Search

Background Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) offers the potential to noninvasively characterize the phenotypic substrate for sudden cardiac death (SCD). Objectives The authors assessed the utility of infarct characterization by CMR, including scar microstructure analysis, to predict SCD in patients with coronary artery disease (CAD). Methods Patients with stable CAD were prospectively recruited into a CMR registry. LGE quantification of core infarction and the peri-infarct zone (PIZ) was performed alongside computational image analysis to extract morphologic and texture scar microstructure features. The primary outcome was SCD or aborted SCD. Results Of 437 patients (mean age: 64 years; mean left ventricular ejection fraction [LVEF]: 47%) followed for a median of 6.3 years, 49 patients (11.2%) experienced the primary outcome. On multivariable analysis, PIZ mass and core infarct mass were independently associated with the primary outcome (per gram: HR: 1.07 [95% CI: 1.02-1.12]; P = 0.002 and HR: 1.03 [95% CI: 1.01-1.05]; P = 0.01, respectively), and the addition of both parameters improved discrimination of the model (Harrell’s C-statistic: 0.64-0.79). PIZ mass, however, did not provide incremental prognostic value over core infarct mass based on Harrell’s C-statistic or risk reclassification analysis. Severely reduced LVEF did not predict the primary endpoint after adjustment for scar mass. On scar microstructure analysis, the number of LGE islands in addition to scar transmurality, radiality, interface area, and entropy were all associated with the primary outcome after adjustment for severely reduced LVEF and New York Heart Association functional class of >1. No scar microstructure feature remained associated with the primary endpoint when PIZ mass and core infarct mass were added to the regression models. Conclusions Comprehensive LGE characterization independently predicted SCD risk beyond conventional predictors used in implantable cardioverter-defibrillator (ICD) insertion guidelines. These results signify the potential for a more personalized approach to determining ICD candidacy in CAD.

Background: Maternal cardiovascular risk factors have been associated with adverse maternal and fetal outcomes. Given the difficulty in establishing causal relationships using epidemiological data, we applied Mendelian randomization to explore the role of cardiovascular risk factors on risk of developing preeclampsia or eclampsia, and low fetal birthweight. Methods: Uncorrelated single-nucleotide polymorphisms associated systolic blood pressure (SBP), body mass index, type 2 diabetes, LDL (low-density lipoprotein) with cholesterol, smoking, urinary albumin-to-creatinine ratio, and estimated glomerular filtration rate at genome-wide significance in studies of 298 957 to 1 201 909 European ancestry participants were selected as instrumental variables. A 2-sample Mendelian randomization study was performed with primary outcome of preeclampsia or eclampsia (PET). Risk factors associated with PET were further investigated for their association with low birthweight. Results: Higher genetically predicted SBP was associated increased risk of PET (odds ratio [OR] per 1-SD SBP increase 1.90 [95% CI=1.45–2.49]; P =3.23×10 −6 ) and reduced birthweight (OR=0.83 [95% CI=0.79–0.86]; P =3.96×10 −18 ), and this was not mediated by PET. Body mass index and type 2 diabetes were also associated with PET (respectively, OR per 1-SD body mass index increase =1.67 [95% CI=1.44–1.94]; P =7.45×10 −12 ; and OR per logOR increase type 2 diabetes =1.11 [95% CI=1.04–1.19]; P =1.19×10 −3 ), but not with reduced birthweight. Conclusions: Our results provide evidence for causal effects of SBP, body mass index, and type 2 diabetes on PET and identify that SBP is associated with reduced birthweight independently of PET. The results provide insight into the pathophysiological basis of PET and identify hypertension as a potentially modifiable risk factor amenable to therapeutic intervention.

Objective The aim of this study is to evaluate the effect of bariatric surgery on long-term risk of VTEs in a large cohort of patients with obesity. Background Obesity is a well-established risk factor for VTEs, such as pulmonary embolism and deep vein thrombosis. The rising prevalence of obesity and its associated co-morbidities, including VTE, represent a growing public health issue. Methods A nested, retrospective matched cohort study was designed and conducted on prospectively collected national electronic healthcare records data from the Clinical Practice Research Datalink. Eight thousand, one hundred twelve patients were included in the study: the 4056 patients on the database who had undergone bariatric surgery, and equal numbers of age, sex, and body mass index matched controls. The primary endpoint was the occurrence of VTEs; secondary endpoints were the occurrence of deep vein thrombosis alone, pulmonary embolism alone. Results Patients were followed up for a median of 10.7 years. The bariatric surgery cohort had a significantly lower occurrence of the primary outcome [hazard ratio (HR) 0.601; 95% confidence interval (CI) 0.430-0.841, P = 0.003]; mainly driven by a reduction in deep vein thrombosis (HR 0.523; 95% CI 0.349-0.783, P = 0·002) and not in pulmonary embolism (HR 0.882; 95% CI 0.511-1.521, P = 0.651). Conclusions The results of this nation-wide study set out to characterize the impact of bariatric surgery on long-term risk of thromboembolic events outline a significant reduction in thromboembolic events, driven by a reduction in deep vein thrombosis.

This chapter introduces the volume’s overarching arguments and contributions to the fields of trauma and motherhood studies in twenty-first-century literature and culture. Echoing Judith Herman’s Trauma and Recovery: The Aftermath of Violence—From Domestic Abuse to Political Terror (1992), this volume is situated in a psychoanalytical framework. While trauma studies have been booming for the past 25 years since the publication of Cathy Caruth’s ground-breaking study, Unclaimed Experience: Trauma, Narrative, and History (1996), surprisingly little critical attention has been given to the intersection of motherhood and trauma. The present volume aims at bridging this gap, as well as bringing to the forefront marginalized maternal experiences and voices, thus challenging stereotypical notions of motherhood as the ultimate fulfillment or as catharsis—especially in the wake of historical catastrophe. The contributions included here engage with a transnational corpus drawn from the five continents and span topics as under-studied as pregnancy denial, surrogacy, voluntary or involuntary childlessness, racism and motherhood, carceral mothering practices, surrogacy, IVF, artificial wombs, and mothering through war, genocide, and migration. Accompanied by an online creative supplement, this volume enhances a better understanding of the cathartic effects of storytelling.

Huntington's disease (HD) is a neurodegenerative disorder characterized by motor disturbances, cognitive decline, and behaviour changes. A well-recognized feature of advanced HD is dysphagia, which leads to malnutrition and aspiration pneumonia, the latter being the primary cause of death in HD. Previous studies have underscored the importance of dysphagia in HD patients with moderate-to-advanced stage disease, but it is unclear whether dysphagia affects patients already at an early stage of disease and whether genetic or clinical factors can predict its severity. We performed fiberoptic endoscopic evaluation of swallowing (FEES) in 61 patients with various stages of HD. Dysphagia was found in 35% of early-stage, 94% of moderate-stage, and 100% of advanced-stage HD. Silent aspiration was found in 7.7% of early-stage, 11.8% of moderate-stage, and 27.8% of advanced-stage HD. A strong correlation was observed between disease progression and dysphagia severity: worse dysphagia was associated with worsening of motor symptoms. Dysphagia severity as assessed by FEES correlated with Huntington’s Disease Dysphagia Scale scores (a self-report questionnaire specific for evaluating swallowing in HD). The present findings add to our understanding of dysphagia onset and progression in HD. A better understanding of dysphagia onset and progression in HD may inform guidelines for standard clinical care in dysphagia, its recognition, and management.

This volume of intervalla centres on the themes of choice and conflict, refusal and rejection, and analyses how mothers and non-mothers are perceived in Italian society. The nine essays cover a variety of genres (novel, auto-fiction, theatre) and predominantly address how these perceptions are translated into literary form, ranging from the 1940s to the early twenty-first century. They study topics such as the ambivalent feelings and difficult experiences associated with motherhood (doubt, post-natal depression, infanticide, IVF), the impact of motherhood and non-motherhood on female identity, attitudes towards childless/childfree women, the stereotype of the “good mother,” and the ways in which such stereotypes are rejected, challenged or subverted. Major Italian writers, such as Lalla Romano, Paola Masino, Oriana Fallaci, Laudomia Bonanni and Elena Ferrante, are included in these analyses, alongside contemporary “momoirs” and works by Valeria Parrella, Lisa Corva, Eleonora Mazzoni, Cristina Comencini and Grazia Verasani.

L’Italia detiene uno dei tassi di natalità più bassi al mondo e infertilità e sterilità stanno diventando realtà sempre più diffuse. Dopo diversi tentativi infruttuosi, alcuni aspiranti genitori intraprendono la strada per avere un figlio attraverso la procreazione assistita: un percorso che richiede tempo, pazienza, denaro, e che non è privo di difficoltà e insidie. Nel contesto italiano la situazione è aggravata dal fatto che non poter avere figli è un tabù di cui non si discute apertamente e coloro che ricorrono alla procreazione assistita spesso lo fanno di nascosto. L’Italia ha, inoltre, una delle leggi più restrittive in materia (la cosiddetta “Legge 40”) e la Chiesa cattolica condanna apertamente questi trattamenti. In un’epoca in cui quasi tutto è considerato possibile, avere figli non è sempre facile, ovvio e “naturale,” come potrebbe sembrare, e la sterilità sta diventando una vera e propria piaga sociale. Tuttavia, è indicativo che nell’editoria e – spesso in forma anonima – su blog e forum, la questione abbia iniziato a essere discussa. Questi sono sintomi di un problema che esiste e sta finalmente cominciando a emergere e a essere affrontato. Nel mio contributo prenderò in considerazione due romanzi contemporanei italiani, pubblicati dopo l’entrata in vigore della “Legge 40” – Confessioni di una aspirante madre di Lisa Corva (2005) e Le difettose di Eleonora Mazzoni (2012) – che raccontano la ricerca, a tratti disperata e ossessiva, della maternità attraverso la procreazione assistita. Le vicende legate al sogno di gravidanza delle protagoniste e le conseguenze derivanti dal fallimento delle tecniche di fecondazione in vitro saranno approfondite con l’ausilio di studi effettuati nell’ambito delle scienze sociali, tra cui quelli di Gayle Letherby, James H. Monach, Karen Throsby e Silvia Vegetti Finzi, nel tentativo di indagare il desiderio di maternità delle protagoniste dei romanzi, il percorso di rinegoziazione della “normalità” e la loro ridefinizione di identità femminile.

The ghrelin gene-derived peptide obestatin promotes survival in different cell types through a yet undefined receptor; however, its potential neuroprotective activities are still unknown. Here, obestatin effects were investigated on proliferation and survival of adult rat hippocampal progenitor cells (AHPs). Obestatin immunoreactivity was found in AHPs; moreover, obestatin binding to AHPs was displaced by the GLP-1R agonist Ex-4 and antagonist Ex-9. Furthermore, obestatin increased cell proliferation and survival in growth factor deprived medium and inhibited apoptosis; these effects were blocked by Ex-9. The underlying mechanisms involved Gαs/cAMP/PKA/CREB signaling, phosphorylation of ERK1/2 and PI3K/Akt, and the PI3K targets GSK-3β/β-catenin and mTOR. Obestatin also counteracted Aβ1-42-induced detrimental effects through inhibition of GSK-3β activity and Tau hyperphosphorylation, main hallmarks of neuronal death in Alzheimer's disease. These findings indicate a novel protective role for obestatin in AHPs and candidate this peptide as potential therapeutic target for increasing neurogenesis and for approaching neurodegenerative disorders.

L’articolo si concentra sugli aspetti identitari e sulla rappresentazione dell’alterità nel romanzo di Laila Wadia, "Amiche per la pelle". Nell’immaginario edificio di Via Ungaretti a Trieste, dove è ambientata la vicenda, convivono diverse tipologie di personaggi appartenenti a varie nazionalità: italiana, albanese, bosniaca, cinese e indiana. Il pluralismo e la diversità che caratterizzano i protagonisti offrono una descrizione complessa degli stranieri che non sono definiti in modo fisso e stereotipato, bensì come personalità ibride, multiculturali e in continua evoluzione. Nel testo sono approfonditi gli aspetti che definiscono l’identità multipla dei personaggi principali, le tappe e le difficoltà riscontrate nel lungo processo d’integrazione nella società italiana (l’apprendimento della lingua e dei costumi locali, la difficoltà nel trovare un alloggio e un lavoro adeguati, il razzismo e i pregiudizi di cui sono vittime, ma anche la solidarietà dimostrata da parte di alcuni italiani). Sono ugualmente analizzati i pregiudizi e i luoghi comuni attribuiti agli stranieri da parte degli abitanti nativi e lo sguardo degli immigrati nei confronti della loro nuova patria.

The accuracy of the sentinel node technique in the evaluation of axillary node involvement in breast cancer was evaluated in 83 consecutive patients with monofocal T1–2 carcinoma, who were clinically N0 and who underwent lymphoscintigraphy with 99mTc-colloid integrated with intraoperative sentinel node detection by a portable probe. Lymphoscintigraphy revealed at least one sentinel node in 75 patients (90.4%), always identified by the probe. In eight patients (9.6%) the sentinel node was detected neither by lymphoscintigraphy nor by the probe. All removed lymph nodes were analyzed by hematoxylin-eosin histology and the sentinel node by immunostaining. In 28/75 patients (37.3%) at least one metastatic axillary lymph node was detected; in 16 of the 28 N+ subjects (57%) only the sentinel node was positive. The false negative rate (sentinel node negative/other axillary lymph nodes positive) was 17.85% (5/28 patients). In 9/23 patients (39%) micrometastases were found in the sentinel node only. In conclusion, specific sentinel node positivity in 57% of cases supports the validity of the sentinel node concept. Moreover, nine patients would have been considered No by standard hematoxylin-eosin histology without sentinel node-aided immunostaining. A 17.8% false negative rate calls for caution in patients with negative sentinel nodes.

This study identified the needs of terminal cancer patients, investigated the factors associated with unmet needs, and assessed psychological and symptom distress associated with unsolved needs. Ninety-four patients were randomly selected from 324 patients admitted for palliative care in 13 Italian centers. Two self-administered questionnaires (the Symptom Distress Scale and the Psychological Distress Inventory) were administered to all the patients. Patients needs were identified using a semi-structured interview, aimed at exploring five areas: physiological needs, safety needs, love and belonging needs, self-esteem needs, self-fulfillment needs. A content analysis of the answers defined 11 needs, and identified patients with unmet needs. The most frequent unmet needs were symptom control (62.8%), occupational functioning (62.1%), and emotional support (51.7%). The less frequently reported needs were those related to personal care (14.6%), financial support (14.1%), and emotional closeness (13.8%). Low functional state was significantly associated with a high proportion of patients with unmet needs of personal care, information, communication, occupational functioning, and emotional closeness. Patients with unmet needs showed significantly higher psychological and symptom distress for most needs. This study provides some suggestions about the concerns that should be carefully considered during the late stage of cancer.