Safety and performance of a novel collagenated xenogeneic bone block for lateral alveolar crest augmentation for staged implant placement

Abstract

Objectives

To evaluate the performance and safety of placing a collagenated xenogeneic bone block (CXBB) graft for the lateral bone augmentation of the alveolar crest prior to implant placement.

Material & Methods

In patients with single or multiple tooth gaps and a severe horizontal collapse of the alveolar ridge, a ridge augmentation procedure was performed using CXBB fixated with osteosynthesis screws to the atrophic bone crest and complemented with deproteinized bovine bone mineral particles (DBBM) and a native bilayer collagen membrane (NBCM). Patients were examined with CBCT prior to and 24 weeks after the augmentation. Twenty-six weeks postoperatively, a re-entry procedure was performed to evaluate the bone width and availability for adequate implant placement.

Results

Fifteen patients received 28 CXBB, and in 13 patients, a re-entry procedure was performed. Eleven patients (84.6%) gained enough bone volume for implant insertion without additional contouring or secondary bone augmentation. The mean crest width at baseline was 2.83 mm (SD 0.57), and the mean crest width at re-entry was 6.90 mm (SD 1.22), with a mean ridge width increase of 4.12 mm (SD 1.32). Soft tissue dehiscence occurred during the follow-up in 5 of 14 patients (35.7%) at various time points. In addition, there was a high incidence of early implant loss (30.8% [patient-based]).

Conclusions

CXBB achieved significant horizontal crestal width gains allowing a secondary implant placement in the majority of the patients. However, the occurrence of soft tissue dehiscence may notably affect the outcome of the subsequent implant therapy.

http://ift.tt/2ukdjTn

Encephalitis lethargica: 100 years after the epidemic

Encephalitis lethargica is a neurological syndrome that spread across Europe and then the world beginning in the winter of 1916–17, and continuing into the 1930s. Although the exact number of people afflicted with encephalitis lethargica during the epidemic period is unknown, it is estimated to be more than one million worldwide (Ravenholt and Foege, 1982). Those who survived were sometimes left with lingering and permanent neurological sequelae that rendered them nearly akinetic. Although 100 years have elapsed since the beginning of the epidemic period, many questions remain about this mysterious illness: What causes it? How is it transmitted? Could an epidemic happen again?

http://ift.tt/2tq2uKM

Maternal pre-pregnancy body mass index, gestational weight gain influence birth weight

Publication date: Available online 14 July 2017
Source:Women and Birth
Author(s): R. Zhao, L. Xu, M.L. Wu, S.H. Huang, X.J. Cao
BackgroundEvidence suggests that pre-pregnancy body mass index and gestational weight gain have impact on pregnancy and birth weight, yet whether maternal gestational weight gain has a differential effect on the rates of adverse birth weight among women with different pre-pregnancy body mass index categories are unknown.MethodsWe selected 1617 children matched with their mothers as study subjects. The subjects were divided into three categories: weight gain below the American Institute of Medicine guidelines, weight gain within the American Institute of Medicine guidelines and weight gain above the American Institute of Medicine guidelines.ResultsThe prevalence of pre-pregnancy underweight and overweight/obese women was 16.3% and 12.3%. And nearly 15.2% of the women had gestational weight gain below American Institute of Medicine guideline, 52.1% of the women had gestational weight gain above American Institute of Medicine guideline. Maternal overweight and obese was associated with increased risk for macrosomia and large-for-gestational age. Women had gestational weight gain below American Institute of Medicine guideline were more likely to have low birth weight and small-for-gestational age than women who had gestational weight gain within American Institute of Medicine guideline. Furthermore, the risks for macrosomia and large-for-gestational age were increased in women with above American Institute of Medicine guideline. And for women with a normal weight before pregnancy, gestational weight gain above the American Institute of Medicine guidelines were associated with higher rates of macrosomia and large-for-gestational age, compared with the women of similar pre-pregnancy weight category but with gestational weight gain within the American Institute of Medicine guidelines.ConclusionsWomen with abnormal pre-pregnancy body mass index and gestational weight gain are at risk for adverse birth weight outcomes. Moreover, gestational weight gain has a differential effect on the rates of adverse birth weight outcomes between women of different pre-pregnancy body mass index categories.



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Regulation of unregistered birth workers in Australia: Homebirth and public safety

Publication date: Available online 13 July 2017
Source:Women and Birth
Author(s): Rebekah McWhirter
BackgroundAustralian midwives are regulated under the National Registration and Accreditation Scheme. Unregistered birth workers may provide midwifery services at homebirths without any regulatory oversight. To address this issue, several states have passed legislation enabling prohibition orders to be made (negative licensing) against unregistered health practitioners who fail to comply with a statutory code of conduct developed for those not covered by the National Scheme.AimTo explore the consequences for the availability of birth choices for women that arise from the introduction of negative licensing.DiscussionAn analysis of the regulatory framework and recent cases of unregistered birth workers attending homebirths reveals problems with equitable access to homebirth support, arising from issues with professional indemnity insurance, geography, and poor integration with hospitals and the wider healthcare system. These problems contribute to women choosing to employ the services of unregistered birth workers.ConclusionNegative licensing provides a useful additional tool for improving the safety of homebirths for mothers and babies, but it does not address the issues leading expectant parents to choose an unregistered birth worker to attend their births, and may contribute to an increase in high-risk behaviours, such as freebirthing.



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Emotional labour and aboriginal maternal infant care workers: The invisible load

Publication date: Available online 14 July 2017
Source:Women and Birth
Author(s): R. Kirkham, A. Rumbold, E. Hoon, D. Stuart-Butler, V. Moore
BackgroundThe term 'emotional labour' has been used to describe the competing demands on midwives to empathize with clients whilst maintaining a level of professional detachment. Previous research indicates that when individuals experience difficulty managing these emotions, burnout may result. Aboriginal health care workers often have roles with large emotional demands, as they are relied upon heavily to engage clients in care. However, the concept of emotional labour has received little attention in relation to this group.AimTo explore potential sources of emotional labour for Aboriginal Maternal Infant Care workers in a maternity care program for Aboriginal women in South Australia. The program involves these workers providing care for women in partnership with midwives.MethodsWe employed a phenomenological approach. Thirty in-depth interviews were conducted with staff and clients of the program. Recorded interviews were transcribed and coded and emerging themes identified.FindingsThis workforce undertakes extensive emotional labour. Key sources include the cultural and family obligations they have to clients, complex social needs of many clients, and potential for community backlash when poor perinatal outcomes occur. A lack of respect for the role within the workplace further contributes to these experiences.ConclusionThis study found that the responsibilities inherent to the role as both cultural broker and carer create significant emotional labour for workers. Recommendations to address this and enhance the sustainability of this workforce include: recognition and valuing of emotional work by management and other staff, enhancing cultural awareness training, and building stress-relieving activities into the workplace.



http://ift.tt/2t11IVl

Analyses of distribution and dosimetry of brain metastases in small cell lung cancer with relation to the neural stem cell regions: feasibility of sparing the hippocampus in prophylactic cranial irradiation

Abstract

Background

This work aims to assess the feasibility of selectively sparing the hippocampus during prophylactic cranial irradiation (PCI) for small cell lung cancer (SCLC).

Methods

SCLC patients with brain metastases (BMs) diagnosed with MRI were enrolled. Lesions localized to the neural stem cell (NSC) compartments [subventricular zone (SVZ) or hippocampus] were analyzed. Patients were categorized by the total number of intracranial metastases, the therapy processes and the symptoms. Hippocampi and enhanced lesions within 15 mm from the hippocampus were contoured. IMRT treatment plans were generated for hippocampal avoidance (HA)-PCI (25Gy in 10 fractions).

Results

From Jan 2011 to Oct 2014, 1511 metastases were identified in 238 patients. The overall ratio of metastatic lesions located in NSC regions was 2.0% in the 1511 total metastases and 9.7% in the 238 overall patients. Among the NSC region metastases, 15 (1.0%) lesions involved the HA region of 14 (5.9%) patients and another 15 (1.0%) involved the SVZ of 15 (6.3%) patients. The involvement of HA region or SVZ was significantly different between patients with oligometastatic and non-oligometastatic BMs (P < 0.05). Based on the dosimetric analysis, 26 (10.9%) patients with 41 (2.7%) metastases within 15 mm from the hippocampus had inadequate dosage in case that HA-PCI was applied.

Conclusions

Our retrospective review of 1511 metastases in 238 patients (among whom 89.5% were male) suggests that the metastatic involvement of the NSC regions (especially hippocampus) is unusual and limited primarily to patients with non-oligometastatic disease in SCLC. Also, dosimetric analysis shows that about 10% of patients may have adequate dosage due to HA-PCI treatment. But we believe that this is still an acceptable clinical treatment strategy for SCLC.

http://ift.tt/2t0CfeI

Distinct Physical Function Profiles in Older Adults Receiving Cancer Chemotherapy

While physical function is an important patient outcome, little is known about changes in physical function in older adults receiving chemotherapy (CTX).

http://ift.tt/2v2GmYP

Evaluation of a pain assessment procedure in long-term care residents with pain and dementia

The management of pain in long-term care residents with dementia is complex. A prospective exploratory study was conducted to describe the course of pain and pain management strategies following a guideline-based pain assessment procedure in long-term care (LTC) residents with pain and dementia.

http://ift.tt/2utv3w0

Healthcare Professionals’ Attitudes About Physician-Assisted Death: An Analysis of Their Justifications and the Roles of Terminology and Patient Competency

Healthcare professionals (HCPs) are crucial to physician-assisted death (PAD) provision.Objectives: To quantitatively assess the favorability of justifications for or against PAD legalization among HCPs, the effect of the terms "suicide" and "euthanasia" on their views, and their support for three forms of PAD.

http://ift.tt/2v2yeYC

A novel use of peer coaching to teach primary palliative care skills: Coaching consultation

We aim to address palliative care workforce shortages by teaching clinicians how to provide primary palliative care through peer coaching.

http://ift.tt/2utm3Xy

Evaluation of a video-based seminar to raise healthcare professionals’ awareness of culturally sensitive end-of-life care

To investigate the effect of a newly developed telenovela, or video soap opera, on healthcare professionals (HCP)' awareness of caregivers' stress and patients' cultural approaches to end-of-life (EOL) care decisions.

http://ift.tt/2v20zy7

Relationship between spirituality, meaning in life, psychological distress, wish for hastened death, and their influence on quality of life in palliative care patients

Spiritual, existential, and psychological issues represent central components of quality of life (QOL) in palliative care. A better understanding of the dynamic underlying these components is essential for the development of interventions tailored to the palliative context.

http://ift.tt/2utwqKS

Development of a Protocol for Successful Palliative Care Consultation in Population of Patients Receiving Mechanical Circulatory Support

In 2014, Joint Commission recommended palliative care (PC) engagement in ventricular assist device (VAD) implantation as destination therapy. Limited information is available on established PC protocols in the mechanical circulatory support (MCS) population.

http://ift.tt/2v2Cves

Dignity Therapy and Life Review for Palliative Care Patients: A Qualitative Study

Dignity Therapy (DT) is a psychotherapeutic intervention whose aim is to bolster the sense of purpose, meaning and sense of dignity in patients with terminal disease.

http://ift.tt/2utGtj7

The effectiveness of distraction as procedural pain management technique in paediatric oncology patients: a meta-analysis and systematic review

Diagnostic tests and treatment regimens for paediatric cancers involve invasive and painful procedures. Effective management of such pain has been shown to be sub-optimal in many parts of the world, often due to the cost and limited availability of appropriate medications. Current evidence suggests that distraction (a relatively low-cost technique) is a promising intervention for procedural pain management. There is, however, limited evidence demonstrating its effectiveness in paediatric oncology patients.

http://ift.tt/2v2cAmY

Attachment insecurity in advanced cancer patients: psychometric properties of the German version of the Brief Experiences in Close Relationships Scale (ECR-M16-G)

Attachment insecurity refers to difficulty in trusting and relying on others in times of need. Its underlying factors attachment anxiety and attachment avoidance have been empirically associated with impaired coping in advanced cancer, and therefore should be considered in individually tailored medical and psychosocial treatment.

http://ift.tt/2utpFcb

Renal Cell Carcinoma, Unclassified with Medullary Phenotype: Poorly-Differentiated Adenocarcinomas Overlapping with Renal Medullary Carcinoma

Renal medullary carcinoma (RMC) is a highly aggressive renal cell carcinoma, arising in the collecting system, and requiring careful correlation with status of sickle cell trait. A panel of international experts has recently proposed provisional diagnostic terminology, renal cell carcinoma, unclassified, with medullary phenotype (RCCU-MP), based on encountering an extraordinarily rare tumor with RMC morphology and immunophenotype in an individual proven not to have a hemoglobinopathy. Herein, we extend this observation to a cohort of five such tumors, morphologically similar to RMC, lacking SMARCB1 expression by immunohistochemistry, but each without evidence of a hemoglobinopathy.

http://ift.tt/2ujV0h4

The Impact of Knowledge Transfer on the Detection of Venous Invasion in Colorectal Cancer

Venous invasion (VI) is an independent predictor of hematogenous metastasis and mortality in colorectal cancer (CRC), yet remains widely under-reported. Its detection may require recognition of subtle morphologic clues which at times are only unmasked with an elastin stain. This study evaluates the impact of a knowledge transfer initiative (KTI) on VI detection in a "real world" pathology practice setting. Following participation in an interobserver variability study of VI detection (Kirsch et al 2013), twelve participants received educational materials highlighting key issues in VI detection.

http://ift.tt/2tVnYBb

Update in enteroscopy: new devices and new indications

Abstract

This review provides an update of the currently available (proto-) types of device-assisted enteroscopy (DAE). In recent years, newly designed double- and single-balloon enteroscopes have emerged. They aim to improve insertion depth into the small bowel, and they also allow more efficient endoscopic interventions. Nowadays, almost all conventional endoscopic procedures are feasible using DAE, opening the door to new indications. Recently, more data have become available on paediatric DAE, DAE-assisted colonoscopy, and DAE in patients with altered anatomy, including DAE-assisted ERCP and direct cholangioscopy. Although new enteroscopes are being developed, little comparative studies are available in order to define which DAE suits best for each indication. It is the duty of the international endoscopy community to set up clinical research projects to provide answers to these open questions.

This article is protected by copyright. All rights reserved.

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Shades of Sexualization: When Sexualization Becomes Sexual Objectification

Abstract

Sexualization in mass media is a widespread phenomenon. Although sexualization and sexual objectification are often used as synonymous, they are two different concepts. Across two studies, we investigated how sexualization affects perceptions of women (Study 1) and men (Study 2) as sexual objects. Participants were asked to judge sexual objectification, competence, and sexiness of female and male models portrayed with different degrees of sexualization, namely, as Non-Revealing (dressed), merely Revealing (undressed), and Sexualized Revealing (undressed and provocative). The results of both studies showed that as the level of sexualization increased so did participants' perceptions of the targets as sexual objects. However, the level of sexualization affected perceived competence and sexiness differently depending on the target's gender. Male models' competence decreased as the level of sexualization increased, whereas female models portrayed as merely Revealing and as Sexualized Revealing were judged as equally incompetent. Male targets' sexiness was not affected by the level of portrayals' sexualization, whereas Sexualized Revealing portrayals enhanced the perceived sexiness of female targets. Finally, in Study 2, the results showed that male targets in Sexualized Revealing portrayals were judged as less masculine. Our findings suggest that sexualization contributes similarly to the perception of both women and men as sexual objects but affects other variables depending on the target's gender. Our work extends previous literature and informs us about the consequences that sexualization of men and women have on others' judgments.

http://ift.tt/2tVaW6x

Incidence of and Risk Factors for Pancreatic Cancer in Chronic Pancreatitis: A Cohort of 1,656 Patients

Risk of pancreatic cancer may increase in chronic pancreatitis patients.

http://ift.tt/2tVBoNs

Axitinib in metastatic renal cell carcinoma: beyond the second-line setting

Future Oncology, Ahead of Print.


http://ift.tt/2uowAT0

Death by food

Abstract

Although death from food is not an uncommon finding in forensic facilities worldwide, the range of underlying lethal mechanisms and associated conditions that should be sought at the time of autopsy is quite disparate. Deaths may occur from i) infectious agents including bacteria, viruses, protozoa, cestodes, nematodes and prions; ii) natural toxins including amanita toxins, tetrodotoxin, ciguatera and scombroid; iii) anaphylaxis; iv) poisoning; v) mechanical issues around airway and gut obstruction and/or perforation; and vi) miscellaneous causes. Food-related deaths are important in terms of global mortality, and thus autopsies need to be comprehensive with full ancillary testing. Medicolegal matters may involve issues concerning likely exposure to infectious agents, possible foods ingested, the declared content and possible components of food, the significance of toxicological analyses, and aspects of duty of care in cases of café coronary syndrome and gastroenteritis while in care.

http://ift.tt/2tcEGPe

Performance of knowledge-based radiation therapy planning for the glioblastoma disease site

A knowledge-based radiation therapy planning model for glioblastoma was created using RapidPlanTM (Varian). 82 patients treated with 60 Gy to the target in 30 fractions were used to train the model. The model was validated on an independent set of 45 patients. The plans created by the model had superior planning target volume dose metrics compared to the manual planning, improved optic apparatus sparing, and order of magnitude reduction in planning time.

http://ift.tt/2uoyZNL

On-line adaptive hyperthermia treatment planning during locoregional heating to suppress treatment limiting hot spots

Adequate tumor temperatures during hyperthermia are essential for good clinical response, but excessive heating of normal tissue should be avoided. This makes locoregional heating using phased array systems technically challenging. On-line application of hyperthermia treatment planning could help to improve the heating quality. The aim of this study was to evaluate the clinical benefit of on-line treatment planning during treatment of pelvic tumors heated with the XXXX locoregional hyperthermia system.

http://ift.tt/2uoCFic

Unexpected increase of seizures in a patient treated with responsive neurostimulation: Check the lead!

The NeuroPace RNS® System provides closed-loop brain stimulation in patients with refractory multifocal epilepsy who are not candidates for resective surgery. The system acts as a sensing and stimulation device by continually monitoring the intracranial EEG (ICEEG) at the seizure focus and delivering brief electrical stimulation pulses as soon as an epileptiform activity is detected. Typically, two depth and/or subdural cortical strips are implanted in the epileptogenic focus. We report here a patient who presented with an acute increase of seizure frequency as a consequence of a lead break, which was not visible on CT scan.

http://ift.tt/2tViG8P

Exploring resting-state EEG brain oscillatory activity in relation to cognitive functioning in multiple sclerosis

Neurophysiologic monitoring parameters related to cognition in Multiple Sclerosis (MS) are sparse. Previous work reported an association between magnetoencephalographic (MEG) alpha-1 activity and information processing speed. While this remains to be replicated by more available electroencephalographic (EEG) methods, also other established EEG markers, e.g. the slow-wave/fast-wave ratio (theta/beta ratio), remain to be explored in this context.

http://ift.tt/2tcYS3r

Left hemispheric breakdown of LTP-like cortico-cortical plasticity in schizophrenic patients

Schizophrenia is a devastating illness, with a prevalence of 1% (Stephan et al, 2009). It is characterized by positive symptoms (delusions, hallucinations and disorganized thoughts) and negative symptoms such as avolition, alogia, and apathy. An emerging hypothesis is that schizophrenia may be interpreted as a brain disconnection syndrome, with abnormal interactions between widespread brain areas (Ribolsi et al., 2009, Wheeler et al., 2014). Schizophrenia has been associated not only to a local dysfunction of specific brain areas but also with a disruption of communication trough a reduced inter-hemispheric connectivity (Stephan et al., 2009; Chang et al., 2015).

http://ift.tt/2tVvewL

Approaches for stricture prevention after esophageal endoscopic resection

Endoscopic resection of extensive esophageal lesions has become more common as endoscopic resection techniques and equipment has developed. However, extensive esophageal endoscopic resections can cause postoperative esophageal strictures, which have a negative impact on the quality of life of patients. We aimed to review current treatments and innovative approaches to prevent esophageal strictures after widespread endoscopic resection of esophageal lesions.

http://ift.tt/2t0UqAA

Partial jejunal diversion using an incisionless magnetic anastomosis system: 1-year interim results in subjects with obesity and diabetes

The majority of patients with type 2 diabetes mellitus (T2DM) have obesity. Studies show that bariatric surgery is superior to medical treatment for remission of T2DM. Nevertheless, very few patients undergo surgery, and a less-invasive endoscopic alternative is desirable.

http://ift.tt/2ujtAHP

Detailed Longitudinal Sampling of Glioma Stem Cells In Situ Reveals Chr7 Gain and Chr10 Loss As Repeated Events in Primary Tumor Formation and Recurrence

Abstract

Intratumoral heterogeneity at the genetic, epigenetic, transcriptomic and morphologic levels is a commonly observed phenomenon in many aggressive cancer types. Clonal evolution during tumor formation as well as in response to therapeutic intervention, can be predicted utilizing reverse engineering approaches on detailed genomic snapshots of heterogeneous patient tumor samples. In this study, we developed an extensive dataset for a GBM case via the generation of polyclonal and monoclonal glioma stem cell lines from initial diagnosis, as well as from multiple sections of distant tumor locations of the deceased patient's brain following tumor recurrence. Our analyses revealed the tissue-wide expansion of a new clone in the recurrent tumor as well as chromosome 7 gain and chromosome 10 loss as repeated genomic events in primary and recurrent disease. Moreover, chromosome 7 gain and chromosome 10 loss produced similar alterations in mRNA expression profiles in primary and recurrent tumors despite possessing other highly heterogeneous and divergent genomic alterations between the tumors. We identified ETV1 and CDK6 as putative candidate genes, and NFKB (complex), IL1B, IL6, Akt and VEGF as potential signaling regulators, as potentially central downstream effectors of chr7 gain and chr10 loss. Finally, the differences caused by the transcriptomic shift following gain of chromosome 7 and loss of chromosome 10 were consistent with those generally seen in GBM samples compared to normal brain in large-scale patient-tumor data sets. This article is protected by copyright. All rights reserved.

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Dietary fiber intake and head and neck cancer risk: A pooled analysis in the International Head and Neck Cancer Epidemiology consortium

Abstract

The possible role of dietary fiber in the etiology of head and neck cancers (HNCs) is unclear. We used individual-level pooled data from 10 case-control studies (5959 cases and 12,248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium, to examine the association between fiber intake and cancer of the oral cavity/pharynx and larynx. Odds Ratios (ORs) and their 95% Confidence Intervals (CIs) were estimated using unconditional multiple logistic regression applied to quintile categories of non-alcohol energy-adjusted fiber intake and adjusted for tobacco and alcohol use and other known or putative confounders.

Fiber intake was inversely associated with oral and pharyngeal cancer combined (OR for 5th vs. 1st quintile category = 0.49, 95% CI: 0.40-0.59; p for trend <0.001) and with laryngeal cancer (OR = 0.66, 95% CI: 0.54-0.82, p for trend <0.001). There was, however, appreciable heterogeneity of the estimated effect across studies for oral and pharyngeal cancer combined. Nonetheless, inverse associations were consistently observed for the subsites of oral and pharyngeal cancers and within most strata of the considered covariates, for both cancer sites.

Our findings from a multicenter large-scale pooled analysis suggest that, although in the presence of between-study heterogeneity, a greater intake of fiber may lower HNC risk. This article is protected by copyright. All rights reserved.

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Panobinostat Sensitizes KRAS-Mutant Non-Small Cell Lung Cancer to Gefitinib by Targeting TAZ

Abstract

Mutation of KRAS in non-small cell lung cancer (NSCLC) shows a poor response to epidermal growth factor receptor (EGFR) inhibitors and chemotherapy. Currently, there are no direct anti-KRAS therapies available. Thus, new strategies have emerged for targeting KRAS downstream signaling. Panobinostat is a clinically available histone deacetylase inhibitor for treating myelomas and also shows potentiality in NSCLC. However, the therapeutic efficacy of panobinostat against gefitinib-resistant NSCLC is unclear. In this study, we demonstrated that panobinostat overcame resistance to gefitinib in KRAS-mutant/EGFR-wild type NSCLC. Combined panobinostat and gefitinib synergistically reduced tumor growth in vitro and in vivo. Mechanistically, we identified that panobinostat, but not gefitinib, inhibited TAZ transcription, and the combination of panobinostat and gefitinib synergistically downregulated TAZ and TAZ downstream targets, including EGFR and EGFR ligand. Inhibition of TAZ by panobinostat or short hairpin RNA sensitized KRAS-mutant/EGFR-wild type NSCLC to gefitinib through abrogating AKT/mammalian target of rapamycin (mTOR) signaling. Clinically, TAZ was positively correlated with EGFR signaling, and coexpression of TAZ/EGFR conferred a poorer prognosis in lung cancer patients. Our findings identify that targeting TAZ-mediated compensatory mechanism is a novel therapeutic approach to overcome gefitinib resistance in KRAS-mutant/EGFR-wild type NSCLC. This article is protected by copyright. All rights reserved.

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Two Types of Etiological Mutation in the Limb-Specific Enhancer of Shh

An enhancer named MFCS1 regulates Sonic hedgehog (Shh) expression in the posterior mesenchyme of limb buds. Several mutations in MFCS1 induce ectopic Shh expression in the anterior limb bud, and these result in preaxial polydactyly (PPD). However, the molecular basis of ectopic Shh expression remains elusive, although some mutations are known to disrupt the negative regulation of Shh expression in the anterior limb bud. Here, we analyzed the molecular mechanism of ectopic Shh expression in PPD including in a mouse mutation—hemimelic extra toes (Hx)—and in other MFCS1 mutations in different species. First, we generated transgenic mouse lines with a LacZ reporter cassette flanked with tandem repeats of 40 bp MFCS1 fragments harboring a mutation. The transgenic mouse line with the Hx-type fragment showed reporter expression exclusively in the anterior, but not in the posterior margins of limb buds. In contrast, no specific LacZ expression was observed in lines carrying the MFCS1 fragment with other mutations. Yeast one-hybrid assays revealed that the msh-like homeodomain protein, MSX1, bound specifically to the Hx sequence of MFCS1. Thus, PPD caused by mutations in MFCS1 has two major types of molecular etiology: loss of a cis motif for negative regulation of Shh, and acquisition of a new cis motif binding to a preexisting transcription factor, as represented by the Hx mutation.

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3'-terminated Overhangs Regulate DNA Double-Strand Break Processing in Escherichia coli

Double-strand breaks (DSBs) are lethal DNA lesions, which are repaired by homologous recombination in Escherichia coli. To study DSB processing in vivo, we induced DSBs into the E. coli chromosome by gamma irradiation and measured chromosomal degradation. We show that the DNA degradation is regulated by RecA protein concentration and its rate of association with ssDNA. RecA decreased DNA degradation in wild-type, recB and recD strains, indicating that it is a general phenomenon in E. coli. On the other hand, DNA degradation was greatly reduced and unaffected by RecA in the recB1080 mutant (which produces long overhangs) and in a strain devoid of four exonucleases that degrade a 3' tail (ssExos). 3'-5' ssExos deficiency is epistatic to RecA deficiency concerning DNA degradation, suggesting that bound RecA is shielding 3' tail from degradation by 3'-5' ssExos. Since 3'-tail preservation is common to all these situations, we infer that RecA polymerization constitutes a subset of mechanisms for preserving the integrity of 3' tails emanating from DSBs, along with 3' tail's massive length, or prevention of their degradation by inactivation of 3'-5' ssExos. Thus, we conclude that 3' overhangs are crucial in controlling the extent of DSB processing in E. coli. This study suggests a regulatory mechanism for DSB processing in E. coli, wherein 3' tails impose a negative feedback loop on DSB processing reactions, specifically on helicase reloading onto dsDNA ends.

http://ift.tt/2t0NlAn

Shallow whole genome sequencing on circulating cell-free DNA allows reliable non-invasive copy number profiling in neuroblastoma patients

Purpose: <p>Neuroblastoma (NB) is a heterogeneous disease characterized by distinct clinical features and by the presence of typical copy number alterations (CNAs). Given the strong association of these CNA profiles with prognosis, analysis of the CNA profile at diagnosis is mandatory. Therefore, we tested whether the analysis of circulating cell-free DNA (cfDNA) present in plasma samples of NB patients could offer a valuable alternative to primary tumor DNA for CNA profiling.</p> <br /><br />Experimental Design: <p>In 37 NB patients cfDNA analysis using shallow whole genome sequencing (sWGS) was compared to arrayCGH analysis of primary tumor tissue.</p> <br /><br />Results: <p>Comparison of CNA profiles on cfDNA showed highly concordant patterns, particularly in high-stage patients. Numerical chromosome imbalances as well as large and focal structural aberrations including MYCN and LIN28B amplification and ATRX deletion could be readily detected with sWGS using a low input of cfDNA.</p> <br /><br />Conclusions: <p>In conclusion, sWGS analysis on cfDNA offers a cost-effective, non-invasive, rapid, robust and sensitive alternative for tumor DNA copy number profiling in most NB patients.

http://ift.tt/2utaXBZ

Aspirin inhibits cancer metastasis and angiogenesis via targeting heparanase

Purpose: <br />Recent epidemiological and clinical studies have suggested the benefit of aspirin for cancer patients, which inspired increasing efforts to demonstrate the anti-cancer ability of aspirin and reveal the molecular mechanisms behind. Nevertheless, the anti-cancer activity and related mechanisms of aspirin remain largely unknown. This study aimed to confirm this observation, and more importantly, to investigate the potential target contributed to the anti-cancer of aspirin.<br /><br />Experimental Design:<br /><span style="font-size: 11px;">A homogeneous time resolved fluorescence (HTRF) assay was used to examine the impact of aspirin on heparanase. Streptavidin pull-down, surface plasmon resonance (SPR) assay and Molecular docking were performed to identify heparanase as an aspirin binding protein. Transwell, rat aortic rings and chicken chorioallantoic membrane model were used to evaluate the anti-metastasis and anti-angiogenesis effects of aspirin. And these phenotypes were tested in B16F10 metastatic model, MDA-MB-231 metastatic model and MDA-MB-435 xenograft model.<br /></span><br />Results: <br />This study identified heparanase, an oncogenic extracellular matrix enzyme involved in cancer metastasis and angiogenesis, as a potential target of aspirin. We had discovered that aspirin directly binds to Glu225 region of heparanase and inhibits the enzymatic activity. Aspirin impeded tumor metastasis, angiogenesis and growth in heparanase-dependent manner.<br /><br />Conclusions:<br />In summary, the present study has illustrated heparanase as a target of aspirin for the first time. It provides insights for a better understanding of the mechanisms of aspirin in anti-cancer effects, and offers a direction for the development of small-molecule inhibitors of heparanase.

http://ift.tt/2v1NEMv

Ex vivo PD-L1/PD-1 pathway blockade reverses dysfunction of circulating CEA specific T cells in pancreatic cancer patients.

Carcinoembryonic antigen (CEA) is a candidate target for cellular immunotherapy of pancreatic cancer (PC). In this study, we have characterised the antigen-specific function of autologous cytotoxic T lymphocytes (CTL) specific for the HLA-A2 restricted peptide, pCEA691-699, isolated from the peripheral T cell repertoire of PC patients and sought to determine if ex vivo PD-L1 & TIM3 blockade could enhance CTL function. CD8⁺ T cell lines were generated from peripheral blood mononuclear cells (PBMCs) of 18 HLA-A2⁺ patients with PC and from 15 healthy controls. In vitro peptide specific responses were evaluated by flow cytometry after staining for intracellular cytokine production and CSFE cytotoxicity assays using pancreatic cancer cell lines as targets. Cytokine secreting functional CEA691-specific CTL lines were successfully generated from 10 of 18 PC patients, with two CTL lines able to recognise and kill both CEA691 peptide-loaded T2 cells and CEA⁺ HLA-A2⁺ pancreatic cancer cell lines. In the presence of ex vivo PD-L1 blockade, functional CEA691-specific CD8⁺ T cell responses, including IFN-g secretion and proliferation, were enhanced and this effect was more pronounced on Ag-specific T cells isolated from tumor draining lymph nodes. These data demonstrate that CEA691-specific CTL can be readily expanded from the self-restricted T cell repertoire of PC patients and that their function can be enhanced by PD-L1 blockade.

http://ift.tt/2usWs0S

Sarcomatoid renal cell carcinoma has a distinct molecular pathogenesis, driver mutation profile and transcriptional landscape

Purpose: Sarcomatoid renal cell carcinoma (SRCC) ranks among the most aggressive clinicopathologic phenotypes of RCC. However, the paucity of high-quality, genome-wide molecular examinations of SRCC has hindered our understanding of this entity.<br /><br />Experimental Design: We interrogated the mutational, copy number, and transcriptional characteristics of SRCC and compared these data with those of non-sarcomatoid RCC (RCC). We evaluated whole exome sequencing, single nucleotide polymorphism, and RNA sequencing data from patients with SRCC (n=65) and RCC (n=598) across different parent RCC subtypes, including clear cell RCC, papillary RCC, and chromophobe RCC subtypes.  <br /><br />Results: SRCC was molecularly discrete from RCC and clustered according to its parent RCC subtype, though with upregulation of TGFβ signaling across all subtypes.  The epithelioid (E-) and spindled (S-) histologic components of SRCC did not show differences in mutational load among cancer related genes, despite a higher mutational burden in S-.  Notably, sarcomatoid clear cell RCC (SccRCC) showed significantly fewer deletions at 3p21-25, a lower rate of two-hit loss for VHL and PBRM1, and more mutations in PTEN, TP53, and RELN compared to clear cell RCC (ccRCC).  A two-hit loss involving VHL predicted for ccRCC and a better prognosis whereas mutations in PTEN, TP53, or RELN predicted for SccRCC and worse prognosis.  <br /><br />Conclusions: Sarcomatoid RCC segregates by parent subtype and SccRCC has a fundamentally different early molecular pathogenesis, usually lacking the classic 3p21-25 deletion and showing distinctive mutational and transcriptional profiles.  These features prompt a more precise molecular classification of RCC with diagnostic, prognostic, and therapeutic implications.

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Clinical features and prognostic impact of PRDM16 expression in adult acute myeloid leukemia

Abstract

High PRDM16 (also known as MEL1) expression is a representative marker of acute myeloid leukemia (AML) with NUP98-NSD1 and is a significant predictive marker for poor prognosis in pediatric AML. However, the clinical features of adult AML with PRDM16 expression remain unclear. PRDM16 is highly homologous to MDS1/EVI1, which is an alternatively spliced transcript of MECOM (also known as EVI1). We investigated PRDM16 expression in 151 AML patients, with 47 (31%) exhibiting high PRDM16 expression (PRDM16/ABL1 ratio ≥ 0.010). High PRDM16 expression significantly correlated with DNMT3A (43% vs. 15%, P < 0.001) and NPM1 (43% vs. 21%, P = 0.010) mutations and partial tandem duplication of KMT2A (22% vs. 1%, P < 0.001). Remarkably, high-PRDM16-expression patients were frequent in the non-complete remission group (48% vs. 21%, P = 0.002). Overall survival (OS) was significantly worse in high-PRDM16-expression patients than in low-PRDM16-expression patients (5-year OS, 18% vs. 34%; P = 0.002). This trend was observed more clearly among patients aged <65 years (5-year OS, 21% vs. 50%; P = 0.001), particularly in FLT3-ITD-negative patients in the intermediate cytogenetic risk group (5-year OS, 25% vs. 59%; P = 0.009). These results suggest that high PRDM16 expression is a significant predictive marker for poor prognosis in adult AML patients, similar to pediatric AML patients. This article is protected by copyright. All rights reserved.

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Association of lipocalin-2 level, glycemic status and obesity in type 2 diabetes mellitus

Management of type 2 diabetes mellitus aims to maintain a normal glycemic status, which if not, it may lead to acute and/or chronic diabetic complications. Earlier studies found Lipocalin-2 elevated in complic...

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Amitriptyline-induced ventricular tachycardia: a case report

In Bangladesh, each emergency physician faces amitriptyline overdose nearly a day. An acute cardiovascular complication, one of the worst complications is mainly responsible for the mortality in tricyclic over...

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Superenhancers Drive Neuroblastoma Differentiation States [Research Watch]

Superenhancer-associated transcriptional networks promote neuroblastoma heterogeneity.

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Transcription Elongation Factors Are Potential Targets in Glioblastoma [Research Watch]

JMJD6 promotes transcription pause-release and elongation and glioblastoma cell survival in vivo.

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Genomic Analysis Detects Recurrent Promoter Mutations in Breast Cancer [Research Watch]

Deep sequencing of 360 primary breast tumors identified 9 genes with recurrently mutated promoters.

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The Telomeric Noncoding RNA TERRA Regulates Telomere Stability [Research Watch]

TERRA activates the DNA damage response at short telomeres to prevent premature senescence.

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Biomarker for Antitumor Immunity Identified [News in Brief]

Researchers discover a subpopulation of T cells in tumors that produces stronger immune responses and improves prognosis.

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Nivolumab Plus Ipilimumab Has Antitumor Activity in Metastatic RCC [Research Watch]

Nivolumab plus ipilimumab achieves durable responses and has manageable safety in metastatic RCC.

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Economic burden of varicella in children 1–12 Years of age in Hungary, 2011–2015

Although live-attenuated varicella-zoster virus (VZV) vaccines have been proven to be safe and effective in preventing varicella and real-word evidence shows routine childhood immunization programs are effecti...

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Etiology and prognosis of acute viral encephalitis and meningitis in Chinese children: a multicentre prospective study

In China, there were few studies about the pathogens of acute viral encephalitis and meningitis in children in recent years. The aims of this study were to characterize the etiology and prognosis of acute vira...

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Hepatitis a virus genotypes and strains from an endemic area of Europe, Bulgaria 2012–2014

Hepatitis A virus (HAV) infection is endemic in Eastern European and Balkan region countries. In 2012, Bulgaria showed the highest rate (67.13 cases per 100,000) in Europe. Nevertheless, HAV genotypes and stra...

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A randomized clinical pharmacokinetic trial of Tenofovir in blood, plasma and urine in adults with perfect, moderate and low PrEP adherence: the TARGET study

Tenofovir disoproxil fumarate (TDF) is key component of pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART) for HIV, but existing tools to monitor drug adherence are often inaccurate. Detection of...

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The clinical and virological features of the first imported case causing MERS-CoV outbreak in South Korea, 2015

In 2015, the largest outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection outside the Middle East occurred in South Korea. We summarized the epidemiological, clinical, and laboratory f...

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Innovating With Rehabilitation Technology in the Real World: Promises, Potentials, and Perspectives.

In this article, we discuss robotic-assisted therapy as an emerging and significant field of clinical rehabilitation and its value proposition for innovating rehabilitation clinical practice. Attempts to achieve integration among clinicians' practices and bioengineers' machines often generate new challenges and controversies. To date, the literature is indicative of a sizeable number and variety of robotic devices in the field of clinical rehabilitation, some are commercially available; however, large-scale clinical outcomes are less positive than expected. The following main themes related to integrating rehabilitation technology in real-world clinical practice will be discussed: the application of current evidence-based practice and knowledge in relation to treatment in the rehabilitation clinic, perspectives from rehabilitation professionals using robotic-aided therapy with regard to challenges, and strategies for problem solving. Lastly, we present innovation philosophies with regard to sustainability of clinical rehabilitation technologies. 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. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Development of Systemic Inflammatory Polyarthritis After Zygapophyseal Joint Injection With Hylan G-F 20 (Synvisc-One).

Hylan G-F 20 (Synvisc-One) is a hyaluronic acid derivative used for viscosupplementation of synovial fluid in osteoarthritic joints. Injection of hylan G-F 20 is Federal Drug Administration approved for use in knee osteoarthritis and is generally well tolerated with few reported adverse effects, the most common being local pain or swelling. We present the case of a 72-year-old man with bilateral, diffuse, joint pain and swelling with elevated inflammatory markers suggestive of a systemic inflammatory polyarthropathy that developed acutely 2 days after lumbar zygapophyseal joint injection with hylan G-F 20. Systemic effects after hylan G-F 20 injection have not been well documented, and this is the first reported case of systemic inflammatory polyarthritis after injection, to our knowledge. Further research is needed to better establish the safety and efficacy of lumbar zygapophyseal joint injections with hylan G-F 20. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Imaging Modalities for Correct Positioning of Percutaneous Right Ventricular Assist Device After Left Ventricular Assist Device Implantation.

No abstract available

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In Response.

No abstract available

http://ift.tt/2tcATl8

Esmolol Administration to Control Tachycardia in an Ovine Model of Peritonitis.

BACKGROUND: Excessive adrenergic signaling may be harmful in sepsis. Using [beta]-blockers to reduce sympathetic overactivity may modulate sepsis-induced cardiovascular, metabolic, immunologic, and coagulation alterations. Using a randomized ovine fecal peritonitis model, we investigated whether administration of a short-acting [beta]-blocker, esmolol, could control tachycardia without deleterious effects on hemodynamics, renal perfusion, cerebral perfusion, cerebral metabolism, or outcome. METHODS: After induction of fecal peritonitis, 14 anesthetized, mechanically ventilated, and hemodynamically monitored adult female sheep were randomly assigned to receive a continuous intravenous infusion of esmolol to control heart rate between 80 and 100 bpm (n = 7) or a saline infusion (control group, n = 7). Esmolol was discontinued when the mean arterial pressure decreased below 60 mm Hg. Fluid resuscitation was titrated to maintain pulmonary artery occlusion pressure at baseline values. Left renal blood flow and cerebral cortex perfusion and metabolism were monitored in addition to standard hemodynamic variables. RESULTS: Esmolol was infused for 11 (9-14) hours; the target heart rate (80-100 bpm) was achieved between 3 and 8 hours after feces injection. In the first 5 hours after the start of the infusion, the decrease in heart rate was compensated by an increase in stroke volume index; later, stroke volume index was not statistically significantly different in the 2 groups, so that the cardiac work index was lower in the esmolol than in the control group. Hypotension (mean arterial pressure

http://ift.tt/2v27k30

Hyperbaric Versus Isobaric Bupivacaine for Spinal Anesthesia: Systematic Review and Meta-analysis for Adult Patients Undergoing Noncesarean Delivery Surgery.

BACKGROUND: It is widely believed that the choice between isobaric bupivacaine and hyperbaric bupivacaine formulations alters the block characteristics for the conduct of surgery under spinal anesthesia. The aim of this study was to systematically review the comparative evidence regarding the effectiveness and safety of the 2 formulations when used for spinal anesthesia for adult noncesarean delivery surgery. METHODS: Key electronic databases were searched for randomized controlled trials, excluding cesarean delivery surgeries under spinal anesthesia, without any language or date restrictions. The primary outcome measure for this review was the failure of spinal anesthesia. Two independent reviewers selected the studies and extracted the data. Results were expressed as relative risk (RR) or mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: Seven hundred fifty-one studies were identified between 1946 and 2016. After screening, there were 16 randomized controlled clinical trials, including 724 participants, that provided data for the meta-analysis. The methodological reporting of most studies was poor, and appropriate judgment of their individual risk of bias elements was not possible. There was no difference between the 2 drugs regarding the need for conversion to general anesthesia (RR, 0.60; 95% CI, 0.08-4.41; P = .62; I2 = 0%), incidence of hypotension (RR, 1.15; 95% CI, 0.69-1.92; P = .58; I2 = 0%), nausea/vomiting (RR, 0.29; 95% CI, 0.06-1.32; P = .11; I2 = 7%), or onset of sensory block (MD = 1.7 minutes; 95% CI, -3.5 to 0.1; P = .07; I2 = 0%). The onset of motor block (MD = 4.6 minutes; 95% CI, 7.5-1.7; P = .002; I2 = 78%) was significantly faster with hyperbaric bupivacaine. Conversely, the duration of motor (MD = 45.2 minutes; 95% CI, 66.3-24.2; P

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Socioeconomic Deprivation and Utilization of Anesthetic Care During Pregnancy and Delivery: A French Retrospective, Multicenter, Cohort Study.

BACKGROUND: Socioeconomic deprivation is associated with reduced use of antenatal resources and poor maternal outcomes with pregnancy. Research examining the association between socioeconomic deprivation and use of obstetric anesthesia care in a country providing universal health coverage is scarce. We hypothesized that in a country providing universal health coverage, France, socioeconomic deprivation is not associated with reduced use of anesthetic care during pregnancy and delivery. This study aimed to examine the association between socioeconomic deprivation and (1) completion of a mandatory preanesthetic evaluation during pregnancy and (2) use of neuraxial analgesia during labor. METHODS: Data were from a cohort of 10,419 women who delivered between 2010 and 2011 in 4 public teaching hospitals in Paris. We used a deprivation index that included 4 criteria: social isolation, poor housing condition, no work-related household income, and state-funded health care insurance. Socioeconomic deprivation was defined as a deprivation index greater than 1. Preanesthetic evaluation was considered completed if performed more than 48 hours before delivery. The association between socioeconomic deprivation and completion of the preanesthetic evaluation and use of neuraxial labor analgesia was assessed by multivariable logistic regression adjusting for education level, country of birth, and maternal and pregnancy characteristics. RESULTS: Preanesthetic evaluation was completed for 8142 of the 8624 women (94.4%) analyzed and neuraxial labor analgesia was used by 6258 of the 6834 women analyzed (91.6%). After adjustment, socioeconomic deprivation was associated with reduced probability of completed preanesthetic evaluation (adjusted odds ratio 0.88 [95% confidence interval, 0.79-0.98]; P = .027) but not use of neuraxial labor analgesia (adjusted odds ratio 0.97 [95% confidence interval, 0.87-1.07]; P = .540). CONCLUSIONS: In a country providing universal health care coverage, women who were socioeconomically deprived showed reduced completion of preanesthetic evaluation during pregnancy but not reduced use of neuraxial labor analgesia. Interventions should be targeted to socioeconomically deprived women to increase the completion of the preanesthetic evaluation. (C) 2017 International Anesthesia Research Society

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Replication of Data Makes Statistical Analysis Difficult.

No abstract available

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Improving the Success Rate of Chest Compression-Only CPR by Untrained Bystanders in Adult Out-of-Hospital Cardiac Arrest: Maintaining Airway Patency May Be the Way Forward.

No abstract available

http://ift.tt/2v1L88U

Fixing Medical Prices.

No abstract available

http://ift.tt/2usHiZB

Closed-Incision Negative-Pressure Therapy in Obese Patients Undergoing Cesarean Delivery: A Randomized Controlled Trial

AJP Rep 2017; 07: e151-e157
DOI: 10.1055/s-0037-1603956

Background Postcesarean wound morbidity is a costly complication of cesarean delivery for which preventative strategies remain understudied. Objective We compared surgical site occurrences (SSOs) in cesarean patients receiving closed-incision negative-pressure therapy (ciNPT) or standard-of-care (SOC) dressing. Study Design A single-center randomized controlled trial compared ciNPT (5–7 days) to SOC dressing (1–2 days) in obese women (body mass index [BMI] ≥ 35), undergoing cesarean delivery between 2012 and 2014. Participants were randomized 1:1 and monitored 42 ± 10 days postoperatively. The primary outcome SSOs included unanticipated local inflammation, wound infection, seroma, hematoma, dehiscence, and need for surgical or antibiotic intervention. Results Of the 92 randomized patients, 82 completed the study. ciNPT and SOC groups had similar baseline characteristics. Mean BMI was 46.5 ± 6.5 and no treatment-related serious adverse events. Compared with SOC, the ciNPT group had fewer SSOs (7/43 [16.3%] vs. 2/39 [5.1%], respectively; p = 0.16); significantly fewer participants with less incisional pain both at rest (39/46 [84.8%] vs. 20/46 [43.5%]; p < 0.001) and with incisional pressure (42/46 [91.3%] vs. 25/46 [54.3%]; p < 0.001); and a 30% decrease in total opioid use (79.1 vs. 55.9 mg morphine equivalents, p = 0.036). Conclusion A trend in SSO reduction and a statistically significant reduction in postoperative pain and narcotic use was observed in women using ciNPT.
[...]

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Article in Thieme eJournals:
Table of contents  |  Abstract  |  open access Full text

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Artemisinin disrupts androgen responsiveness of human prostate cancer cells by stimulating the 26S proteasome-mediated degradation of the androgen receptor protein.

Androgen receptor (AR) expression and activity is highly linked to the development and progression of prostate cancer and is a target of therapeutic strategies for this disease. We investigated whether the antimalarial drug artemisinin, which is a sesquiterpene lactone isolated from the sweet wormwood plant Artemisia annua, could alter AR expression and responsiveness in cultured human prostate cancer cell lines. Artemisinin treatment induced the 26S proteasome-mediated degradation of the receptor protein, without altering AR transcript levels, in androgen-responsive LNCaP prostate cancer cells or PC-3 prostate cancer cells expressing exogenous wild-type AR. Furthermore, artemisinin stimulated AR ubiquitination and AR receptor interactions with the E3 ubiquitin ligase MDM2 in LNCaP cells. The artemisinin-induced loss of AR protein prevented androgen-responsive cell proliferation and ablated total AR transcriptional activity. The serine/threonine protein kinase AKT-1 was shown to be highly associated with artemisinin-induced proteasome-mediated degradation of AR protein. Artemisinin treatment activated AKT-1 enzymatic activity, enhanced receptor association with AKT-1, and induced AR serine phosphorylation. Treatment of LNCaP cells with the PI3-kinase inhibitor LY294002, which inhibits the PI3-kinase-dependent activation of AKT-1, prevented the artemisinin-induced AR degradation. Furthermore, in transfected receptor-negative PC-3 cells, artemisinin failed to stimulate the degradation of an altered receptor protein (S215A/S792A) with mutations in its two consensus AKT-1 serine phosphorylation sites. Taken together, our results indicate that artemisinin induces the degradation of AR protein and disrupts androgen responsiveness of human prostate cancer cells, suggesting that this natural compound represents a new potential therapeutic molecule that selectively targets AR levels. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Brain Gray Matter MRI Morphometry for Neuroprognostication After Cardiac Arrest

Objectives: We hypothesize that the combined use of MRI cortical thickness measurement and subcortical gray matter volumetry could provide an early and accurate in vivo assessment of the structural impact of cardiac arrest and therefore could be used for long-term neuroprognostication in this setting. Design: Prospective cohort study. Setting: Five Intensive Critical Care Units affiliated to the University in Toulouse (France), Paris (France), Clermont-Ferrand (France), Liège (Belgium), and Monza (Italy). Patients: High-resolution anatomical T1-weighted images were acquired in 126 anoxic coma patients ("learning" sample) 16 ± 8 days after cardiac arrest and 70 matched controls. An additional sample of 18 anoxic coma patients, recruited in Toulouse, was used to test predictive model generalization ("test" sample). All patients were followed up 1 year after cardiac arrest. Interventions: None. Measurements and Main Results: Cortical thickness was computed on the whole cortical ribbon, and deep gray matter volumetry was performed after automatic segmentation. Brain morphometric data were employed to create multivariate predictive models using learning machine techniques. Patients displayed significantly extensive cortical and subcortical brain volumes atrophy compared with controls. The accuracy of a predictive classifier, encompassing cortical and subcortical components, has a significant discriminative power (learning area under the curve = 0.87; test area under the curve = 0.96). The anatomical regions which volume changes were significantly related to patient's outcome were frontal cortex, posterior cingulate cortex, thalamus, putamen, pallidum, caudate, hippocampus, and brain stem. Conclusions: These findings are consistent with the hypothesis of pathologic disruption of a striatopallidal-thalamo-cortical mesocircuit induced by cardiac arrest and pave the way for the use of combined brain quantitative morphometry in this setting.

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Pulmonary Arterial Compliance and Pulmonary Vascular Resistance as a Predictor of Survival in Acute Respiratory Distress Syndrome: More Questions Than Answers

No abstract available

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Antibiotic Therapy in Comatose Mechanically Ventilated Patients Following Aspiration: Differentiating Pneumonia From Pneumonitis*

Objectives: To determine the proportion of patients with documented bacterial aspiration pneumonia among comatose ICU patients with symptoms suggesting either bacterial aspiration pneumonia or non-bacterial aspiration pneumonitis. Design: Prospective observational study. Setting: University-affiliated 30-bed ICU. Patients: Prospective cohort of 250 patients admitted to the ICU with coma (Glasgow Coma Scale score ≤ 8) and treated with invasive mechanical ventilation. Interventions: None. Measurements and Main Results: The primary outcome was the proportion of patients with microbiologically documented bacterial aspiration pneumonia. Patients meeting predefined criteria for aspiration syndrome routinely underwent telescopic plugged catheter sampling during bronchoscopy before starting probabilistic antibiotic treatment. When cultures were negative, the antibiotic treatment was stopped. Of 250 included patients, 98 (39.2%) had aspiration syndrome, including 92 before mechanical ventilation discontinuation. Telescopic plugged catheter in these 92 patients showed bacterial aspiration pneumonia in 43 patients (46.7%). Among the remaining 49 patients, 16 continued to receive antibiotics, usually for infections other than pneumonia; of the 33 patients whose antibiotics were discontinued, only two subsequently showed signs of lung infection. In the six patients with aspiration syndrome after mechanical ventilation, and therefore without telescopic plugged catheter, antibiotic treatment was continued for 7 days. Mechanical ventilation duration, ICU length of stay, and mortality did not differ between the 43 patients with bacterial aspiration pneumonia and the 49 patients with non-bacterial aspiration pneumonitis. The 152 patients without aspiration syndrome did not receive antibiotics. Conclusions: Among comatose patients receiving mechanical ventilation, those without clinical, laboratory, or radiologic evidence of bacterial aspiration pneumonia did not require antibiotics. In those with suspected bacterial aspiration pneumonia, stopping empirical antibiotic therapy when routine telescopic plugged catheter sampling recovered no microorganisms was nearly always effective. This strategy may be a valid alternative to routine full-course antibiotic therapy. Only half the patients with suspected bacterial aspiration pneumonia had this diagnosis confirmed by telescopic plugged catheter sampling.

http://ift.tt/2t06j9Z

High-Fat Feeding Protects Mice From Ventilator-Induced Lung Injury, Via Neutrophil-Independent Mechanisms

Objective: Obesity has a complex impact on acute respiratory distress syndrome patients, being associated with increased likelihood of developing the syndrome but reduced likelihood of dying. We propose that such observations are potentially explained by a model in which obesity influences the iatrogenic injury that occurs subsequent to intensive care admission. This study therefore investigated whether fat feeding protected mice from ventilator-induced lung injury. Design: In vivo study. Setting: University research laboratory. Subjects: Wild-type C57Bl/6 mice or tumor necrosis factor receptor 2 knockout mice, either fed a high-fat diet for 12–14 weeks, or age-matched lean controls. Interventions: Anesthetized mice were ventilated with injurious high tidal volume ventilation for periods up to 180 minutes. Measurements and Main Results: Fat-fed mice showed clear attenuation of ventilator-induced lung injury in terms of respiratory mechanics, blood gases, and pulmonary edema. Leukocyte recruitment and activation within the lungs were not significantly attenuated nor were a host of circulating or intra-alveolar inflammatory cytokines. However, intra-alveolar matrix metalloproteinase activity and levels of the matrix metalloproteinase cleavage product soluble receptor for advanced glycation end products were significantly attenuated in fat-fed mice. This was associated with reduced stretch-induced CD147 expression on lung epithelial cells. Conclusions: Consumption of a high-fat diet protects mice from ventilator-induced lung injury in a manner independent of neutrophil recruitment, which we postulate instead arises through blunted up-regulation of CD147 expression and subsequent activation of intra-alveolar matrix metalloproteinases. These findings may open avenues for therapeutic manipulation in acute respiratory distress syndrome and could have implications for understanding the pathogenesis of lung disease in obese patients.

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Repeated Critical Illness and Unplanned Readmissions Within 1 Year to PICUs*

Objectives: To determine the occurrence rate of unplanned readmissions to PICUs within 1 year and examine risk factors associated with repeated readmission. Design: Retrospective cohort analysis. Setting: Seventy-six North American PICUs that participated in the Virtual Pediatric Systems, LLC (VPS, LLC, Los Angeles, CA). Patients: Ninety-three thousand three hundred seventy-nine PICU patients discharged between 2009 and 2010. Interventions: None. Measurements and Main Results: Index admissions and unplanned readmissions were characterized and their outcomes compared. Time-to-event analyses were performed to examine factors associated with readmission within 1 year. Eleven percent (10,233) of patients had 15,625 unplanned readmissions within 1 year to the same PICU; 3.4% had two or more readmissions. Readmissions had significantly higher PICU mortality and longer PICU length of stay, compared with index admissions (4.0% vs 2.5% and 2.5 vs 1.6 d; all p

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Respiratory Muscle Weakness and Extubation Failure in Critically Ill Children*

No abstract available

http://ift.tt/2ujmuDf

Clinical Experience With IV Angiotensin II Administration: A Systematic Review of Safety

Objective: Angiotensin II is an endogenous hormone with vasopressor and endocrine activities. This is a systematic review of the safety of IV angiotensin II. Data Sources: PubMed, Medline, Scopus, and Cochrane. Study Selection: Studies in which human subjects received IV angiotensin II were selected whether or not safety was discussed. Data Extraction: In total, 18,468 studies were screened by two reviewers and one arbiter. One thousand one hundred twenty-four studies, in which 31,281 participants received angiotensin II (0.5–3,780 ng/kg/min), were selected. Data recorded included number of subjects, comorbidities, angiotensin II dose and duration, pressor effects, other physiologic and side effects, and adverse events. Data Synthesis: The most common nonpressor effects included changes in plasma aldosterone, renal function, cardiac variables, and electrolytes. Adverse events were infrequent and included headache, chest pressure, and orthostatic symptoms. The most serious side effects were exacerbation of left ventricular failure in patients with congestive heart failure and bronchoconstriction. One patient with congestive heart failure died from refractory left ventricular failure. Refractory hypotensive shock was fatal in 55 of 115 patients treated with angiotensin II in case studies, cohort studies, and one placebo-controlled study. One healthy subject died after a pressor dose of angiotensin II was infused continuously for 6 days. No other serious adverse events attributable to angiotensin II were reported. Heterogeneity in study design prevented meta-analysis. Conclusion: Adverse events associated with angiotensin II were infrequent; however, exacerbation of asthma and congestive heart failure and one fatal cerebral hemorrhage were reported. This systematic review supports the notion that angiotensin II has an acceptable safety profile for use in humans.

http://ift.tt/2t04JFn

Risk Factors for Pediatric Extubation Failure: The Importance of Respiratory Muscle Strength*

Objective: Respiratory muscle weakness frequently develops during mechanical ventilation, although in children there are limited data about its prevalence and whether it is associated with extubation outcomes. We sought to identify risk factors for pediatric extubation failure, with specific attention to respiratory muscle strength. Design: Secondary analysis of prospectively collected data. Setting: Tertiary care PICU. Patients: Four hundred nine mechanically ventilated children. Interventions: Respiratory measurements using esophageal manometry and respiratory inductance plethysmography were made preextubation during airway occlusion and on continuous positive airway pressure of 5 and pressure support of 10 above positive end-expiratory pressure 5 cm H2O, as well as 5 and 60 minutes postextubation. Measurements and Main Results: Thirty-four patients (8.3%) were reintubated within 48 hours of extubation. Reintubation risk factors included lower maximum airway pressure during airway occlusion (aPiMax) preextubation, longer length of ventilation, postextubation upper airway obstruction, high respiratory effort postextubation (pressure rate product, pressure time product, tension time index), and high postextubation phase angle. Nearly 35% of children had diminished respiratory muscle strength (aPiMax ≤ 30 cm H2O) at the time of extubation, and were nearly three times more likely to be reintubated than those with preserved strength (aPiMax > 30 cm H2O; 14% vs 5.5%; p = 0.006). Reintubation rates exceeded 20% when children with low aPiMax had moderately elevated effort after extubation (pressure rate product > 500), whereas children with preserved aPiMax had reintubation rates greater than 20% only when postextubation effort was very high (pressure rate product > 1,000). When children developed postextubation upper airway obstruction, reintubation rates were 47.4% for those with low aPiMax compared to 15.4% for those with preserved aPiMax (p = 0.02). Multivariable risk factors for reintubation included acute neurologic disease, lower aPiMax, postextubation upper airway obstruction, higher preextubation positive end-expiratory pressure, higher postextubation pressure rate product, and lower height. Conclusions: Neuromuscular weakness at the time of extubation was common in children and was independently associated with reintubation, particularly when postextubation effort was high.

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Preoperative Cognitive Performance and Postoperative Delirium Are Independently Associated With Future Dementia in Older People Who Have Undergone Cardiac Surgery: A Longitudinal Cohort Study*

Objective: To investigate if postoperative delirium was associated with the development of dementia within 5 years after cardiac surgery. Design: Longitudinal cohort study. Setting: Cardiothoracic Division, Umeå University Hospital, Sweden. Patients: Patients aged 70 years old or older (n = 114) scheduled for routine cardiac procedures with cardiopulmonary bypass without documented dementia were enrolled in 2009. Intervention: Structured assessments were performed preoperatively, 1 and 4 days after extubation, and 1, 3, and 5 years postoperatively. Measurements and Main Results: Patients were assessed comprehensively, including cognitive and physical function, coexisting medical conditions, demographic characteristics, and medications. Diagnoses of delirium, depression, and dementia were made according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision criteria. During the 5-year period, 30 of 114 participants (26.3%) developed dementia. Postoperative delirium had occurred in 87% of those who later developed dementia. A multivariable logistic regression model showed a lower preoperative Mini-Mental State Examination score (p

http://ift.tt/2ujgESp

Lower Cranial Nerves Paralysis Following Prone-Position Mechanical Ventilation

Objective: To communicate a complication of prone-position ventilation. Data Sources: Case history. Study Selection: Case report. Data Extraction and Data Synthesis: Clinical information from medical record. Conclusions: This is a very infrequent cause of dysphagia following prone-position ventilation.

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Recommendations for Methicillin-Resistant Staphylococcus aureus Prevention in Adult ICUs: A Cost-Effectiveness Analysis*

Objective: Patients in the ICU are at the greatest risk of contracting healthcare-associated infections like methicillin-resistant Staphylococcus aureus. This study calculates the cost-effectiveness of methicillin-resistant S aureus prevention strategies and recommends specific strategies based on screening test implementation. Design: A cost-effectiveness analysis using a Markov model from the hospital perspective was conducted to determine if the implementation costs of methicillin-resistant S aureus prevention strategies are justified by associated reductions in methicillin-resistant S aureus infections and improvements in quality-adjusted life years. Univariate and probabilistic sensitivity analyses determined the influence of input variation on the cost-effectiveness. Setting: ICU. Patients: Hypothetical cohort of adults admitted to the ICU. Interventions: Three prevention strategies were evaluated, including universal decolonization, targeted decolonization, and screening and isolation. Because prevention strategies have a screening component, the screening test in the model was varied to reflect commonly used screening test categories, including conventional culture, chromogenic agar, and polymerase chain reaction. Measurements and Main Results: Universal and targeted decolonization are less costly and more effective than screening and isolation. This is consistent for all screening tests. When compared with targeted decolonization, universal decolonization is cost-saving to cost-effective, with maximum cost savings occurring when a hospital uses more expensive screening tests like polymerase chain reaction. Results were robust to sensitivity analyses. Conclusions: As compared with screening and isolation, the current standard practice in ICUs, targeted decolonization, and universal decolonization are less costly and more effective. This supports updating the standard practice to a decolonization approach.

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Is Early Goal-Directed Therapy Harmful to Patients With Sepsis and High Disease Severity?

No abstract available

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Should All Massively Transfused Patients Be Treated Equally? An Analysis of Massive Transfusion Ratios in the Nontrauma Setting

Objectives: Although balanced resuscitation has become integrated into massive transfusion practice, there is a paucity of evidence supporting the delivery of high ratios of plasma and platelet to RBCs in the nontrauma setting. This study investigated the administration of blood component ratios in the massively transfused nontrauma demographic. Design: Retrospective analysis of a prospective, observational cohort of massively bleeding patients. Setting: Surgical and critically ill patients at a tertiary medical center between 2011 and 2015. Patients: Massively transfused nontrauma patients. Interventions: Patients receiving plasma, platelet, and RBC transfusions were categorized into high and low ratio groups and analyzed for differences in characteristics and clinical outcomes. Measurements and Main Results: The primary outcome was 30-day mortality. Secondary outcomes included 48-hour mortality, hospital length of stay, ICU length of stay, and ventilator-free days. Among 601 massively transfused nontrauma patients, cardiothoracic surgery and gastrointestinal or hepato-pancreatico-biliary bleeds were the most common indications for massive transfusion. Higher fresh frozen plasma ratios (> 1:2) were not associated with increased 30-day mortality. A high platelets-to-packed RBCs ratio (> 1:2) was associated with decreased 48-hour mortality (10.5% vs 19.3%; p = 0.032), but not 30-day mortality. Fresh frozen plasma-to-packed RBCs and platelets-to-packed RBCs ratios were not associated with 30-day mortality hazard ratios after controlling for baseline characteristics and disease severity. Conclusions: The benefits of higher ratios of fresh frozen plasma-to-packed RBCs and platelets-to-packed RBCs described in trials of trauma patients were not observed in this analysis of a nontrauma, massively transfused population. These data suggest that greater than 1:2 ratio transfusion in the setting of massive hemorrhage may not be appropriate for all patients, and that further research to guide appropriate resuscitation strategies in nontrauma patients is warranted.

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Both Positive and Negative Fluid Balance May Be Associated With Reduced Long-Term Survival in the Critically Ill

Objectives: Among critically ill patients with acute kidney injury, exposure to positive fluid balance, compared with negative fluid balance, has been associated with mortality and impaired renal recovery. However, it is unclear whether positive and negative fluid balances are associated with poor outcome compared to patients with even fluid balance (euvolemia). In this study, we examined the association between exposure to positive or negative fluid balance, compared with even fluid balance, on 1-year mortality and renal recovery. Design: Retrospective cohort study. Setting: Eight medical-surgical ICUs at the University of Pittsburgh Medical Center, Pittsburgh, PA. Patients: Critically ill patients admitted between July 2000 and October 2008. Interventions: None. Measurements and Main Results: Among 18,084 patients, fluid balance was categorized as negative (

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Nonlinear Imputation of PaO2/FIO2 From SpO2/FIO2 Among Mechanically Ventilated Patients in the ICU: A Prospective, Observational Study

Objectives: In the contemporary ICU, mechanically ventilated patients may not have arterial blood gas measurements available at relevant timepoints. Severity criteria often depend on arterial blood gas results. Retrospective studies suggest that nonlinear imputation of PaO2/FIO2 from SpO2/FIO2 is accurate, but this has not been established prospectively among mechanically ventilated ICU patients. The objective was to validate the superiority of nonlinear imputation of PaO2/FIO2 among mechanically ventilated patients and understand what factors influence the accuracy of imputation. Design: Simultaneous SpO2, oximeter characteristics, receipt of vasopressors, and skin pigmentation were recorded at the time of a clinical arterial blood gas. Acute respiratory distress syndrome criteria were recorded. For each imputation method, we calculated both imputation error and the area under the curve for patients meeting criteria for acute respiratory distress syndrome (PaO2/FIO2 ≤ 300) and moderate-severe acute respiratory distress syndrome (PaO2/FIO2 ≤ 150). Setting: Nine hospitals within the Prevention and Early Treatment of Acute Lung Injury network. Patients: We prospectively enrolled 703 mechanically ventilated patients admitted to the emergency departments or ICUs of participating study hospitals. Interventions: None. Measurements and Main Results: We studied 1,034 arterial blood gases from 703 patients; 650 arterial blood gases were associated with SpO2 less than or equal to 96%. Nonlinear imputation had consistently lower error than other techniques. Among all patients, nonlinear had a lower error (p

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Organizational Issues, Structure, and Processes of Care in 257 ICUs in Latin America: A Study From the Latin America Intensive Care Network

Objective: Latin America bears an important burden of critical care disease, yet the information about it is scarce. Our objective was to describe structure, organization, processes of care, and research activities in Latin-American ICUs. Design: Web-based survey submitted to ICU directors. Settings: ICUs located in nine Latin-American countries. Subjects: Individual ICUs. Interventions: None. Measurements and Main Results: Two hundred fifty-seven of 498 (52%) of submitted surveys responded: 51% from Brazil, 17% Chile, 13% Argentina, 6% Ecuador, 5% Uruguay, 3% Colombia, and 5% between Mexico, Peru, and Paraguay. Seventy-nine percent of participating hospitals had less than 500 beds; most were public (59%) and academic (66%). ICUs were mainly medical-surgical (75%); number of beds was evenly distributed in the entire cohort; 77% had 24/7 intensivists; 46% had a physician-to-patient ratio between 1:4 and 7; and 69% had a nurse-to-patient ratio of 1 ≥ 2.1. The 24/7 presence of other specialists was deficient. Protocols in use averaged 9 ± 3. Brazil (vs the rest) had larger hospitals and ICUs and more quality, surveillance, and prevention committees, but fewer 24/7 intensivists and poorer nurse-to-patient ratio. Although standard monitoring, laboratory, and imaging practices were almost universal, more complex measurements and treatments and portable equipment were scarce after standard working hours, and in public hospitals. Mortality was 17.8%, without differences between countries. Conclusions: This multinational study shows major concerns in the delivery of critical care across Latin America, particularly in human resources. Technology was suboptimal, especially in public hospitals. A 24/7 availability of supporting specialists and of key procedures was inadequate. Mortality was high in comparison to high-income countries.

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Challenging Authority During an Emergency—the Effect of a Teaching Intervention

Objectives: Previous research has shown that residents were unable to effectively challenge a superior's wrong decision during a crisis situation, a problem that can contribute to preventable mortality. We aimed to assess whether a teaching intervention enabled residents to effectively challenge clearly wrong clinical decisions made by their staff. Subjects and Intervention: Following ethics board approval, second year residents were randomized to a teaching intervention targeting cognitive skills needed to challenge a superior's decision, or a control group receiving general crisis management instruction. Two weeks later, subjects participated in a simulated crisis that presented them with opportunities to challenge clearly wrong decisions in a can't-intubate-can't-ventilate scenario. It was only disclosed that the staff was a confederate during the debriefing. Performances were video recorded and assessed by two raters blinded to group allocation using the modified Advocacy-Inquiry Score. Measurements and Main Results: Fifty residents completed the study. The interrater reliability of the modified Advocacy-Inquiry Scores (intraclass correlation coefficient = 0.87) was excellent. The median (interquartile range) best modified Advocacy-Inquiry Score was significantly better in the intervention group 5.0 (4.50–5.62 [4–6]) than in the control group 3.5 (3.0–4.75 [3–6]) (p

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Dysglycemia, Glycemic Variability, and Outcome After Cardiac Arrest and Temperature Management at 33°C and 36°C*

Objectives: Dysglycemia and glycemic variability are associated with poor outcomes in critically ill patients. Targeted temperature management alters blood glucose homeostasis. We investigated the association between blood glucose concentrations and glycemic variability and the neurologic outcomes of patients randomized to targeted temperature management at 33°C or 36°C after cardiac arrest. Design: Post hoc analysis of the multicenter TTM-trial. Primary outcome of this analysis was neurologic outcome after 6 months, referred to as "Cerebral Performance Category." Setting: Thirty-six sites in Europe and Australia. Patients: All 939 patients with out-of-hospital cardiac arrest of presumed cardiac cause that had been included in the TTM-trial. Interventions: Targeted temperature management at 33°C or 36°C. Measurements and Main Results: Nonparametric tests as well as multiple logistic regression and mixed effects logistic regression models were used. Median glucose concentrations on hospital admission differed significantly between Cerebral Performance Category outcomes (p

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Hydrogen Sulfide Confers Lung Protection During Mechanical Ventilation via Cyclooxygenase 2, 15-deoxy Δ12,14-Prostaglandin J2, and Peroxisome Proliferator-Activated Receptor Gamma

Objectives: Hydrogen sulfide reduces ventilator-induced lung injury in mice. Here, we have examined the underlying mechanisms of hydrogen sulfide-mediated lung protection and determined the involvement of cyclooxygenase 2, 15-deoxy Δ12,14-prostaglandin J2, and peroxisome proliferator-activated receptor gamma in this response. Design: Randomized, experimental study. Setting: University medical center research laboratory. Subjects: C57BL/6 mice and in vitro cell catheters. Interventions: The effects of hydrogen sulfide were analyzed in a mouse ventilator-induced lung injury model in vivo as well as in a cell stretch model in vitro in the absence or presence of hydrogen sulfide. The physiologic relevance of our findings was confirmed using pharmacologic inhibitors of cyclooxygenase 2 and peroxisome proliferator-activated receptor gamma. Measurements and Main Results: Mechanical ventilation caused significant lung inflammation and injury that was prevented in the presence of hydrogen sulfide. Hydrogen sulfide-mediated protection was associated with induction of cyclooxygenase 2 and increases of its product 15-deoxy Δ12,14-prostaglandin J2 as well as cyclooxygenase 2/15-deoxy Δ12,14-prostaglandin J2-dependent activation of peroxisome proliferator-activated receptor gamma. Hydrogen sulfide-dependent effects were mainly observed in macrophages. Applied mechanical stretch to RAW 264.7 macrophages resulted in increased expression of interleukin receptor 1 messenger RNA and release of macrophage inflammatory protein-2. In contrast, incubation of stretched macrophages with sodium hydrosulfide prevented the inflammatory response dependent on peroxisome proliferator-activated receptor gamma activity. Finally, application of a specific peroxisome proliferator-activated receptor gamma inhibitor abolished hydrogen sulfide-mediated protection in ventilated animals. Conclusions: One hydrogen sulfide-triggered mechanism in the protection against ventilator-induced lung injury involves cyclooxygenase 2/15-deoxy Δ12,14-prostaglandin J2-dependent activation of peroxisome proliferator-activated receptor gamma and macrophage activity.

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Chemotherapy-induced peripheral neuropathy: a review of recent findings.

Purpose of review: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, frequently chronic condition characterized by pain and decreased function. Given the growing number of cancer survivors and an increasing recognition of opioid therapy limitations, there is a need for critical analysis of the literature in directing an informed and thoughtful approach for the management of painful CIPN. Recent findings: A PubMed search for 'chemotherapy-induced peripheral neuropathy AND pain' identifies 259 publications between 1 January 2016 and 31 March 2017. Based on review of this literature, we aim to present a clinically relevant update of painful CIPN. Notably, the use of duloxetine as a first-line agent in treatment of CIPN is confirmed. Moreover, clinical trials focus on nonpharmacologic strategies for managing painful CIPN. Summary: Despite the volume of recent publications, there are limited preventive or therapeutic strategies for CIPN supported by high-level evidence. Duloxetine remains the only pharmacologic agent with demonstrated benefit; its clinical use should be routinely considered. Moving forward, nonopioid analgesic therapies will likely play an increasing role in CIPN treatment, but further research is necessary to confirm their utility. Promising therapies include vitamin B12 supplementation, physical therapy, and various forms of neuromodulation. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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The courage to fail.

No abstract available

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Inspiratory IVC Collapse: some physiological considerations by Jon-Emile Kenny

some physio behind the IVC debate

EMCrit by Guest Author.

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Moringa isothiocyanate complexed with α-cyclodextrin: a new perspective in neuroblastoma treatment

Several lines of evidence suggest the consume of natural products for cancer prevention or treatment. In particular, isothiocyanates (ITCs) exerting anti-cancer properties, have received great interest as pote...

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Erratum to: toxicity and antitumor potential of Mesosphaerum sidifolium (Lamiaceae) oil and fenchone, its major component

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Influence of the patient-practitioner interaction context on acupuncture outcomes in functional dyspepsia: study protocol for a multicenter randomized controlled trial

In the treatment of functional dyspepsia, the placebo effect has been reported to be high, and the influence of the patient-practitioner relationship may be a major component of this effect. The specific and n...

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Effect of manufacturing and experimental conditions on the mechanical and surface properties of silicone elastomer scaffolds used in endothelial mechanobiological studies

Mechanobiological studies allow the characterization of cell response to mechanical stresses. Cells need to be supported by a material with properties similar to the physiological environment. Silicone elastom...

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Systems Biology of Phenotypic Robustness and Plasticity

Abstract

Gene regulatory networks, cellular biochemistry, tissue function, and whole body physiology are imbued with myriad overlapping and interacting homeostatic mechanisms that ensure that many phenotypes are robust to genetic and environmental variation. Animals also often have plastic responses to environmental variables, which means that many different phenotypes can correspond to a single genotype. Since natural selection acts on phenotypes, this raises the question of how selection can act on the genome if genotypes are decoupled from phenotypes by robustness and plasticity mechanisms. The answer can be found in the systems biology of the homeostatic mechanisms themselves. First, all such mechanisms operate over a limited range and outside that range the controlled variable changes rapidly allowing natural selection to act. Second, mutations and environmental stressors can disrupt homeostatic mechanisms, exposing cryptic genetic variation and allowing natural selection to act. We illustrate these ideas by examining the systems biology of four specific examples. We show how it is possible to analyze and visualize the roles of specific genes and specific polymorphisms in robustness in the context of large and realistic nonlinear systems. We also describe a new method, system population models, that allows one to connect causal dynamics to the variable outcomes that one sees in biological populations with large variation.

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The Milan System for Reporting Salivary Gland Cytopathology: Analysis and suggestions of initial survey

BACKGROUND

An international panel of experts in the field of salivary gland cytology (SGC), supported by the American Society of Cytopathology (ASC) and the International Academy of Cytology, conducted a survey to seek evidence and practice patterns regarding SGC. Results were used to provide focus for the proposed Milan System for Reporting Salivary Gland Cytopathology.

METHODS

The study group, formed during the 2015 European Congress of Cytology held in Milan, Italy, generated a survey that included 49 specific questions related to the taxonomies, practices, and diagnostic entities of salivary cytology. Qualtrics software was used as the study platform. Software and server support were provided by the division of information technology at the University of Wisconsin. The survey was available online from November 2015 until February 2016. Participants were invited through the Web sites of the ASC, the International Academy of Cytology, and the Papanicolaou Society of Cytopathology as well as by the ASC e-mail "ListServe"; responses were evaluated by the Milan System editors.

RESULTS

Responses from a total of 515 participants were collected and reviewed. A total of 347 participants provided demographic data information. Responses revealed variations in diagnostic practice and subsequent management. Participants believed that the acceptable rate for nondiagnostic samples should not be higher than 10%. There were varied opinions regarding the approach to neoplastic lesions of uncertain malignant potential, those that may or may have not local invasion and distant spread.

CONCLUSIONS

Results of the survey demonstrated strong support for the development of a unified system for reporting SGC. Cancer Cytopathol 2017. © 2017 American Cancer Society.

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A rare case of gastric mixed adenoneuroendocrine carcinoma (MANEC) with gastric Helicobacter pylori-negative mucosa-associated lymphoid tissue (MALT) lymphoma

Description

A 47-year-old African-American man presented to the emergency department with upper abdominal pain, nausea and vomiting. His symptoms were aggravated by eating. He reported 32 kg unintentional weight loss over 2 months' period. Abdominal examination revealed tenderness in the epigastric region. Abdominal CT scan showed mural wall thickening involving the gastric antrum and pylorus (figure 1). Subsequent oesophagogastroduodenoscopy (EGD) revealed a large mass occupying the gastric antrum (figure 2). Initial biopsy from the gastric mass showed poorly differentiated adenocarcinoma.

Figure 1

(A) Coronal section of the CT abdomen with intravenous and oral contrast showing wall thickening at the level of the gastric antrum. (B) Axial section of the CT abdomen with intravenous and oral contrast showing wall thickening at the level of the gastric antrum and pylorus.

Figure 2

Upper gastrointestinal endoscopy showing a mass in...

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Renal fistulae: different aetiologies, similar management

Iatrogenic renocolic fistulae, although have been described in literature, is a rare clinical complication. Recently its incidence is on rise due to advent of minimally invasive surgery and percutaneous surgery of kidney. It has been reported after percutaneous nephrolithotomy but its incidence after percutaneous nephrostomy is quite uncommon and rarely reported. Though spontaneous renocutaneous fistula has been reported, acquired renocutaneous fistula is very uncommon and fistula after gun shot injury has not been reported to the best of our knowledge. Herein, we present two different varieties of renal fistula with completely different history and presentation. But the interesting point is that both were managed conservatively in a similar fashion and both of them responded well

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Pseudomonas aeruginosa as an unusual cause of cavitating lung lesion

A 31-year-old woman with systemic lupus erythematosus presented to the emergency department with cough for 1âweek. Chest radiograph demonstrated cavitating lesion in the right upper zone with surrounding ground-glass change. Blood culture results from the day of hospital presentation grew Pseudomonas aeruginosa. Sputum sample and pleural fluid grew P. aeruginosa and were negative for acid-fast bacilli. P. aeruginosa is a rare cause of cavitating lung lesion and has been associated with immunocompromised hosts. Most reports of cavitating P. aeruginosa lesions have been identified in patients who are immunocompromised secondary to HIV.The current case highlights the potential for infection in patients who are immunosuppressed therapeutically and appropriate investigations are necessary to rule out common causes of cavitating lung lesions.

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Complement factor B mutation-associated aHUS and myocardial infarction

A 6-month-old female infant was referred with a 3-day history of low-grade fever, slight nasal congestion and rhinorrhoea. On admission, the clinical findings were unremarkable and she was discharged home. However, she became progressively more listless with a decreased urine output and was once again seen in the emergency department. Analytically she was found to have metabolic acidosis, hyperkalaemia, thrombocytopaenia, anaemia and schistocytes in the peripheral blood smear. Based on these findings, the diagnosis of haemolyticâ-uremic syndrome was made. A few hours postadmission, there was an abrupt clinical deterioration. She went into cardiorespiratory arrest and she was successfully resuscitated. An ST-segment elevation was noted on the ECG monitor and the troponin I levels were raised, suggesting myocardial infarction. Despite intensive supportive therapy, she went into refractory shock and died within 30 hours.

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Anaphylaxis secondary to Parietaria judaica (wall pellitory)

Aeroallergens are an unusual cause of anaphylaxis with sparse reports in the literature. We describe a case of suspected anaphylaxis to Parietaria judaica pollen and the difficulties encountered in confirming this diagnosis.

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Focal neurological presentation in Hashimoto's encephalopathy mimicking a vascular occlusion of the middle cerebral artery

Hashimoto's encephalopathy is a rare form of autoimmune encephalopathy. It is likely an underdiagnosed entity especially in the setting of focal neurological defects. We report a case of a 49-year-old man who presented with "strange behavior"of a day's duration. Examination was significant only for lethargy, poor attention span and agitation. Routine labs revealed leucocytosis. Head CT scan was unremarkable. Lumbar puncture showed high white blood cells with lymphocytosis and elevated protein level. The patient was empirically treated for meningitis without improvement. His symptoms progressed to sudden right-sided weakness, ataxia and right facial droop. The MRI and magnetic resonance angiogram (MRA)were normal. The patientâ™s focal neurological signs improved spontaneously. Encephalopathy work-up was negative except for positive anti-Thyroid Peroxidaseand antithyroglobulin. The patient was treated as Hashimoto encephalopathy with steroids and azathioprine with marked improvement. Our case highlights how focal neurological findings can potentially mislead the provider to consider vascular aetiologies in Hashimoto's encephalopathy.

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Peritoneal tuberculosis as a cause of ascites in a patient with cirrhosis

A 59-year-old Portuguese Caucasian man with a history of heavy alcohol intake and no significant medical history presented with ascites, weight loss and general malaise. The ascitic fluid analysis showed 921 cells/mm³ with mononuclear predominance (93.6%), elevated total proteins and a slightly elevated serum-ascites albumin gradient. The abdominal ultrasound confirmed the presence of chronic liver disease with ascites, and additionally on CT there was evidence of peritoneal thickening. On repeat paracentesis, the ascitic fluid analysis showed elevated adenosine deaminase but it was negative for the presence of mycobacteria by Ziehl-Neelsen stain, Löwenstein-Jensen culture and PCR amplification. Due to the persistent suspicion of tuberculosis, a laparoscopy was performed showing multiple small white tubercles scattered over the peritoneum. Peritoneal biopsies showed the presence of necrotising granulomas and cultures were positive for Mycobacterium tuberculosis complex. After a 6-month course of tuberculostatics, the ascites resolved completely. The patient remained asymptomatic.

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Is FCH PET able to identify foci of infection superiorly to FDG PET?

We report a case of a brain abscess identified on fluorine-18 choline (FCH) positron emission tomography (PET) scan, which was not identified on fluorodeoxyglucose (FDG) PET scan. To our knowledge, there are no previous case reports of incidental brain abscess identified by FCH PET imaging. A 51-year-old man, with liver cirrhosis complicated by hepatocellular carcinoma (HCC) was enrolled in a research trial comparing HCC detection in FCH PET versus FDG PET. During the course of the trial, he underwent radiofrequency ablation (RFA) for HCC. A repeat FCH PET scan post-RFA incidentally revealed a 2.5âcm lesion with avid uptake in the left occipital area of the brain. The patient was asymptomatic. MRI suggested this was an abscess. A craniotomy and drainage was performed, with culture of Streptococcus intermedius (S. milleri group) from the thick-walled collection, a causative organism for previous episode of pneumonia. He successfully completed a 6 week course of antibiotics.

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External revascularisation for pseudochronic total occlusion of the dorsal pedis artery due to foot drop with severe diabetes mellitus

Description

A 45-year-old woman with end-stage renal disease and severe diabetes mellitus (haemoglobin A1c (HbA1c) 9.5%) suffered from critical limb ischaemia (CLI). Her right ankle brachial pressure index (ABPI) was 0.77; however, her left ABPI was immeasurable with flat waveform. Additionally, skin perfusion pressure was 34 mm Hg on the left dorsal and 22 mm Hg on the left planter. The angiography showed chronic total occlusion (CTO) of the dorsal pedis artery (DPA) (figure 1, left panel). We electively performed endovascular therapy. The soft wire smoothly passed the CTO of the DPA. We dilated the CTO with a 2.0 mm balloon several times; however, blood flow could not be restored. This discrepancy suggested an unusual CTO. Intravascular ultrasound showed an intact DPA. She also had foot drop due to diabetic neuropathy. Since the entry of CTO was at the dorsal ankle joint, this joint abnormality was considered the cause of the CTO....

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Abciximab-induced acute profound thrombocytopenia postpercutaneous coronary intervention

Abciximab (c7E3 Fab) is one of the three potent intravenous glycoprotein IIb/IIIa receptor inhibitors (along with eptifibatide and tirofiban) that have shown significant positive outcomes when used in patients with intracoronary thrombus. However, major side effects have been reported with its use including hypotension, major bleeding and thrombocytopenia. This case is a 53-year-old man presenting with acute chest pain diagnosed with non-ST-elevation myocardial infarction, who underwent percutaneous coronary intervention with abciximab and heparin infusion and developed acute profound thrombocytopenia (platelet count <20,000/L) within 9 hours of infusion. This case demonstrates the importance of routinely monitoring the platelet count prior to and 2–4 hours following abciximab infusion and differentiating other causes of acute profound thrombocytopenia, particularly pseudothrombocytopenia and heparin-induced thrombocytopenia.

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Venobiliary fistula with haemobilia: a rare complication of percutaneous liver biopsy

We describe a case of a 36-year-old man with a history of chronic hepatitis C who presented with abdominal pain 3 days after undergoing a percutaneous ultrasound-guided liver biopsy. Initial investigations revealed a venobiliary fistula with haemobilia and obstructive jaundice with direct bilirubin peaking at 9.2 mg/dL. He underwent an endoscopic retrograde cholangiopancreatography with sphincterotomy and stent placement, bilirubin decreased to 3.7 mg/dL, and the patient was discharged. The patient returned with recurrent abdominal pain and upper gastrointestinal bleeding with haemoglobin of 8.6 g/dL, requiring multiple transfusions. He underwent transcatheter arterial embolisation but continued bleeding. Radiofrequency ablation was pursued and was able to achieve haemostasis. The patient was discharged. The patient returned again with a fever of 39.2 °C and was found to have a large right hepatic lobe abscess. The patient underwent abscess drainage with drain placement and was treated with antibiotics for 6 weeks. He followed up in the clinic with resolution of symptoms and infection.

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