Preoperative MRI radiomic analysis for predicting local tumor progression in colorectal liver metastases before microwave ablation.

PURPOSE: Radiomics may aid in predicting prognosis in patients with colorectal liver metastases (CLM). Consistent data is available on CT, yet limited data is available on MRI. This study assesses the capability of MRI-derived radiomic features (RFs) to predict local tumor progression-free survival (LTPFS) in patients with CLMs treated with microwave ablation (MWA). METHODS: All CLM patients with pre-operative Gadoxetic acid-MRI treated with MWA in a single institution between September 2015 and February 2022 were evaluated. Pre-procedural information was retrieved retrospectively. Two observers manually segmented CLMs on T2 and T1-Hepatobiliary phase (T1-HBP) scans. After inter-observer variability testing, 148/182 RFs showed robustness on T1-HBP, and 141/182 on T2 (ICC > 0.7).Cox multivariate analysis was run to establish clinical (CLIN-mod), radiomic (RAD-T1, RAD-T2), and combined (COMB-T1, COMB-T2) models for LTPFS prediction. RESULTS: Seventy-six CLMs (43 patients) were assessed. Median follow-up was 14 months. LTP occurred in 19 lesions (25%).CLIN-mod was composed of minimal ablation margins (MAMs), intra-segment progression and primary tumor grade and exhibited moderately high discriminatory power in predicting LTPFS (AUC = 0.89, p = 0.0001). Both RAD-T1 and RAD-T2 were able to predict LTPFS: (RAD-T1: AUC = 0.83, p = 0.0003; RAD-T2: AUC = 0.79, p = 0.001). Combined models yielded the strongest performance (COMB-T1: AUC = 0.98, p = 0.0001; COMB-T2: AUC = 0.95, p = 0.0003). Both combined models included MAMs and tumor regression grade; COMB-T1 also featured 10th percentile of signal intensity, while tumor flatness was present in COMB-T2. CONCLUSION: MRI-based radiomic evaluation of CLMs is feasible and potentially useful for LTP prediction. Combined models outperformed clinical or radiomic models alone for LTPFS prediction.

Perinatal serotonergic manipulation shapes anhedonic and cognitive behaviors in a sex- and age-dependent manner: Identification of related biological functions at central and peripheral level.

Poor knowledge about psychiatric disorders often results in similar diagnoses for patients with different symptoms, thus limiting the effectiveness of the available medications. As suggested by several lines of evidence, to improve these shortcomings, it is essential to identify biomarkers associated with specific symptoms and to stratify patients into more homogeneous populations taking a further step toward personalized medicine. Here, we aimed to associate specific behavioral phenotypes with specific molecular alterations by employing an animal model based on the pharmacological manipulation of the serotonergic system, which mimics a condition of vulnerability to develop psychiatric disorders. In particular, we treated female and male rats with fluoxetine (FLX 15 mg/kg dissolved in drinking water) during prenatal or early postnatal life, and we evaluated different pathological-like phenotypes (cognitive deficit, anhedonia, and anxiety) by exposing the rats to a battery of behavioral tests during adolescence and adulthood. In addition, we carried out molecular analyses on specific brain areas and in the blood. Our results showed that perinatal FLX administration determined age- and sex-dependent effects, with males being more sensitive to prenatal manipulation and manifesting anhedonic-like behavior and females to early postnatal exposure, exhibiting cognitive deficits and a less anxious phenotype. Furthermore, we identified, peripherally and centrally, biological functions altered by perinatal serotonin modulation regardless of the timing of exposure and sex, and other pathways specific for the pathological-like phenotypes. The results presented here provide new insights into potential biomarkers associated with specific behavioral phenotypes that may be useful for broadening knowledge about psychiatric conditions.

Resilience to chronic mild stress-induced anhedonia preserves the ability of the ventral hippocampus to respond to an acute challenge.

Stress is a major precipitating factor for psychiatric disorders and its effects may depend on its duration and intensity. Of note, there are differences in individual susceptibility to stress, with some subjects displaying vulnerability and others showing resistance. Furthermore, the ability to react to stressful-life events can alter the response to a subsequent new stressor. Hence, we investigated whether the vulnerability and resilience to the chronic mild stress (CMS) paradigm, in terms of the hedonic phenotype, are paralleled by a different response when facing a novel acute challenge. Specifically, rats submitted to CMS were stratified based on their sucrose intake into vulnerable (anhedonic rats showing reduce intake of sucrose) and resilient (rats not showing the anhedonic-like behavior) subgroups and then further exposed to an acute restraint stress (ARS). Then, neuronal activation was investigated by measuring the gene expression of early immediate (IEG) genes such as Arc and Cfos and early response (ERG) genes, such as Gadd45ß, Sgk1, Dusp1, and Nr4a1, in brain regions that play a crucial role in the stress response. We found that resilient rats preserve the ability to increase ERG expression following the ARS selectively in the ventral hippocampus. Conversely, such ability is lost in vulnerable rats. Interestingly, the recovery from the anhedonic phenotype observed in vulnerable rats after 3 weeks of rest from the CMS procedure also parallels the restoration of the ability to adequately respond to the challenge. In conclusion, these findings support the role of the ventral subregion of the hippocampus in the management of both chronic and acute stress response and point to this brain subregion as a critical target for a potential therapeutic strategy aimed at promoting stress resilience.

Chronic N-Acetyl-Cysteine Treatment Enhances the Expression of the Immediate Early Gene Nr4a1 in Response to an Acute Challenge in Male Rats: Comparison with the Antidepressant Venlafaxine.

Despite several antidepressant treatments being available in clinics, they are not effective in all patients. In recent years, N-acetylcysteine (NAC) has been explored as adjunctive therapy for many psychiatric disorders, including depression, for its antioxidant properties. Given the promising efficacy of this compound for the treatment of such pathologies, it is fundamental to investigate, at the preclinical level, the ability of the drug to act in the modulation of neuroplastic mechanisms in basal conditions and during challenging events in order to highlight the potential features of the drug useful for clinical efficacy. To this aim, adult male Wistar rats were treated with the antidepressant venlafaxine (VLX) (10 mg/kg) or NAC (300 mg/kg) for 21 days and then subjected to 1 h of acute restraint stress (ARS). We found that NAC enhanced the expression of several immediate early genes, markers of neuronal plasticity in the ventral and dorsal hippocampus, prefrontal cortex and amygdala, and in particular it mediated the acute-stress-induced upregulation of Nr4a1 expression more than VLX. These data suggested the ability of NAC to induce coping strategies to face external challenges, highlighting its potential for the improvement of neuroplastic mechanisms for the promotion of resilience, in particular via the modulation of Nr4a1.

Diabetic Encephalopathy in a Preclinical Experimental Model of Type 1 Diabetes Mellitus: Observations in Adult Female Rat.

Patients affected by diabetes mellitus (DM) show diabetic encephalopathy with an increased risk of cognitive deficits, dementia and Alzheimer's disease, but the mechanisms are not fully explored. In the male animal models of DM, the development of cognitive impairment seems to be the result of the concomitance of different processes such as neuroinflammation, oxidative stress, mitochondrial dysfunction, and aberrant synaptogenesis. However, even if diabetic encephalopathy shows some sex-dimorphic features, no observations in female rats have been so far reported on these aspects. Therefore, in an experimental model of type 1 DM (T1DM), we explored the impact of one month of pathology on memory abilities by the novel object recognition test and on neuroinflammation, synaptogenesis and mitochondrial functionality. Moreover, given that steroids are involved in memory and learning, we also analysed their levels and receptors. We reported that memory dysfunction can be associated with different features in the female hippocampus and cerebral cortex. Indeed, in the hippocampus, we observed aberrant synaptogenesis and neuroinflammation but not mitochondrial dysfunction and oxidative stress, possibly due to the results of locally increased levels of progesterone metabolites (i.e., dihydroprogesterone and allopregnanolone). These observations suggest specific brain-area effects of T1DM since different alterations are observed in the cerebral cortex.

Cerebral hyperdensity on CT imaging (CTHD) post-reperfusion treatment in patients with acute cerebral stroke: understanding its clinical meaning.

OBJECTIVES: To investigate the clinical meaning of brain parenchymal computed-tomography hyperdensities (CTHD) in patients treated of anterior circulation acute stroke with reperfusion therapy. METHODS: Patients were retrospectively enrolled from three different hospitals. Brain CT scans were assessed at four time points: We recorded ASPECT scores of pre-treatment CTs, assessed ASPECT scores and the presence of CTHD on post-treatment CTs acquired within 24-30 h and 24-72 h, and examined a one-month CTs follow-up to determine the ischemic evolution of CTHD. We correlated the presence of CTHD with clinical and radiological data to define its predictive and prognostic factors. RESULTS: In total, 165 patients were evaluated. At post-treatment CTs acquired within 24-30 h, 68 (41%) patients showed the presence of CTHD. On post-treatment CTs acquired within 24-72 h, 43 (63%) of the CTHD showed hemorrhagic transformation. Sixty-five (95%) out of the 68 CTHD evolved in a final ischemic brain area. Multivariate statistical analysis identified puncture to recanalization time to be the only independent factors predicting the presence of CTHD (p = 0.045). The presence of CTHD at the first post-treatment CTs was an independent factor for clinical outcome determined with mRS scores at 3-month follow-up (p = 0.05). Outcomes were worse for hemorrhagic transformation at follow-up CTs compared to the ischemic evolution of the CTHD (p = 0.01). CONCLUSIONS: The presence of CTHD at CTs imaging acquired within 24-30 h after reperfusion therapy is an independent prognostic factor of a worse clinical outcome, regardless of its ASPECT score at baseline CTs and of its hemorrhagic evolution.

Peripheral Serotonin Deficiency Affects Anxiety-like Behavior and the Molecular Response to an Acute Challenge in Rats.

Serotonin is synthetized through the action of tryptophan hydroxylase (TPH) enzymes. While the TPH2 isoform is responsible for the production of serotonin in the brain, TPH1 is expressed in peripheral organs. Interestingly, despite its peripheral localization, alterations of the gene coding for TPH1 have been related to stress sensitivity and an increased susceptibility for psychiatric pathologies. On these bases, we took advantage of newly generated TPH1-/- rats, and we evaluated the impact of the lack of peripheral serotonin on the behavior and expression of brain plasticity-related genes under basal conditions and in response to stress. At a behavioral level, TPH1-/- rats displayed reduced anxiety-like behavior. Moreover, we found that neuronal activation, quantified by the expression of Bdnf and the immediate early gene Arc and transcription of glucocorticoid responsive genes after 1 h of acute restraint stress, was blunted in TPH1-/- rats in comparison to TPH1+/+ animals. Overall, we provided evidence for the influence of peripheral serotonin levels in modulating brain functions under basal and dynamic situations.

Subarachnoid haemorrhage due to the rupture of a high flow aneurysm developed on an intradural artery feeding a jugulotympanic paraganglioma.

BACKGROUND: Head and neck paragangliomas are extradural masses rarely associated with subarachnoid haemorrhage. CASE: This case, for the first time, reports a fatal subarachnoid haemorrhage due to the rupture of a high-flow aneurysm located on an intradural artery feeding a jugulotympanic paraganglioma. Interestingly, this aneurysm was not present on an angiogram performed 7 years before, during the pre-surgical embolisation of the tumour. CONCLUSIONS: To avoid fatal consequences, a preventive investigation of potential aneurysms located on intradural vessels feeding paragangliomas may be suggested.

BDNF Overexpression in the Ventral Hippocampus Promotes Antidepressant- and Anxiolytic-Like Activity in Serotonin Transporter Knockout Rats.

BDNF plays a pivotal role in neuroplasticity events, vulnerability and resilience to stress-related disorders, being decreased in depressive patients and increased after antidepressant treatment. BDNF was found to be reduced in patients carrying the human polymorphism in the serotonin transporter promoter region (5-HTTLPR). The serotonin knockout rat (SERT-/-) is one of the animal models used to investigate the underlying molecular mechanisms of depression in humans. They present decreased BDNF levels, and anxiety- and depression-like behavior. To investigate whether upregulating BDNF would ameliorate the phenotype of SERT-/- rats, we overexpressed BDNF locally into the ventral hippocampus and submitted the animals to behavioral testing. The results showed that BDNF overexpression in the vHIP of SERT-/- rats promoted higher sucrose preference and sucrose intake; on the first day of the sucrose consumption test it decreased immobility time in the forced swim test and increased the time spent in the center of a novel environment. Furthermore, BDNF overexpression altered social behavior in SERT-/- rats, which presented increased passive contact with test partner and decreased solitary behavior. Finally, it promoted decrease in plasma corticosterone levels 60 min after restraint stress. In conclusion, modulation of BDNF IV levels in the vHIP of SERT-/- rats led to a positive behavioral outcome placing BDNF upregulation in the vHIP as a potential target to new therapeutic approaches to improve depressive symptoms.

Stress Modifies the Expression of Glucocorticoid-Responsive Genes by Acting at Epigenetic Levels in the Rat Prefrontal Cortex: Modulatory Activity of Lurasidone.

Epigenetics is one of the mechanisms by which environmental factors can alter brain function and may contribute to central nervous system disorders. Alterations of DNA methylation and miRNA expression can induce long-lasting changes in neurobiological processes. Hence, we investigated the effect of chronic stress, by employing the chronic mild stress (CMS) and the chronic restraint stress protocol, in adult male rats, on the glucocorticoid receptor (GR) function. We focused on DNA methylation specifically in the proximity of the glucocorticoid responsive element (GRE) of the GR responsive genes Gadd45ß, Sgk1, and Gilz and on selected miRNA targeting these genes. Moreover, we assessed the role of the antipsychotic lurasidone in modulating these alterations. Chronic stress downregulated Gadd45ß and Gilz gene expression and lurasidone normalized the Gadd45ß modification. At the epigenetic level, CMS induced hypermethylation of the GRE of Gadd45ß gene, an effect prevented by lurasidone treatment. These stress-induced alterations were still present even after a period of rest from stress, indicating the enduring nature of such changes. However, the contribution of miRNA to the alterations in gene expression was moderate in our experimental conditions. Our results demonstrated that chronic stress mainly affects Gadd45ß expression and methylation, effects that are prolonged over time, suggesting that stress leads to changes in DNA methylation that last also after the cessation of stress procedure, and that lurasidone is a modifier of such mechanisms.

Acute Stress Induces Cognitive Improvement in the Novel Object Recognition Task by Transiently Modulating Bdnf in the Prefrontal Cortex of Male Rats.

Stress response involves several mechanisms and mediators that allow individuals to adapt to a changing environment. The effects of stress may be adaptive or maladaptive, based on the timing and intensity of exposure as well as on the individual vulnerability. In particular, exposure to mild and brief stressors provides beneficial advantages in a short-term period, by activating protective functions to react with the external demands. On these bases, the purpose of our study was to establish the time-dependent effects of acute stress exposure on neuroplastic mechanisms in adult male rats. Moreover, we aim at establishing the consequences of the acute challenge on memory processes by testing rats in the Novel Object Recognition (NOR) test. We found that acute restraint stress up-regulated total Bdnf expression 1 h post stress specifically in rat prefrontal cortex, an effect that was sustained by the increase of Bdnf isoform IV as well as by the pool of Bdnf transcripts with long 3'UTR. Furthermore, in the same brain region, the acute stress modulated in a time-specific manner the expression of different activity-dependent genes, namely Arc, Gadd45ß and Nr4a1. At behavioral level, the challenge was able to improve the performance in the NOR test specifically 1 h post stress, an effect that positively correlated with the expression of the neurotrophic factors. Taken together, our results suggest that a single session of acute stress enhances memory and learning functions with a specific temporal profile, by improving neuroplastic mechanisms within the prefrontal cortex.

Systemic sclerosis Progression INvestiGation (SPRING) Italian registry: demographic and clinico-serological features of the scleroderma spectrum.

OBJECTIVES: Systemic sclerosis (SSc) is a severe multiple-organ disease characterised by unpredictable clinical course, inadequate response to treatment, and poor prognosis. National SSc registries may provide large and representative patients cohorts required for descriptive and prognostic studies. Therefore, the Italian Society for Rheumatology promoted the registry SPRING (Systemic sclerosis Progression INvestiGation). METHODS: The SPRING is a multi-centre rheumatological cohort study encompassing the wide scleroderma spectrum, namely the primary Raynaud's phenomenon (pRP), suspected secondary RP, Very Early Diagnosis of Systemic Sclerosis (VEDOSS), and definite SSc. Here we describe the demographic and clinical characteristics of a population of 2,028 Italian patients at the initial phase of enrolment, mainly focusing on the cohort of 1,538 patients with definite SSc. RESULTS: Definite SSc showed a significantly higher prevalence of digital ulcers, capillaroscopic 'late' pattern, oesophageal and cardio-pulmonary involvement compared to VEDOSS, as expected on the basis of the followed classification criteria. The in-depth analysis of definite SSc revealed that male gender, diffuse cutaneous subset, and anti-Scl70 seropositivity were significantly associated with increased prevalence of the most harmful disease manifestations. Similarly, patients with very short RP duration (≤1 year) at SSc diagnosis showed a statistically increased prevalence of unfavourable clinico-serological features. CONCLUSIONS: Nationwide registries with suitable subsetting of patients and follow-up studies since the prodromal phase of the disease may give us valuable insights into the SSc natural history and main prognostic factors.

The role of dopamine D3 receptors in the mechanism of action of cariprazine.

Cariprazine is a new atypical antipsychotic drug (APD) with a unique pharmacodynamic profile, different from both typical and atypical APDs. Specifically, cariprazine acts as a partial agonist at the dopamine (DA) D2 and D3 receptors and serotonin 5-HT1A receptors, and as an antagonist at the 5-HT2B receptors. Moreover, it shows moderate affinities for adrenergic, histaminergic, and cholinergic receptors that are involved in mediating the side effects characteristic of typical APDs. In this review, we discuss the contribution of DA D3 receptors (D3Rs) in the etiology and pathophysiology of schizophrenia and the potential benefits that may be associated with a more selective targeting of D3R by APDs, as compared to other dopaminergic and non-dopaminergic receptor subtypes. Cariprazine, by acting on D3Rs, ameliorates anhedonia and cognitive deficits in animal models based on environmental or pharmacological manipulation. The reviewed results support the potential benefits of cariprazine in treating negative symptoms and cognitive deficits of schizophrenia, and therefore representing a promising approach in addressing the unmet clinical needs for the improved treatment of this serious neuropsychiatric disorder.

Chronic Restraint Stress Inhibits the Response to a Second Hit in Adult Male Rats: A Role for BDNF Signaling.

Depression is a recurrent disorder, with about 50% of patients experiencing relapse. Exposure to stressful events may have an adverse impact on the long-term course of the disorder and may alter the response to a subsequent stressor. Indeed, not all the systems impaired by stress may normalize during symptoms remission, facilitating the relapse to the pathology. Hence, we investigated the long-lasting effects of chronic restraint stress (CRS) and its influence on the modifications induced by the exposure to a second hit on brain-derived neurotrophic factor (BDNF) signaling in the prefrontal cortex (PFC). We exposed adult male Sprague Dawley rats to 4 weeks of CRS, we left them undisturbed for the subsequent 3 weeks, and then we exposed animals to one hour of acute restraint stress (ARS). We found that CRS influenced the release of corticosterone induced by ARS and inhibited the ability of ARS to activate mature BDNF, its receptor Tropomyosin receptor kinase B (TRKB), and their associated intracellular cascades: the TRKB-PI3K-AKT), the MEK-MAPK/ERK, and the Phospholipase C γ (PLCγ) pathways, positively modulated by ARS in non-stressed animals. These results suggest that CRS induces protracted and detrimental consequences that interfere with the ability of PFC to cope with a challenging situation.

Alterations of Glutamatergic Markers in the Prefrontal Cortex of Serotonin Transporter Knockout Rats: A Developmental Timeline.

The serotoninergic system plays a key role in environmental sensitivity, potentially through down-stream effects on the GABAergic and glutamatergic systems. We previously demonstrated that juvenile serotonin transporter knockout (SERT-/-) rats, showing increased environmental sensitivity, exhibit a decreased GABA-mediated inhibitory tone in the cortex. Since the GABAergic and glutamatergic systems are tightly interconnected, we here analyzed glutamatergic markers in the prefrontal cortex of SERT-/- rats, from the early stages of life until adulthood. We found that SERT inactivation in pre-weaning, juvenile, and adult rats was associated with reduced expression of proteins essential for the glutamatergic synapses such as GluN1, PSD95, CDC42, and SEPT7. These lifelong molecular changes may destabilize glutamatergic signaling and possibly contribute to stress sensitivity and vulnerability to stress-related disorders associated with SERT alteration.

Chronic vortioxetine treatment improves the responsiveness to an acute stress acting through the ventral hippocampus in a glucocorticoid-dependent way.

Vortioxetine is a novel multimodal antidepressant approved in 2013 by the Food and Drug Administration and the European Medicines Agency for the treatment of major depressive disorder (MDD). It combines the modulation of serotonin receptors activity with the inhibition of serotonin transporter (SERT). In this study, we aim at establishing the effect of chronic vortioxetine treatment (5 mg/kg twice/daily) in modulating neuroplastic mechanisms as well as hypothalamic pituitary adrenal axis (HPA) activity under basal condition and in response to an acute challenge. We found that prolonged vortioxetine administration significantly increased total Bdnf expression in the dorsal and ventral hippocampus of adult male rats and affected the stress-induced modulation of the immediate early genes Arc and Zif268, mainly in the ventral sub-region. Moreover, we also found that, within this brain area, chronic drug treatment was able to modulate glucocorticoid responsiveness at genomic level by enhancing the translocation of the glucocorticoid receptor (GR) in the nuclear compartment in response to the acute stress. Interestingly, this effect was mirrored by the up-regulation of different GR responsive-genes. Taken together, our data suggest that repeated exposure to vortioxetine specifically targets the ventral hippocampus by improving the ability to cope with stressful conditions. Moreover, its ability to facilitate HPA axis function might provide an indication to use this drug in patients characterized by glucocorticoid resistance.

d-Cycloserine enhanced extinction of cocaine-induced conditioned place preference is attenuated in serotonin transporter knockout rats.

d-Cycloserine (DCS), a partial NMDA receptor agonist, has been proposed as a cognitive enhancer to facilitate the extinction of drug-related memories. However, it is unknown whether there are individual differences in the efficacy of DCS. Here, we set out to investigate the influence of serotonin transporter (5-HTT) genotype on DCS treatment outcome and the underlying neural mechanism. To that end, we first determined the mRNA levels of several NMDA receptor subunits and observed a reduction in NR1/NR2C receptors in the ventromedial prefrontal cortex and nucleus accumbens of 5-HTT-/- compared with 5-HTT+/+ rats. Based on this finding, we hypothesized a lower sensitivity to DCS in the 5-HTT-/- rats. To test this, rats were trained in a cocaine-induced conditioned place preference (CPP) paradigm. A significant extinction of CPP was observed in 5-HTT+/+ rats receiving 1 mg/kg i.v. DCS, while a similar effect was found in the 5-HTT-/- rats only after 5 mg/kg. Following CPP, we tested if DCS were able to reduce FosB/∆FosB protein expression, a molecular switch for cocaine-seeking behaviour. We observed an overall lower number of FosB/∆FosB positive cells in 5-HTT-/- ventromedial prefrontal cortex and amygdala and an overall effect of DCS treatment on the number of positive cells in the nucleus accumbens. In conclusion, in this study, we show that the dosing of DCS to facilitate the extinction of cocaine-seeking behaviour is, at least partially, determined by 5-HTT genotype.

Upregulation of neurotrophins by S 47445, a novel positive allosteric modulator of AMPA receptors in aged rats.

At molecular levels, it has been shown that aging is associated with alterations in neuroplastic mechanisms. In this study, it was examined if the altered expression of neurotrophins observed in aged rats could be corrected by a chronic treatment with S 47445 (1-3-10mg/kg, p.o.), a novel selective positive allosteric modulator of the AMPA receptors. Both the mRNA and the protein levels of the neurotrophins Bdnf, NT-3 and Ngf were specifically measured in the prefrontal cortex and hippocampus (ventral and dorsal) of aged rats. It was found that 2-week-treatment with S 47445 corrected the age-related deficits of these neurotrophins and/or positively modulated their expression in comparison to vehicle aged rats in the range of procognitive and antidepressant active doses in rodents. Collectively, the ability of S 47445 to modulate various neurotrophins demonstrated its neurotrophic properties in two major brain structures involved in cognition and mood regulation suggesting its therapeutic potential for improving several diseases such as Alzheimer's disease and/or Major Depressive Disorders.

Single-center experience in urgent lung transplantation program in a country with a shortage of donors: Does the end justify the means?

In rapidly deteriorating patients awaiting lung transplantation (LT), supportive strategies are only temporary and urgent lung transplant (ULT) remains the last option. The few publications on this topic report conflicting results. According to the Italian national program, patients on mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO) may be included in urgent list. We reviewed our experience from January 2012 to December 2014 with ULT and elective lung transplantation (ELT), focusing on outcomes. In the study period, 16 patients received ULT, while 51 received ELT. Among ULT, 1 patient (5.8%) died in waiting list (WL) while 16 patients underwent LT with a median WL time of 6 days. ELT WL mortality was 13.5%, and median WL time 368 days. In-hospital mortality was lower in ELT group (5.8% vs 37.5%, P < .01), while the other postoperative outcomes were not significantly different. For ULT patients, the highest impact risk factors for in-hospital mortality were pretransplant plasma transfusion, recipient Pseudomonas aeruginosa colonization, and high level of reactive C-protein and lactic acid. A ULT program with an accurate recipient selection allows earlier transplantation, reducing WL mortality, with acceptable outcomes, although with a higher in-hospital mortality. Larger studies are needed to validate our results.

Botanicals as Modulators of Neuroplasticity: Focus on BDNF.

The involvement of brain-derived neurotrophic factor (BDNF) in different central nervous system (CNS) diseases suggests that this neurotrophin may represent an interesting and reliable therapeutic target. Accordingly, the search for new compounds, also from natural sources, able to modulate BDNF has been increasingly explored. The present review considers the literature on the effects of botanicals on BDNF. Botanicals considered were Bacopa monnieri (L.) Pennell, Coffea arabica L., Crocus sativus L., Eleutherococcus senticosus Maxim., Camellia sinensis (L.) Kuntze (green tea), Ginkgo biloba L., Hypericum perforatum L., Olea europaea L. (olive oil), Panax ginseng C.A. Meyer, Rhodiola rosea L., Salvia miltiorrhiza Bunge, Vitis vinifera L., Withania somnifera (L.) Dunal, and Perilla frutescens (L.) Britton. The effect of the active principles responsible for the efficacy of the extracts is reviewed and discussed as well. The high number of articles published (more than one hundred manuscripts for 14 botanicals) supports the growing interest in the use of natural products as BDNF modulators. The studies reported strengthen the hypothesis that botanicals may be considered useful modulators of BDNF in CNS diseases, without high side effects. Further clinical studies are mandatory to confirm botanicals as preventive agents or as useful adjuvant to the pharmacological treatment.