Therapeutic reduction of cell-mediated immunosuppression in mycosis fungoides and Sézary syndrome

Abstract

Tumor progression is associated with progressive immunosuppression mediated in part by T regulatory cell(s) (Treg) and/or myeloid-derived suppressor cell(s) (MDSC). Development of strategies to reduce populations of immune cells with suppressive function in cancer patients may enable the induction or recovery of immunity against tumor cells, which may limit or reverse disease progression. With a goal of developing Treg and MDSC neutralizing strategies to treat mycosis fungoides (MF) and Sézary syndrome (SzS), we determined the association between disease stage and suppressor cell populations in patients with MF/SzS, including those responding to therapy. We found elevations in Treg populations, across Treg subtypes, in patients with SzS, and these Treg markedly suppressed proliferation of autologous CD4⁺CD25⁻ responder T cells. Interestingly, while MDSC numbers were not increased in MF/SzS patients, MDSC from patients with stage IB and above produced significantly more reactive oxygen species than those from stage IA MF patients and control cohorts. Therapy with the CD25-targeting agent denileukin diftitox or IFN-α2b was associated with a reduction in Treg numbers or MDSC function, respectively. These studies identify potential mechanisms of action for these therapies and support the development of coordinated strategies targeting both Treg and MDSC activities in patients with MF/SzS.

http://ift.tt/2jHWv16

Interactive effects of seizure frequency and lateralization on intratemporal effective connectivity in temporal lobe epilepsy

Summary

Objective

Patients with temporal lobe epilepsy (TLE) show brain connectivity changes in association with cognitive impairment. Seizure frequency and lateralization are 2 important clinical factors that characterize epileptic seizures. In this study, we sought to examine an interactive effect of the 2 seizure factors on intratemporal effective connectivity based on resting-state functional magnetic resonance imaging (rsfMRI) in patients with TLE.

Methods

For rsfMRI data acquired from 48 TLE patients and 45 healthy controls, we applied stochastic dynamical causal modeling to infer effective connectivity between 3 medial temporal lobe (MTL) regions, including the hippocampus (Hipp), parahippocampal gyrus (PHG), and amygdala (Amyg), ipsilateral to the seizure focus. We searched for the effect of the 2 seizure factors, seizure frequency (good vs poor seizure control) and lateralization (left vs right TLE), on connection strengths and their relationship with the level of verbal memory and language impairment.

Results

Impairment of verbal memory and language function was mainly affected by seizure lateralization, consistent with preferential involvement of the left MTL in verbal mnemonic processing. For the fully connected model, which was selected as the effective connectivity structure that best explained the observed rsfMRI time series, alterations in connection strengths were primarily influenced by seizure frequency; there was an increase in the strength of the Hipp to PHG connection in TLE patients with poor seizure control, whereas the strength of the Amyg to PHG connection increased in those with good seizure control. Furthermore, the association between connection strength alterations and cognitive impairment was interactively affected by both seizure frequency and lateralization.

Significance

These findings suggest an interactive effect as well as an individual effect of seizure frequency and lateralization on neuroimaging features and cognitive function. This potential interaction needs to be evaluated in the consideration of multiple seizure factors.

http://ift.tt/2jK0Y3r

Efficacy of One-Year Treatment with Aflibercept for Diabetic Macular Edema with Practical Protocol

The purpose of this study was to determine the efficacy of one-year treatment of diabetic macular edema (DME) with intravitreal aflibercept (IVA) injections on a practical protocol. The medical records of 51 eyes of 43 patients who were diagnosed with DME and had received IVA treatments were reviewed. The best-corrected visual acuity (BCVA) and the central macular thickness (CMT) were measured at the baseline and at 1, 3, 6, and 12 months after the IVA. The mean number of IVA injections was . The mean BCVA was significantly better and the CMT was thinner after the IVA at all follow-up times (). The BCVA was better in eyes with a serous retinal detachment (SRD) than without a SRD (). There was a significant correlation between the photoreceptor outer segment (PROS) length and BCVA at the baseline and at 12 months after the IVA (). A fewer number of IVA injections significantly improved the BCVA and the CMT in eyes with DME after one-year treatment. IVA was more effective in the SRD+ group than in the SRD− group. The PROS length may be a predictive marker for visual outcomes after one-year treatment with IVA for DME (IRB#2272).

http://ift.tt/2nrYsny

A 3D Self-Shaping Strategy for Nanoresolution Multicomponent Architectures

Abstract

3D printing or fabrication pursues the essential surface behavior manipulation of droplets or a liquid for rapidly and precisely constructing 3D multimaterial architectures. Further development of 3D fabrication desires a self-shaping strategy that can heterogeneously integrate functional materials with disparate electrical or optical properties. Here, a 3D liquid self-shaping strategy is reported for rapidly patterning materials over a series of compositions and accurately achieving micro- and nanoscale structures. The predesigned template selectively pins the droplet, and the surface energy minimization drives the self-shaping processing. The as-prepared 3D circuits assembled by silver nanoparticles carry a current of 208–448 µA at 0.01 V impressed voltage, while the 3D architectures achieved by two different quantum dots show noninterfering optical properties with feature resolution below 3 µm. This strategy can facilely fabricate micro-nanogeometric patterns without a modeling program, which will be of great significance for the development of 3D functional devices.

A 3D self-shaping strategy is proposed for rapidly patterning different materials and accurately achieving micro- and nanoscale structures. Micro-nanogeometric patterns can be achieved without a modeling program, which will be of great significance for the development of 3D devices.

http://ift.tt/2jcsebf

Thermally Induced Bending of ReS2 Nanowalls

Abstract

Among the variety of stimuli-responsive materials, temperature-responsive materials (TRMs) can adapt to the surrounding environment in the presence of a thermal stimulus, and they have attracted considerable attention in sensors, actuators, and surface engineering. However, polymers, as the most representative TRMs, are far from ideal with respect to long-term reliability and durability. Here, for the first time, an inorganic material, ReS₂, is analyzed, which possesses an unexpected temperature-responsive behavior that is triggered by stable and reversible thermally induced bending (TIB). Due to thermal fluctuations in the ReS₂ layers, intrinsic ripples tend to aggravate rapidly with rising temperature. Then, the weak interlayer interaction of ReS₂ is further weakened, thus resulting in interlayer sliding. Due to a decrease in bending rigidity with increasing temperature, out-of-plane bending spontaneously occurs in the ReS₂ layers. Interestingly, this TIB of ReS₂ can recover to its initial configuration when the temperature drops, which is further confirmed by the reversible wetting measurement. Above all, the TIB behavior of ReS₂ exhibits great potential in smart applications, such as smart windows and microfluidic devices, and fills the significant gaps of inorganic TRMs.

An inorganic material, ReS₂, is demonstrated, which unexpectedly possesses temperature-responsive behavior that is implemented by stable and reversible thermally induced bending (TIB). Triggered by thermal fluctuations, the TIB process relies on ripple evolution, interlayer sliding, and out-of-plane bending. The TIB of ReS₂ recovers to the original configuration when the temperature decreases, which is further confirmed by reversible wetting measurements.

http://ift.tt/2BvqW1W

Polar Elastomers as Novel Materials for Electromechanical Actuator Applications

Abstract

Dielectric elastomer actuators are stretchable capacitors capable of a musclelike actuation when charged. They will one day be used to replace malfunctioning muscles supposing the driving voltage can be reduced below 24 V. This focus here is on polar dielectric elastomers and their behavior under an electric field. Emphasis is placed on all the features that are correlated with the molecular structure, its synthetic realization, and its impact on properties. Regarding the polymer class, the focus, to some degree, is on polysiloxanes because of their attractively low glass transition temperatures. This enables introduction of highly polar groups to the backbone while maintaining soft elastic properties. The goal is to provide a few guidelines for future research in this emerging field that may be useful for those considering entering this fascinating endeavor. Because of the large number of materials available, a few restrictions in the selection have to be applied.

The development of stimuli responsive materials that provide forces and shape changes comparable to natural muscles has been the dream of many scientists. This dream will become reality one day due to the progress in dielectric elastomer actuators technology.

http://ift.tt/2jaTWVO

Advanced Biomass-Derived Electrocatalysts for the Oxygen Reduction Reaction

Abstract

Recent progress in advanced nanostructures synthesized from biomass resources for the oxygen reduction reaction (ORR) is reviewed. The ORR plays a significant role in the performance of numerous energy-conversion devices, including low-temperature hydrogen and alcohol fuel cells, microbial fuel cells, as well as metal–air batteries. The viability of such fuel cells is strongly related to the cost of the electrodes, especially the cathodic ORR electrocatalyst. Hence, inexpensive and abundant plant and animal biomass have become attractive options to obtain electrocatalysts upon conversion into active carbon. Bioresource selection and processing criteria are discussed in light of their influence on the physicochemical properties of the ORR nanostructures. The resulting electrocatalytic activity and durability are introduced and compared to those from conventional Pt/C-based electrocatalysts. These ORR catalysts are also active for oxygen or hydrogen evolution reactions.

Recent progress on biomass-derived electrocatalysts for the oxygen reduction reaction (ORR) is reviewed. The ORR plays a significant role in the performance of numerous energy-conversion devices, including low-temperature hydrogen and alcohol fuel cells and microbial fuel cells, as well as metal–air batteries. Those ORR catalysts are also active for oxygen or hydrogen evolution reactions for application in electrolyzers.

http://ift.tt/2noHuGv

Highly Stretchable and Reliable, Transparent and Conductive Entangled Graphene Mesh Networks

Abstract

A highly stretchable and reliable, transparent and conductive entangled graphene mesh network (EGMN) exhibits an interconnected percolation network, as usually shown in 1D nanowires, but with the electrical, mechanical, and thermal properties of 2D graphene. The unique combination of the 2D material properties and the network structure of wrinkled, waved, and crumpled graphene enables the EGMN to demonstrate excellent electrical reliability, mechanical durability, and thermal stability, even under harsh environmental and external conditions such as very high temperature, humidity, bending, and stretching. Specifically, after 100 000 cycles of bending with radius of 2 mm, the EGMN maintains its resistance similar to its initial value. The EGMN shows a steady monotonic response in resistance to strain cycles of 50 000 times with nearly constant gauge factors of 0.76, 1.67, and 2.55 at 10%, 40%, and 70% strains, respectively. Moreover, the EGMN shows very little change in resistance with the temperature increasing up to 1000 °C, by in situ thermal analysis with transmission electron microscopy and also by long-term stability testing at 70 °C and 70% relative humidity for 30 d. These results demonstrate that this novel entangled graphene mesh network can significantly broaden the application areas for various types of wearable and stretchable devices.

A highly stretchable and reliable, transparent and conductive entangled graphene mesh network (EGMN) exhibits an interconnected percolation network of 2D graphene. The unique combination of 2D material and structure in the EGMN enables excellent electrical reliability, mechanical durability, and environmental robustness. Therefore, the EGMN provides broad applicability to wearable and stretchable devices for challenging requirements such as high stretchability, temperature, and humidity.

http://ift.tt/2zKp2Kg

Structuring of Functional Spider Silk Wires, Coatings, and Sheets by Self-Assembly on Superhydrophobic Pillar Surfaces

Abstract

Spider silk has recently become a material of high interest for a large number of biomedical applications. Previous work on structuring of silk has resulted in particles (0D), fibers (1D), films (2D), and foams, gels, capsules, or microspheres (3D). However, the manufacturing process of these structures is complex and involves posttreatment of chemicals unsuitable for biological applications. In this work, the self-assembly of recombinant spider silk on micropatterned superhydrophobic surfaces is studied. For the first time, structuring of recombinant spider silk is achieved using superhydrophobic surfaces under conditions that retain the bioactivity of the functionalized silk. By tuning the superhydrophobic surface geometry and the silk solution handling parameters, this approach allows controlled generation of silk coatings, nanowires, and sheets. The underlying mechanisms and governing parameters are discussed. It is believed that the results of this work pave the way for fabrication of silk formations for applications including vehicles for drug delivery, optical sensing, antimicrobial coatings, and cell culture scaffolds.

Superhydrophobic surfaces are used to pattern bioactive silk under mild conditions, preserving its bioactivity. The interaction between the liquid:solid and the liquid:air interfaces supports spontaneous transformation of soluble silk proteins to defined silk structures. Using this approach, silk in the form of localized coatings, directional nanowires, and sheets is generated.

http://ift.tt/2jIfZTo

HER2/HER3-positive metastatic salivary duct carcinoma in the pleural effusion: A case report

Salivary duct carcinoma (SDC) is an aggressive form of salivary gland tumor, and SDC patients tend to be older men, more commonly in advanced stage with a poorer prognosis. Although the cytological characteristics of SDC on fine-needle aspiration cytology have been well-described at the primary site, they have not been explored in metastasis. Here we reported a case of HER2/HER3-positive metastatic SDC in the lung and pleural effusion. The patient was a man in his 50s who had undergone extended total parotidectomy in 2008. He was originally diagnosed as having HER2-positive left parotid SDC. Six years later a mass was discovered in the left lung by chest computed tomography (CT) and was diagnosed as metastatic SDC by both bronchial biopsy and cytology. Subsequently he had a recurrent SDC in the left pleural effusion and died of respiratory failure. Cytological findings from bronchial brushing smear showed small sheet clusters in a slightly necrotic background. In the pleural effusion cytology, tumor cells appeared as ball-like clusters of epithelioid cells with apocrine-like findings. In immunocytochemistry, HER3 of SDC cells in pleural effusion was significantly overexpressed relative to the matched primary tumor, even though HER2 amplification did not change. Cytological findings and HER family receptors differed between the primary and metastatic SDC. Therefore, molecular tests, such as protein expression and gene amplification using cytological specimens, may become important in future when determining therapy strategies in patients with distant metastasis.

http://ift.tt/2ihaECh

Clinical and economic impact of the introduction of a nucleic acid amplification assay for Clostridium difficile

The clinical outcomes and cost implications of a diagnostic shift from an EIA- to PCR-based assay for Clostridium difficile infection (CDI) have not been completely described in the literature.

http://ift.tt/2nqpf3D

Trends in incidence, mortality and survival of penile squamous cell carcinoma in Norway 1956-2015

Abstract

We examine trends in incidence, mortality and survival of penile squamous cell carcinoma (SCC) in Norway over 60 years. Data on all cases of penile cancer diagnosed in Norway during 1956-2015 was obtained from the Cancer Registry of Norway. Trends in age-standardised rates of penile SCC incidence, mortality and 5-year relative survival were assessed by the annual percentage change statistic and joinpoint regression. A total of 1596 penile cancer cases were diagnosed during 1956-2015, among which 1474 (92.4%) were SCC. During 2011-2015, the age-standardised incidence and mortality of penile SCC were 0.91 (95% confidence interval (CI): 0.78;1.05) and 0.50 (0.42;0.60) per 100,000, respectively, and the 5-year relative survival was 61.6% (41.9;76.4). The incidence of SCC increased during 1956-2015, with an average annual percentage change (AAPC) of 0.80% (0.46;1.15). The increase was strongest among men diagnosed at a relatively early age (age<=64 years; AAPC: 1.47% (0.90;2.05)). Mortality also increased over the study period (AAPC: 0.47% (0.10;0.85)), whereas 5-year relative survival did not change (AAPC: 0.08% (-0.19; 0.36)). We conclude that the incidence of penile SCC has increased at a moderate and constant rate during 1956-2015, and that the most consistent increase occurred among younger men. Mortality also increased during the study period. However, survival did not change, thus changes in diagnostics and treatment had little impact on survival from penile SCC. Since a substantial proportion of penile SCC is caused by human papillomavirus (HPV), the incidence increase may in part be attributed to increased exposure to HPV in the population. This article is protected by copyright. All rights reserved.

http://ift.tt/2AT7jEK

Sodium glucose cotransporter 2 inhibitor canagliflozin attenuates liver cancer cell growth and angiogenic activity by inhibiting glucose uptake

Abstract

Sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) comprise a new class of antidiabetic agents that inhibit glucose reabsorption in the renal proximal tubules. Although a recent report demonstrated the potential ability of SGLT2-Is to attenuate cancer growth of SGLT2-expressing cancer cells, little is known about the effects of SGLT2-Is on hepatocellular carcinoma (HCC). Here, we investigate the anti-cancer properties of a SGLT2-I, canagliflozin, against human liver cancer cells. SGTL2 mRNA and protein expression were detected in Huh7 and HepG2 cells, although not in HLE as well as primary human hepatocytes and hepatic stellate cells. Canagliflozin exerted antiproliferative effects on SGLT2-expressing Huh7 and HepG2 cells in a dose-dependent manner by inhibiting glycolytic metabolism including glucose uptake, lactate and intracellular ATP production. This agent also induced G2/M arrest and apoptosis with inhibited phosphorylation of ERK, p38 and AKT and cleavage of caspase3.

Xenograft tumor growth assay showed that oral administration of canagliflozin (10 mg/kg/day) significantly reduced subcutaneous tumor burdens in a glycemic status-independent manner, and attenuated intratumor vascularization in Huh7- and HepG2-derived xenograft tumors in BALB/c nude mice. In vitro, canagliflozin suppressed the increased human umbilical vein endothelial cell (HUVEC) proliferation and tubular formation which were observed in Huh7 or HepG2 co-cultures. By contrast, canagliflozin had no effect on tumor growth and intratumor angiogenesis in SGLT2-null HLE-derived xenograft models. These results indicate that SGLT2-I therapy is a potential new strategy for the treatment of HCC. This article is protected by copyright. All rights reserved.

http://ift.tt/2A1lSpL

Acne in late adolescence and risk of prostate cancer

Abstract

Accumulating evidence suggest that Propionibacterium acnes may play a role in prostate carcinogenesis, but data are so far limited and inconclusive. The aim of this population-based cohort study was therefore to test whether presence of acne vulgaris during late adolescence is associated with an increased risk of prostate cancer later in life.

We identified a large cohort of young men born in Sweden between 1952 and 1956, who underwent mandatory assessment for military conscription around the age of 18 (n= 243,187). Test information along with health data including medical diagnoses at time of conscription was available through the Swedish Military Conscription Register and the National Patient Register. The cohort was followed through linkages to the Swedish Cancer Register to identify the occurrence of prostate cancer until December 31^st 2009. We used Cox regression to calculate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between acne in adolescence and prostate cancer risk.

A total of 1,633 men were diagnosed with prostate cancer during a median follow-up of 36.7 years. A diagnosis of acne was associated with a statistically significant increased risk for prostate cancer (adjusted HR: 1.43 95%; CI: 1.06-1.92), particularly for advanced stage disease (HR: 2.37 95%; CI 1.19-4.73). A diagnosis of acne classified as severe conferred a 6-fold increased risk of prostate cancer (HR: 5.70 95% CI 1.42-22.85). Data from this large prospective population-based cohort add new evidence supporting a role of P acnes infection in prostate cancer. This article is protected by copyright. All rights reserved.

http://ift.tt/2ATejBc

Therapeutic reduction of cell-mediated immunosuppression in mycosis fungoides and Sézary syndrome

Abstract

Tumor progression is associated with progressive immunosuppression mediated in part by T regulatory cell(s) (Treg) and/or myeloid-derived suppressor cell(s) (MDSC). Development of strategies to reduce populations of immune cells with suppressive function in cancer patients may enable the induction or recovery of immunity against tumor cells, which may limit or reverse disease progression. With a goal of developing Treg and MDSC neutralizing strategies to treat mycosis fungoides (MF) and Sézary syndrome (SzS), we determined the association between disease stage and suppressor cell populations in patients with MF/SzS, including those responding to therapy. We found elevations in Treg populations, across Treg subtypes, in patients with SzS, and these Treg markedly suppressed proliferation of autologous CD4⁺CD25⁻ responder T cells. Interestingly, while MDSC numbers were not increased in MF/SzS patients, MDSC from patients with stage IB and above produced significantly more reactive oxygen species than those from stage IA MF patients and control cohorts. Therapy with the CD25-targeting agent denileukin diftitox or IFN-α2b was associated with a reduction in Treg numbers or MDSC function, respectively. These studies identify potential mechanisms of action for these therapies and support the development of coordinated strategies targeting both Treg and MDSC activities in patients with MF/SzS.

http://ift.tt/2jHWv16

Mental health care and suicide in pregnancy and postpartum [Letters]

http://ift.tt/2AHThW2

Validation and diagnostic accuracy of predictive curves for age-associated longitudinal cognitive decline in older adults [Research]

BACKGROUND:

The Mini-Mental State Examination continues to be used frequently to screen for cognitive impairment in older adults, but it remains unclear how to interpret changes in its score over time to distinguish age-associated cognitive decline from an early degenerative process. We aimed to generate cognitive charts for use in clinical practice for longitudinal evaluation of age-associated cognitive decline.

METHODS:

We used data from the Canadian Study of Health and Aging from 7569 participants aged 65 years or older who completed a Mini-Mental State Examination at baseline, and at 5 and 10 years later to develop a linear regression model for the Mini-Mental State Examination score as a function of age and education. Based on this model, we generated cognitive charts designed to optimize accuracy for distinguishing participants with dementia from healthy controls. We validated our model using a separate data set of 6501 participants from the National Alzheimer's Coordinating Center's Uniform Data Set.

RESULTS:

For baseline measurement, the cognitive charts had a sensitivity of 80% (95% confidence interval [CI] 75% to 84%) and a specificity of 89% (95% CI 88% to 90%) for distinguishing healthy controls from participants with dementia. Similar sensitivities and specificities were observed for a decline over time greater than 1 percentile zone from the first measurement. Results in the validation sample were comparable, albeit with lower sensitivities. Negative predictive value was 99%.

INTERPRETATION:

Our innovative model, which factors in age and education, showed validity and diagnostic accuracy for determining whether older patients show abnormal performance on serial Mini-Mental State Examination measurements. Similar to growth curves used in pediatrics, cognitive charts allow longitudinal cognitive evaluation and enable prompt initiation of investigation and treatment when appropriate.

http://ift.tt/2iNySaV

Charting age-associated cognitive decline [Commentary]

http://ift.tt/2AH9mLF

Diagnosis and treatment of obstructive sleep apnea in adults [Review]

http://ift.tt/2iLN2cM

Postsecondary campuses responding to record anxiety and depression levels [News]

http://ift.tt/2AH91sn

Congenitally transmitted Chagas disease in Canada: a family cluster [Practice]

http://ift.tt/2iLpPqV

Could changes in pharmacotherapy peripregnancy contribute to the shift in means of suicide? [Letters]

http://ift.tt/2AH8F51

Majocchi granuloma in a 58-year-old man with treatment-resistant annular scaling plaque [Practice]

http://ift.tt/2ALCFMQ

Quebec medical schools slow to adopt pass/fail system [News]

http://ift.tt/2iJE93r

Hearing between wor(l)ds: rhetorical space and disrupting narratives in medicine [Humanities]

http://ift.tt/2AHLSWH

Quebec grants health minister power to impose duties on doctors [News]

http://ift.tt/2iHArat

Issue Information

Cover of this issue. Vash2 contributes to gastric tumor growth. See also Suzuki et al. (pp. 2342-2351 of this issue).

http://ift.tt/2AJ1OI5

Reviewers

http://ift.tt/2AHhX0R

In This Issue

http://ift.tt/2iJDj6N

The Anti-inflammatory Effect of Personalized Omega-3 Fatty Acid Dosing for Reducing Prostaglandin E2 in the Colonic Mucosa Is Attenuated in Obesity

This clinical trial developed a personalized dosing model for reducing prostaglandin E₂ (PGE₂) in colonic mucosa using -3 fatty acid supplementation. The model utilized serum eicosapentaenoic acid (EPA, -3):arachidonic acid (AA, -6) ratios as biomarkers of colonic mucosal PGE₂ concentration. Normal human volunteers were given low and high -3 fatty acid test doses for 2 weeks. This established a slope and intercept of the line for dose versus serum EPA:AA ratio in each individual. The slope and intercept was utilized to calculate a personalized target dose that was given for 12 weeks. This target dose was calculated on the basis of a model, initially derived from lean rodents, showing a log-linear relationship between serum EPA:AA ratios and colonic mucosal PGE₂ reduction. Bayesian methods allowed addition of human data to the rodent model as the trial progressed. The dosing model aimed to achieve a serum EPA:AA ratio that is associated with a 50% reduction in colonic PGE₂. Mean colonic mucosal PGE₂ concentrations were 6.55 ng/mg protein (SD, 5.78) before any supplementation and 3.59 ng/mg protein (SD, 3.29) after 12 weeks of target dosing. In secondary analyses, the decreases in PGE₂ were significantly attenuated in overweight and obese participants. This occurred despite a higher target dose for the obese versus normal weight participants, as generated by the pharmacodynamic predictive model. Large decreases also were observed in 12-hydroxyicosatetraenoic acids, and PGE₃ increased substantially. Future biomarker-driven dosing models for cancer prevention therefore should consider energy balance as well as overall eicosanoid homeostasis in normal tissue. Cancer Prev Res; 10(12); 729–37. ©2017 AACR.

http://ift.tt/2BwsRmH

The Next Frontier: Head and Neck Cancer Immunoprevention

Restoring T cell–mediated antitumor immunity by targeting immune checkpoint inhibitors in head and neck squamous cell carcinoma (HNSCC) results in immunomodulation and durable remissions. However, the overall response rate to these immunotherapies in HNSCC is only approximately 20%. This raises the possibility that immunologic intervention earlier in the HNSCC continuum, such as in oral premalignant lesions (OPL) could elicit an increased therapeutic response. New experimental studies suggest that immune therapies can be used for HNSCC prevention rather than therapy. Given the current excitement for precision medicine, these findings support the future development of multimodality approaches for preventive immune oncology. Cancer Prev Res; 10(12); 681–3. ©2017 AACR.

See related article by Jin Wang, et al., p. 684

http://ift.tt/2jbf2TY

PD-1 Blockade Prevents the Development and Progression of Carcinogen-Induced Oral Premalignant Lesions

Oral squamous cell carcinoma (OSCC) is preceded by progressive oral premalignant lesions (OPL). Therefore, therapeutic strategies that prevent malignant progression of OPLs are expected to reduce the incidence of OSCC development. Immune checkpoint inhibitors that target the interaction of programmed death receptor 1 (PD-1) on T cells with the PD-1 ligand PD-L1 on cancer cells have been shown to extend the survival of patients with advanced OSCC. Here, we used the 4-nitroquinoline-1-oxide (4-NQO) mouse model of oral carcinogenesis to test the hypothesis that PD-1 blockade may control the progression of OPLs. Mice were exposed to 4-NQO in their drinking water and then randomly assigned to two treatment groups that received either a blocking antibody for PD-1 or a control IgG. We found that anti–PD-1 treatment significantly reduced the number of oral lesions that developed in these mice and prevented malignant progression. Low-grade dysplastic lesions responded to PD-1 blockade with a significant increase in the recruitment of CD8⁺ and CD4⁺ T cells and the accumulation of CTLA-4⁺ T cells in their microenvironment. Notably, PD-1 inhibition was accompanied by induction of IFN, STAT1 activation and the production of the T-cell effector granzyme B in infiltrating cells, and by the induction of apoptosis in the epithelial cells of the oral lesions, suggesting that T-cell activation mediates the immunopreventive effects of anti–PD-1. These results support the potential clinical benefit of PD-1 immune checkpoint blockade to prevent OSCC development and progression and suggest that CTLA-4 inhibitors may enhance the preventive effects of anti–PD-1. Cancer Prev Res; 10(12); 684–93. ©2017 AACR.

See related editorial by Gutkind et al., p. 681

http://ift.tt/2BvkfwQ

Risk Prediction of Cervical Cancer and Precancers by Type-Specific Human Papillomavirus: Evidence from a Population-Based Cohort Study in China

Risk stratification of human papillomavirus (HPV)-positive women is needed to avoid excessive colposcopy and overtreatment in cervical cancer screening. We aimed to evaluate the predictive value of type-specific HPV in detecting cervical cancer and precancers in a Chinese population–based cohort and provide evidence of HPV genotyping to triage HPV-positive women. We typed all Hybrid Capture 2–positive cytologic samples of 1,742 women in Shanxi Province Cervical Cancer Screening Study cohort. Cumulative risks of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) among HPV-positive women and cumulative detection rates of CIN2+ among general women by type-specific HPV were estimated during the course of 10-year follow-up. HPV 16 and HPV 52 were most prevalent types among the screening population. Ten-year cumulative risk of CIN2+ was 47.5% [95% confidence interval (CI), 31.6–62.3] for HPV 16–positive women and 46.3% (95% CI, 15.3–75.4) for HPV 31–positive women. Ten-year cumulative risks of CIN2+ among HPV 58, 39, 33, 18, and 52 positive women ranged from 34.3% to 12.0% in a decreasing order. CIN2+ risks were found to be positively associated with infection times of the same genotypes of HPV 16, 31, 33, and 58 (all P_trend < 0.001). Cumulative detection rates of CIN2+ within 10 years were predominantly contributed by HPV 16, 31, and 58. Our results support the risk-based management of HPV-positive women using HPV genotyping and also indicate the significance of including HPV 31 and 58 apart from commonly acknowledged HPV 16 and HPV 18 in achieving better risk stratification. Cancer Prev Res; 10(12); 745–51. ©2017 AACR.

http://ift.tt/2jbRrT2

Differential Gene Regulation and Tumor-Inhibitory Activities of Alpha-, Delta-, and Gamma-Tocopherols in Estrogen-Mediated Mammary Carcinogenesis

Despite experimental evidence elucidating the antitumor activities of tocopherols, clinical trials with α-tocopherol (α-T) have failed to demonstrate its beneficial effects in cancer prevention. This study compared the chemopreventive efficacy of individual tocopherols (α-, -, and -T) and a -T–rich tocopherol mixture (-TmT) in the August-Copenhagen Irish (ACI) rat model of estrogen-mediated mammary cancer. Female ACI rats receiving 17β-estradiol (E2) implants were administered with 0.2% α-T, -T, -T, or -TmT for 30 weeks. Although α-T had no significant effects on mammary tumor growth in ACI rats, -T, -T, and -TmT reduced mammary tumor volume by 51% (P < 0.05), 60% (P < 0.01), and 59% (P < 0.01), respectively. Immunohistochemical analysis revealed that -T, -T, and -TmT reduced levels of the cell proliferation marker, proliferating cell nuclear antigen, in the rat mammary tumors. To gain further insight into the biological functions of different forms of tocopherols, RNA-seq analysis of the tumors was performed. Treatment with -T induced robust gene expression changes in the mammary tumors of ACI rats. Ingenuity Pathway Analysis identified "Cancer" as a top disease pathway and "Tumor growth" and "Metastasis" as the top signaling pathways modulated by -T. Although the results need further functional validation, this study presents an unbiased attempt to understand the differences between biological activities of individual forms of tocopherols at the whole transcriptome level. In conclusion, -T and -T have superior cancer preventive properties compared to α-T in the prevention of estrogen-mediated mammary carcinogenesis. Cancer Prev Res; 10(12); 694–703. ©2017 AACR.

http://ift.tt/2BwAbi8

Voluntary Wheel Running Reduces the Acute Inflammatory Response to Liver Carcinogen in a Sex-specific Manner

Inflammation contributes to the development of cancer, yet acute inflammatory responses are also needed to eradicate tumorigenic cells and activate adaptive immune responses to combat cancer. Physical exercise has direct immunomodulatory effects, and in line with this, exercise has been demonstrated to inhibit tumor growth, including diethylnitrosamine-(DEN)-induced hepatocarcinoma. Having observed a sex-dependent development of DEN-induced hepatocarcinoma, we aimed to evaluate the effect of exercise and sex on the acute inflammatory response to DEN. Thus, we randomized male and female mice to cages with or without running wheels for 6 weeks, whereafter DEN was administered and the inflammatory response was evaluated for up to 96 hours. DEN administration caused marked acute inflammatory responses in female mice with weight loss, reduced food intake, release of liver enzymes, and increased systemic levels of IL6. Moreover, DEN caused increased hepatic expression of cytokines, immune cell markers, and components of the toll-like receptor signaling pathway. In male mice, DEN administration provoked similar physiologic effects with weight loss and reduced food intake, but less systemic and hepatic acute inflammation, which was associated with a higher baseline expression of the detoxifying enzyme glutathione S-transferase and lower expression of ERα in male mice. Voluntary wheel running attenuated systemic and hepatic inflammation, in particular in the female mice, and shifted the peak time of the inflammatory response. In conclusion, DEN elicited an acute inflammatory response in particular in female mice, and this response was attenuated by prior exercise. Cancer Prev Res; 10(12); 719–28. ©2017 AACR.

http://ift.tt/2jdhr0l

Association between Cigar or Pipe Smoking and Cancer Risk in Men: A Pooled Analysis of Five Cohort Studies

Introduction: Use of non-cigarette tobacco products such as cigars and pipe has been increasing, even though these products entail exposure to similar carcinogens to those in cigarettes. More research is needed to explore the risk of these products to guide cancer prevention efforts.

Methods: To measure the association between cigars and/or pipe smoking, and cancer incidence in men, we performed meta-analyses of data from five prospective cohorts. Cox regression was used to evaluate the association between different aspects of cigars and pipe smoking and risk of each smoking-related cancer (head and neck, esophagus, lung, stomach, liver, pancreas, kidney, and bladder) for each study. Adjusted HRs were combined using random-effects models.

Results: Cigars and/or pipe smokers were at increased risk for head and neck [HR, 1.51; 95% confidence interval (CI), 1.22–1.87], lung (HR, 2.04; 95% CI, 1.68–2.47), and liver cancers (HR, 1.56; 95% CI, 1.08–2.26). Ever-smokers of cigars and/or pipe had an increased risk of developing a smoking-related cancer when compared with never smokers of any tobacco product (overall HR, 1.07; 95% CI, 1.03–1.12). The risk for smoking-related cancers was also increased in mixed smokers who smoked cigars or pipe as well as cigarettes, even when they were smoking predominantly pipe or cigars.

Discussion: This pooled analysis highlights the increased risk for smoking-related cancers, particularly for lung and head and neck cancers in exclusive and predominant smokers (former and current) of cigars and pipe. Tobacco prevention efforts should include these products in addition to cigarettes. Cancer Prev Res; 10(12); 704–9. ©2017 AACR.

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IKZF1 Gene in Childhood B-cell Precursor Acute Lymphoblastic Leukemia: Interplay between Genetic Susceptibility and Somatic Abnormalities

SNPs in IKZF1 are associated with inherited susceptibility to B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Besides, somatic copy number abnormalities (CNA) in genes related to lymphopoiesis (e.g., IKZF1, CDKN2A/B, BTG1) impact patient's outcome. Therefore, this study aimed to investigate an association between germline susceptibility and CNAs in BCP-ALL. The IKZF1 SNPs (rs11978267 and rs4132601) were genotyped in 276 cases and 467 controls. Bone marrow samples were used to determine the presence of somatic abnormalities. The IKZF1 transcript levels were quantified and associated with the SNPs and CNAs. Categorical variables were compared by ² test. ORs were estimated with unconditional logistic regression with 95% confidence interval (CI). The variant allele of IKZF1 rs4132601 conferred increased risk of BCP-ALL (OR, 2.09; 95% CI, 1.16–3.74). Individuals with either rs11978267 or rs4132601 had an increased risk for harboring IKZF1 deletion (OR, 2.80; 95% CI, 1.25–6.23 and OR, 2.88; 95% CI, 1.24–6.69, respectively). Increased risks were observed for individuals harboring both IKZF1 and BTG1 deletions (OR, 4.90; 95% CI, 1.65–14.55, rs11978267 and OR, 5.80; 95% CI, 1.94–17.41, rs4132601). Germline genetic variation increases the risk for childhood ALL in general, but also acts as a susceptibility factor bound for risk of specific somatic alterations. These findings provide new insight into the development of childhood ALL regarding causal variants and the biological basis of the risk association, offering the opportunity for future tailored research. Cancer Prev Res; 10(12); 738–44. ©2017 AACR.

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A Randomized Controlled Trial of Green Tea Extract Supplementation and Mammographic Density in Postmenopausal Women at Increased Risk of Breast Cancer

Epidemiologic and animal studies suggest a protective role of green tea against breast cancer. However, the underlying mechanism is not understood. We conducted a randomized, double-blinded, placebo-controlled phase II clinical trial to investigate whether supplementation with green tea extract (GTE) modifies mammographic density (MD), as a potential mechanism, involving 1,075 healthy postmenopausal women. Women assigned to the treatment arm consumed daily 4 decaffeinated GTE capsules containing 1,315 mg total catechins, including 843 mg epigallocatechin-3-gallate (EGCG) for 12 months. A computer-assisted method (Madena) was used to assess MD in digital mammograms at baseline and month 12 time points in 932 completers (462 in GTE and 470 in placebo). GTE supplementation for 12 months did not significantly change percent MD (PMD) or absolute MD in all women. In younger women (50–55 years), GTE supplementation significantly reduced PMD by 4.40% as compared with the placebo with a 1.02% PMD increase from pre- to postintervention (P = 0.05), but had no effect in older women (P_interaction = 0.07). GTE supplementation did not induce MD change in other subgroups of women stratified by catechol-O-methyltransferase genotype or level of body mass index. In conclusion, 1-year supplementation with a high dose of EGCG did not have a significant effect on MD measures in all women, but reduced PMD in younger women, an age-dependent effect similar to those of tamoxifen. Further investigation of the potential chemopreventive effect of green tea intake on breast cancer risk in younger women is warranted. Cancer Prev Res; 10(12); 710–8. ©2017 AACR.

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Acknowledgment to Reviewers

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Severe multiple sclerosis reactivation during prolonged lymphopenia after dimethyl fumarate discontinuation

Background

Delayed-release dimethyl fumarate (DMF) treatment can be associated with reduced lymphocyte and leucocyte counts, which might persist after DMF discontinuation.

Case presentation

We report the case of a patient with severe disease reactivation despite prolonged lymphopenia after DMF discontinuation. We describe the frequency and impact of prolonged lymphopenia after DMF discontinuation at two tertiary MS centres. A 36-year-old female patient with multiple sclerosis was switched to DMF after 14 years of treatment with interferon beta-1a. DMF was suspended after 4 months because of persistent lymphopenia for 3 months. Six months later, the patient had a severe relapse with multiple enhancing brain lesions at MRI although lymphopenia was still persistent. Haematological assessment excluded other causes of lymphopenia, which was evaluated as a probable iatrogenic complication of DMF. The patient was treated with i.v. methylprednisolone 1 gr daily for 3 days with clinical recovery.

Conclusions

Prolonged lymphopenia after DMT discontinuation does not protect against disease reactivation. Starting a new immune therapy should be balanced against the option of a "wait and see." A different immunotherapeutic strategy such as an anti-B therapeutic approach could be considered.

http://ift.tt/2A1Spf7

Frequencies and ethnic distribution of ABO and RhD blood groups in China: a population-based cross-sectional study

Objectives

ABO and RhD blood groups are key factors affecting blood transfusion safety. The distribution of ABO and RhD blood groups varies globally, but limited data exist for ethnic distributions of these blood groups in Asian populations. We aimed to evaluate the distribution of ABO and RhD blood groups among Chinese ethnic groups.

Design

A population-based cross-sectional study.

Setting

Data on ABO groups and ethnicities were obtained from the National Free Preconception Health Examination Project (NFPHEP) with participants from 220 counties of 31 provinces in China

Participants

There were 3 832 034 participants aged 21–49 years who took part in the NFPHEP from January 2010 to December 2012 and were included in this study.

Outcome Measures

The proportion of ABO and RhD blood groups among different ethnic groups was calculated.

Results

ABO and RhD blood distribution was significantly different among nine ethnic groups (P<0.001). Compared with other ethnic groups, the Yi group had more A phenotypes (34.0%), and the Manchu (33.7%) and Mongolian (33.3%) ethnic groups had more B phenotypes. The Zhuang group had the greatest proportion of O phenotypes (41.8%), followed by the Miao group (37.7%). AB phenotypes were more frequent in the Uygur ethnic group (10.6%) but lower in the Zhuang group (5.5%). Meanwhile, RhD negativity (RhD–) was greater in the Uygur group (3.3%) than in the Mongolian (0.3%) and Manchu ethnic groups (0.4%). O RhD– blood groups were more frequent in the Uygur group (0.8%) than in the other ethnic groups (0.1%–0.4%, P<0.001).

Conclusion

ABO and RhD blood phenotypes vary across different ethnic groups in China. The diversity in the distribution of the ABO and RhD blood groups in different ethnic groups should be considered when developing rational and evidence-based strategies for blood collection and management.

http://ift.tt/2jK76IT

Characteristics of NPS use in patients admitted to acute psychiatric services in Southeast Scotland: a retrospective cross-sectional analysis following public health interventions

Objectives

Assess the impact of selective prohibition and seizure of novel psychoactive substances (NPS) supply on NPS use prevalence within psychiatric admissions and evaluate demographic characteristics of current NPS users.

Design

A 6-month retrospective cross-sectional analysis of discharge letters between 1 October 2015 and 31 March 2016.

Setting

General psychiatry inpatients and intensive home treatment team (IHTT) community patients at a psychiatric hospital in a Scottish city.

Participants

All participants were between the ages of 18 and 65 years. After application of exclusion criteria, 473 discharge letters of general psychiatry patients were deemed suitable for analysis and 264 IHTT patient discharge letters were analysed.

Interventions

A nationwide temporary class drug order (TCDO) was placed on 10 April 2015 reclassifying methylphenidate-related compounds as class B substances. On 15 October 2015, local forfeiture orders were granted to trading standards permitting the seizure of NPS supplies.

Primary and secondary outcome measures

The primary outcome measure was to determine the prevalence of NPS use in two cohorts. Second, demographic features of patients and details regarding their psychiatric presentation were analysed.

Results

The prevalence of NPS use in general psychiatry and IHTT patients was 6.6% and 3.4%, respectively. Inpatients using NPS compared with non-users were more likely to be men (OR 2.92, 95% CI 1.28 to 6.66, P=0.009), have a forensic history (OR 5.03, CI 2.39 to 10.59, P<0.001) and be detained under an Emergency Detention Certificate (OR 3.50, CI 1.56 to 7.82, P=0.004). NPS users were also more likely to be diagnosed under International Statistical Classification of Diseases and Related Health Problems, Version 10, F10–19 (OR 9.97, CI 4.62 to 21.49, P<0.001).

Conclusions

Compared with previous work, psychiatric inpatient NPS use has fallen. NPS continue to be used by a demographic previously described resulting in presentations consistent with a drug-induced psychosis and at times requiring detention under the Mental Health Act. Further research is required to evaluate the effectiveness of the recent prohibition of all NPS.

http://ift.tt/2jK7fMr

Multicentre prospective randomised single-blind controlled study protocol of the effect of an additional parent-administered sensorimotor stimulation on neurological development of preterm infants: Primebrain

Introduction

Preterm and very low birthweight infants are at increased risk for neurodevelopmental disorders, including cerebral palsy, sensory impairment and intellectual disability. Several early intervention approaches have been designed in the hope of optimising neurological development in this context. It seems important that the intervention takes into account parental mental health, focuses on parent–child interactions and lasts sufficiently long. This study aims to evaluate the effects of a stimulation programme administered by parents until 6 months post-term on motor and neurophysiological development of infants born preterm.

Methods and analysis

Participants will be infants born <32 weeks' gestation and/or with a birth weight <1500 g recruited prospectively from two tertiary neonatal intensive care units. They will be randomly assigned to receive nationally recommended follow-up only (control group) or also a stimulation programme between 37 weeks' gestation and 6 months' corrected age. Perinatal, clinical neurodevelopmental, socio-demographic and neuroimaging (ultrasonography or MRI) data will be collected. Bayley Scales of Infant Development will be used up to 24 months' corrected age and Parental Stress Index at 6, 12, 18 and 24 months' corrected age. High-density (64 or 128 electrodes) EEG, visual, somatosensory and long latency auditory evoked potentials will be recorded at term age, 3, 6, 12, 18 and 24 months' corrected age. They will be analysed for spatiotemporal frequency bands contents and source localisation.

Ethics and dissemination

The study was approved by the Ethics Committees of the Hôpital Universitaire des Enfants Reine Fabiola and CHU Saint-Pierre. Results dissemination will be made for stakeholders and families, reports will be written for parents, healthcare providers and policymakers, and scientific papers will be published.

Trial registration number

NCT02159534; Pre-results.

http://ift.tt/2idiaOb

Effectiveness of preoperative medical consultations by internal medicine physicians: a systematic review

Objective

Clinics have been established to provide preoperative medical consultations, and enable the anaesthetist and surgeon to deliver the best surgical outcome for patients. However, there is uncertainty regarding the effect of such clinics on surgical, in-hospital and long-term outcomes. A systematic review of the literature was conducted to determine the effectiveness of preoperative medical consultations by internal medicine physicians for patients listed for elective surgery.

Design

Systematic searches of MEDLINE, EMBASE, CINAHL, PubMed, Current Contents and the NHS Centre for Reviews and Dissemination were conducted up to 30 April 2017.

Setting

Elective surgery.

Study selection

Randomised controlled trials and non-randomised comparative studies conducted in adults.

Outcome measures

Length of hospital stay, perioperative morbidity and mortality, costs and quality of life.

Results

The one randomised trial reported that preadmission preoperative assessment was more effective than the option of an inpatient medical assessment in reducing the frequency of unnecessary admissions with significantly fewer surgical cancellations following admission for surgery. A small reduction in length of stay in patients was also observed. The three non-randomised studies reported increased lengths of stay, costs and postoperative complications in patients who received preoperative assessment. The timing and delivery of the preoperative medical consultation in the intervention group differed across the included studies.

Conclusion

Further research is required to inform the design and implementation of coordinated involvement of physicians and surgeons in the provision of care for high-risk surgical patients. A standardised approach to perioperative decision-making processes should be developed with a clear protocol or guideline for the assessment and management of surgical patients.

http://ift.tt/2ig89A0

The short-term health and economic burden of gestational diabetes mellitus in China: a modelling study

Objectives

Gestational diabetes mellitus (GDM) is associated with a higher risk for adverse health outcomes during pregnancy and delivery for both mothers and babies. This study aims to assess the short-term health and economic burden of GDM in China in 2015.

Design

Using TreeAge Pro, an analytical decision model was built to estimate the incremental costs and quality-of-life loss due to GDM, in comparison with pregnancy without GDM from the 28th gestational week until and including childbirth. The model was populated with probabilities and costs based on current literature, clinical guidelines, price lists and expert interviews. Deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results.

Participants

Chinese population who gave birth in 2015.

Results

On average, the cost of a pregnancy with GDM was ¥6677.37 (in 2015 international $1929.87) more (+95%) than a pregnancy without GDM, due to additional expenses during both the pregnancy and delivery: ¥4421.49 for GDM diagnosis and treatment, ¥1340.94 (+26%) for the mother's complications and ¥914.94 (+52%) for neonatal complications. In China, 16.5 million babies were born in 2015. Given a GDM prevalence of 17.5%, the number of pregnancies affected by GDM was estimated at 2.90 million in 2015. Therefore, the annual societal economic burden of GDM was estimated to be ¥19.36 billion (international $5.59 billion). Sensitivity analyses were used to confirm the robustness of the results. Incremental health losses were estimated to be approximately 260 000 quality-adjusted life years.

Conclusion

In China, the GDM economic burden is significant, even in the short-term perspective and deserves more attention and awareness. Our findings indicate a clear need to implement GDM prevention and treatment strategies at a national level in order to reduce the economic and health burden at both the population and individual levels.

http://ift.tt/2jIW0nm

Early warning scores for detecting deterioration in adult hospital patients: a systematic review protocol

Introduction

Early warning scores (EWSs) are used extensively to identify patients at risk of deterioration in hospital. Previous systematic reviews suggest that studies which develop EWSs suffer methodological shortcomings and consequently may fail to perform well. The reviews have also identified that few validation studies exist to test whether the scores work in other settings. We will aim to systematically review papers describing the development or validation of EWSs, focusing on methodology, generalisability and reporting.

Methods

We will identify studies that describe the development or validation of EWSs for adult hospital inpatients. Each study will be assessed for risk of bias using the Prediction model Risk of Bias ASsessment Tool (PROBAST). Two reviewers will independently extract information. A narrative synthesis and descriptive statistics will be used to answer the main aims of the study which are to assess and critically appraise the methodological quality of the EWS, to describe the predictors included in the EWSs and to describe the reported performance of EWSs in external validation.

Ethics and dissemination

This systematic review will only investigate published studies and therefore will not directly involve patient data. The review will help to establish whether EWSs are fit for purpose and make recommendations to improve the quality of future research in this area.

PROSPERO registration number

CRD42017053324.

http://ift.tt/2id5Bm3

Protocol for a feasibility study and randomised pilot trial of a low-intensity psychological intervention for depression in adults with autism: the Autism Depression Trial (ADEPT)

Introduction

High rates of co-occurring depression are reported in autism spectrum disorder (ASD), a neurodevelopmental condition characterised by social communication impairments and repetitive behaviours. Cognitive-behavioural interventions adapted for ASD have been effective for anxiety problems. There have been evaluation studies of group cognitive-behavioural therapy for co-occurring depression, but no randomised trials investigating low-intensity psychological interventions as recommended in clinical guidelines for mild-moderate depression.

Methods and analysis

A feasibility study comprising a randomised controlled trial (RCT) and nested qualitative evaluation is under way as preparation for a definitive RCT. Participants (n=70) will be randomised to Guided Self-Help: a low-intensity psychological intervention based on behavioural activation adapted for ASD or treatment as usual. Outcomes including depression symptoms, anxiety, social function and service use will be measured at 10, 16 and 24 weeks postrandomisation and will be blind to group allocation for measures that are not self-administered. The analysis will aim to establish the rates of recruitment and retention for a larger-scale RCT as well as the most appropriate measure of depression to serve as primary outcome. The qualitative study will purposively sample up to 24 participants from each treatment group to consider the acceptability and feasibility of the intervention and the trial design.

Ethics and dissemination

Ethical approval has been received from WALES REC 3 (IRAS project ID: 191558) and the Health Research Authority with R&D approval from Avon and Wiltshire Mental Health Partnership and Northumberland, Tyne and Wear Foundation NHS Trusts. To our knowledge, this is the first study of a low-intensity intervention for depression in adults with autism. The results will inform the design of a definitive RCT. Dissemination will include peer-reviewed journal publications reporting the quantitative and qualitative research findings of the study and presentations at national and international conferences.

Trial registration number

ISRCTN54650760; Pre-results.

http://ift.tt/2jJOAk3

Effect of a newly designed observation, response and discharge chart in the Post Anaesthesia Care Unit on patient outcomes: a quasi-expermental study in Australia

Objectives

This study aimed to evaluate whether use of a discharge criteria tool for nursing assessment of patients in Post Anaesthesia Care Unit (PACU) would enhance nurses' recognition and response to patients at-risk of deterioration and improve patient outcomes.

Methods

A prospective non-randomised pre–post intervention study was conducted in three hospitals in Australia. Participants were adults undergoing elective surgery before (n=723) and after (n=694) implementation of the Post-Anaesthetic Care Tool (PACT).

Results

Nursing response to patients at-risk of deterioration was higher using PACT, with more medical consultations initiated by PACU nurses (19% vs 30%, P<0.001) and more patients with Medical Emergency Team activation criteria modified by an anaesthetist while in PACU (6.5% vs 13.8%, P<0.001). There were higher rates of analgesia administration (37.3% vs 54.2%, P=0.001), nursing assessment of pain and documentation of ongoing analgesia prior to discharge (55% vs 85%, P<0.001). More adverse events were recorded in PACU after introduction of the PACT (8.3% vs 16.7%, P<0.001). The rate of adverse events after discharge from PACU remained constant (16.5%), but the rate of cardiac events (5.1% vs 2.6%, P=0.021) and clinical deterioration (8.7% vs 4.3%, P=0.001) following PACU discharge significantly decreased, using the PACT. Despite the increased number of patients with adverse events in phase 2, healthcare costs did not increase significantly. Length of stay in PACU and length of hospital admission for those patients who had an adverse event in PACU were significantly reduced after implementation of the PACT.

Conclusion

This study found that using a structured discharge criteria tool, the PACT, enhanced nurses' recognition and response to patients who experienced clinical deterioration, reduced length of stay for patients who experienced an adverse event in PACU and was cost-effective.

http://ift.tt/2icVv4P

Atypical presentations of dysembryoplastic neuroepithelial tumors

Summary

Dysembryoplastic neuroepithelial tumors (DNETs) are World Health Organization grade 1 neoplasms, typically present as isolated cortical lesions with no associated edema. We present 3 rare cases of DNETs that were atypical in location (all were subcortical and 1 was bilateral), 2 of which displayed substantial growth over time. All 3 cases presented with seizures that were not well controlled on medications, followed by a successful cure of the epilepsy when these lesions were removed. These cases uniquely illustrate that DNETs can be present throughout the brain and may generate seizures even in a subcortical location, possibly due to containing neurons with the potential for aberrant microcircuitry. The slow, nonmalignant proliferation of these lesions may engage epileptogenic networks, leading to the onset of seizures. These cases carry implications for the management of these surgically treatable lesions. Thus far, there have only been a handful of cases of growth reported in nonmalignant DNETs, and 2 of these cases displayed growth over the interval of monitoring.

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Brain regions and epileptogenicity influence epileptic interictal spike production and propagation during NREM sleep in comparison with wakefulness

Summary

Objective

Non–rapid eye movement (NREM) sleep is known to be a brain state associated with an activation of interictal epileptic activity. The goal of this work was to quantify topographic changes occurring during NREM sleep in comparison with wakefulness.

Method

We studied intracerebral recordings of 20 patients who underwent stereo-electroencephalography (SEEG) during presurgical evaluation for pharmacoresistant focal epilepsy. We measured the number of interictal spikes (IS) and quantified the co-occurrence of IS between brain regions during 1 hour of NREM sleep and 1 hour of wakefulness. Co-occurrence is a method to estimate IS networks based on a temporal concordance between IS of different brain regions. Each studied region was labeled as "seizure-onset zone" (SOZ), "propagation zone" (PZ), or "not involved region" (NIR).

Results

During NREM sleep, the number of interictal spikes significantly increased in all regions (mean of 68%). This increase was higher in medial temporal regions than in other regions, whether involved in the SOZ. Spike co-occurrence increased significantly in all regions during NREM sleep in comparison with wakefulness but was greater in neocortical regions. Spike co-occurrence in medial temporal regions was not higher than in other regions, suggesting that the increase of the number of spikes in this region was in great part a local effect.

Significance

This study demonstrated that medial temporal regions show a greater propensity to spike production or propagation during NREM sleep compared to other brain regions, even when the medial temporal lobe is not involved in the SOZ.

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Metformin and melatonin inhibit DMBA-induced mammary tumorigenesis in rats fed a high-fat diet

The data from in-vitro and in-vivo studies show that both peroral antidiabetic metformin (MF) and pineal hormone melatonin (MT) inhibit the growth of many cancers, including breast cancer. However, most in-vivo studies used standard-type diet with low fat content. Therefore, in this study, we evaluated the chemopreventive effect of MF and MT in an in-vivo model of breast cancer in rats on a high-fat diet (10% of total fat). Mammary carcinogenesis was induced by 7,12-dimethylbenz[a]anthracene (DMBA) in female Sprague-Dawley rats. Chemoprevention with MF (administered in a diet, 0.2%) and MT (administered in tap water, 20 mg/l) was induced 20 days before the carcinogen administration through the termination of the experiment (14 weeks after carcinogen administration). Tumor growth parameters were analyzed together with histopathological examination and immunohistochemical detection of KI67 (proliferation marker), caspase-3, BAX, BCL-2 (apoptosis markers), and CD24 and CD44 (cancer stem cell markers) in mammary tumor samples. The combination of chemopreventive agents decreased tumor incidence by 29%. Cumulative tumor volume was lower in all groups treated with chemoprevention. Histopathology did not show significant changes in high-grade/low-grade tumor ratio. Immunohistochemistry showed increased expression of BAX in the MT group, and caspase-3 expression increased in both MT and combination groups. MT, and particularly the MF and MT combination, inhibited DMBA-induced mammary tumor growth in rats by apoptosis stimulation in cancer cells. Our results indicate that MT supplements in patients treated with MF may have a considerable effect on the incidence of breast cancer. Correspondence to Bianka Bojková, PhD, Department of Animal Physiology, Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Šafárik University in Košice, Šrobárová 2, 041 54 Košice, Slovak Republic Tel: +421 552 341 209; fax: +421 556 222 124; e-mail: bianka.bojkova@upjs.sk Received August 23, 2017 Accepted November 6, 2017 Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Rare aggressive natural killer cell leukemia presented with leukopenia and disseminated intravascular coagulation—a diagnostic challenge

Abstract

Aggressive natural killer cell leukemia/lymphoma (ANKL) is a rare and aggressive malignancy of natural killer (NK) cells. It is now regarded as a distinct subtype of leukemia as a provisional entity: "NK cell lymphoblastic leukemia/lymphoma" in the 2016 revision to the World Health Organization classification. It is important to diagnose ANKL early due to its fulminant clinical features that may rapidly progress to multiorgan failure (MOF). However, there is no definite diagnostic marker of the disease so it is difficult to make differential diagnosis from other lymphoproliferative disorders. The case reported here is of a 27-year-old male patient who initially presented with leukopenia, disseminated intravascular coagulation (DIC), and MOF during the early stages of illness, and a diagnosis of ANKL was made after a series of examinations. He had no opportunity to take chemotherapy due to the extremely short and aggressive disease course. To the best of our knowledge, this was the first case with ANKL reported from our hospital and the second case from Turkey.

http://ift.tt/2AH2iP7

Perceptions on the value of bodily functions in multiple sclerosis

Background

In neurological diseases presenting with a plethora of symptoms, the value of bodily functions for a given patient might be a guide for clinical management. Multiple sclerosis (MS) is paradigmatic in this respect, and little is known about the value of different bodily functions of patients and their physicians' perceptions.

Methods

In a multicenter study, 171 patients with relapsing-remitting multiple sclerosis (RRMS), 61% with a clinically active disease within the last 2 years were followed over up to 3 years and yearly patients and their study physician rated on the perceived value of 13 bodily functions via a priority list. Differences between patients and physicians as well as modulating disease demographic factors were analyzed.

Results

Patients with RRMS rated visual function followed by thinking and memory and walking highest while physicians stressed mobility, followed by thinking and memory and alertness most. Ratings were independent from disease duration or disability. Strongest value judgment differences were seen in swallowing regarded more relevant by patients and hand function regarded more relevant by physicians. In general, patients' and physicians' ratings through time were quite stable. Collapsing physical items into a physical functioning scale and mental items in a mental function scale, both dimensions were regarded equally important by patients while physicians underscored physical functioning (P = .016).

Conclusion

There are differences between patients and physicians in value statements of bodily functions in MS. In particular, visual functioning is under-recognized by physicians.

http://ift.tt/2AudJam

The applications of regenerative medicine in sinus lift procedures: A systematic review

Abstract

Background

Findings in regenerative medicine applied to the sinus lift procedures.

Purpose

Evaluate the effectiveness of regenerative medicine in sinus lift.

Materials and Methods

An extensive search for manuscripts were performed by using different combinations of keywords and MeSH terms (Pub-med; Embase; Scopus; Web of Science Core Collection; Medline; Current Contents Connect; Derwent Innovations Index; Scielo Citation Index; Cochrane library). The full text selected articles are written in English, Portuguese, Spanish, Italian, German, or French, and published until 28 of November 2016. Inclusion criteria were: implant osteointegration, radiographic, histologic, and/or histomorphometric analysis, clinical studies in humans using of regenerative medicine. This systematic review was performed by selecting only randomized controlled clinical trials and controlled clinical trials.

Results

Eighteen published studies (11 CT and 7 RCT) were considered eligible for inclusion in the present systematic review. These studies demonstrated considerable variation of biomaterial and cell technics used, study design, sinus lift technic, outcomes, follow-up, and results.

Conclusion

Only few studies have demonstrated potential of regenerative medicine in sinus lift; further randomized clinical trials are needed to achieve more accurate results.

http://ift.tt/2kkiBe7

Three-dimensional morphology and volume of the free Achilles tendon at rest and under load in people with unilateral mid-portion Achilles tendinopathy

Abstract

Mid-portion Achilles tendinopathy (MAT) adversely affects free Achilles tendon (AT) structure and composition. However, it is not known how these pathological alterations associated with MAT change the normal three-dimensional (3D) morphology of free AT at rest and under load throughout the entire free tendon length. Here, we used 3D ultrasound to examine the effect of unilateral MAT on free tendon 3D morphology [length, cross-sectional area (CSA), antero-posterior (AP) diameter, and medio-lateral (ML) diameter] and volume at rest and during a sub-maximal (50%) voluntary isometric plantarflexion contraction bilaterally in individuals with unilateral MAT (n = 10) compared to a matched healthy control group (n = 10). The tendinopathic free AT had a greater CSA relative to the control tendons along the entire tendon length which was mainly driven by a greater tendon AP diameter. Under load, the tendinopathic tendon experienced greater longitudinal and transverse strains than the control tendons. In contrast to the control tendons, which experienced a reduction in tendon CSA and ML diameter and bulged along the AP axis and behaved iso-volumetrically under load, the tendinopathic tendon experienced a reduction in tendon CSA, AP diameter, ML diameter, and an overall volume reduction. Overall, these findings suggest that the magnitude of longitudinal strain and volume change and the corresponding magnitude and direction of transverse strain under load are altered in MAT compared to normal tendon. These findings are indicative of a fundamental reorganization of the tendon matrix and alterations in tendon fluid content and distribution under load in tendinopathic tendon.

This article is protected by copyright. All rights reserved

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Announcements

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Response: Neurocysticercosis and epilepsy

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What proportion of cases of epilepsy are actually caused by neurocysticercosis?

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Issue Information–ISSN page

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Crohn's disease involving ileal conduit: a case report

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Prognostic significance of pre-operative inflammatory markers in resected gallbladder cancer: a systematic review

Background

Neutrophil to lymphocyte ratio (NLR), C-reactive protein (CRP) and Glasgow Prognostic Score (GPS) have demonstrated good prognostic value in several cancers but their role in gallbladder cancer (GBC) remains unclear. The aim of this study is to systematically review the current literature to determine their role in predicting survival outcomes in GBC.

Methods

Using a pre-specified inclusive search strategy MEDLINE, EMBASE and CINAHL databases were used to identify studies describing survival in patients after GBC resection with high or low pre-operative CRP, GPS or NLR. A proforma was used to extract study author and date, number of patients, age, gender, tumour stage, use of adjuvant therapy and primary outcome data.

Results

In all, 46 studies were identified after initial screening with four studies reporting survival outcomes. All studies described a reduction in survival in patients with an elevated NLR, GPS or CRP. Three studies showed NLR to be an independent prognostic marker and one study additionally demonstrated that elevated CRP and GPS were associated with poorer survival.

Conclusions

Elevated pre-operative inflammatory markers are inversely related to survival outcomes. They are relatively inexpensive, easy measurable parameters that could aid in the decision making process involved in the management of GBC. Sub-stratification of groups utilizing inflammatory markers may help guide surgical strategy. However, these studies are retrospective and of low to moderate quality. High quality, prospective studies with well-defined inclusion criteria and outcomes are needed to guide the role of inflammatory markers in the management of GBC.

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Combined treatment approach to chronic anal fissure with associated anal fistula

Background

Anal fistula in association with chronic anal fissure (fissure-fistula) is infrequently described. Recognizing this association and managing both components may help prevent some treatment failures seen with chronic anal fissure. This study aims to report on the outcomes of 20 consecutive patients with fissure-fistula managed with fistulotomy and injection of botulinum A toxin.

Methods

The study is a retrospective, observational study, assessing the success of symptom resolution following fistulotomy with botulinum A toxin, in patients identified as having a chronic anal fissure with associated anal fistula. The study included all patients with this condition treated with combination treatment by a single surgeon at a tertiary care hospital between January 2013 and January 2016.

Results

Twenty patients with fissure-fistula treated with fistulotomy and botulinum toxin A were identified. The median cohort age was 44 years (range 25–78), with a predominance of males (80%) and posterior fissure position (80%). The most common presenting symptoms were anal pain (70%), rectal bleeding (55%), anal discharge (35%) and anal pruritus (35%). Mean follow-up was 10.5 weeks and all patients who attended follow-up appointments reported resolution of symptoms. There were no cases of incontinence and none of the cohort required further surgical intervention for the condition.

Conclusion

Chronic anal fissure with associated anal fistula can be successfully managed with fistulotomy and injection of botulinum toxin A. Further studies would be helpful in determining if recognition and management of the fistula component in isolation with fistulotomy is as effective as fistulotomy plus botulinum A toxin.

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Transanal endoscopic microsurgery: a New Zealand experience

Background

Transanal endoscopic microsurgery (TEMS) is a proven alternative therapy to either radical surgery or endoscopic mucosal resection for rectal neoplasms. It has proven benefits with lower morbidity and mortality compared with total mesorectal excision, and a lower local recurrence rate when compared to endoscopic mucosal techniques.

Methods

A retrospective data collection of TEMS procedures performed through Waikato District Health Board, New Zealand, from 2010 to 2015 was conducted. Supportive follow-up data were sourced from patient records and from local centres around New Zealand.

Results

A total of 137 procedures were performed over the study period, with five being repeat procedures. Procedures were mostly performed for benign lesions (66.4%) with an overall complication rate of 15.3%, only five of which were Clavien–Dindo grade III (3.6%). Our local recurrence rate after resection of benign lesions was 5.1%.

Conclusion

Our data set demonstrates the TEMS procedure to be safe compared to radical resection (total mesorectal excision) for sessile rectal lesions. Close endoscopic follow-up is recommended, especially for close or incomplete margins. Good therapeutic results can be obtained for appropriately selected early malignant lesions. TEMS provides better oncological results than endoscopic mucosal resection or transanal excision.

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Cosmetic tourism for breast augmentation: a systematic review

Background

The medical tourism industry, and in particular cosmetic tourism for breast augmentation, is becoming an increasingly popular global phenomenon. The objective of this study is to determine the extent of medical literature and the patient risk profiles associated with cosmetic tourism for breast augmentation both locally and abroad. Data sources: OVID MEDLINE, OVID Embase, Cochrane Central and Proquest electronic databases.

Methods

The search was conducted through to April 2017. Studies pertaining entirely or partly to cosmetic tourism for breast augmentation were considered for inclusion. Exclusion criteria included non-English articles, studies relating to non-cosmetic or non-implant breast augmentation, and studies that did not separately report on findings associated with breast augmentation abroad.

Results

We identified 17 observational studies. Common destinations included Europe, South America and South East Asia. Infectious complications were common. Wound dehiscence and aesthetic dissatisfaction also featured. Catastrophic outcomes such as sepsis, intubation and ventilation, radical bilateral mastectomy, irreversible hypoxic brain injury and death were also reported. There were expectations that home country health systems would treat complications and provide non-medically indicated revision procedures. The burden on home country health systems was evident from a public health perspective.

Conclusion

Determining the extent of cosmetic tourism for breast augmentation, including outcomes and complications, will help to inform Australian patients who this seek procedure abroad. Furthermore, it will aid in better understanding the health system implications and may help to guide future research and public health interventions both locally and internationally.

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Further classification of neutrophil non-muscle myosin heavy chain-IIA localization for efficient genetic diagnosis of MYH9 disorders

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Primary effusion lymphoma-like lymphoma with a T cell phenotype

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Altered Cerebral Perfusion in Infants Born Preterm Compared with Infants Born Full Term

To compare regional cerebral cortical blood flow (CBF) in infants born very preterm at term-equivalent age (TEA) and healthy newborns born full term and to examine the impact of clinical risk factors on CBF in the cohort born preterm.

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Changing Default Ventilator Settings on Anesthesia Machines Improves Adherence to Lung-Protective Ventilation Measures

Perioperative lung-protective ventilation (LPV) can reduce perioperative pulmonary morbidity. We hypothesized that modifying default anesthesia machine ventilator settings would increase the use of intraoperative LPV. Default tidal volume settings on our anesthesia machines were decreased from 600 to 400 mL, and default positive end-expiratory pressure was increased from 0 to 5 cm H2O. This modification increased mean positive end-expiratory pressure from 3.1 to 5.0 cm H2O and decreased mean tidal volume from 8.2 to 6.7 mL/kg predicted body weight. Notably, increased adherence to LPV from 1.6% to 23.0% occurred quickly with the rate of increase more than doubling from 1.8% to 3.9% per year. Accepted for publication September 12, 2017. Funding: This work was supported by Institutional and Departmental Sources. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Katherine T. Forkin, MD, Department of Anesthesiology, University of Virginia Health System, PO Box 800710, Charlottesville, VA 22908. Address e-mail to ket2a@hscmail.mcc.virginia.edu. © 2017 International Anesthesia Research Society

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Respiratory Gas Analysis—Technical Aspects

A technology-focused review of respiratory gas analysis, with an emphasis on carbon dioxide analysis, is presented. The measurement technologies deployed commercially are highlighted, and the basic principles and technical concerns of infrared spectroscopy and mainstream versus sidestream gas sampling are discussed. The specifications of particular interest to the clinician, accuracy and response time, and the related standard, with typical values for a capnometer, are presented. Representative time and volumetric capnograms are shown with the clinically relevant parameters described. Aspects of the terminology in present-day use and the need for clarity in defining what is a breath and an end-tidal value are reviewed. The applications of capnography of particular interest to the anesthesiologist are noted, and key references are provided. Ongoing developments with respect to respiratory gas analysis, and those that will impact it, are noted. Accepted for publication June 28, 2017. Funding: None. The author declares no conflicts of interest. Reprints will not be available from the author. Address correspondence to Michael B. Jaffe, PhD, Cardiorespiratory Consulting, LLC, 410 Mountain Rd, Cheshire, CT 06410. Address e-mail to mbjengineering@cox.net. © 2017 International Anesthesia Research Society

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Is Compliance With Surgical Care Improvement Project Cardiac (SCIP-Card-2) Measures for Perioperative β-Blockers Associated With Reduced Incidence of Mortality and Cardiovascular-Related Critical Quality Indicators After Noncardiac Surgery?

BACKGROUND: While continuation of β-blockers (BBs) perioperatively has become a national quality improvement measure, the relationship between BB withdrawal and mortality and cardiovascular-related critical quality indicators has not been studied in a contemporary cohort of patients undergoing noncardiac surgery. METHODS: For this retrospective study, the quality assurance database of a large community-based anesthesiology group practice was used to identify 410,288 surgical cases, 18 years of age or older, who underwent elective or emergent noncardiac surgical procedures between January 1, 2009, and December 31, 2014. Each surgical case that was withdrawn from BBs perioperatively was propensity matched by clinical and surgical characteristics to 4 cases that continued BBs perioperatively. Subsequently, multivariable conditional logistic regression analyses were performed in the matched cohort to determine the extent to which withdrawal of perioperative BBs was independently associated with mortality as the primary outcome and cardiovascular-related critical quality indicators as the secondary outcome (need for vasopressor, electrocardiographic changes requiring treatment, unplanned admission to intensive care unit, postanesthesia care unit stay >2 hours, and a combination of cardiac arrest and myocardial infarction) within 48 hours postoperatively. RESULTS: Of the 66,755 (16%) cases in the cohort admitted on BB therapy, BBs were withdrawn in 3829 (6%) and continued in 62,926 (94%). Propensity score matching resulted in an analysis cohort of 19,145 cases. Withdrawal of perioperative BBs in the multivariable conditional logistic regression analysis was significantly associated with an increased risk for mortality (odds ratio [OR], 3.61; 95% confidence interval [CI], 1.75–7.35; P = .0003), but a significantly decreased risk for need of blood pressure support requiring vasopressor initiation (OR, 0.84; 95% CI, 0.76–0.92; P = .0003) and extended postanesthesia care unit stay (OR, 0.69; 95% CI, 0.54–0.88; P = .004) within 48 hours after noncardiac surgery. CONCLUSIONS: Perioperative withdrawal of BBs was associated with increased risk for mortality within 48 hours after noncardiac surgery and with decreased risk for need of vasopressor during the early postoperative period and a shorter stay in the postanesthesia care unit. Accepted for publication September 12, 2017. M. D. Kertai is currently affiliated with the Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee. Funding: None. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Miklos D. Kertai, MD, PhD, Department of Anesthesiology, Vanderbilt University Medical Center, 1215 21st Ave S, Suite 5160, Nashville, TN 37232. Address e-mail to miklos.kertai@vanderbilt.edu. © 2017 International Anesthesia Research Society

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In Response

No abstract available

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Informed Consent and Cognitive Dysfunction After Noncardiac Surgery in the Elderly

Cognitive dysfunction 3 months after noncardiac surgery in the elderly satisfies informed consent thresholds of foreseeability in 10%–15% of patients, and materiality with new deficits observed in memory and executive function in patients with normal test performance beforehand. At present, the only safety step to avoid cognitive dysfunction after surgery is to forego surgery, thereby precluding the benefits of surgery with removal of pain and inflammation, and resumption of normal nutrition, physical activity, and sleep. To assure that consent for surgery is properly informed, risks of both cognitive dysfunction and alternative management strategies must be discussed with patients by the surgery team before a procedure is scheduled. Accepted for publication October 23, 2017. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Kirk J. Hogan, MD, JD, Department of Anesthesiology, School of Medicine and Public Health, University of Wisconsin, B6/319 Clinical Science Center, 600 Highland Ave, Madison, WI 53792. Address e-mail to khogan@wisc.edu. © 2017 International Anesthesia Research Society

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Cardiac Arrest in the Operating Room: Part 2—Special Situations in the Perioperative Period

As noted in part 1 of this series, periprocedural cardiac arrest (PPCA) can differ greatly in etiology and treatment from what is described by the American Heart Association advanced cardiac life support algorithms, which were largely developed for use in out-of-hospital cardiac arrest and in-hospital cardiac arrest outside of the perioperative space. Specifically, there are several life-threatening causes of PPCA of which the management should be within the skill set of all anesthesiologists. However, previous research has demonstrated that continued review and training in the management of these scenarios is greatly needed and is also associated with improved delivery of care and outcomes during PPCA. There is a growing body of literature describing the incidence, causes, treatment, and outcomes of common causes of PPCA (eg, malignant hyperthermia, massive trauma, and local anesthetic systemic toxicity) and the need for a better awareness of these topics within the anesthesiology community at large. As noted in part 1 of this series, these events are always witnessed by a member of the perioperative team, frequently anticipated, and involve rescuer–providers with knowledge of the patient and the procedure they are undergoing or have had. Formulation of an appropriate differential diagnosis and rapid application of targeted interventions are critical for good patient outcome. Resuscitation algorithms that include the evaluation and management of common causes leading to cardiac in the perioperative setting are presented. Practicing anesthesiologists need a working knowledge of these algorithms to maximize good outcomes. Accepted for publication September 8, 2017. Funding: This review was developed from previous iterations on behalf of the American Society of Anesthesiologists and the Society of Critical Care Anesthesiologists. Portions of those documents appear verbatim and are used with the permission of the ASA. Conflicts of Interest: See Disclosures at the end of the article. Implication statement: The spectrum of causes of periprocedural cardiac arrest warrants specific adaptations of the advanced circulatory life support algorithms. A number of rare, life-threatening etiologies of profound hemodynamic and respiratory disturbance leading to cardiac arrest are reviewed. Good patient outcomes in these special situations can be achieved by vigilance, timely formulation of a differential diagnosis for the crisis, and adherence to best practices. Reprints will not be available from the authors. Address correspondence to Matthew D. McEvoy, MD, Department of Anesthesiology, Vanderbilt University Medical Center, 1301 Medical Center Dr, TVC 4648, Nashville, TN 37232. Address e-mail to matthew.d.mcevoy@vanderbilt.edu. © 2017 International Anesthesia Research Society

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Reduced Left Ventricular Global Longitudinal Strain Predicts Prolonged Hospitalization: A Cohort Analysis of Patients Having Aortic Valve Replacement Surgery

BACKGROUND: Left ventricular ejection fraction (LVEF) is often preserved in patients with aortic stenosis and thus cannot distinguish between normal myocardial contractile function and subclinical dysfunction. Global longitudinal strain and strain rate (SR), which measure myocardial deformation, are robust indicators of myocardial function and can detect subtle myocardial dysfunction that is not apparent with conventional echocardiographic measures. Strain and SR may better predict postoperative outcomes than LVEF. The primary aim of our investigation was to assess the association between global longitudinal strain and serious postoperative outcomes in patients with aortic stenosis having aortic valve replacement. Secondarily, we also assessed the associations between global longitudinal SR and LVEF and the outcomes. METHODS: In this post hoc analysis of data from a randomized clinical trial (NCT01187329), we examined the association between measures of myocardial function and the following outcomes: (1) need for postoperative inotropic/vasopressor support; (2) prolonged hospitalization (>7 days); and (3) postoperative atrial fibrillation. Standardized transesophageal echocardiographic examinations were performed after anesthetic induction. Myocardial deformation was measured using speckle-tracking echocardiography. Multivariable logistic regression was used to assess associations between measures of myocardial function and outcomes, adjusted for potential confounding factors. The predictive ability of global longitudinal strain, SR, and LVEF was assessed as area under receiver operating characteristics curves (AUCs). RESULTS: Of 100 patients enrolled in the clinical trial, 86 patients with aortic stenosis had acceptable images for global longitudinal strain analysis. Primarily, worse intraoperative global longitudinal strain was associated with prolonged hospitalization (odds ratio [98.3% confidence interval], 1.22 [1.01–1.47] per 1% decrease [absolute value] in strain; P = .012), but not with other outcomes. Secondarily, worse global longitudinal SR was associated with prolonged hospitalization (odds ratio [99.7% confidence interval], 1.68 [1.01–2.79] per 0.1 second−1 decrease [absolute value] in SR; P = .003), but not other outcomes. LVEF was not associated with any outcomes. Global longitudinal SR was the best predictor for prolonged hospitalization (AUC, 0.72), followed by global longitudinal strain (AUC, 0.67) and LVEF (AUC, 0.62). CONCLUSIONS: Global longitudinal strain and SR are useful predictors of prolonged hospitalization in patients with aortic stenosis having an aortic valve replacement. Accepted for publication October 10, 2017. Funding: This investigation was supported by National Institutes of Health K23 HL093065 (A.E.D.) and the Departments of Cardiothoracic Anesthesia and Outcomes Research at the Cleveland Clinic. None of the investigators has a personal financial interest in this research. Conflicts of Interest: See Disclosures at the end of the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Abraham Sonny, MD, is currently affiliated with the Harvard Medical School, Boston, Massachusetts; and Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. Clinical Trial Registry: Clinical Trials.gov #NCT01187329. Reprints will not be available from the authors. Address correspondence to Andra E. Duncan, MD, MS, FASE, Departments of Cardiothoracic Anesthesia and Outcomes Research, Cleveland Clinic, 9500 Euclid Ave/J4, Cleveland, OH 44195. Address e-mail to duncana@ccf.org. © 2017 International Anesthesia Research Society

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Randomized Clinical Trial of Preoperative High-Dose Methylprednisolone on Postoperative Pain at Rest After Laparoscopic Appendectomy

BACKGROUND: Methylprednisolone administered intravenously preoperatively has been shown to reduce pain, nausea, and fatigue after elective surgery. We aimed to show that 125 mg of methylprednisolone given intravenously 30 minutes before laparoscopic surgery for suspected appendicitis would reduce pain at rest during the first 3 postoperative days. METHODS: A multicenter, parallel-group, double-blind, placebo-controlled study was conducted including patients 18 years of age and older with an American Society of Anesthesiologist class of I–III undergoing laparoscopic surgery for suspected appendicitis. The primary outcome was pain at rest measured on the 11-point numerical rating scale 5 times during the first 3 days after surgery. The effect of 125 mg of methylprednisolone on postoperative pain at rest during the first 3 days was assessed using a mixed-effects model with time and intervention as main effects. RESULTS: From April 2016 to August 2016, 78 patients were included, and all were eligible for analysis of the primary outcome. The estimated effect of 125 mg of methylprednisolone on pain at rest during the first 3 days after surgery was a nonsignificant increase of 0.2 (95% confidence interval, −0.5 to 0.9; P = .571) on the 11-point numerical rating scale. There was no difference between the 2 groups regarding the need for opioid agonists during hospital stay on the first postoperative day (P = .381). CONCLUSIONS: A 125-mg dose of methylprednisolone given intravenously 30 minutes before laparoscopic surgery for appendicitis seemed no better than placebo at providing a clinical meaningful reduction in postoperative pain at rest. Accepted for publication October 24, 2017. Funding: This work was supported by the A.P. Møller Foundation for the Advancement of Medical Science, Grosserer L.F. Foghts Fond, and the Augustinus Foundation. The primary author received a research grant from Nordsjællands Hospital and financial support from the Department of Surgery, Nordsjællands Hospital, Copenhagen University Hospital. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Trial Registration: Registered at http://ift.tt/PmpYKN (NCT02711449) and EudraCT (2015-004800-46). All authors agree to be accountable for all aspects of the work presented. Reprints will not be available from the authors. Address correspondence to Jakob Kleif, MD, Department of Surgery, Nordsjællands Hospital, Copenhagen University Hospital, Dyrehavevej 29, 3400 Hillerød, Denmark. Address e-mail to kleifen@dadlnet.dk. © 2017 International Anesthesia Research Society

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Distracted Doctoring: Returning to Patient-Centered Care in the Digital Age. Do We Have Time for This?

No abstract available

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Visualization Improves Supraclavicular Access to the Subclavian Vein in a Mixed Reality Simulator

BACKGROUND: We investigated whether visual augmentation (3D, real-time, color visualization) of a procedural simulator improved performance during training in the supraclavicular approach to the subclavian vein, not as widely known or used as its infraclavicular counterpart. METHODS: To train anesthesiology residents to access a central vein, a mixed reality simulator with emulated ultrasound imaging was created using an anatomically authentic, 3D-printed, physical mannequin based on a computed tomographic scan of an actual human. The simulator has a corresponding 3D virtual model of the neck and upper chest anatomy. Hand-held instruments such as a needle, an ultrasound probe, and a virtual camera controller are directly manipulated by the trainee and tracked and recorded with submillimeter resolution via miniature, 6 degrees of freedom magnetic sensors. After Institutional Review Board approval, 69 anesthesiology residents and faculty were enrolled and received scripted instructions on how to perform subclavian venous access using the supraclavicular approach based on anatomic landmarks. The volunteers were randomized into 2 cohorts. The first used real-time 3D visualization concurrently with trial 1, but not during trial 2. The second did not use real-time 3D visualization concurrently with trial 1 or 2. However, after trial 2, they observed a 3D visualization playback of trial 2 before performing trial 3 without visualization. An automated scoring system based on time, success, and errors/complications generated objective performance scores. Nonparametric statistical methods were used to compare the scores between subsequent trials, differences between groups (real-time visualization versus no visualization versus delayed visualization), and improvement in scores between trials within groups. RESULTS: Although the real-time visualization group demonstrated significantly better performance than the delayed visualization group on trial 1 (P = .01), there was no difference in gain scores, between performance on the first trial and performance on the final trial, that were dependent on group (P = .13). In the delayed visualization group, the difference in performance between trial 1 and trial 2 was not significant (P = .09); reviewing performance on trial 2 before trial 3 resulted in improved performance when compared to trial 1 (P

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