Morbidity of cholecystectomy and gastric bypass in a national database

Background

There is a strong association between obesity and gallstones. However, there is no clear evidence regarding the optimal order of Roux-en-Y gastric bypass (RYGB) and cholecystectomy when both procedures are clinically indicated.

Methods

Based on cross-matched data from the Swedish Register for Cholecystectomy and Endoscopic Retrograde Cholangiopancreatography (GallRiks; 79 386 patients) and the Scandinavian Obesity Surgery Registry (SOReg; 36 098 patients) from 2007 to 2013, complication rates, reoperation rates and operation times related to the timing of RYGB and cholecystectomy were explored.

Results

There was a higher aggregate complication risk when cholecystectomy was performed after RYGB rather than before (odds ratio (OR) 1·35, 95 per cent c.i. 1·09 to 1·68; P = 0·006). A complication after the first procedure independently increased the complication risk of the following procedure (OR 2·02, 1·44 to 2·85; P < 0·001). Furthermore, there was an increased complication risk when cholecystectomy was performed at the same time as RYGB (OR 1·72, 1·14 to 2·60; P = 0·010). Simultaneous cholecystectomy added 61·7 (95 per cent c.i. 56·1 to 67·4) min (P < 0·001) to the duration of surgery.

Conclusion

Cholecystectomy should be performed before, not during or after, RYGB.

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Direct medical costs associated with the extrahepatic manifestations of hepatitis C virus infection in France

Summary

Background

The economic impact of extrahepatic manifestations of hepatitis C virus (HCV) infection remains unknown for France.

Aim

To estimate the prevalence of extrahepatic manifestations of HCV and the direct medical costs associated with them.

Methods

Estimates of 13 extrahepatic manifestations prevalence were obtained from (1) a retrospective data analysis of HCV-infected patients in a specialised centre and the baseline prevalence in the general French population and (2) an international systematic review. Per-patient-per-year costs to treat these manifestations were obtained from the literature, national databases or expert opinion. The impact of achieving HCV cure after anti-viral therapy was applied to the French healthcare costs.

Results

Using approach (1), increased prevalence rates in HCV patients compared to the general population were observed for most extrahepatic manifestations. The mean per-patient-per-year cost of these manifestations in the tertiary centre was 3296 € [95% CI 1829; 5540]. In France, HCV-extrahepatic manifestations amounted to a total cost of 215 million (M) € per year [144; 299]. Using approach (2), the mean per-patient-per-year cost was estimated to be 1117 €. The estimated total cost reduction in France associated with HCV cure was 13.9 M€ for diabetes, 8.6 M€ for cryoglobulinemia vasculitis, 6.7 M€ for myocardial infarction, 2.4 M€ for end-stage renal disease and 1.4 M€ for stroke.

Conclusion

Extrahepatic manifestations of HCV infection substantially add to the overall economic burden of the disease in France. HCV cure after anti-viral therapy is expected to significantly reduce the total costs of managing these manifestations in France.

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Consecutive cases of thyrolipomatosis and thymolipoma: a case report

http://ift.tt/2xMET9q

Adult intussusception: a rare but important clinical entity

http://ift.tt/2yw94Fk

Firework-related injury in the Top End: a 16-year review

Background

On July 1st on 'Territory Day', the public in the Northern Territory are permitted to purchase and operate consumer fireworks without a licence. Serious permanent injuries from fireworks are well described, leading to their banning in many other jurisdictions. This study describes those seriously injured by fireworks in the Top End of the Northern Territory, with the aim of identifying opportunities for prevention and harm minimization.

Methods

This is a retrospective audit of all admitted patients with an injury from fireworks at the Royal Darwin Hospital between 2000 and 2015. The variables collected included demographic data and the circumstances around injury (operator versus bystander, alcohol involvement and day of device operation). The consequences such as injuries, operating theatre visits, length of stay and outpatient visits are described.

Results

Fifty-five patients (including 17 children) suffered 67 injuries over the study period, resulting in 68 operating theatre visits, 322 hospital days and 380 outpatient appointments. Burns, hand and eye injuries predominate. Females (P = 0.000) and children (P = 0.029) were more likely to be injured as bystanders. Injuries on a day other than Territory Day were more likely to have alcohol involvement (P = 0.01), and occur in the operator (P = 0.017).

Conclusion

Consumer firework usage results in a small number of life altering injuries annually. Previous prevention campaigns focusing on device user safety should be expanded to include the safety of bystanders and children and reduce firework usage outside of the Territory Day.

http://ift.tt/2yvUrlj

Ethnic disparities in rates of publicly funded bariatric surgery in New Zealand (2009–2014)

Background

Publicly funded bariatric surgery in New Zealand (NZ) is steadily on the rise to meet the obesity epidemic. Ethnic disparities in obesity rates exist in NZ with Māori and Pacific people having three to five times higher rates than all other ethnic groups within NZ. Ethnic disparities in rates of bariatric surgery have been reported internationally. This research sought to describe rates of publically funded bariatric surgery by self-identified ethnicity in NZ.

Methods

Using reported census and hospitalization discharge data from Statistics NZ and the NZ Ministry of Health, we calculated estimate rates of publicly funded bariatric surgery in the morbidly obese population from June 2009 to July 2014.

Results

The average number of publicly funded bariatric procedures performed per 1000 morbidly obese patients from June 2009 to July 2014 was 3.0 for European, 1.4 for Māori and 0.7 for Pacific ethnicities.

Conclusion

While these data should be interpreted cautiously due to data limitations, the estimated rates may indicate that bariatric services are currently being provided inequitably across the major ethnic groups within NZ. We suggest that further studies should be performed to explore potential patient, healthcare provider and system-level factors that may contribute to ethnic disparities in the rates of publicly funded bariatric surgery in NZ.

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Trends in non-lactation breast abscesses in a tertiary hospital setting

Background

The aim of this paper was to retrospectively review non-lactation breast abscesses treated in Princess Alexandra Hospital over a 10-year period and to illustrate the trends in size, risk factors, microbiological profile and management.

Methods

A computerized search of the medical records was undertaken to identify all adult patients with a diagnosis of breast abscesses during June 2005–June 2015. Patients concurrently breastfeeding were excluded. A retrospectively review of the clinical records was performed.

Results

Eighty-five abscesses were identified in 77 patients. The median patient age was 45 years and 93.7% were females. Smoking and diabetes mellitus were associated with a longer inpatient hospital stay. There was a significant difference in microbiology of abscesses in relation to size. Smaller abscesses (≤3.0 cm) predominantly had mixed anaerobes (54%), whereas larger abscesses had a dominance of Staphylococcus aureus (29%) and other aerobic microbes (33%) (P < 0.05). Seven percent of all abscesses had methicillin-resistant S. aureus. Flucloxacillin was prescribed solely in majority of the cases (45%) with addition of suitable mixed anaerobic cover in 12% cases. Of the 85 abscesses, 58.8% were managed non-operatively with antibiotics ± percutaneous drainage. Percutaneous aspiration had a shorter inpatient stay compared with patients who underwent operative management.

Conclusion

This represents the first Australian study solely analysing non-lactation breast abscess. Size was correlated significantly to characteristic bacteriology and empiric therapy should include both aerobic and anaerobic cover. The majority of non-lactation breast abscesses can be managed non-operatively with a combination of antibiotics and percutaneous aspiration.

http://ift.tt/2yvZQsE

Short and Long Term Complications of In Utero Exposure to Lamotrigine

Summary

AIM

The present study evaluates the effect of antenatal lamotrigine exposure, on short and long term pediatric outcome.

METHODS

The study included the children of 83 epileptic women treated with lamotrigine during pregnancy, at a tertiary medical center between 2004-2014. All newborns were monitored for vital signs, congenital malformations and Finnegan score. In addition, the parents completed a questionnaire regarding child's development and health up to the age of 12 years.

Results

No major malformations were found in the newborns. None of the newborns had significant withdrawal symptoms by Finnegan score. The children were followed up to the age of 12 years (56.6% of the group 6-12 years at the time of evaluation). There were no significant findings in the incidence of neurodevelopmental disorders.

Conclusions

According to our experience, lamotrigine is generally safe for pregnancy use, associated with minimal short term complications with no long term effects on the outcome.

http://ift.tt/2yRsc1W

Designing immunostimulatory double stranded messenger RNA with maintained translational activity through hybridization with poly A sequences for effective vaccination.

Related Articles

Designing immunostimulatory double stranded messenger RNA with maintained translational activity through hybridization with poly A sequences for effective vaccination.

Biomaterials. 2017 Sep 27;:

Authors: Uchida S, Yoshinaga N, Yanagihara K, Yuba E, Kataoka K, Itaka K

Abstract
Messenger (m)RNA vaccines require a safe and potent immunostimulatory adjuvant. In this study, we introduced immunostimulatory properties directly into mRNA molecules by hybridizing them with complementary RNA to create highly immunogenic double stranded (ds)RNAs. These dsRNA formulations, comprised entirely of RNA, are expected to be safe and highly efficient due to antigen expression and immunostimulation occurring simultaneously in the same antigen presenting cells. In this strategy, design of dsRNA is important. Indeed, hybridization using full-length antisense (as)RNA drastically reduced translational efficiency. In contrast, by limiting the hybridized portion to the mRNA poly A region, efficient translation and intense immunostimulation was simultaneously obtained. The immune response to the poly U-hybridized mRNAs (mRNA:pU) was mediated through Toll-like receptor (TLR)-3 and retinoic acid-inducible gene (RIG)-I. We also demonstrated that mRNA:pU activation of mouse and human dendritic cells was significantly more effective than activation using single stranded mRNA. In vivo mouse immunization experiments using ovalbumin showed that mRNA:pU significantly enhanced the intensity of specific cellular and humoral immune responses, compared to single stranded mRNA. Our novel mRNA:pU formulation can be delivered using a variety of mRNA carriers depending on the purpose and delivery route, providing a versatile platform for improving mRNA vaccine efficiency.

PMID: 29031816 [PubMed - as supplied by publisher]

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Engineering intranasal mRNA vaccines to enhance lymph node trafficking and immune responses.

Related Articles

Engineering intranasal mRNA vaccines to enhance lymph node trafficking and immune responses.

Acta Biomater. 2017 Oct 10;:

Authors: Li M, Li Y, Peng K, Wang Y, Gong T, Zhang Z, He Q, Sun X

Abstract
Intranasal mRNA vaccination provides immediate immune protection against pandemic diseases. Recent studies have shown that diverse forms of polyethyleneimine (PEI) have potent mucosal adjuvant activity, which could significantly facilitate the delivery of intranasal mRNA vaccines. Nevertheless, optimizing the chemical structure of PEI to maximize its adjuvanticity and decrease its toxicity remains a challenge. Here we show that the chemical structure of PEI strongly influences how well nanocomplexes of PEI and mRNA migrate to the lymph nodes and elicit immune responses. Conjugating cyclodextrin (CD) with PEI600 or PEI2k yielded CP (CD-PEI) polymers with different CD/PEI ratios. We analyzed the delivery efficacy of CP600, CP2k, and PEI25k as intranasal mRNA vaccine carriers by evaluating the lymph nodes migration and immune responses. Among these polymers, CP2k/mRNA showed significantly higher in vitro transfection efficiency, stronger abilities to migrate to lymph nodes and stimulate dendritic cells maturation in vivo, which further led to potent humoral and cellular immune responses, and showed lower local and systemic toxicity than PEI25k/mRNA. These results demonstrate the potential of CD-PEI2k/mRNA nanocomplex as a self-adjuvanting vaccine delivery vehicle that traffics to lymph nodes with high efficiency.
SIGNIFICANCE: As we face outbreaks of pandemic diseases such as Zika virus, intranasal mRNA vaccination provides instant massive protection against highly variant viruses. Various polymer-based delivery systems have been successfully applied in intranasal vaccine delivery. However, the influence of molecular structure of the polymeric carriers on the lymph node trafficking and dendritic cell maturation is seldom studied for intranasal vaccination. Therefore, engineering polymer-based vaccine delivery system and elucidating the relationship between molecular structure and the intranasal delivery efficiency are essential for maximizing the immune responses. We hereby construct self-adjuvanting polymer-based intranasal mRNA vaccines to enhance lymph node trafficking and further improve immune responses.

PMID: 29030308 [PubMed - as supplied by publisher]

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Tolerogenic Vaccination with MOG/VitD Overcomes Aggravating Effect of C. albicans in Experimental Encephalomyelitis.

Related Articles

Tolerogenic Vaccination with MOG/VitD Overcomes Aggravating Effect of C. albicans in Experimental Encephalomyelitis.

CNS Neurosci Ther. 2016 Oct;22(10):807-16

Authors: Fraga-Silva TF, Mimura LA, Zorzella-Pezavento SF, Ishikawa LL, França TG, Thomé R, Verinaud L, Arruda MS, Sartori A

Abstract
AIMS: Multiple sclerosis (MS) is an immune-mediated demyelinating disorder of the central nervous system (CNS). We described that Candida albicans (Ca) aggravates experimental autoimmune encephalomyelitis (EAE) that is a model to study MS. We also observed that vaccination with a myelin peptide (MOG) in the presence of vitamin D (VitD) protected mice against EAE. In this work, we investigated whether Ca infection interferes with the efficacy of this vaccine.
METHODS: EAE was induced in C57BL/6 female mice previously vaccinated with MOG+VitD and then infected 3 days before encephalomyelitis induction.
RESULTS: Vaccination was able to control EAE development in infected mice. These animals gained weight, and only a few progressed to very low clinical scores. Protection was confirmed by a lower inflammatory infiltration in the CNS and was also associated with a reduced production of encephalitogenic cytokines by spleen and CNS cell cultures. The elevated percentage of CD25(+) FoxP3(+) cells suggests that regulatory T cells are involved in the protection. Adoptive transfer of splenocytes from mice vaccinated with MOG+VitD supports the view that protection is mediated by immunoregulatory cells.
CONCLUSION: Together, these experiments provide evidence demonstrating that EAE can be prevented by the inverse vaccination with MOG+VitD even in the presence of a disease-aggravating infectious agent.

PMID: 27321391 [PubMed - indexed for MEDLINE]

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Correction to: Contribution of the MRPS22 variant and a Down mosaic to the phenotype

Abstract

In the original publication of the article, the title was incorrectly written as "The cerebellum is a common site of affection in Leigh syndrome." The correct title is "Contribution of the MRPS22 variant and a Down mosaic to the phenotype."

http://ift.tt/2ywW6aG

Proline dehydrogenase gene (PRODH) polymorphisms and schizophrenia susceptibility: a meta-analysis

Abstract

Previous studies have been conducted to explore the association between proline dehydrogenase gene (PRODH) polymorphisms and schizophrenia (SZ) susceptibility, but providing the controversial results. Here we performed this meta-analysis to determine whether PRODH variants were associated with SZ risk. Relevant studies were screened by retrieving online database PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI) and SZGene from inception to December 2016. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated based on genotype data or allele frequency to evaluate the strength of this association. For rs372055, eleven studies with 3398 SZ patients and 3171 controls were included and the results indicated that people carrying the T allele was not associated with SZ risk in allele frequency model (C vs T, OR = 1.12, 95%CI = 0.96–1.32). However, results from subgroup analysis showed a significant relationship between rs372055 and SZ risk in dominant genetic model (CC + CT vs TT, OR = 1.26, 95% CI = 1.05–1.50) and heterogeneous model (CT vs TT, OR = 1.26, 95% CI = 1.05–1.52) in Asian, but not in Caucasian. For polymorphisms rs383964, rs450046, rs385440 and rs2870983, no associations were found between these polymorphisms and SZ susceptibility in allele frequency. This meta-analysis suggests that rs372055 (C/T) polymorphism in PRODH gene is associated with increased SZ risk only in Asian.

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Issue Information

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ESGCT XXV Anniversary Congress in collaboration with the German Society for Gene Therapy; Abstract Author Index

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


http://ift.tt/2zi5Oek

ESGCT XXV Anniversary Congress in Collaboration with the German Society for Gene Therapy October 17–20, 2017 Berlin, Germany

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


http://ift.tt/2yubwKO

Desmoplastic Small Round Cell Tumor Presenting as an Ocular Mass: Unusual Localization and Remarkable Surgical Approach

Abstract

Desmoplastic small round cell tumor (DSRCT) is a rare tumor that was first described by Gerald and Rosai in 1989 as a mesenchymal entity. This tumor has a unique translocation t (11:22) (p:13, q:12) resulting in EWS/WT1 gene fusion that is diagnostic for DSCRT. The overall prognosis for desmoplastic small round cell tumor remains extremely poor, with reported rates of death as high as 90%. Although the majority of patients undergo chemotherapy following surgery, the prognosis has been shown to be independent of whether the surgical process preceded or followed chemotherapy. In this review, we provide insights for the management of DSCRT that requires aggressive multimodality therapy.

http://ift.tt/2xMJzvM

A Horizontally Transferred Autonomous Helitron Became a Full Polydnavirus Segment in Cotesia vestalis

Bracoviruses associate symbiotically with thousands of parasitoid wasp species in the family Braconidae, working as virulence gene vectors, and allowing the development of wasp larvae within hosts. These viruses are composed by multiple DNA circles that are packaged into infective particles and injected together with wasp's eggs during parasitization. One of the viral segments of Cotesia vestalis bracovirus contains a gene that has been previously described as a helicase of unknown origin. Here we demonstrate that this gene is a Rep/Helicase from an intact Helitron transposable element that covers the viral segment almost entirely. We also provide evidence that this element underwent at least two horizontal transfers, which appear to have occurred consecutively: first from a Drosophila host ancestor to the genome of the parasitoid wasp Cotesia vestalis and its bracovirus, and then from C. vestalis to a lepidopteran host (Bombyx mori). Our results reinforce the idea of parasitoid wasps as frequent agents of horizontal transfers in eukaryotes. Additionally, this Helitron-bracovirus segment is the first example of a transposable element that effectively became a whole viral circle.

http://ift.tt/2x3LA7v

H+ and Pi Byproducts of Glycosylation Affect Ca2+ Homeostasis and Are Retrieved from the Golgi Complex by Homologs of TMEM165 and XPR1

Glycosylation reactions in the Golgi complex and the endoplasmic reticulum utilize nucleotide sugars as donors and produce inorganic phosphate (Pi) and acid (H⁺) as byproducts. Here we show that homologs of mammalian XPR1 and TMEM165 (termed Erd1 and Gdt1) recycle luminal Pi and exchange luminal H⁺ for cytoplasmic Ca²⁺, respectively, thereby promoting growth of yeast cells in low Pi and low Ca2+ environments. As expected for reversible H⁺/Ca²⁺ exchangers, Gdt1 also promoted growth in high Ca²⁺ environments when the Golgi-localized V-ATPase was operational but had the opposite effect when the V-ATPase was eliminated. Gdt1 activities were negatively regulated by calcineurin signaling and by Erd1, which recycled the Pi byproduct of glycosylation reactions and prevented the loss of this nutrient to the environment via exocytosis. Thus, Erd1 transports Pi in the opposite direction from XPR1 and other EXS family proteins and facilitates byproduct removal from the Golgi complex together with Gdt1.

http://ift.tt/2yuyce1

Renal cell -like carcinoma of the nasal cavity: a case report and review of the literature

Sinonasal renal cell-like carcinoma (SRCLC) is an extremely rare low malignant tumor arising in the sinonasal tract, with histological mimicry of renal cell carcinoma.

http://ift.tt/2x2VZ3d

SOCS1 gene therapy improves radiosensitivity and enhances irradiation-induced DNA damage in esophageal squamous cell carcinoma

STAT3 has been implicated recently in radioresistance in cancer. In this study, we investigated the association between STAT3 and radioresistance in esophageal squamous cell carcinoma (ESCC). Strong expression of activated phospho-STAT3 (p-STAT3) was observed in 16/22 ESCC patients with preoperative chemoradiotherapy (CRT), compared to 9/24 patients with surgery alone, where the prognosis of those with CRT was poor. Expression of p-STAT3 and the anti-apoptotic proteins Mcl-1 and survivin was strongly induced in ESCC cells by irradiation. Ectopic STAT3 expression increased radioresistance, whereas expression of the STAT3 negative regulator SOCS1 via an adenoviral vector improved radioresponse. Inhibiting the STAT3-Mcl-1 axis by SOCS1 enhanced DNA damage after irradition and induced apoptosis. Combining SOCS1 with radiotherapy enhanced antitumor responses in a murine xenograft model compared to the individual therapies. Tumor repopulation occurred transiently after treatment by irradiation but not the combination SOCS1/radiotherapy. Tumors subjected to this combination expressed high levels of γ-H2AX and low levels of Ki-67, which was maintained after cessation of treatment. Overall, we demonstrated that inhibiting the STAT3-Mcl-1 signaling axis by ectopic SOCS1 improved radiosensitivity by inducing apoptosis and enhancing DNA damage after radiotherapy, offering a mechanistic rationale for a new ESCC treatment.

http://ift.tt/2yxrkhZ

Restoration of natural killer cell anti-metastatic activity by IL-12 and checkpoint blockade

Immune checkpoint therapies target tumor antigen-specific T cells, but less is known about their effects on natural killer (NK) cells, which help control metastasis. In studying the development of lung metastases, we found that NK cells lose their cytotoxic capacity and acquire a molecular signature defined by the expression of co-inhibitory receptors. In an effort to overcome this suppressive mechanism, we evaluated NK cell responses to the immunostimulatory cytokine IL-12. Exposure to IL-12 rescued the cytotoxicity of NK cells but also led to the emergence of an immature NK cell population which expressed high levels of the co-inhibitory molecules PD-1, Lag-3 and TIGIT, thereby limiting NK cell-mediated control of pulmonary metastases. Notably, checkpoint blockade therapy synergized with IL-12 to fully enable tumor control by NK cells, demonstrating that checkpoint blockers are not only applicable to enhance T cell-mediated immunotherapy, but also to restore the tumor-suppressive capacity of NK cells.

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Table of Contents

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Editorial Board

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Limitations of high throughput methods for miRNA expression profiles in non-functioning pituitary adenomas

Abstract

Microarray, RT-qPCR based arrays and next-generation-sequencing (NGS) are available high-throughput methods for miRNA profiling (miRNome). Analytical and biological performance of these methods were tested in identification of biologically relevant miRNAs in non-functioning pituitary adenomas (NFPA). miRNome of 4 normal pituitary (NP) and 8 NFPA samples was determined by these platforms and expression of 21 individual miRNAs was measured on 30 (20 NFPA and 10 NP) independent samples. Complex bioinformatics was used. 132 and 137 miRNAs were detected by all three platforms in NP and NFPA, respectively, of which 25 were differentially expressed (fold change > 2). The strongest correlation was observed between microarray and TaqMan-array, while the data obtained by NGS were the most discordant despite of various bioinformatics settings. As a technical validation we measured the expression of 21 selected miRNAs by individual RT-qPCR and we were able to validate 35.1%, 76.2% and 71.4% of the miRNAs revealed by SOLiD, TLDA and microarray result, respectively. We performed biological validation using an extended number of samples (20 NFPAs and 8 NPs). Technical and biological validation showed high correlation (p < 0.001; R = 0.96). Pathway and network analysis revealed several common pathways but no pathway showed the same activation score. Using the 25 platform-independent miRNAs developmental pathways were the top functional categories relevant for NFPA genesis. The difference among high-throughput platforms is of great importance and selection of screening method can influence experimental results. Validation by another platform is essential in order to avoid or to minimalize the platform specific errors.

http://ift.tt/2gs0stl

STAMPS: development and verification of swallowing kinematic analysis software

Swallowing impairment is a common complication in various geriatric and neurodegenerative diseases. Swallowing kinematic analysis is essential to quantitatively evaluate the swallowing motion of the oropharyng...

http://ift.tt/2yvuj8Q

Just-in-time simulation-based training

Simulation-based training and assessment in healthcare are now commonplace in the majority of industrialised nations. The role of standardised patients, high-fidelity and low-fidelity manikins, synthetic, animal and virtual reality platforms, and simulation suites, are accepted, and integrated into training curricula in medical and nursing schools, and residency programmes. Despite this widespread use, only a handful of studies have assessed the impact of simulation-based education on patient and health system outcomes, and these studies have their focus on procedural skills such as central line insertion or laparoscopic surgery.1 2 Furthermore, the emphasis of such studies has been on simulation-based education as a tool to impact early learners, with minimal consideration of its use for independent practitioners such as attending physicians and experienced nurses.

An emerging area of simulation-based education is just-in-time training, or as it was termed by Niles et al in 2009, 'rolling refreshers', which...

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Randomised controlled trial to assess the effect of a Just-in-Time training on procedural performance: a proof-of-concept study to address procedural skill decay

Background

A subset of high-risk procedures present significant safety threats due to their (1) infrequent occurrence, (2) execution under time constraints and (3) immediate necessity for patient survival. A Just-in-Time (JIT) intervention could provide real-time bedside guidance to improve high-risk procedural performance and address procedural deficits associated with skill decay.

Objective

To evaluate the impact of a novel JIT intervention on transvenous pacemaker (TVP) placement during a simulated patient event.

Methods

This was a prospective, randomised controlled study to determine the effect of a JIT intervention on performance of TVP placement. Subjects included board-certified emergency medicine physicians from two hospitals. The JIT intervention consisted of a portable, bedside computer-based procedural adjunct. The primary outcome was performance during a simulated patient encounter requiring TVP placement, as assessed by trained raters using a technical skills checklist. Secondary outcomes included global performance ratings, time to TVP placement, number of critical omissions and System Usability Scale scores (intervention only).

Results

Groups were similar at baseline across all outcomes. Compared with the control group, the intervention group demonstrated statistically significant improvement in the technical checklist score (11.45 vs 23.44, p<0.001, Cohen's d effect size 4.64), the global rating scale (2.27 vs 4.54, p<0.001, Cohen's d effect size 3.76), and a statistically significant reduction in critical omissions (2.23 vs 0.68, p<0.001, Cohen's d effect size –1.86). The difference in time to procedural completion was not statistically significant between conditions (11.15 min vs 12.80 min, p=0.12, Cohen's d effect size 0.65). System Usability Scale scores demonstrated excellent usability.

Conclusion

A JIT intervention improved procedure perfromance, suggesting a role for JIT interventions in rarely performed procedures.

http://ift.tt/2zhn8Af

Determining the optimal place and time for procedural education

Just-in-time performance support as an educational process

In an apprenticeship model, for a trainee who is developing their skills, situating them in the workplace has distinct advantages. Starting from legitimate peripheral participation, the developing clinician is moulded by social interaction and collaboration while they learn from the spectrum of patients that make up a given clinical population.1 The goal is lasting behavioural and cognitive changes in the trainee as they take up the mantle of 'expert clinician'.

However, to take on legitimate roles in the clinical workplace, a trainee requires direct just-in-time support, or 'scaffolding', in the form of supervision. Their preceptors provide enough support to ensure that safe and successful patient management can be accomplished. This is analogous to training wheels for someone learning to ride a bicycle—a scaffolding mechanism that enables a relative novice to perform the activity from start to finish when they...

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Reliable adherence to a COPD care bundle mitigates system-level failures and reduces COPD readmissions: a system redesign using improvement science

Background

Readmissions of chronic obstructive pulmonary disease (COPD) have devastating effects on patient quality-of-life, disease progression and healthcare cost. Effective interventions to reduce COPD readmissions are needed.

Objectives

Reduce 30-day all-cause readmissions by (1) creating a COPD care bundle that addresses care delivery failures, (2) using improvement science to achieve 90% bundle adherence.

Setting

An 800-bed academic hospital in Ohio, USA. The COPD 30-day all-cause readmission rate was 22.7% from August 2013 to September 2015.

Method

We performed a cross-sectional study of COPD 30-day readmissions from October 2014 to March 2015 to identify care delivery failures. We interviewed readmitted patients with COPD to identify their needs after discharge. A multidisciplinary team created a care bundle designed to mitigate system failures. Using a quasi-experimental study and 'Model for Improvement', we redesigned care delivery to improve bundle adherence. We used statistical process control charts to analyse bundle adherence and all-cause 30-day readmissions.

Results

Cross-sectional review of the index (first-time) admissions revealed COPD was the most common readmission diagnosis and identified 42 system-level failures. The most prevalent failures were deficient inhaler regimen at discharge, late or non-existent follow-up appointments, and suboptimal discharge instructions. Patient interviews revealed confusing discharge instructions, especially regarding inhaler use. The COPD care-bundle components were: (1) appropriate inhaler regimen, (2) 30-day inhaler supply, (3) inhaler education on the device available postdischarge, (4) follow-up within 15 days (5) standardised patient-centred discharge instructions. The adherence to completing bundle components reached 90% in 5.5 months and was sustained. The COPD 30-day readmission rate decreased from 22.7% to 14.7%. Patients receiving all bundle components had a readmission rate of 10.9%. As a balancing measure for the targeted reduction in readmission rate, we assessed length of stay, which did not change (4.8 days before vs 4.6 days after; p=0.45).

Conclusion

System-level failures and unmet patient needs are modifiable risks for readmissions. Development and reliable implementation of a COPD care bundle that mitigates these failures reduced COPD readmissions.

http://ift.tt/2zhmZwH

Identifying patient and practice characteristics associated with patient-reported experiences of safety problems and harm: a cross-sectional study using a multilevel modelling approach

Objective

To identify patient and family practice characteristics associated with patient-reported experiences of safety problems and harm.

Design

Cross-sectional study combining data from the individual postal administration of the validated Patient Reported Experiences and Outcomes of Safety in Primary Care (PREOS-PC) questionnaire to a random sample of patients in family practices (response rate=18.4%) and practice-level data for those practices obtained from NHS Digital. We built linear multilevel multivariate regression models to model the association between patient-level (clinical and sociodemographic) and practice-level (size and case-mix, human resources, indicators of quality and safety of care, and practice safety activation) characteristics, and outcome measures.

Setting

Practices distributed across five regions in the North, Centre and South of England.

Participants

1190 patients registered in 45 practices purposefully sampled (maximal variation in practice size and levels of deprivation).

Main outcome measures

Self-reported safety problems, harm and overall perception of safety.

Results

Higher self-reported levels of safety problems were associated with younger age of patients (beta coefficient 0.15) and lower levels of practice safety activation (0.44). Higher self-reported levels of harm were associated with younger age (0.13) and worse self-reported health status (0.23). Lower self-reported healthcare safety was associated with lower levels of practice safety activation (0.40). The fully adjusted models explained 4.5% of the variance in experiences of safety problems, 8.6% of the variance in harm and 4.4% of the variance in perceptions of patient safety.

Conclusions

Practices' safety activation levels and patients' age and health status are associated with patient-reported safety outcomes in English family practices. The development of interventions aimed at improving patient safety outcomes would benefit from focusing on the identified groups.

http://ift.tt/2zvTuYO

Comparison of control charts for monitoring clinical performance using binary data

Background

Time series charts are increasingly used by clinical teams to monitor their performance, but statistical control charts are not widely used, partly due to uncertainty about which chart to use. Although there is a large literature on methods, there are few systematic comparisons of charts for detecting changes in rates of binary clinical performance data.

Methods

We compared four control charts for binary data: the Shewhart p-chart; the exponentially weighted moving average (EWMA) chart; the cumulative sum (CUSUM) chart; and the g-chart. Charts were set up to have the same long-term false signal rate. Chart performance was then judged according to the expected number of patients treated until a change in rate was detected.

Results

For large absolute increases in rates (>10%), the Shewhart p-chart and EWMA both had good performance, although not quite as good as the CUSUM. For small absolute increases (<10%), the CUSUM detected changes more rapidly. The g-chart is designed to efficiently detect decreases in low event rates, but it again had less good performance than the CUSUM.

Implications

The Shewhart p-chart is the simplest chart to implement and interpret, and performs well for detecting large changes, which may be useful for monitoring processes of care. The g-chart is a useful complement for determining the success of initiatives to reduce low-event rates (eg, adverse events). The CUSUM may be particularly useful for faster detection of problems with patient safety leading to increases in adverse event rates.  

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Incorporating nursing complexity in reimbursement coding systems: the potential impact on missed care

Introduction 

Globally, nurses constitute the largest segment of healthcare professionals; therefore, they are also the most expensive, and in a hospital these costs can reach 25% of the total expenditure.1 When costs are calculated, usually the monthly sum of nursing working hours and nursing labour costs is divided by the total number of patient days to produce mean general measures such as 'nursing hours per patient' or 'nursing costs per patient day.' This is only a general average cost calculation that takes into account large groups of nurses caring for large groups of patients, but through this system it is difficult to accurately control costs if the specific costs are unknown.2 In this regard, Needleman3 pointed to the 'invisibility' of a significant portion of nursing today, which explains why this discipline in many countries around the world is still not fully recognised by...

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How to attribute causality in quality improvement: lessons from epidemiology

Background

Quality improvement and implementation (QI&I) initiatives face critical challenges in an era of evidence-based, value-driven patient care. Whether front-line staff, large organisations or government bodies design and run QI&I, there is increasing need to demonstrate impact to justify investment of time and resources in implementing and scaling up an intervention.

Decisions about sustaining, scaling up and spreading an initiative can be informed by evidence of causation and the estimated attributable effect of an intervention on observed outcomes. Achieving this in healthcare can be challenging, where interventions often are multimodal and applied in complex systems.1 Where there is weak evidence of causation, credibility in the effectiveness of the intervention is reduced with a resultant reduced desire to replicate. The greater confidence of a causal relationship between QI&I interventions and observed results, the greater our confidence that improvement will result when the intervention occurs in different settings.

...

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Standard admission order sets promote ordering of unnecessary investigations: a quasi-randomised evaluation in a simulated setting

Introduction

Standard admission order sets have become ubiquitous across hospitals to promote adherence to practice guidelines and increase ordering efficiency.1 2 This standardisation arose in part out of a need to minimise waste in healthcare, a phenomenon identified as a major barrier to reducing future healthcare costs.3 However, few studies have systematically evaluated whether these standardised orders can actually promote overordering of investigations. At our academic hospital's coronary care unit (CCU), a single mandatory generic order set is used regardless of admitting diagnosis and includes optional check boxes for serum thyroid-stimulating hormone (TSH) and brain natriuretic peptide (BNP). We postulated that physicians order investigations differently on admission based on which investigations are included in the admission order set.

Methods

We quasi-randomised a convenience sample of participants in a double-blind fashion to receive either our standard CCU admission order set or...

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Speaking up against unsafe unprofessional behaviours: the difficulty in knowing when and how

Patient safety is a core focus now in medical education, with an increasing number of training programmes educating learners about its key tenets.1–3 Residents now undergo formal training about the importance of contributing to a culture of safety by speaking up to avoid errors or harm, but still face difficulties enacting these behaviours in practice.4 In this issue of the journal, Martinez et al have attempted to tease out differences in speaking-out behaviours between traditional and professionalism-related patient safety threats.5 The authors have raised several interesting points worthy of further exploration. In this editorial we focus on unprofessional behaviour as a potential threat to patient safety and propose some new ways of thinking about how to integrate research and lessons from both the patient safety and professionalism literature.

In the study by Martinez and colleagues, residents reported witnessing unprofessional...

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Kidney Transplantation and the Impact on Health-Related Quality of Life in Frail Patients.

No abstract available

http://ift.tt/2zwnow0

Unsuspected schwannomas of the gallbladder

Schwannomas are neurogenic tumors that originate from the nerve sheaths of the peripheral nerves. Schwannomas arising from the gallbladder are extremely rare. In the present case, we report a 70-year-old man, who was admitted the hospital because of epigastric pain and jaundice. Based on the evidence of blood tests, ultrasonography and magnetic resonance imaging, a diagnosis of cholecystitis and cholangitis caused by stone was considered preoperatively. He underwent laparoscopic cholecystectomy and laparoscopic common bile duct exploration.

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Widening the spectrum of deletions and molecular mechanisms underlying alpha-thalassemia

Abstract

Inherited deletions of α-globin genes and/or their upstream regulatory elements (MCSs) give rise to α-thalassemia, an autosomal recessive microcytic hypochromic anemia. In this study, multiplex ligation-dependent probe amplification performed with commercial and synthetic engineered probes, Gap-PCR, and DNA sequencing were used to characterize lesions in the sub-telomeric region of the short arm of chromosome 16, possibly explaining the α-thalassemia/HbH disease phenotype in ten patients. We have found six different deletions, in heterozygosity, ranging from approximately 3.3 to 323 kb, two of them not previously described. The deletions fall into two categories: one includes deletions which totally remove the α-globin gene cluster, whereas the other includes deletions removing only the distal regulatory elements and keeping the α-globin genes structurally intact. An indel was observed in one patient involving the loss of the MCS-R2 and the insertion of 39 bp originated from a complex rearrangement spanning the deletion breakpoints. Finally, in another case, no α-globin gene cluster deletion was found and the patient revealed to be a very unusual case of acquired α-thalassemia-myelodysplastic syndrome. This study further illustrates the diversity of genomic lesions and underlying molecular mechanisms leading to α-thalassemia.

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The impact of antimicrobial prophylaxis in morbidity and infections during azacitidine treatment

Abstract

The clinical consequences of the infectious events in patients receiving azacitidine are poorly documented. Likewise, the role of primary antimicrobial prophylaxis is unknown. In this retrospective, single-center study, we compare the impact of prophylaxis on the incidence of infection and morbidity in all consecutive higher-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients, during the first 4 azacitidine cycles. Seventy-six patients, corresponding to 283 azacitidine cycles, were studied. There were infectious events in 43% of the patients. Development of infections led to more hospital admissions, increased red blood cells and platelet requirements, and a delay in subsequent cycles. Median overall survival was comparable between patients with or without infections. In the multivariate analysis, a neutrophil count below 0.5 × 10⁹/L (OR 12.5 [2.6–50]) and antimicrobial prophylaxis (OR 0.1 [0.02–04]) were independent factors for the development of infection. We conclude that infectious events have a significant impact in the early clinical course of azacitidine-treated patients by increasing hospital admissions and transfusion requirements. Antimicrobial prophylaxis may prevent infections, leading to a decreased need for supportive care in these patients with poor outcome.

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Relative abundance of β-thalassemia-related mutations in southern China correlates with geographical coordinates

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Therapeutic decision-making in elderly patients with acute myeloid leukemia: conventional intensive chemotherapy versus hypomethylating agent therapy

Abstract

Standards of care for elderly acute myeloid leukemia (AML) patients unfit for intensive chemotherapy remain undefined. We aimed to compare outcomes of hypomethylating agent (HMA) therapy and intensive chemotherapy (IC) in elderly AML patients and identify the subgroup of patients who are eligible for HMA therapy. We reviewed data on the outcomes of 86 AML patients aged ≥ 65 years, who had undergone treatment between 2010 and 2015. These treatments included IC (25 patients, 29.1%) or therapy using HMA including azacitidine or decitabine (61 patients, 70.9%). The overall response rates were 32 and 19.7%, respectively. Median overall survival (OS) (8 vs. 8 months) and progression-free survival (PFS) (6 vs. 7 months) durations were similar in the two groups. Patients in the HMA group with less than 10% peripheral blood (PB) blasts achieved significantly better OS duration than patients in the IC group (P = 0.043). Patients in the IC group with PB blasts and bone marrow blast of ≥ 10 and ≥ 50%, respectively, achieved better PFS durations than the corresponding patients in the HMA group (P = 0.038). Multivariate analysis identified the hematologic improvement-platelet (HI-P) as an independent prognostic factor for survival in the HMA group (P = 0.005). Our results showed that HMA therapy and IC were associated with similar survival duration in elderly AML patients. This study was noteworthy because it assessed prognostic factors that would help to select elderly patients who could expect actual benefits from undergoing the different therapeutic options available, especially HMA therapy.

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PD-L1 expression correlates with VEGF and microvessel density in patients with uniformly treated classical Hodgkin lymphoma

Abstract

Recent studies have reported the associations between programmed death-ligand 1 (PD-L1) or PD-L2/PD-1 pathways and pro-angiogenic genes including hypoxia-inducible factors (HIFs) and vascular endothelial growth factor (VEGF) in several malignancies. However, no study has examined the relationship or prognostic implication of PD-L1, PD-L2, PD-1, VEGF expression, and microvessel density (MVD) in classical Hodgkin lymphoma (cHL) patients. Diagnostic tissues from 109 patients with doxorubicin, bleomycin, vinblastine, and dacarbazine-treated cHL were evaluated retrospectively by immunohistochemical analysis for PD-L1, PD-L2, PD-1, VEGF expression, and for CD31 expression as a measure of MVD. There was a positive correlation between PD-L1 and VEGF expression (P = 0.008) and additionally between PD-L2 and VEGF expression (P = 0.001). The mean MVD in tumors positive for both PD-L1 and VEGF was significantly (P = 0.022) higher than the mean MVD in tumors negative for both markers. High PD-1 expression group had lower (P = 0.019) 5-year overall survival rate than low PD-1 expression group. Multivariate analysis revealed that PD-1 was an independent prognostic factor for cHL with significance (P = 0.026). However, PD-L1, PD-L2, and VEGF expression had no prognostic impact. Our data confirmed the positive correlations between PD-L1, VEGF, or MVD. Our findings provided evidence supporting new therapeutic approaches including combinations of anti-PD-L1/PD-1 and anti-VEGF therapy in addition to the current standard regimen for cHL.

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Clinical outcomes in patients with diffuse large B cell lymphoma with a partial response to first-line R-CHOP chemotherapy: prognostic value of secondary International Prognostic Index scores and Deauville scores

Abstract

After introducing a rituximab-containing chemoimmunotherapy (R-CHOP) for diffuse large B cell lymphoma (DLBCL), a partial response (PR) which is regarded as treatment failure is still observed. To investigate the prognostic factors for the DLBCL patients with a PR to R-CHOP, we retrospectively evaluated 758 newly diagnosed DLBCL patients. After R-CHOP, 88 (11.6%) achieved a PR. Three-year progression-free and overall survival rates measured from the date of PR achievement (PFS2 and OS2) were 57.4 and 67.8%, respectively. The secondary International Prognostic Index (IPI2) scores after R-CHOP were low (0–1) in 68.2% and high (2–3) in 31.8% of the patients. The Deauville scores from 18-fluorodeoxyglucose positron emission tomography after R-CHOP showed low (2–3) in 58.0% and high (4) in 42.0% of the patients. High IPI2 and high Deauville scores were associated with worse PFS2 (P < 0.001 and P = 0.009) and OS2 (P = 0.013 and P = 0.067). The high-risk group defined by the IPI2 and Deauville scores, whose scores were both high, showed significantly lower 3-year PFS2 (P < 0.001) and OS2 (P = 0.006) rates compared with those of the other groups. In multivariate analyses, the IPI score of ≥ 3 at diagnosis and bone marrow involvement at diagnosis were independent prognostic factors. In addition, high IPI2-Deauville score after R-CHOP was significantly associated with poor PFS2 (P = 0.009) and demonstrated a trend toward inferior OS2. In conclusion, DLBCL patients who partially responded to R-CHOP are still a heterogeneous group, for which IPI2 and Deauville scores should be evaluated for prediction of prognosis.

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Plasma levels of complement activation fragments C3b and sC5b-9 significantly increased in patients with thrombotic microangiopathy after allogeneic stem cell transplantation

Abstract

Transplantation-associated thrombotic microangiopathy (TA-TMA) is an uncommon but severe complication in patients undergoing allogeneic stem cell transplantation (allo-SCT). However, the mechanism is unclear. From 2011 to 2014, 20 patients with TA-TMA, 20 patients without, and 54 patients with various other complications, including veno occlusive disease (VOD), graft-versus-host disease (GVHD), and infection, were recruited in the study. Plasma vWF antigen (vWFAg), vWF activity (vWFAc), and ADAMTS13 activity were determined in these patients by ELISAs and FRETS-vWF73 assay, respectively. Plasma C3b, sC5b-9, and CH50 were also determined by ELISAs. Plasma levels of C3b were significantly increased in patients with either TA-TMA (p < 0.0001) or GVHD (p < 0.01). Plasma sC5b-9 and CH50 levels in patients with TA-TMA were also significantly increased (p < 0.001). Plasma ADAMTS13 activity was lower in patients with VOD, but normal with other complications. Both plasma vWFAg and vWFAc levels were not elevated in patients with TA-TMA or VOD compared with those of other groups. Complement activation likely via an alternative pathway (increased C3b, sC5b-9, and CH50) may play a role in the pathogenesis of TA-TMA. ADAMTS13 activity is reduced in VOD, but the ADAMTS13/vWF axis appears to be unaffected in patients with TA-TMA.

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Effectivity of a modified Sanz risk model for early death prediction in patients with newly diagnosed acute promyelocytic leukemia

Abstract

Early death is the main obstacle for the cure of patients with acute promyelocytic leukemia (APL). We have analyzed risk factors of early death from 526 consecutive newly diagnosed APL patients between 2004 and 2016. The overall incidence of early death was 7.2% (38/526). The peak hazard of early death occurred in the first 0–3 days. Multivariate logistic analysis demonstrated white blood cell (WBC) counts [odds ratio (OR) = 1.039; 95% confidence interval (CI): 1.024–1.055; P < 0.001], age (OR = 1.061; 95% CI: 1.025–1.099; P = 0.001) and platelet counts (OR = 0.971; 95% CI: 0.944–0.999; P = 0.038) were independent risk factors for early death. Furthermore, receiver-operator characteristic (ROC) curve analyses revealed a simple WBC/platelet ratio was significantly more accurate in predicting early death [areas under the ROC curve (AUC) = 0.842, 95% CI: 0.807–0.872) than WBC counts (AUC = 0.793; 95% CI: 0.756–0.827) or Sanz score (AUC = 0.746; 95% CI: 0.706–0.783). We stratified APL patients into four risk subgroups: low risk (WBC ≤ 10 × 10⁹/L, platelet >40 × 10⁹/L), intermediate risk (WBC/platelet <0.2 and age ≤ 60, not in low risk), high risk (WBC/platelet ≥0.2 or age > 60, not in low and ultra-high risk) and ultra-high risk (WBC > 50 × 10⁹/L), the early death rates were 0, 0.6, 12.8, and 41.2%, respectively. In conclusion, we proposed a modified Sanz risk model as a useful predictor of early death risk in patients with APL.

http://ift.tt/2gMnEzi

A cross-sectional study on late taste disorders in survivors of allogeneic hematopoietic cell transplantation

Abstract

Taste disorders are one of the most common complications in patients undergoing allogeneic hematopoietic cell transplantation (HCT). They persist in some patients as a late complication 3 months or more after HCT. Therefore, we conducted a cross-sectional study to evaluate the prevalence and predictive factors of late taste disorders, with the help of a self-reporting and closed-ended questionnaire, which was distributed among 91 patients in our institute. The median age at this study was 50 (range, 25–69) years. The median follow-up period was 54 (range, 3–234) months after HCT. Taste disorders were observed in 43 patients (47%). The most frequent form of late taste disorders was reduced appetite in 18 patients (20%). The most frequent form of decline of basic taste was umami, which was observed in 12 patients (13%). Almost all taste disorders were mild in their severity. Multivariate logistic regression analyses showed that the duration of less than 1 year post HCT and the presence of oral chronic graft-versus-host disease are important risk factors for late taste disorders in survivors of HCT. These data suggested that taste disorders usually return to normal levels more than a year after HCT in most recipients.

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Effects of realgar (As 4 S 4 ) on degradation of PML-RARA harboring acquired arsenic-resistance mutations

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Patients with primary breast and primary female genital tract diffuse large B cell lymphoma have a high frequency of MYD88 and CD79B mutations

Abstract

This study is to retrospectively evaluate the prevalence of MYD88 and CD79B mutations and the clinicopathologic characteristics of patients with primary diffuse large B cell lymphoma (DLBCL) of the female genital tract and breast. The characteristics, treatments, and outcomes of 19 patients diagnosed with primary DLBCL of the female genital tract and breast, who had formalin-fixed and paraffin-embedded tissues obtained from diagnostic samples diagnosed between January 2004 and June 2016, were analyzed retrospectively. Nineteen female patients (7 with primary breast and 12 with primary female genital tract DLBCL) were included in this retrospective study. Eleven patients (57.9%) carried a MYD88 mutation, including 10 with MYD8 L265P and 1 with the MYD88 L265S mutation. Seven patients (36.8%) harbored a CD79B mutation, which included two cases with CD79B Y196H, two cases with CD79B Y196N, one case with CD79B Y196D, one case with CD79B Y196F, and one case with CD79B Y196X. Four cases had both MYD88 and CD79B mutations. The clinicopathologic parameters, progression-free survival (PFS), and overall survival (OS) of the MYD88 mutation-carrying group were not significantly different from those of the MYD88 wild-type group except for higher LDH levels. Six patients received cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP), while 13 patients received rituximab plus CHOP, and 13 patients received central nervous system prophylaxis. The median OS and PFS were 73 and 56 months, respectively. Patients with primary breast and primary female genital tract DLBCL have a high frequency of MYD88 and CD79B mutations. The presence of these mutations does not affect survival but may offer additional therapeutic options.

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Durable remission is achievable with localized treatment and reduction of immunosuppression in limited stage EBV-related plasmablastic lymphoma

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Uterine intravascular lymphoma as a cause of fever of unknown origin

Abstract

Primary intravascular large B cell lymphoma (IVL) remains a diagnostic challenge because of non-specific clinical, laboratory and imaging findings. The aim of the study was to analyse the major characteristics of IVL with uterine involvement. We retrospectively collected features of IVL with uterine involvement that was proven histologically or demonstrated by significant ¹⁸FDG uptake on ¹⁸FDG-PET/CT. Findings were compared to a comprehensive literature review. Five patients were identified. All of them were admitted for fever of unknown origin (FUO), with haemophagocytic lymphohistiocytosis in three cases. None had gynaecological symptom, contrasting with the literature data. Structural imaging (including whole-body CT scan and pelvic RMI) failed to yield any diagnosis. ¹⁸FDG-PET/CT showed intense uterine uptake in all cases. Endometrial biopsy was performed in three cases and was positive in one. Diagnosis was obtained from coelioscopic iliac adenopathy biopsy in one case and from total hysterectomy in another. Punch biopsy of skin lesions led to diagnosis in the two remaining cases. Bone marrow biopsy was normal in all cases. Clinicians should be aware of potential isolated uterine involvement in IVL, especially in elderly women with FUO. Normal structural imaging does not rule out the diagnosis and ¹⁸FDG-TEP/CT should be performed to guide high-yielding biopsy.

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Extracorporeal Membrane Oxygenation Is First-Line Therapy for Acute Respiratory Distress Syndrome.

No abstract available

http://ift.tt/2gsMfw1

Intermittent Versus Continuous and Intermittent Medications for Pain and Sedation After Pediatric Cardiothoracic Surgery; A Randomized Controlled Trial.

Objectives: Compare continuous infusions of morphine and midazolam in addition to intermittent doses with an intermittent only strategy for pain and sedation after pediatric cardiac surgery. Design: Randomized controlled trial. Setting: Advocate Children's Hospital, Oak Lawn, IL. Patients: Sixty patients 3 months to 4 years old with early extubation after pediatric cardiac surgery. Interventions: Patients received a continuous infusion of morphine and midazolam or placebo for 24 hours. Both groups received intermittent morphine and midazolam doses as needed. Measurements and Main Results: Gender, age, bypass time, and surgical complexity were not different between groups. Scheduled ketorolac and acetaminophen were used in both groups and were not associated with adverse events. The mean, median, and maximum Faces, Legs, Activity, Cry, And Consolability score were not different between groups. There was no significant difference in number of intermittent doses received between groups. The total morphine dose was higher in the continuous/intermittent group (0.90 vs 0.23 mg/kg; p

http://ift.tt/2gr852V

Effects of Hyperoxia During Resuscitation From Hemorrhagic Shock in Swine With Preexisting Coronary Artery Disease.

Objectives: Investigation of the effects of hyperoxia during resuscitation from hemorrhagic shock in swine with preexisting coronary artery disease. Design: Prospective, controlled, randomized trial. Setting: University animal research laboratory. Subjects: Nineteen hypercholesterolemic pigs with preexisting coronary artery disease. Interventions: Anesthetized, mechanically ventilated, and surgically instrumented pigs underwent 3 hours of hemorrhagic shock (removal of 30% of the calculated blood volume and subsequent titration of mean arterial blood pressure [almost equal to]40 mm Hg). Postshock resuscitation (48 hr) comprised retransfusion of shed blood, crystalloids (balanced electrolyte solution), and norepinephrine support. Pigs were randomly assigned to "control" (FIO2 0.3, adjusted for arterial oxygen saturation >= 90%) and "hyperoxia" (FIO2 1.0 for 24 hr) groups. Measurements and Main Results: Before, at the end of shock and every 12 hours of resuscitation, datasets comprising hemodynamics, calorimetry, blood gases, cytokines, and cardiac and renal function were recorded. Postmortem, organs were sampled for immunohistochemistry, western blotting, and mitochondrial high-resolution respirometry. Survival rates were 50% and 89% in the control and hyperoxia groups, respectively (p = 0.077). Apart from higher relaxation constant [tau] at 24 hours, hyperoxia did not affect cardiac function. However, troponin values were lower (2.2 [0.9-6.2] vs 6.9 [4.8-9.8] ng/mL; p

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The Prognostic Value of MRI in Moderate and Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Objectives: Traumatic brain injury is a major cause of death and disability, yet many predictors of outcome are not precise enough to guide initial clinical decision-making. Although increasingly used in the early phase following traumatic brain injury, the prognostic utility of MRI remains uncertain. We thus undertook a systematic review and meta-analysis of studies evaluating the predictive value of acute MRI lesion patterns for discriminating clinical outcome in traumatic brain injury. Data Sources: MEDLINE, EMBASE, BIOSIS, and CENTRAL from inception to November 2015. Study Selection: Studies of adults who had MRI in the acute phase following moderate or severe traumatic brain injury. Our primary outcomes were all-cause mortality and the Glasgow Outcome Scale. Data Extraction: Two authors independently performed study selection and data extraction. We calculated pooled effect estimates with a random effects model, evaluated the risk of bias using a modified version of Quality in Prognostic Studies and determined the strength of evidence with the Grading of Recommendations, Assessment, Development, and Evaluation. Data Synthesis: We included 58 eligible studies, of which 27 (n = 1,652) contributed data to meta-analysis. Brainstem lesions were associated with all-cause mortality (risk ratio, 1.78; 95% CI, 1.01-3.15; I2 = 43%) and unfavorable Glasgow Outcome Scale (risk ratio, 2.49; 95% CI, 1.72-3.58; I2 = 81%) at greater than or equal to 6 months. Diffuse axonal injury patterns were associated with an increased risk of unfavorable Glasgow Outcome Scale (risk ratio, 2.46; 95% CI, 1.06-5.69; I2 = 74%). MRI scores based on lesion depth demonstrated increasing risk of unfavorable neurologic outcome as more caudal structures were affected. Most studies were at high risk of methodological bias. Conclusions: MRI following traumatic brain injury yields important prognostic information, with several lesion patterns significantly associated with long-term survival and neurologic outcome. Given the high risk of bias in the current body of literature, large well-controlled studies are necessary to better quantify the prognostic role of early MRI in moderate and severe traumatic brain injury. Copyright (C) by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Dysphagia in Mechanically Ventilated ICU Patients (DYnAMICS): A Prospective Observational Trial.

Objectives: Swallowing disorders may be associated with adverse clinical outcomes in patients following invasive mechanical ventilation. We investigated the incidence of dysphagia, its time course, and association with clinically relevant outcomes in extubated critically ill patients. Design: Prospective observational trial with systematic dysphagia screening and follow-up until 90 days or death. Settings: ICU of a tertiary care academic center. Patients: One thousand three-hundred four admissions of mixed adult ICU patients (median age, 66.0 yr [interquartile range, 54.0-74.0]; Acute Physiology and Chronic Health Evaluation-II score, 19.0 [interquartile range, 14.0-24.0]) were screened for postextubation dysphagia. Primary ICU admissions (n = 933) were analyzed and followed up until 90 days or death. Patients from an independent academic center served as confirmatory cohort (n = 220). Interventions: Bedside screening for dysphagia was performed within 3 hours after extubation by trained ICU nurses. Positive screening triggered confirmatory specialist bedside swallowing examinations and follow-up until hospital discharge. Measurements and Main Results: Dysphagia screening was positive in 12.4% (n = 116/933) after extubation (18.3% of emergency and 4.9% of elective patients) and confirmed by specialists within 24 hours from positive screening in 87.3% (n = 96/110, n = 6 missing data). The dysphagia incidence at ICU discharge was 10.3% (n = 96/933) of which 60.4% (n = 58/96) remained positive until hospital discharge. Days on feeding tube, length of mechanical ventilation and ICU/hospital stay, and hospital mortality were higher in patients with dysphagia (all p

http://ift.tt/2gr09yS

Prevention of Ventilator-Associated Pneumonia: The Multimodal Approach of the Spanish ICU "Pneumonia Zero" Program.

Objectives: The "Pneumonia Zero" project is a nationwide multimodal intervention based on the simultaneous implementation of a comprehensive evidence-based bundle measures to prevent ventilator-associated pneumonia in critically ill patients admitted to the ICU. Design: Prospective, interventional, and multicenter study. Setting: A total of 181 ICUs throughout Spain. Patients: All patients admitted for more than 24 hours to the participating ICUs between April 1, 2011, and December 31, 2012. Intervention: Ten ventilator-associated pneumonia prevention measures were implemented (seven were mandatory and three highly recommended). The database of the National ICU-Acquired Infections Surveillance Study (Estudio Nacional de Vigilancia de Infecciones Nosocomiales [ENVIN]) was used for data collection. Ventilator-associated pneumonia rate was expressed as incidence density per 1,000 ventilator days. Ventilator-associated pneumonia rates from the incorporation of the ICUs to the project, every 3 months, were compared with data of the ENVIN registry (April-June 2010) as the baseline period. Ventilator-associated pneumonia rates were adjusted by characteristics of the hospital, including size, type (public or private), and teaching (postgraduate) or university-affiliated (undergraduate) status. Measurements and Main Results: The 181 participating ICUs accounted for 75% of all ICUs in Spain. In a total of 171,237 ICU admissions, an artificial airway was present on 505,802 days (50.0% of days of stay in the ICU). A total of 3,474 ventilator-associated pneumonia episodes were diagnosed in 3,186 patients. The adjusted ventilator-associated pneumonia incidence density rate decreased from 9.83 (95% CI, 8.42-11.48) per 1,000 ventilator days in the baseline period to 4.34 (95% CI, 3.22-5.84) after 19-21 months of participation. Conclusions: Implementation of the bundle measures included in the "Pneumonia Zero" project resulted in a significant reduction of more than 50% of the incidence of ventilator-associated pneumonia in Spanish ICUs. This reduction was sustained 21 months after implementation. 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) by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Ventriculo-Arterial Coupling Analysis Predicts the Hemodynamic Response to Norepinephrine in Hypotensive Postoperative Patients: A Prospective Observational Study.

Objectives: The objectives of the present study were to evaluate, in patients with persistent arterial hypotension in the immediate postcardiac surgery period, the effects of norepinephrine infusion on ventriculo-arterial coupling, its determinants: arterial elastance and end-systolic ventricular elastance, and to test the ability of arterial elastance to end-systolic ventricular elastance ratio to predict stroke volume increases. Design: Prospective observational study. Setting: Cardiac-vascular surgical ICU. Patients: Twenty-eight postoperative cardiac surgery patients, in whom physicians decided to administer norepinephrine infusion, were included. Measurements and Main Results: Arterial pressure, stroke volume index, cardiac index, indexed total peripheral resistance, arterial compliance, arterial elastance, and end-systolic ventricular elastance, were measured before and after norepinephrine infusion. We estimated ventriculo-arterial coupling by the arterial elastance to end-systolic ventricular elastance ratio and defined stroke volume responders by a stroke volume increase greater than or equal to 15%. Twenty-two of the 28 subjects had altered ventriculo-arterial coupling (1.87 [1.57-2.51] vs 1.1 [1-1.18]). Fifteen of the 28 subjects (54%) were stroke volume responders. At baseline, stroke volume responders had similar arterial pressure, higher indexed total peripheral resistance, arterial elastance, arterial elastance to end-systolic ventricular elastance ratio (2.21 [1.69-2.89] vs 1.33 [1.1-1.56]; p

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Outcomes of ICU Patients With a Discharge Diagnosis of Critical Illness Polyneuromyopathy: A Propensity-Matched Analysis.

Objectives: To assess the impact of a discharge diagnosis of critical illness polyneuromyopathy on health-related outcomes in a large cohort of patients requiring ICU admission. Design: Retrospective cohort with propensity score-matched analysis. Setting: Analysis of a large multihospital database. Patients: Adult ICU patients without preexisting neuromuscular abnormalities and a discharge diagnosis of critical illness polyneuropathy and/or myopathy along with adult ICU propensity-matched control patients. Interventions: None. Measurements and Main Results: Of 3,567 ICU patients with a discharge diagnosis of critical illness polyneuropathy and/or myopathy, we matched 3,436 of these patients to 3,436 ICU patients who did not have a discharge diagnosis of critical illness polyneuropathy and/or myopathy. After propensity matching and adjusting for unbalanced covariates, we used conditional logistic regression and a repeated measures model to compare patient outcomes. Compared to patients without a discharge diagnosis of critical illness polyneuropathy and/or myopathy, patients with a discharge diagnosis of critical illness polyneuropathy and/or myopathy had fewer 28-day hospital-free days (6 [0.1] vs 7.4 [0.1] d; p

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Modification of Tracheal Cuff Shape and Continuous Cuff Pressure Control to Prevent Microaspiration in an Ex Vivo Pig Tracheal Two-Lung Model.

Objectives: Microaspiration of subglottic secretions plays a pivotal role in ventilator-associated pneumonia. Impact of endotracheal tube cuff material and shape on tracheal sealing performance remains debated. The primary objective was to compare the tracheal sealing performance of polyvinyl chloride tapered, cylindrical and spherical cuffs. Secondary objectives were to determine the impact of continuous cuff pressure control on sealing performance and pressure variability. Design: Prospective randomized ex vivo animal study. Setting: French research laboratory. Subjects: Seventy-two ex vivo pig tracheal two-lung blocks. Interventions: Blocks were randomly intubated with cylindrical (n = 26), tapered (n = 24), or spherical (n = 22) polyvinyl chloride endotracheal tube cuffs. Two milliliter of methylene blue were instilled above the cuff to quantify microaspirations, and lungs were ventilated for 2 hours. Continuous cuff pressure control was implemented in 33 blocks. Measurements and Main Results: Cuff pressures were continuously recorded, and after 2 hours, a microaspiration score was calculated. Tapered cuffs improved cuff sealing performance compared with spherical cuffs with or without continuous cuff pressure control. Compared with spherical cuffs, tapered cuffs reduced the microaspiration score without and with continuous pressure control by 65% and 72%, respectively. Continuous cuff pressure control did not impact sealing performance. Tapered cuffs generated higher cuff pressures and increased the time spent with overinflation compared with spherical cuffs (median [interquartile range], 77.9% [0-99.8] vs. 0% [0-0.5]; p = 0.03). Continuous cuff pressure control reduced the variability of tapered and spherical cuffs likewise the time spent with overinflation of tapered and cylindrical cuffs. Conclusions: Polyvinyl chloride tapered cuffs sealing enhanced performance at the cost of an increase in cuff pressure and in time spent with overinflation. Continuous cuff pressure control reduced the variability and normalized cuff pressures without impacting sealing performance. Copyright (C) by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Burnout and Psychological Distress Among Pediatric Critical Care Physicians in the United States.

Objectives: To estimate the prevalence of physician burnout, psychological distress, and its association with selected personal and practice characteristics among pediatric critical care physicians and to evaluate the relationship between burnout and psychological distress. Design: Cross-sectional, online survey. Setting: Pediatric critical care practices in the United States. Subjects: Pediatric critical care physicians. Interventions: None. Measurement and Main Results: A nonrandom sample of 253 physicians completed an online survey consisting of personal and practice characteristics, the Maslach Burnout Inventory, and the General Health Questionnaire. Nearly half of the participants (49%; 95% CI, 43-55%; n = 124) scored high burnout in at least one of the three subscales of the Maslach Burnout Inventory and 21% reported severe burnout. The risk of any burnout was about two times more in women physicians (odds ratio, 1.97; 95% CI, 1.2-3.4). Association between other personal or practice characteristics and burnout was not evident in this study, while regular physical exercise appeared to be protective. One third of all participants (30.5%) and 69% of those who experienced severe burnout screened positive for psychological distress. About 90% of the physicians reporting severe burnout have considered leaving their practice. Conclusions: Burnout is high among pediatric critical care physicians in the United States. About two thirds of the physicians with severe burnout met the screening criteria for psychological distress that suggests possible common mental disorders. Significant percentages of physicians experiencing burnout and considering to leave the profession has major implications for the critical care workforce. Copyright (C) by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Racial Differences in Palliative Care Use After Stroke in Majority-White, Minority-Serving, and Racially Integrated U.S. Hospitals.

Objectives: Racial/ethnic differences in palliative care resource use after stroke have been recognized, but it is unclear whether patient or hospital characteristics drive this disparity. We sought to determine whether palliative care use after intracerebral hemorrhage and ischemic stroke differs between hospitals serving varying proportions of minority patients. Design: Population-based cross-sectional study. Setting: Inpatient hospital admissions from the Nationwide Inpatient Sample between 2007 and 2011. Patients: A total of 46,735 intracerebral hemorrhage and 331,521 ischemic stroke cases. Interventions: Palliative care use. Measurements and Main Results: Intracerebral hemorrhage and ischemic stroke admissions were identified from the Nationwide Inpatient Sample between 2007 and 2011. Hospitals were categorized based on the percentage of ethnic minority stroke patients ( 50% minorities ["minority hospitals"]). Logistic regression was used to evaluate the association between race/ethnicity and palliative care use within and between the different hospital strata. Stroke patients receiving care in minority hospitals had lower odds of palliative care compared with those treated in white hospitals, regardless of individual patient race/ethnicity (adjusted odds ratio, 0.65; 95% CI, 0.50-0.84 for intracerebral hemorrhage and odds ratio, 0.62; 95% CI, 0.50-0.77 for ischemic stroke). Ethnic minorities had a lower likelihood of receiving palliative care compared with whites in any hospital stratum, but the odds of palliative care for both white and minority intracerebral hemorrhage patients was lower in minority compared with white hospitals (odds ratio, 0.66; 95% CI, 0.50-0.87 for white and odds ratio, 0.64; 95% CI, 0.46-0.88 for minority patients). Similar results were observed in ischemic stroke. Conclusions: The odds of receiving palliative care for both white and minority stroke patients is lower in minority compared with white hospitals, suggesting system-level factors as a major contributor to explain race disparities in palliative care use after stroke. Copyright (C) by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Respiratory Viruses in Invasively Ventilated Critically Ill Patients-A Prospective Multicenter Observational Study.

Objectives: The presence of respiratory viruses and the association with outcomes were assessed in invasively ventilated ICU patients, stratified by admission diagnosis. Design: Prospective observational study. Setting: Five ICUs in the Netherlands. Patients: Between September 1, 2013, and April 30, 2014, 1,407 acutely admitted and invasively ventilated patients were included. Interventions: None. Measurements and Main Results: Nasopharyngeal swabs and tracheobronchial aspirates were collected upon intubation and tested for 14 respiratory viruses. Out of 1,407 patients, 156 were admitted because of a severe acute respiratory infection and 1,251 for other reasons (non-severe acute respiratory infection). Respiratory viruses were detected in 28.8% of severe acute respiratory infection patients and 17.0% in non-severe acute respiratory infection (p

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Mortality Benefit of Recombinant Human Interleukin-1 Receptor Antagonist for Sepsis Varies by Initial Interleukin-1 Receptor Antagonist Plasma Concentration.

Objective: Plasma interleukin-1 beta may influence sepsis mortality, yet recombinant human interleukin-1 receptor antagonist did not reduce mortality in randomized trials. We tested for heterogeneity in the treatment effect of recombinant human interleukin-1 receptor antagonist by baseline plasma interleukin-1 beta or interleukin-1 receptor antagonist concentration. Design: Retrospective subgroup analysis of randomized controlled trial. Setting: Multicenter North American and European clinical trial. Patients: Five hundred twenty-nine subjects with sepsis and hypotension or hypoperfusion, representing 59% of the original trial population. Interventions: Random assignment of placebo or recombinant human interleukin-1 receptor antagonist x 72 hours. Measurements and Main Results: We measured prerandomization plasma interleukin-1 beta and interleukin-1 receptor antagonist and tested for statistical interaction between recombinant human interleukin-1 receptor antagonist treatment and baseline plasma interleukin-1 receptor antagonist or interleukin-1 beta concentration on 28-day mortality. There was significant heterogeneity in the effect of recombinant human interleukin-1 receptor antagonist treatment by plasma interleukin-1 receptor antagonist concentration whether plasma interleukin-1 receptor antagonist was divided into deciles (interaction p = 0.046) or dichotomized (interaction p = 0.028). Interaction remained present across different predicted mortality levels. Among subjects with baseline plasma interleukin-1 receptor antagonist above 2,071 pg/mL (n = 283), recombinant human interleukin-1 receptor antagonist therapy reduced adjusted mortality from 45.4% to 34.3% (adjusted risk difference, -0.12; 95% CI, -0.23 to -0.01), p = 0.044. Mortality in subjects with plasma interleukin-1 receptor antagonist below 2,071 pg/mL was not reduced by recombinant human interleukin-1 receptor antagonist (adjusted risk difference, +0.07; 95% CI, -0.04 to +0.17), p = 0.230. Interaction between plasma interleukin-1 beta concentration and recombinant human interleukin-1 receptor antagonist treatment was not statistically significant. Conclusions: We report a heterogeneous effect of recombinant human interleukin-1 receptor antagonist on 28-day sepsis mortality that is potentially predictable by plasma interleukin-1 receptor antagonist in one trial. A precision clinical trial of recombinant human interleukin-1 receptor antagonist targeted to septic patients with high plasma interleukin-1 receptor antagonist may be worthy of consideration. Copyright (C) by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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The [beta]-Blocker Esmolol Restores the Vascular Waterfall Phenomenon After Acute Endotoxemia.

Background: A vascular waterfall occurs when the critical closing pressure is greater than the mean systemic filling pressure. Because the waterfall phenomenon likely exists in the microcirculation, [beta]1-receptor blockers such as esmolol could have some effect on microcirculation and vascular waterfall. Objectives: To determine whether a vascular waterfall exists during septic shock and to assess the effects of vasopressors and [beta]-blockers on vascular waterfall. Design: Sixteen mongrel dogs were mounted with ultrasonic flow probes to measure renal blood flow. The hemodynamic variables of 16 animals were measured at baseline, after induction of acute endotoxemia; then, they underwent volume expansion, and norepinephrine was used to achieve baseline. After achieving septic myocardial depression, the animals were randomly divided into two groups (esmolol vs control groups) after reaching septic myocardial depression. Measurements and Main Results: There was a pressure gap of 41.9 +/- 13.9 mm Hg between the arterial critical closing pressure and the mean systemic filling pressure, indicating that a vascular waterfall was present under baseline conditions. Endotoxemia caused a decrease in cardiac output, mean arterial pressure, and critical closing pressure. Endotoxemia also caused the vascular waterfall to disappear. Neither volume expansion nor norepinephrine had any effect on the vascular waterfall. Esmolol infusion restored the vascular waterfall effect following endotoxemia and resuscitation. The 24-hour survival was 75% in the esmolol group versus 12.5% in controls (p = 0.041). Conclusions: Vascular pressure gradients in renal vasculature suggest the presence of a vascular waterfall at baseline. Although this phenomenon disappeared in endotoxemic dogs, it could be restored with [beta]-blocker therapy (esmolol). Copyright (C) by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Evaluation of Vasopressin for Septic Shock in Patients on Chronic Renin-Angiotensin-Aldosterone System Inhibitors.

Objectives: To compare the hemodynamic response in septic shock patients receiving vasopressin who were on chronic renin-angiotensin-aldosterone system inhibitor therapy with those who were not. Design: Single-center, retrospective cohort study. Setting: Medical and surgical ICUs at a 1,100-bed academic medical center. Patients: Medical and surgical ICU patients with septic shock who received vasopressin infusion added to at least one concomitant vasopressor agent between January 2014 and December 2015, then divided into two cohorts: 1) patients who were on chronic renin-angiotensin-aldosterone system inhibitor therapy as outpatients and 2) patients who were not on chronic renin-angiotensin-aldosterone system inhibitor therapy as outpatients. Interventions: None. Measurements and Main Results: Mean arterial pressure at 6 hours was 72.2 mm Hg in the renin-angiotensin-aldosterone system inhibitor group versus 69.7 mm Hg in the non-renin-angiotensin-aldosterone system inhibitor group (p = 0.298). There was no difference in mean arterial pressure at 1, 24, or 48 hours between groups. Total concomitant vasopressor requirements, based on norepinephrine equivalents excluding vasopressin, were significantly lower at 24 hours in the renin-angiotensin-aldosterone system inhibitor group versus the non-renin-angiotensin-aldosterone system inhibitor group (10.7 vs 18.1 [micro]g/min, respectively; p = 0.007), but no significant differences were seen at the other time points assessed. There were no significant differences in ICU or hospital length of stay or mortality. Conclusions: There was no significant difference in the primary outcome of 6-hour mean arterial pressure in septic shock patients receiving vasopressin who were on chronic renin-angiotensin-aldosterone system inhibitor therapy versus those receiving vasopressin who were not on chronic renin-angiotensin-aldosterone system inhibitor therapy. Renin-angiotensin-aldosterone system inhibitor patients had lower total concomitant vasopressor requirements at 24 hours compared with non-renin-angiotensin-aldosterone system inhibitor patients. Copyright (C) by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Relationship of at Admission Lactate, Unmeasured Anions, and Chloride to the Outcome of Critically Ill Patients.

Objectives: To investigate the association between the concentration of the causative anions responsible for the main types of metabolic acidosis and the outcome. Design: Prospective observational study. Setting: Teaching ICU. Patients: All patients admitted from January 2006 to December 2014. Interventions: None. Measurements and Main Results: Four thousand nine hundred one patients were admitted throughout the study period; 1,609 met criteria for metabolic acidosis and 145 had normal acid-base values. The association between at admission lactate, unmeasured anions, and chloride concentration with outcome was assessed by multivariate analysis in the whole cohort and in patients with metabolic acidosis. We also compared the mortality of patients with lactic, unmeasured anions, and hyperchloremic metabolic acidosis with that of patients without acid-base disorders. In the whole population, increased lactate and unmeasured anions were independently associated with increased mortality, even after adjusting for potential confounders (odds ratio [95% CI], 1.14 (1.08-1.20); p

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Pediatric Sepsis Endotypes Among Adults With Sepsis.

Objectives: Recent transcriptomic studies describe two subgroups of adults with sepsis differentiated by a sepsis response signature. The implied biology and related clinical associations are comparable with recently reported pediatric sepsis endotypes, labeled "A" and "B." We classified adults with sepsis using the pediatric endotyping strategy and the sepsis response signature and determined how endotype assignment, sepsis response signature membership, and age interact with respect to mortality. Design: Retrospective analysis of publically available transcriptomic data representing critically ill adults with sepsis from which the sepsis response signature groups were derived and validated. Setting: Multiple ICUs. Patients: Adults with sepsis. Interventions: None. Measurements and Main Results: Transcriptomic data were conormalized into a single dataset yielding 549 unique cases with sepsis response signature assignments. Each subject was assigned to endotype A or B using the expression data for the 100 endotyping genes. There were 163 subjects (30%) assigned to endotype A and 386 to endotype B. There was a weak, positive correlation between endotype assignment and sepsis response signature membership. Mortality rates were similar between patients assigned endotype A and those assigned endotype B. A multivariable logistic regression model fit to endotype assignment, sepsis response signature membership, age, and the respective two-way interactions revealed that endotype A, sepsis response signature 1 membership, older age, and the interactions between them were associated with mortality. Subjects coassigned to endotype A, and sepsis response signature 1 had the highest mortality. Conclusions: Combining the pediatric endotyping strategy with sepsis response signature membership might provide complementary, age-dependent, biological, and prognostic information. Copyright (C) by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Standardized Method for High-throughput Sterilization of Arabidopsis Seeds

The objective of this study was to determine the effects of bleach and chlorine gas sterilization on seed germination of a range of Arabidopsis genotypes grown on sterile media. Optimized sterilization protocols have been developed to prevent the growth of microbial contaminants while providing satisfactory seed survival.

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Analysis of molecular subtypes for the increased HER2 equivocal cases caused by application of the updated 2013 ASCO/CAP HER2 testing guidelines in breast cancer

Abstract

Purpose

Accurate testing of the status of human epidermal growth factor receptor type 2 (HER2) is a prerequisite for HER2-directed therapy. The American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) published joint guideline recommendations for HER2 testing in breast cancer in 2007 and it was updated in 2013. We compared the HER2 gene amplification status based on these two guidelines and analyzed the molecular characteristics of the equivocal cases.

Patients and methods

A total of 1894 patient samples were analyzed for both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). HER2 FISH amplification was examined and re-assessed using 2013 guidelines.

Results

According to the 2013 ASCO/CAP recommendations, 763 (40.3%) cases were classified as HER2 positive compared with 729 (38.5%) cases defined by 2007 guidelines. There was a significant increase of 6.1% in the proportion of HER2 FISH equivocal cases that were interpreted using ASCO/CAP 2013 (7.3%) compared with 2007 (1.2%) guidelines (P < 0.001). Of 138 FISH equivocal cases defined by 2013 guidelines, 125 cases were IHC2+ and 13 cases were IHC1+. These 125 cases included 4 double equivocal cases which were defined as equivocal by both 2007 and 2013 guidelines and 121 cases whose status was changed from negative defined by 2007 guidelines to equivocal defined by 2013 guidelines. Compared with luminal A type and luminal B type respectively, these 121 equivocal cases demonstrated no significant difference with luminal B type in T stage and N stage (P = 0.192, P = 0.421). When we divided the luminal B type into two parts that included HER2 negative cases and HER2 positive cases, the equivocal cases also showed no significant difference with these two subtypes in T stage and N stage.

Conclusions

Our study suggested that implementation of the revised ASCO/CAP 2013 guidelines resulted in an increase of 1.7% in overall HER2 positivity rate and of 6.1% in equivocal cases. Pathological analysis revealed that these equivocal cases exhibit similar biological behavior with luminal B type tumors. Clinical utility data on targeted therapy in equivocal patients should be further investigated.

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Hereditary diffuse gastric cancer and lynch syndromes in a BRCA1/2 negative breast cancer patient

Abstract

Introduction

Genetic counseling and testing is recommended for women with a personal and/or family history of breast and other cancers (ovarian, pancreatic, male breast and others). Mutations in the BRCA1 and BRCA2 genes (BRCA1/2) are the most common causes of hereditary breast and ovarian cancer. Additional genetic counseling and testing with a multi-gene panel may be considered in breast cancer patients who tested negative for mutations in these two genes. In about 11% of BRCA1/2-negative patients, further genetic testing reveals pathogenic mutations in other high or moderate cancer risk genes. In 0.2% of cases, an individual may carry pathogenic mutations in more than one high penetrance gene (a double heterozygote). Finding one or more pathogenic mutations is important for cancer prevention in patients and/or their families.

Case presentation

Here we present a case of a breast cancer patient who did not have a pathogenic mutation in BRCA1/2 and had a family history of breast and stomach cancers. On an additional multi-gene panel testing, she was found to carry pathogenic mutations in the CDH1 and PMS2 genes, which cause Hereditary Diffuse Gastric Cancer and Lynch syndromes, respectively. To our knowledge, this is the first description of such a double heterozygote.

Discussion

Clinical manifestations, genetics, and management of both syndromes are reviewed, including prophylactic surgery and screening for unaffected family members. Management challenges for a mutation carrier with advanced breast cancer are discussed. Our case supports the clinical utility of additional multi-gene panel testing for breast cancer patients who do not have a pathogenic mutation in BRCA1/2 genes.

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Erratum to: Peroxisome proliferator-activated receptor gamma activates fas ligand gene promoter inducing apoptosis in human breast cancer cells

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A small-molecule inhibitor of SMAD3 attenuates resistance to anti-HER2 drugs in HER2-positive breast cancer cells

Abstract

Purpose

Resistance against anti-HER2 drugs in HER2-positive breast cancer is a major obstacle to the improving prognosis. Transforming growth factor β (TGFβ) is a cytokine involved in the acquisition of more malignant phenotypes through epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties. The aim of this study was to investigate the effects of TGFβ and its downstream SMAD pathway on resistance to anti-HER2 drugs.

Methods

HER2-positive breast cancer cell lines were stimulated with TGFβ for 14 days. Then, the sensitivity to trastuzumab and lapatinib and the expression levels of various EMT and CSC markers were examined. The correlation of nuclear SMAD3 expression in untreated breast tumor tissues with trastuzumab efficacy in neoadjuvant settings was examined. The effect of a small-molecule inhibitor of SMAD3 (SIS3) on resistance to anti-HER2 drugs was explored.

Results

We found that continuous activation of the TGFβ-SMAD3 pathway induced resistance to anti-HER2 drugs and CSC traits in HER2-positive breast cancer cells. The induction of drug resistance by TGFβ required strong activation of SMAD3. In fact, activated SMAD3 regulated multiple genes that harbor SMAD-binding elements and are involved in trastuzumab resistance. Nuclear SMAD3 expression in tumor tissue was inversely correlated with sensitivity to neoadjuvant treatment with trastuzumab. SIS3 not only prevented the acquisition of resistance to anti-HER2 drugs but also restored trastuzumab sensitivity in trastuzumab-resistant cells.

Conclusions

This study indicates that the TGFβ-SMAD3 pathway plays an important role in the induction and maintenance of resistance to anti-HER2 drugs. Thus, SMAD3 is a potential therapeutic target that can inhibit resistance and restore sensitivity to anti-HER2 drugs.

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Breast cancer neoplastic seeding in the setting of image-guided needle biopsies of the breast

Abstract

Purpose

To identify clinicopathologic, technical, and imaging features associated with neoplastic seeding (NS) following image-guided needle breast biopsy.

Methods

We performed an institutional review board-approved retrospective review of patients presenting with a new diagnosis of breast cancer or suspicious breast findings requiring biopsy with subsequent diagnosis of NS. The time from biopsy to NS diagnosis was calculated. Histology, grade, estrogen receptor (ER) status, progesterone receptor (PR) status, HER2 status, T category, and N category were recorded. Biopsy guidance method, needle gauge, and number of passes were reviewed in addition to the mammographic and sonographic features of the primary tumors and the NS.

Results

Eight cases of NS were identified in 4010 patients. The mean time from biopsy to NS diagnosis was 60.8 days. The most frequent histology was invasive ductal carcinoma (7/8). Six cases were grade 3 (75.0%). Five primary breast cancers were ER, PR, and HER2 negative (62.5%). Seven patients underwent biopsy with ultrasound guidance. Multiple-insertion, non-coaxial ultrasound-guided core-needle biopsy was done in 6 cases. Mammographic presentation of NS was focal asymmetry (3/7 cases), mass (1/7), calcifications only (1/7), or occult (2/7). Sonographic presentation of NS was most often a mass (7/8) with irregular shape (5/7) and without circumscribed margins (6/7) and was occult in 1 case (1/8). NS distribution was subdermal and intradermal.

Conclusion

High-grade, triple-negative breast cancers and multiple-insertion, non-coaxial biopsies may be risk factors for NS. NS should be suspected on the basis of the superficial and linear pattern of disease progression in these patients.

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Fatty liver decreases the risk of liver metastasis in patients with breast cancer: a two-center cohort study

Abstract

Background

The influence of hepatic steatosis (HS) on liver metastasis in patients with non-metastatic breast cancer (BC) remains unclear. The aim of this study was to clarify the relationship between HS and liver metastasis in non-metastatic BC patients.

Methods

Patients who underwent treatment for BC at two affiliated hospitals of Southern Medical University, between January 1, 2005 and December 31, 2015, were retrospectively reviewed. BC patients were divided into the study and control groups based on the presence of HS. The association between HS and liver metastasis was analyzed, adjusting for the confounding factors using Cox regression and propensity score case-match analysis.

Results

In total, 1230 female BC patients were included, and 372 (30.2%) patients were diagnosed with HS (at the time of diagnosis BC or before). The cumulative liver metastasis-free survival (MFS) rate was significantly higher in the study group than in the control group (hazard ratio 0.61; 95% confidence interval 0.40–0.94; P = 0.024). On multivariate analysis, HS was an independent protective factor for local liver metastasis (HR 0.55; 0.35–0.86; P = 0.008). After one-to-one matching of the study group (344) with the control group (344), liver MFS remained significantly better in the study group (HR 0.42; 0.26–0.69; P = 0.001).

Conclusion

This study indicated that HS may serve as an independent factor to decrease liver metastasis in patients with BC. Additional prospective studies are necessary to validate this finding.

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Pharmaceutically treated anxiety but not depression prior to cancer diagnosis predicts the onset of cardiovascular disease among breast cancer survivors

Abstract

Purpose

To examine the associations between pharmaceutically treated anxiety and depression present in the year prior to breast cancer diagnosis and the risk of incident cardiovascular disease (CVD), while controlling for traditional cardiovascular risk factors and clinical characteristics in a population-based observational study.

Methods

Adult 1-year breast cancer survivors (n = 7227), diagnosed between 01-01-1999 and 12-31-2010, with no history of CVD, were selected from the Netherlands Cancer Registry. Drug dispensing data were derived from the PHARMO Database Network and used as proxy for CVD, anxiety, and depression. By multivariable Cox regression analysis, we examined the risk associated with pharmaceutically treated anxiety and depression for developing CVD after cancer diagnosis, adjusting for age, pharmaceutically treated hypertension, hypercholesterolemia, and diabetes mellitus in the year prior to cancer diagnosis, tumor stage, and cancer treatment.

Results

During the 13-year follow-up period, 193 (3%) breast cancer survivors developed CVD. Women pharmaceutically treated for anxiety in the year prior to their cancer diagnosis had a 48% increased hazard for CVD [HR = 1.48; 95% CI 1.05–1.08] after full adjustment. This association was restricted to breast cancer survivors who were 65 years or younger. Depression was not associated with CVD risk [HR = 0.89; 95% CI 0.52–1.53]. Older age [HR = 1.06; 95% CI 1.05–1.08], hypertension [HR = 1.80; 95% CI 1.32–2.46], and hypercholesterolemia [HR = 1.63; 95% CI 1.15–2.33] were associated with an increased hazard for incident CVD, whereas hormone therapy [HR = 0.59; 95% CI 0.42–0.83] was protective.

Conclusions

Anxiety present in the year prior to breast cancer diagnosis increases the risk of incident CVD in 1-year breast cancer survivors, after adjustment for depression, traditional cardiovascular risk factors, and clinical characteristics.

http://ift.tt/2gN0Qj2