Clinical outcomes and predictors of success with Impella weaning in cardiogenic shock: a single-center experience.

Introduction: Cardiogenic shock (CS) is a severe syndrome with poor prognosis. Short-term mechanical circulatory support with Impella devices has emerged as an increasingly therapeutic option, unloading the failing left ventricle (LV) and improving hemodynamic status of affected patients. Impella devices should be used for the shortest time necessary to allow LV recovery because of time-dependent device-related adverse events. The weaning from Impella, however, is mostly performed in the absence of established guidelines, mainly based on the experience of the individual centres. Methods: The aim of this single center study was to retrospectively evaluate whether a multiparametrical assessment before and during Impella weaning could predict successful weaning. The primary study outcome was death occurring during Impella weaning and secondary endpoints included assessment of in-hospital outcomes. Results: Of a total of 45 patients (median age, 60 [51-66] years, 73% male) treated with an Impella device, 37 patients underwent impella weaning/removal and 9 patients (20%) died after the weaning. Non-survivors patients after impella weaning more commonly had a previous history of known heart failure (p = 0.054) and an implanted ICD-CRT (p = 0.01), and were more frequently treated with continuous renal replacement therapy (p = 0.02). In univariable logistic regression analysis, lactates variation (%) during the first 12-24 h of weaning, lactate value after 24 h of weaning, left ventricular ejection fraction (LVEF) at the beginning of weaning, and inotropic score after 24 h from weaning beginning were associated with death. Stepwise multivariable logistic regression identified LVEF at the beginning of weaning and lactates variation (%) in the first 12-24 h from weaning beginning as the most accurate predictors of death after weaning. The ROC analysis indicated 80% accuracy (95% confidence interval = 64%-96%) using the two variables in combination to predict death after weaning from Impella. Conclusions: This single-center experience on Impella weaning in CS showed that two easily accessible parameters as LVEF at the beginning of weaning and lactates variation (%) in the first 12-24 h from weaning begin were the most accurate predictors of death after weaning.

Efficacy of bio- and neurofeedback for depression: a meta-analysis.

BACKGROUND: For many years, biofeedback and neurofeedback have been implemented in the treatment of depression. However, the effectiveness of these techniques on depressive symptomatology is still controversial. Hence, we conducted a meta-analysis of studies extracted from PubMed, Scopus, Web of Science and Embase. METHODS: Two different strings were considered for each of the two objectives of the study: A first group comprising studies patients with major depressive disorder (MDD) and a second group including studies targeting depressive symptomatology reduction in other mental or medical conditions. RESULTS: In the first group of studies including patients with MDD, the within-group analyses yielded an effect size of Hedges' g = 0.717, while the between-group analysis an effect size of Hedges' g = 1.050. Moderator analyses indicate that treatment efficacy is only significant when accounting for experimental design, in favor of randomized controlled trials (RCTs) in comparison to non RCTs, whereas the type of neurofeedback, trial design, year of publication, number of sessions, age, sex and quality of study did not influence treatment efficacy. In the second group of studies, a small but significant effect between groups was found (Hedges' g = 0.303) in favor of bio- and neurofeedback against control groups. Moderator analyses revealed that treatment efficacy was not moderated by any of the sociodemographic and clinical variables. CONCLUSIONS: Heart rate variability (HRV) biofeedback and neurofeedback are associated with a reduction in self-reported depression. Despite the fact that the field has still a large room for improvement in terms of research quality, the results presented in this study suggests that both modalities may become relevant complementary strategies for the treatment of MDD and depressive symptomatology in the coming years.

Neurological outcomes after surgery for spinal metastases in symptomatic patients: Does the type of decompression play a role? A comparison between different strategies in a 10-year experience.

INTRODUCTION: The impact of neurological deficits plays a role of inestimable importance in patients with a neoplastic disease. The role of surgery for the management of symptomatic spinal cord compression (SSCC) cannot be overemphasized, as surgery represents often the first and paramount step in patients presenting with motor deficits. The traditional paradigm of simple bilateral laminectomy for the treatment of spinal cord compression has been reviewed. The need to achieve a proper circumferential decompression of the spinal sac has been progressively highlighted in combination with the development of the more comprehensive and multidisciplinary concept of separation surgery. OBJECTIVE: The aim of this paper is to analyze different strategies of decompression, while evaluating whether circumferential/anterior decompression is able to guarantee a better control and restoration of neurological functions in patients with motor impairment, if compared to traditional posterior decompression. MATERIALS AND METHODS: This is a retrospective observational study investigating symptomatic patients that underwent surgical treatment for spinal metastases at author's Institutions from January 2010 to June 2019. Data recorded concerned patient demographics, tumor histology, peri-operative and follow-up neurological status (ASIA), ambulation ability, stability (SINS), grade (ESCC) and source of epidural compression and type of decompression (anterior/anterior-lateral (AD); posterior/posterior-lateral (PD/PDL); circumferential (CD)). RESULTS: A total number of 84 patients was included. AD/CD patients showed higher chance of neurological improvement and reduced rates of worsening compared to PD/PLD group (94.1%/100% vs 60.4%; 11.8% vs 45.8% respectively). Univariate logistic regression identified immediate post-operative improvement to be a significative protective factor for worsening at last follow-up. Stratifying patients for site of compression and considering anterior and circumferential groups, immediate post-operative neurological improvement, was mostly associated with AD and CD (p 0.011 and 0.025 respectively). Walking at last follow up was influenced by post-operative maintenance of ambulation (p 0.001). CONCLUSION: The necessity to remove the epidural metastatic compression from its source should be considered of paramount importance. Since the majority of spinal cord compression involves firstly the ventral part of the sac, CD/AD are associated with better neurological outcomes and should be achieved in case of circumferential or anterior/anterolateral compression.

Psychopharmacological treatment in borderline personality disorder: A pilot observational study in a real-world setting.

Psychotherapy is the cornerstone of treatment for borderline personality disorder (BPD) while pharmacotherapy should be considered only as an adjunctive intervention. In clinical practice, however, most of BPD patients only receive medication. The aim of the study is to first describe pharmacological treatment in BPD patients in Italy and secondly to evaluate if comorbidity or illness severity are associated with the prescription of different class compounds. Data on pharmacological treatment and clinical evaluation of 75 BPD patients were collected in 5 clinical settings. The association between comorbidity and medication was assessed. Moreover, we evaluated the association between pharmacotherapy and severity, defined by a cluster analysis aimed at detecting different groups of patients. Most of the participants (82.7%) were characterized by polypharmacy, with a mean of 2.4 medications per person. Interestingly, the prescription didn't seem to depend on/be based on the severity of the disorder and was only partially determined by the presence of comorbidity. In conclusion, our findings are similar to what described in other clinical studies, supporting the idea that medication management for BPD is only partially coherent with international guidelines. This pilot study confirms the need for more rigorous studies to gain greater understanding of this topic and diminish the gap between guidelines and the real clinical world.

Recognition of healthy and cancerous breast cells: Sensing the differences by dielectric spectroscopy.

PURPOSE: The response of human cells to applied electrical signals depends on the cellular health status, because it is influenced by the composition and structure of the main cellular components. Therefore, electrical impedance-based techniques can be considered as sensitive tools to investigate healthy or disease state at cellular level. The goal of this study is to show that different types of in vitro cellular lines, related to different health status, can be differentiated using impedance spectra analysis. METHODS: Three different types of human breast cell line, corresponding to healthy, cancerous, and metastatic adenocarcinoma cells, were measured by means of electrical impedance spectroscopy. By modeling the investigated cells with proper resistive and capacitive circuital elements, the magnitude of the cell electrical components and spectra of real and imaginary part of dielectric permittivity were obtained. The latter were subsequently examined with a commonly adopted mathematical model, in order to estimate the values of specific dielectric parameters for the three different cellular lines. RESULTS: The relative variation of cellular capacitance with respect to that of the culture medium, estimated at 100 Hz, has a larger value for the two types of cancerous cells with respect to the noncancerous type. Furthermore, the ratio between the real and imaginary part of the dielectric permittivity function has larger values for metastatic cells with respect to the normal and nonmetastatic ones. Therefore, the mentioned relative capacitance allows to discriminate between normal and cancerous cells, whereas the results obtained for the dielectric function can discriminate between metastatic and nonmetastatic cells. CONCLUSIONS: This study can be considered as an exploratory investigation of evaluating in vitro the health status of humans cells using selected electrical impedance parameters as potential markers. The obtained results highlight that a standard cultureware system, provided with interdigitated electrodes and appropriate impedance parameters, that is, cellular capacitance and the ratio between the imaginary and real part of cellular dielectric function, can be used to discriminate between healthy and cancerous breast cell lines, as well as different malignancy degrees.

Raman spectroscopy for the evaluation of the radiobiological sensitivity of normal human breast cells at different time points after irradiation by a clinical proton beam.

Among different radiotherapy techniques, proton irradiation is an established and effective method for treatment of several types of cancer, because less healthy tissue is exposed with respect to conventional radiotherapy by photons/electrons. Recently, proton therapy has been proposed for the treatment of breast cancer. In vitro studies of proton irradiated normal human breast cells can provide information about cellular radioresponse, particularly as far as healthy tissue is concerned. In this paper, a study of the effects at different time points, following proton irradiation at different doses, of human normal MCF10A breast cells is performed by Raman spectroscopy. The aim of this investigation is to detect the unwanted effects of proton treatment and to investigate the possibility of monitoring them and of making an assessment of the cellular sensitivity by means of such a technique. The obtained results seem to indicate a rather significant sensitivity of MCF10A cells to proton irradiation. In fact, even at doses as low as 0.5 Gy, biological effects are clearly detectable in Raman spectra. In particular, ratiometric analysis of the Raman spectra measured from the nucleoplasm compartment showed that DNA/RNA damage increases with time, suggesting that most cells are unable to repair DNA/RNA broken bonds. The results obtained by the Raman spectroscopy analysis exhibit a similar trend with regard to dose to those obtained by commonly used radiobiological assays (i.e. MTT, clonogenic assay, senescence, apoptosis and necrosis). The results of this study strongly suggest the possibility that the Raman technique can be used to identify molecular markers predicting radiation response.

X-ray irradiation effects on nuclear and membrane regions of single SH-SY5Y human neuroblastoma cells investigated by Raman micro-spectroscopy.

Raman micro-spectroscopy was performed in vitro on nuclear and membrane regions of single SH-SY5Y human neuroblastoma cells after irradiation by graded X-ray doses (2, 4, 6, 8 Gy). The acquired spectra were analyzed by principal component analysis (PCA) and interval-PCA (i-PCA) methods. Biochemical changes occurring in the different regions of single cells as a consequence of the radiation exposure were observed in cells fixed immediately after the irradiation. The most relevant effects arose from the analysis of the spectra from the cell nucleus region. The observed changes were discussed in terms of the modifications in the cell cycle, resulting in an increase in the DNA-related signal, a protein rearrangement and changes in lipid and carbohydrates profiles within the nucleus. Potential markers of an apoptotic process in cell population irradiated with 6 and 8-Gy X-ray doses could have been singled out. No significant effects were found in spectra from cells fixed 24 h after the irradiation, thus suggesting the occurrence of repairing processes of the X-ray induced damage.

Correction: Exposure to 1.8 GHz electromagnetic fields affects morphology, DNA-related Raman spectra and mitochondrial functions in human lympho-monocytes.

[This corrects the article DOI: 10.1371/journal.pone.0192894.].

Exposure to 1.8 GHz electromagnetic fields affects morphology, DNA-related Raman spectra and mitochondrial functions in human lympho-monocytes.

Blood is a fluid connective tissue of human body, where it plays vital functions for the nutrition, defense and well-being of the organism. When circulating in peripheral districts, it is exposed to some physical stresses coming from outside the human body, as electromagnetic fields (EMFs) which can cross the skin. Such fields may interact with biomolecules possibly inducing non thermal-mediated biological effects at the cellular level. In this study, the occurrence of biochemical/biological modifications in human peripheral blood lympho-monocytes exposed in a reverberation chamber for times ranging from 1 to 20 h to EMFs at 1.8 GHz frequency and 200 V/m electric field strength was investigated. Morphological analysis of adherent cells unveiled, in some of these, appearance of an enlarged and deformed shape after EMFs exposure. Raman spectra of the nuclear compartment of cells exposed to EMFs revealed the onset of biochemical modifications, mainly consisting in the reduction of the DNA backbone-linked vibrational modes. Respirometric measurements of mitochondrial activity in intact lympho-monocytes resulted in increase of the resting oxygen consumption rate after 20 h of exposure, which was coupled to a significant increase of the FoF1-ATP synthase-related oxygen consumption. Notably, at lower time-intervals of EMFs exposure (i.e. 5 and 12 h) a large increase of the proton leak-related respiration was observed which, however, recovered at control levels after 20 h exposure. Confocal microscopy analysis of the mitochondrial membrane potential supported the respiratory activities whereas no significant variations in the mitochondrial mass/morphology was observed in EMFs-exposed lympho-monocytes. Finally, altered redox homeostasis was shown in EMFs-exposed lympho-monocytes, which progressed differently in nucleated cellular subsets. This results suggest the occurrence of adaptive mechanisms put in action, likely via redox signaling, to compensate for early impairments of the oxidative phosphorylation system caused by exposure to EMFs. Overall the data presented warn for health safety of people involved in long-term exposure to electromagnetic fields, although further studies are required to pinpoint the leukocyte cellular subset(s) selectively targeted by the EMFs action and the mechanisms by which it is achieved.

The revolution of personalized psychiatry: will technology make it happen sooner?

Personalized medicine (PM) aims to establish a new approach in clinical decision-making, based upon a patient's individual profile in order to tailor treatment to each patient's characteristics. Although this has become a focus of the discussion also in the psychiatric field, with evidence of its high potential coming from several proof-of-concept studies, nearly no tools have been developed by now that are ready to be applied in clinical practice. In this paper, we discuss recent technological advances that can make a shift toward a clinical application of the PM paradigm. We focus specifically on those technologies that allow both the collection of massive as much as real-time data, i.e., electronic medical records and smart wearable devices, and to achieve relevant predictions using these data, i.e. the application of machine learning techniques.

The potential for coral reef establishment through free-living stabilization.

Corals thrive in a variety of environments, from low wave and tidal energy lagoons, to high energy tidal reef flats, but remain dependent upon suitable substrate. Herein we reviewed the phenomenon of free-living corals (coralliths), examined whether they have the capacity to create their own stable habitat in otherwise uninhabitable, poor substrate environments through 'free-living stabilization', and explore their potential ecological role on coral reefs. This stabilization could be achieved by coral settlement and survival on mobile substrate, with subsequent growth into free-living coralliths until a critical mass is reached that prevents further movement. This allows for secondary reef colonization by other coral species. To preliminarily test this hypothesis we provide evidence that the potential to support secondary coral colonisation increases with corallith size. Due to the limited diversity of corallith species observed here and in the literature, and the lack of physiological differences exhibited by coralliths here to static controls, it seems likely that only a small selection of coral species have the ability to form coralliths, and the potential to create their own stable habitat.

Coralline algae in a naturally acidified ecosystem persist by maintaining control of skeletal mineralogy and size.

To understand the effects of ocean acidification (OA) on marine calcifiers, the trade-offs among different sublethal responses within individual species and the emergent effects of these trade-offs must be determined in an ecosystem setting. Crustose coralline algae (CCA) provide a model to test the ecological consequences of such sublethal effects as they are important in ecosystem functioning, service provision, carbon cycling and use dissolved inorganic carbon to calcify and photosynthesize. Settlement tiles were placed in ambient pH, low pH and extremely low pH conditions for 14 months at a natural CO2 vent. The size, magnesium (Mg) content and molecular-scale skeletal disorder of CCA patches were assessed at 3.5, 6.5 and 14 months from tile deployment. Despite reductions in their abundance in low pH, the largest CCA from ambient and low pH zones were of similar sizes and had similar Mg content and skeletal disorder. This suggests that the most resilient CCA in low pH did not trade-off skeletal structure to maintain growth. CCA that settled in the extremely low pH, however, were significantly smaller and exhibited altered skeletal mineralogy (high Mg calcite to gypsum (hydrated calcium sulfate)), although at present it is unclear if these mineralogical changes offered any fitness benefits in extreme low pH. This field assessment of biological effects of OA provides endpoint information needed to generate an ecosystem relevant understanding of calcifying system persistence.

An update of safety of clinically used atypical antipsychotics.

INTRODUCTION: The atypical antipsychotic (APs) drugs have become the most widely used agents to treat a variety of psychoses because of their superiority with regard to safety and tolerability profile compared to conventional/'typical' APs. AREAS COVERED: We aimed at providing a synthesis of most current evidence about the safety and tolerability profile of the most clinically used atypical APs so far marketed. Qualitative synthesis followed an electronic search made inquiring of the following databases: MEDLINE, Embase, PsycINFO and the Cochrane Library from inception until January 2016, combining free terms and MESH headings for the topics of psychiatric disorders and all atypical APs as following: ((safety OR adverse events OR side effects) AND (aripiprazole OR asenapine OR quetiapine OR olanzapine OR risperidone OR paliperidone OR ziprasidone OR lurasidone OR clozapine OR amisulpride OR iloperidone)). EXPERT OPINION: A critical issue in the treatment with atypical APs is represented by their metabolic side effect profile (e.g. weight gain, lipid and glycaemic imbalance, risk of diabetes mellitus and diabetic ketoacidosis) which may limit their use in particular clinical samples. Electrolyte imbalance, ECG abnormalities and cardiovascular adverse effects may recommend a careful baseline and periodic assessments.

The prevalence and predictors of bipolar and borderline personality disorders comorbidity: Systematic review and meta-analysis.

INTRODUCTION: Data about the prevalence of borderline personality (BPD) and bipolar (BD) disorders comorbidity are scarce and the boundaries remain controversial. We conducted a systematic review and meta-analysis investigating the prevalence of BPD in BD and BD in people with BPD. METHODS: Two independent authors searched MEDLINE, Embase, PsycINFO and the Cochrane Library from inception till November 4, 2015. Articles reporting the prevalence of BPD and BD were included. A random effects meta-analysis and meta-regression were conducted. RESULTS: Overall, 42 papers were included: 28 considering BPD in BD and 14 considering BD in BPD. The trim and fill adjusted analysis demonstrated the prevalence of BPD among 5273 people with BD (39.94 ± 11.78 years, 44% males) was 21.6% (95% CI 17.0-27.1). Higher comorbid BPD in BD were noted in BD II participants (37.7%, 95% CI 21.9-56.6, studies=6) and North American studies (26.2%, 95% CI 18.7-35.3, studies=11). Meta regression established that a higher percentage of males and higher mean age significantly (p<0.05) predicted a lower prevalence of comorbid BPD in BD participants. The trim and fill adjusted prevalence of BD among 1814 people with BPD (32.22 ± 7.35 years, 21.5% male) was 18.5% (95% CI 12.7-26.1). LIMITATIONS: Paucity of longitudinal/control group studies and accurate treatment records. CONCLUSIONS: BPD-BD comorbidity is common, with approximately one in five people experiencing a comorbid diagnosis. Based on current diagnostic constructs, and a critical interpretation of results, both qualitative and quantitative syntheses of the evidence prompt out the relevance of differences rather similarities between BD and BPD.

Does the "Silver Bullet" Lose its Shine Over the Time? Assessment of Loss of Lithium Response in a Preliminary Sample of Bipolar Disorder Outpatients.

BACKGROUND: Though often perceived as a "silver bullet" treatment for bipolar disorder (BD), lithium has seldom reported to lose its efficacy over the time. OBJECTIVE: The aim of the present study was to assess cases of refractoriness toward restarted lithium in BD patients who failed to preserve maintenance. METHOD: Treatment trajectories associated with re-instituted lithium following loss of achieved lithium-based maintenance in BD were retrospectively reviewed for 37 BD-I patients (median age 52 years; F:M=17:20 or 46% of the total) over an 8.1-month period on average. RESULTS: In our sample only 4 cases (roughly 11% of the total, of whom F:M=2:2) developed refractoriness towards lithium after its discontinuation. Thirty-three controls (F:M=15:18) maintained lithium response at the time of re-institution. No statistically significant difference between cases and controls was observed with respect to a number of demographic and clinical features but for time spent before first trial ever with lithium in life (8.5 vs. 3 years; U=24.5, Z=-2.048, p=.041) and length of lithium discontinuation until new therapeutic attempt (5.5 vs. 2 years; U=8, Z=-2.927, p=.003) between cases vs. controls respectively. Tapering off of lithium was significantly faster among cases vs. controls (1 vs. 7 days; U=22, Z=-2.187), though both subgroups had worrisome high rates of poor adherence overall. CONCLUSION: Although intrinsic limitations of the present preliminary assessment hamper the validity and generalizability of overall results, stating the clinical relevance of the topic further prospective research is warranted. The eventual occurrence of lithium refractoriness may indeed be associated with peculiar course trajectories and therapeutic outcomes ultimately urging the prescribing clinicians to put efforts in preserving maintenance of BD in the absence of any conclusive research insight on the matter.

Hidden impacts of ocean acidification to live and dead coral framework.

Cold-water corals, such as Lophelia pertusa, are key habitat-forming organisms found throughout the world's oceans to 3000 m deep. The complex three-dimensional framework made by these vulnerable marine ecosystems support high biodiversity and commercially important species. Given their importance, a key question is how both the living and the dead framework will fare under projected climate change. Here, we demonstrate that over 12 months L. pertusa can physiologically acclimate to increased CO2, showing sustained net calcification. However, their new skeletal structure changes and exhibits decreased crystallographic and molecular-scale bonding organization. Although physiological acclimatization was evident, we also demonstrate that there is a negative correlation between increasing CO2 levels and breaking strength of exposed framework (approx. 20-30% weaker after 12 months), meaning the exposed bases of reefs will be less effective 'load-bearers', and will become more susceptible to bioerosion and mechanical damage by 2100.

Morphology of synthetic DOPA-eumelanin deposited on glass and mica substrates: an atomic force microscopy investigation.

Bright field microscopy and atomic force microscopy techniques are used to investigate morphological properties of synthetic eumelanin, obtained by oxidation of L-DOPA solution, deposited on glass and mica substrates. Deposits of eumelanin are characterized by aggregates with different shape and size. On a micrometric scale, filamentous as well as granular structures are present on glass and mica substrates, with a larger density on the former than on the latter. On a nanometric scale, filamentous aggregates, several microns long and about 100 nm wide and high, and granular aggregates, ∼50 nm high and 100 nm wide, are found on both substrates, whereas point-like deposits less than 10nm high and less than 50 nm wide are found on mica substrate. Dynamic light scattering measurements and atomic force microscopy images support the evidence that eumelanin presents only nanometric point-like aggregates in aqueous solution, whereas such nanoaggregates organize themselves according to granular and filamentous structures when deposition occurs, as a consequence of interactions with the substrate surface.

Care manager to control cardiovascular risk factors in primary care: the Raffaello cluster randomized trial.

BACKGROUND AND AIM: This cluster randomized trial evaluated the efficacy of a disease and care management (D&CM) model in cardiovascular (CVD) prevention in primary care. METHODS AND RESULTS: Eligible subjects had ≥ 1 among: blood pressure ≥ 140/90 mmHg; glycated hemoglobin ≥ 7%; LDL-cholesterol ≥ 160 or ≥ 100 mg/dL (primary or secondary prevention, respectively); BMI ≥ 30; current smoking. The D&CM intervention included a teamwork including nurses as care managers for the implementation of tailored care plans. Control group was allocated to usual-care. The main outcome was the proportion of subjects achieving recommended clinical targets for ≥ 1 of uncontrolled CVD risk factors at 12-month. During 2008-2009 we enrolled 920 subjects in the Abruzzo/Marche regions, Italy. Following the exclusion of L'Aquila due to 2009 earthquake, final analyses included 762 subjects. The primary outcome was achieved by 39.1% (95%CI: 34.2-44.2) and 25.2% (95%CI: 20.9-29.9) of subjects in the intervention and usual-care group, respectively (p < 0.001). The D&CM intervention significantly increased the proportion of subjects who achieved clinical targets for both diabetes and hypertension, with no differences in hypercholesterolemia, smoking status and obesity. CONCLUSIONS: The D&CM intervention was effective in controlling cardiovascular risk factors, in particular hypertension and diabetes. Numbers needed to treat were small. Such intervention may deserve further consideration in clinical practice. REGISTRATION NUMBER: ACTRN12611000813987.