Case Report Lifetime Autism Spectrum Features in a Patient with a Psychotic Mixed Episode Who Attempted Suicide

We present a case report of a young man who attempted suicide during a mixed episode with psychotic symptoms. The patient's history revealed the lifetime presence of signs and features belonging to the autism spectrum realm that had been completely overlooked. We believe that this case is representative of an important and barely researched topic: what happens to children with nondiagnosed and nontreated subthreshold forms of autism when they grow old. The issue of early recognition of autism spectrum signs and symptoms is discussed, raising questions on the diagnostic boundaries between autism and childhood onset psychotic spectrums among patients who subsequently develop a full-blown psychotic disorder

Inhibition of ERK1/2 signaling prevents bone marrow fibrosis by reducing osteopontin plasma levels in a myelofibrosis mouse model

Clonal myeloproliferation and development of bone marrow (BM) fibrosis are the major pathogenetic events in myelofibrosis (MF). The identification of novel antifibrotic strategies is of utmost importance since the effectiveness of current therapies in reverting BM fibrosis is debated. We previously demonstrated that osteopontin (OPN) has a profibrotic role in MF by promoting mesenchymal stromal cells proliferation and collagen production. Moreover, increased plasma OPN correlated with higher BM fibrosis grade and inferior overall survival in MF patients. To understand whether OPN is a druggable target in MF, we assessed putative inhibitors of OPN expression in vitro and identified ERK1/2 as a major regulator of OPN production. Increased OPN plasma levels were associated with BM fibrosis development in the Romiplostim-induced MF mouse model. Moreover, ERK1/2 inhibition led to a remarkable reduction of OPN production and BM fibrosis in Romiplostim-treated mice. Strikingly, the antifibrotic effect of ERK1/2 inhibition can be mainly ascribed to the reduced OPN production since it could be recapitulated through the administration of anti-OPN neutralizing antibody. Our results demonstrate that OPN is a novel druggable target in MF and pave the way to antifibrotic therapies based on the inhibition of ERK1/2-driven OPN production or the neutralization of OPN activity

Prediction of early recurrent thromboembolic event and major bleeding in patients with acute stroke and atrial fibrillation by a risk stratification schema: the ALESSA score study

Background and Purposes—This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. Methods—The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00–1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08–2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P=0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30–1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632–0.763; P=0.0001) for ischemic outcome events and 0.585 (0.493–0.678; P=0.10) for major bleedings. Results—The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529–0.763; P=0.009) for ischemic outcome events and 0.407 (0.275–0.540; P=0.14) for hemorrhagic outcome events. Conclusions—In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings

The risk of stroke recurrence in patients with atrial fibrillation and reduced ejection fraction

Abstract Background: Atrial fibrillation (AF) and congestive heart failure often coexist due to their shared risk factors leading to potential worse outcome, particularly cerebrovascular events. The aims of this study were to calculate the rates of ischemic and severe bleeding events in ischemic stroke patients having both AF and reduced ejection fraction (rEF) (⩽40%), compared to ischemic stroke patients with AF but without rEF. Methods: We performed a retrospective analysis that drew data from prospective studies. The primary outcome was the composite of either ischemic (stroke or systemic embolism), or hemorrhagic events (symptomatic intracranial bleeding and severe extracranial bleeding). Results: The cohort for this analysis comprised 3477 patients with ischemic stroke and AF, of which, 643 (18.3%) had also rEF. After a mean follow-up of 7.5 ± 9.1 months, 375 (10.8%) patients had 382 recorded outcome events, for an annual rate of 18.0%. While the number of primary outcome events in patients with rEF was 86 (13.4%), compared to 289 (10.2%) for the patients without rEF; on multivariable analysis rEF was not associated with the primary outcome (OR 1.25; 95% CI 0.84–1.88). At the end of follow-up, 321 (49.9%) patients with rEF were deceased or disabled (mRS ⩾3), compared with 1145 (40.4%) of those without rEF; on multivariable analysis, rEF was correlated with mortality or disability (OR 1.35; 95% CI 1.03–1.77). Conclusions: In patients with ischemic stroke and AF, the presence of rEF was not associated with the composite outcome of ischemic or hemorrhagic events over short-term follow-up but was associated with increased mortality or disability

Anticoagulation After Stroke in Patients With Atrial Fibrillation : To Bridge or Not With Low-Molecular-Weight Heparin?

Background and Purpose- Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods- We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results- Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P Conclusions- Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.Peer reviewe

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Affective lability in Bipolar Disorder: the Attention Deficit/Hyperactivity and Borderline Personality connection

Introduction: Attention Deficit/Hyperactivity Disorder (ADHD) is a Neurodevelopmental Disorder that onsets during the childhood and persists into adulthood in two-thirds of the cases. The comorbidity with other psychiatric disorders such as Bipolar Disorder (BD) and Borderline Personality Disorder (BPD) can influence the developmental trajectory. The presence of mood symptoms may complicate the diagnosis of adult ADHD. On the other hand, psychiatric comorbidity may disguise ADHD clinical picture making it difficult to have an appropriate diagnosis. A failure to distinguish or correctly identify the coexistence of BD, BPD, and ADHD can result in treatment and therapeutic mistakes; it can also be one of the reasons for the underachievement of therapeutic and outcome targets in several patients. Aims of the study: The main purpose is to examine clinical differences and similarities in mood symptoms, illness course, temperamental and clinical associated features in a BD sample grouped on the basis of the presence/absence of ADHD diagnosis and BPD features. The secondary objective is the identification of clinical features useful to differentiate ADHD from BPD patients. Material and Methods: 374 patients meeting the DSM-IV criteria for BD were consecutively recruited in the inpatient and outpatient settings of the Psychiatry Unit (UO 1) of Azienda Ospedaliero-Universitaria of Pisa over a period of about 1 year. The sample includes 184 female (48.1%) and 194 male subjects (51.9%). All the patients were evaluated with the SCID I for the assessment of Axis I psychiatric disorders and the BPD module of SCID II. Data regarding the diagnosis of BD were recorded by means of SIMD, semi-structured interview allowing the systematic collection of information regarding the current episode, the course and family history. ADHD has been confirmed with the DIVA 2.0, a semi-structured interview for the diagnosis of ADHD according to DSM-IV, whereas BPD diagnosis was confirmed throughout the DIB. The functioning and the severity of the illness were evaluated with GAF and CGI scales respectively. Statistical analyses: For comparison between groups, we used chi-square test for categorical variables and Student’s t-test for continuous variables, using p< .05. Two stepwise forward logistic regression models were then used to identify DSM-IV BPD criteria and BD clinical variables predicting the diagnosis of ADHD with p<.05 . Results: The study population included 374 patients suffering for BD (BD-I 52.7%, BD-II 47.3%); 180 were females (48.1%) and 194 males (51.9%), with a mean age of 45.57 years (SD 15.06, range 18-79). Comorbid ADHD and BPD rated 7.8% and 19.5% respectively. The three-group comparison showed that female gender was prominent in the BPD group. ADHD and BPD patients were younger, more frequently never married or divorced and unemployed comparing to BD patients. With respect to the clinical features of BD, BD-II was more frequent in BPD patients, which presented a clinical profile similar to ADHD, clearly differentiated from BD patients as shown by the earlier age at onset of BD, high rates of comorbid Cyclothymic Disorder, similar rates of rapid cycling, similar rates in the mean number of previous depressive, manic and mixed episodes, comparable severity and functional impairment. ADHD and BPD also showed similar comorbidity pattern with alcohol and substance abuse disorders as well as similar temperamental profiles: indeed all the affective temperaments reached mean scores higher than BD patients. Some differences in the clinical profiles emerged: BPD presented higher mean number of previous suicide attempts, more frequently atypical features and higher comorbidity rates with anxiety (namely panic and generalized anxiety disorders) and eating disorders. By the contrary ADHD reported a higher number of hypomanic episodes. Noteworthy, the 41.4% of ADHD patients met the criteria for a BPD diagnosis too. The regression analyses confirmed that the presence of more hypomanic episodes and male gender predicted the ADHD diagnosis, whereas atypical features and suicidality were associated to BPD. Therefore, a two-group comparison was performed concerning DSM-IV BPD criteria: no differences emerged for 4 out of the 9 criteria (emotional instability, difficulty in controlling rage, transient paranoia/dissociation and with less extent impulsivity). In comparison with ADHD, BPD reported more frequently frantic efforts to avoid real or imaged abandonment, unstable and intense relationships, identity disturbance, recurrent suicidal behavior, gestures or threats and chronic feelings of emptiness. The regression analysis, involving also the gender among the independent variables, showed that ADHD diagnosis was actually not predicted only by female gender, recurrent suicidal behaviors, self-injury and chronic feelings of emptiness. Limitations: Low number of ADHD patients. Retrospective, non-blind design, may affect the ADHD diagnosis with recall bias. Selection bias in treatment-seeking patients in a third level university center. Discussion: In our clinical sample, BPD and ADHD patients showed few clinical differences. BPD patients were more frequently females with prevalently depressive course and showed more atypical features, higher rate of suicide attempts, and a different pattern of comorbidities with higher rates of anxiety and eating disorders. ADHD patients were more frequently males with a prevalently hypomanic course. However, most of the bipolar clinical variables considered such as BD-II subtype, very high rate of Cyclothymic Disorder, early age at onset, number of different polarity mood episodes, rapid cycling, severity of the illness and its impact on functioning, temperamental features and familial load for mood disorders resulted similar in patients with comorbid ADHD and BPD and different from other BD patients. Moreover, about half of the ADHD subsample had an adjunctive BPD diagnosis. This overlap supports the hypothesis that ADHD and BPD might be related each other and represent distinct clinical BD phenotypes. Alternatively, a shared factor may influence the similarities in temperamental and course characteristics. In a more hypothetical vein, we submit that affective lability disposition might represent the mediating core characteristic in the complex pattern of mood, anxiety, and impulsive disorders that ADHD and BPD patients report in developmental age. Anxious-sensitive symptomatology and hostile-impulsive-addictive behavior, rather than being considered independent comorbidities, might represent features related to such affective lability diathesis, largely pinpointed by common familial traits. Some differences however can be detected in the context of this instability diathesis as BPD patients showed a prominent depressive-anxious course, whereas affective instability in ADHD may assume more a hypomanic-colored course. Anyway, in this perspective cyclothymic-type mood instability may represent a neurodevelopmental condition shared by other disorders of the same nature such as ADHD, autistic spectrum disorder, Tourette’s plus syndrome and cognitive disability. Further prospective longitudinal study on high risk populations are necessary to better define the possible relationships among BD, ADHD and BPD and other neurodevelopmental disorders

Disturbo da deficit di attenzione e iperattività (ADHD) nell'adulto: rassegna critica della letteratura e indagine clinico-epidemiologica su 109 soggetti con disturbo da uso di sostanze

Attraverso uno studio clinico-epidemiologico su un campione di 109 soggetti con disturbo da uso di sostanze, abbiamo valutato la presenza e la gravità dei sintomi dell'ADHD (disturbo da deficit di attenzione e iperattività) e come questo incida sulla storia clinica del paziente. Analizzando la comorbidità psichiatrica si evidenzia che il disturbo bipolare è più frequente nel gruppo ADHD rispetto ai soggetti senza ADHD, e che la risposta ai farmaci antidepressivi è peggiore