfascial fat herniation: sonographic features of back mice

Abstract

Three adult patients are described with sonographic features of subfascial fat hernation. Each patient presented to the musculoskeletal ultrasound department at our institution for the evaluation of a palpable mass of the low back. Subfascial fat hernation, also known as back mice and fibro-fatty nodule, are an uncommon cause of a palpable mass in the low back or low back pain. They are small mobile subcutaneous nodules in a characteristic location near the posterior superior iliac spine. This entity has not been described in the radiology literature. These cases are presented in order to demonstrate the sonographic findings of back mice and to describe key anatomic features.

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Combined classical spindle cell/pleomorphic lipoma spectrum imaging and clinical data

Abstract

Objectives

Compile the largest study to date on the imaging and clinical features of the classic spindle cell/pleomorphic lipoma spectrum and suggest this diagnosis be included in the differential for benign and malignant macroscopic fat-containing soft tissue masses regardless of the mass location or patient demographics.

Materials and methods

An institutional search was performed to identify all available classic-type spindle cell/pleomorphic lipomas with available demographic and imaging data. Images and reports were analyzed by one MSK-trained radiologist and radiographic, anatomic and clinical data were recorded. Additionally, a literature search was performed to identify studies describing the spindle cell lipoma spectrum imaging features and were combined with institutional data.

Results

Forty-two institutional cases were identified, 37 of which had MRIs performed among which 21 had images available (T1- and T2-weighted pulse sequences) for review while the remainder had outside reports detailing the mass imaging features. There was a mean age of 57 with 79% of cases occurring in males. Contrary to prior reports, 57% of masses were subcutaneous, and the neck and back region accounted for 26% of cases. When the institutional cases were combined with available data in the literature, there was a new sample size of 91 masses, 74 of which had MRI and/or CT data. Eighty-seven percent of masses were heterogeneous, 51% were composed of less than 75% fat, 65% were in the back, neck or shoulder region, 27% of masses were deep and 91% demonstrated enhancement. Eighty-two percent of patients were males with a mean age of 58 at excision.

Conclusion

Imaging features, patient demographics and tumor location alone are not enough to differentiate tumors of the spindle cell lipoma spectrum from other macroscopic fat-containing benign and malignant tumors, and these entities should be included in the same imaging differential diagnosis.

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Multiple skeletal muscle metastases revealing a cardiac intimal sarcoma

Abstract

We report the case of a 59-year-old female with progressive bilateral painful swelling of the thighs. MRI revealed multiple intramuscular necrotic masses with similar morphologic patterns. Whole-body CT and 18-FDG PET-CT scans demonstrated additional hypermetabolic muscular masses and a lobulated lesion within the left atrial cavity. As biopsy of a muscular mass was compatible with a poorly differentiated sarcoma with MDM2 oncogene amplification, two diagnoses were discussed: a dedifferentiated liposarcoma with muscle and heart metastases or a primary cardiac sarcoma, mainly a cardiac intimal sarcoma, with muscular metastases, which was finally confirmed by array-comparative genomic hybridization (aCGH) in a sarcoma reference center. This case emphasizes the potential for intimal sarcoma to disseminate in skeletal muscle prior to any other organ and the need for a genomic approach in addition to classical radiopathologic analyses to distinguish primary from secondary locations facing simultaneous tumors of the heart and skeletal muscles with MDM2 amplification.

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Osseous spurs at the fovea capitis femoris—a frequent finding in asymptomatic volunteers

Abstract

Objective

To investigate the different morphologic types of the fovea capitis femoris and the spectrum of osseous spurs/osteophytes of the fovea in asymptomatic volunteers and patients with hip osteoarthritis.

Material and methods

Sixty-five patients (mean age 63.6 years) with radiographically confirmed osteoarthritis of the hip and 59 asymptomatic healthy volunteers (mean age 33.9 years) underwent non-contrast MRI of the hip joint. Two radiologists independently evaluated all images. Fovea morphology (standard type, diamond type, flat type, triangular type) as well as the frequency, size and location of spurs/osteophytes of the fovea were assessed. Descriptive and inferential statistics were applied.

Results

The most frequent morphologic type of the fovea capitis femoris was the standard type for both asymptomatic volunteers (average 45%) and patients (average 49%). Osseous spurs were detected in 70% of the asymptomatic volunteers, and 97% of the patients had osteophytes. Spur size at all locations was significantly smaller in asymptomatic volunteers (range 1–2 mm) than osteophyte size in patients (range 1-4 mm) (p ≤ 0.035). In volunteers and patients, the spurs/osteophytes were most frequently located at the anterior border of the fovea capitis femoris.

Conclusion

Smaller osseous spurs (<2 mm) at the border of the fovea capitis femoris are very common in asymptomatic volunteers and do not seem to be pathologic.

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Imaging features of glenoid bare spot in a pediatric population

Abstract

Objective

The bare spot (BaS) is a central, well-circumscribed focal defect in the glenoid articular surface, with reported adult incidence of 1–2%. We aimed to reassess MRI features of BaS in the pediatric population and determine its etiology.

Materials and methods

A retrospective search of our database from June 2014 to October 2015 was performed for shoulder MRI in patients between 5 and 25 years and then subdivided into four groups: group 1, 5–10 years; group 2, 10–15 years; group 3, 15–18 years; group 4, 20–25 years. BaS was defined as a well-marginated, central defect of increased signal in the articular surface of the glenoid, seen on at least two planes, without evidence of underlying glenoid pathology. Presence, location and size along with clinical indications were documented.

Results

A final cohort of 253 patients revealed 23 BaS, 3.5% in group 1, 20% in group 2, 5% in group 3 and 4% in group 4. There was a significantly higher incidence in group 2 (p = 0.007) compared to group 3 and p = 0.002 compared to group 4. Location was mainly central. Mean size was significantly bigger in group 2 compared to group 3 and 4. Distribution showed the highest number at 14–15 years of age. Instability was higher in groups 3 and 4.

Conclusion

Incidence of BaS in group 2 was significantly higher than in other age groups and higher than in adults. BaS was also larger compared to other populations. These findings support a developmental theory, explained by the centripetal ossification of the glenoid.

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Pitfalls in soft tissue sarcoma imaging: chronic expanding hematomas

Abstract

Solid or nodular enhancement is typical of soft tissue sarcomas although high grade soft tissue sarcomas and those with internal hemorrhage often appear heterogeneous with areas of nonenhancement and solid or nodular enhancement. These MRI findings often prompt an orthopedic oncology referral, a biopsy or surgery. However, not all masses with these imaging findings are malignant. We report the multimodality imaging findings of two surgically proven chronic expanding hematomas (CEH) with imaging features that mimicked sarcomas. A third case of nonenhancing CEH of the lower extremity is also presented as a comparison. It is important that in the correct clinical scenario with typical imaging findings, the differential diagnosis of a chronic expanding hematoma be included in the workup of these patients. An image-guided biopsy of nodular tissue within such masses that proves to be negative for malignancy should not necessarily be considered discordant. A correct diagnosis may prevent a morbid unnecessary surgery and may indicate the need for a conservative noninvasive follow-up with imaging.

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Reliability of standing weight-bearing (0.25T) MR imaging findings and positional changes in the lumbar spine

Abstract

Objective

To test the reliability and absolute agreement of common degenerative findings in standing positional magnetic resonance imaging (pMRI).

Methods and materials

Low back pain patients with and without sciatica were consecutively enrolled to undergo a supine and standing pMRI. Three readers independently evaluated the standing pMRI for herniation, spinal stenosis, spondylolisthesis, HIZ lesions and facet joint effusion. The evaluation included a semi-quantitative grading of spinal stenosis, foraminal stenosis and spinal nerve root compression. The standing pMRI images were evaluated with full access to supine MRI. In case lower grades or the degenerative findings were not present in the supine images, this was reported separately as position-dependent changes. A subsample of 20 pMRI examinations was reevaluated after two months. The reproducibility was assessed by inter- and intra-reader reliability (kappa statistic) and absolute agreement between readers.

Results

Fifty-six patients were included in this study. There was fair-to-substantial inter-reader reliability (κ 0.47 to 0.82) and high absolute agreement (72.3% to 99.1%) for the pMRI findings. The intra-reader assessment showed similar reliability and agreement (κ 0.36 to 0.85; absolute agreement: 62.5% to 98.8%). Positional changes between the supine and standing position showed a fair-to-moderate inter- and intra-reader reliability (κ 0.25 to 0.52; absolute agreement: 97.0% to 99.1).

Conclusion

Evaluation of the lumbar spine for degenerative findings by standing pMRI has acceptable reproducibility; however, positional changes from the supine to the standing position as an independent outcome should be interpreted with caution because of lower reliability, which calls for further standardisation.

http://ift.tt/2hJmS62