Long-term outcome predictors after functional remediation in patients with bipolar disorder.

BACKGROUND: Improving functioning in patients with bipolar disorder (BD) is one of the main objectives in clinical practice. Of the few psychosocial interventions that have been specifically developed to enhance the psychosocial outcome in BD, functional remediation (FR) is one which has demonstrated efficacy. The aim of this study was to examine which variables could predict improved functional outcome following the FR intervention in a sample of euthymic or subsyndromal patients with BD. METHODS: A total of 92 euthymic outpatients were included in this longitudinal study, with 62 completers. Partial correlations controlling for the functional outcome at baseline were calculated between demographic, clinical and neurocognitive variables, and functional outcome at endpoint was assessed by means of the Functioning Assessment Short Test scale. Next, a multiple regression analysis was run in order to identify potential predictors of functional outcome at 2-year follow-up, using the variables found to be statistically significant in the correlation analysis and other variables related to functioning as identified in the previous scientific literature. RESULTS: The regression model revealed that only two independent variables significantly contributed to the model (F(6,53): 4.003; p = 0.002), namely verbal memory and inhibitory control. The model accounted for 31.2% of the variance. No other demographic or clinical variable contributed to the model. CONCLUSIONS: Results suggest that patients with better cognitive performance at baseline, especially in terms of verbal memory and executive functions, may present better functional outcomes at long term follow-up after receiving functional remediation.

Intensive intervention for adolescents with autism spectrum disorder: comparison of three rehabilitation treatments.

INTRODUCTION: Autism spectrum disorder (ASD) is a set of heterogeneous neurodevelopmental conditions, characterised by difficulties in social communication and restricted, repetitive behaviours and interests. There are several rehabilitative interventions for individuals with ASD but the evidence of their effectiveness is low or moderate overall. The transition phase of ASD individuals from adolescence to adulthood represents an important challenge. Adults with ASD struggle to access employment or independent living. METHODS: In our study, we evaluated the effect of three different high-intensity interventions, namely Applied Behaviour Analysis (ABA), Treatment and Education of Autistic and Communication-Handicapped Children (TEACCH) and Behavioural Educational Intervention (BEI), in 93 ASD (levels 2 and 3) adolescents (age range 12-18 years). RESULTS: Our results showed that all adolescents with ASD reported an improvement of core symptoms, regardless of the type of treatment. CONCLUSIONS: A high intensity intervention ameliorates the core symptoms of ASD, enriching evidence of effectiveness regarding adolescents with ASD.KEY POINTSIndividuals with ASD need lifespan support and they struggle to access employment, independent living and community inclusion.There are several rehabilitative interventions for individuals with ASD but the evidence of their effectiveness in adolescents is insufficient.The main purpose of this study was to evaluate the possible enhancement produced by three intensive interventions (ABA, TEACCH, BEI) of symptom severity and adaptive functions.Results show that independently of the treatment, individuals with ASD decrease in ASD severity.Individuals who were treated with the BEI and TEACCH programmes reported improvements in the adaptive domains.

Diet: the keystone of autism spectrum disorder?

Children with autism are characterized by an impairment of social interaction and repetitive patterns of behaviour. Autism is a heterogeneous span of disorders with unknown aetiology. Research has grown significantly and has suggested that environmental risk factors acting during the prenatal period could influence the neurodevelopment of offspring. The literature suggests that the maternal diet during pregnancy has a fundamental role in the etiopathogenesis of autism. Indeed, a maternal diet that is high in some nutrients has been associated with an increase or reduction in the risk of develop Autism Spectrum Disorders (ASD). The diet of ASD children is also a key factor for the worsening of ASD symptoms. Children with autism have food selectivity and limited diets due to smell, taste, or other characteristics of foods. This determines eating routines and food intake patterns, with consequent deficiency or excess of some aliments. Several studies have tried to show a possible relationship between nutritional status and autism. In this review we describe, emphasizing the limits and benefits, the main current empirical studies that have examined the role of maternal diet during gestation and diet of ASD children as modifiable risk factors at the base of development or worsening of symptoms of autism.

Bone histomorphometry in acromegaly patients with fragility vertebral fractures.

CONTEXT: The high risk of vertebral fractures (VFs) in acromegaly patients despite normal bone mineral density (BMD) is well known. The reasons for this paradoxical finding of skeleton fragility are poorly understood due to the limited data on bone histomorphometry in acromegaly. OBJECTIVE: This study aimed to analyze histomorphometric parameters including bone microarchitecture in acromegaly patients with VFs and normal BMD compared to normal subjects, and also to evaluate the differences between active and controlled acromegaly patients. PATIENTS AND METHODS: Forty-seven acromegaly patients (17 active, 30 controlled), median (range) age 57 years (30-88) were evaluated for bone turnover, morphometric VFs and BMD by dual-energy X-ray absorptiometry at lumbar spine and hip; 12 patients with VFs and normal BMD underwent iliac crest bone biopsy; 12 biopsies were taken at the autopsy in healthy sex and age-matched control subjects. RESULTS: The histomorphometric evaluation of acromegaly fractured patients was compared with that of normal controls and showed significantly reduced median (range) levels of bone volume/tissue volume (BV/TV: 15.37% (7.93-26.75) vs. 18.61% (11.75-27.31), p = 0.036), trabecular thickness (TbTh: 77.6 µm (61.7-88.3) vs. 82.7 µm (72.3-92.0) p = 0.045), with increased trabecular separation (TbSp: 536.4 µm (356.2-900.6) vs. 370.3 µm (377.1-546.3) p = 0.038) and increased cortical thickness (1268 µm (752-2521) vs. 1065 µm (851-1205) p = 0.025) and porosity (11.9% (10.2-13.3) vs. 4.8% (1.6-8.8) p = 0.0008). While active acromegaly patients showed histomophometric features of increased bone turnover, patients with controlled disease presented normal bone turnover with significantly lower osteoblastic activity, expressed as osteoblast number (p = 0.001), active osteoblasts and vigor (p = 0.014) in the presence of reduced osteocyte number (p = 0.008) compared to active disease. CONCLUSIONS: The apparent paradox of bone fragility in acromegaly patients with a normal BMD can be explained by increased cortical thickness and porosity and reduced trabecular thickness with increased trabecular separation. These structural and microarchitectural abnormalities persist in the controlled phase of acromegaly despite bone turnover normalization. The main determinant of bone disease after hormonal control is severe osteoblastic dysfunction.

Pure endoscopic management of epileptogenic hypothalamic hamartomas.

Hypothalamic hamartomas (HH) are rare congenital malformations located in the region of the tuber cinereum and third ventricle. Their usual clinical presentation is characterized by gelastic/dacrystic seizures which often become pharmaco-resistant and progress to secondary focal/generalized intractable epilepsy causing mostly in children cognitive and behavioral problems (particularly in cases of progressive epileptic encephalopathy) and precocious puberty. Whereas gelastic seizures can be surgically controlled either by resection of the lesion or disconnection (tissue-destructive) procedures, aimed at functionally prevent the spreading of the epileptic burst; generalized seizures tend to respond better to HH excision rather than isolated neocortical resections, which generally fail to control them. Prospective analysis of 14 consecutive patients harboring HH treated in an 8-year period; 12 patients had unilateral and two bilateral HH. All patients were managed by pure endoscopic excision of the HH. The mean operative time was 48 min and mean hospital stay was 2 days; perioperative blood loss was negligible in all cases. Two patients showed a transient diabetes insipidus (DI); no transient or permanent postoperative neurological deficit or memory impairment was recorded. Complete HH excision was achieved in 10/14 patients. At a mean follow-up of 48 months, no wound infection, meningitis, postoperative hydrocephalus, and/or mortality were recorded in this series of patients. Eight patients became seizure free (Engel class I), 2 other experienced worthwhile improvement of disabling seizures (Engel class II); 2 patients were cured from gelastic attacks while still experiencing focal dyscognitive seizures; and 2, having bilateral HH (both undergoing unilateral HH excision), did not experience significant improvement and required later on a temporal lobectomy coupled to amygdalohyppocampectomy. Overall, the followings resulted to be predictive factors for better outcomes in terms of seizure control: (1) cases of unilateral, Delalande class B, HH, (2) shorter history of epilepsy. Endoscopic resection of HH proved, in our series, to be effective in achieving complete control or in reducing the frequency of seizures. Furthermore, this approach has confirmed its minimally invasive nature with a very low morbidity rate: of note, it allowed to better preserve short-term memory and hypothalamic function.

Brain functional changes in first-degree relatives of patients with bipolar disorder: evidence for default mode network dysfunction.

BACKGROUND: Relatively few studies have investigated whether relatives of patients with bipolar disorder show brain functional changes, and these have focused on activation changes. Failure of de-activation during cognitive task performance is also seen in the disorder and may have trait-like characteristics since it has been found in euthymia. METHOD: A total of 20 euthymic patients with bipolar disorder, 20 of their unaffected siblings and 40 healthy controls underwent functional magnetic resonance imaging during performance of the n-back working memory task. An analysis of variance (ANOVA) was fitted to individual whole-brain maps from each set of patient-relative-matched pair of controls. Clusters of significant difference among the groups were used as regions of interest to compare mean activations/de-activations between them. RESULTS: A single cluster of significant difference among the three groups was found in the whole-brain ANOVA. This was located in the medial prefrontal cortex, a region of task-related de-activation in the healthy controls. Both the patients and their siblings showed significantly reduced de-activation compared with the healthy controls in this region, but the failure was less marked in the relatives. CONCLUSIONS: Failure to de-activate the medial prefrontal cortex in both euthymic bipolar patients and their unaffected siblings adds to evidence for default mode network dysfunction in the disorder, and suggests that it may act as a trait marker.

Acquired resistance to EGFR tyrosine kinase inhibitors alters the metabolism of human head and neck squamous carcinoma cells and xenograft tumours.

BACKGROUND: Acquired resistance to molecularly targeted therapeutics is a key challenge in personalised cancer medicine, highlighting the need for identifying the underlying mechanisms and early biomarkers of relapse, in order to guide subsequent patient management. METHODS: Here we use human head and neck squamous cell carcinoma (HNSCC) models and nuclear magnetic resonance (NMR) spectroscopy to assess the metabolic changes that follow acquired resistance to EGFR tyrosine kinase inhibitors (TKIs), and which could serve as potential metabolic biomarkers of drug resistance. RESULTS: Comparison of NMR metabolite profiles obtained from control (CAL(S)) and EGFR TKI-resistant (CAL(R)) cells grown as 2D monolayers, 3D spheroids or xenograft tumours in athymic mice revealed a number of differences between the sensitive and drug-resistant models. In particular, we observed elevated levels of glycerophosphocholine (GPC) in CAL(R) relative to CAL(S) monolayers, spheroids and tumours, independent of the growth rate or environment. In addition, there was an increase in alanine, aspartate and creatine+phosphocreatine in resistant spheroids and xenografts, and increased levels of lactate, branched-chain amino acids and a fall in phosphoethanolamine only in xenografts. The xenograft lactate build-up was associated with an increased expression of the glucose transporter GLUT-1, whereas the rise in GPC was attributed to inhibition of GPC phosphodiesterase. Reduced glycerophosphocholine (GPC) and phosphocholine were observed in a second HNSCC model probably indicative of a different drug resistance mechanism. CONCLUSIONS: Our studies reveal metabolic signatures associated not only with acquired EGFR TKI resistance but also growth pattern, microenvironment and contributing mechanisms in HNSCC models. These findings warrant further investigation as metabolic biomarkers of disease relapse in the clinic.

Bipolar disorder in the elderly: a cohort study comparing older and younger patients.

OBJECTIVE: The purpose of this study was to analyze differences in clinical and socio-demographic characteristics between older and younger bipolar outpatients paying special attention to depressive symptoms in a large, naturalistic cohort. METHOD: Five hundred and ninety-three DSM-IV-TR bipolar outpatients were enrolled. Clinical characteristics were assessed according to DSM-IV-TR (SCID-I). Subjects were categorized into two groups according to current age (older OBD: age > 65 years; younger-YBD: age < 65 years). RESULTS: About 80% of patients were younger (N = 470), and a fifth were older (N = 123), with a mean age of 77.30 years in OBD. Older patients were more likely to be married, not qualified, bipolar II, with depressive polarity of first episode, higher age at illness onset, higher age at first hospitalization. They were more likely to present with depressive predominant polarity, with lifetime history of catatonic, psychotic and melancholic features, age at illness onset >40 years, as well as suffering from more medical comorbidities when compared to younger bipolars. CONCLUSION: The clinical presentation of bipolar disorder in late life would be defined more frequently by melancholic depressive features and a predominantly depressive polarity. These results suggest that treatment strategies for elderly bipolar patients should focus in the prevention of depressive episodes.

The impact of repeated manic episodes and executive dysfunction on work adjustment in bipolar disorder.

The aim of this study was to study the clinical and neurocognitive variables that best explain poor work adjustment in a sample of bipolar I euthymic patients. Eighty-five euthymic patients at the Hospital Clinic of Barcelona were assessed for this study by means of a comprehensive neuropsychological battery and a work-focused interview to determine work adjustment. Clinical and sociodemographic variables were also collected. Direct logistic regression was performed to assess the impact of demographic, clinical and neuropsychological variables on the likelihood of presenting poor work adjustment. The model that best fitted contained five variables (Hamilton Depression Rating scores, number of manic episodes, number of perseverative errors in the Wisconsin Card Sorting Test (WCST), number of depressive episodes and Trail Making Test-part B). However, only two out of these variables made a unique statistically significant contribution to the model, which were number of manic episodes (OR 1.401; CI 1.05-1.86; p = 0.021) and number of perseverative errors in the WCST (OR 1.062; CI 1.00-1.12; p = 0.044). The model explained up to 36 % of the variance in work adjustment. This study highlights the role of manic relapses and neurocognitive impairment, specifically the role of executive function, in work adjustment.

Adaptive response of Italian young adults with autism to the COVID-19 pandemic: A longitudinal study.

The COVID-19 pandemic has represented a hazardous situation for individuals with Autism Spectrum Disorder (ASD) and their families. The difficulties, following the COVID-19-derived lockdown, have involved working from home or loss of employment, and the demands of looking after their children without the daily support of specialists. The aim of this study was to evaluate the adaptive behaviour of young adult participants with ASD after the enforcement of lockdown measures in March 2020 in a specialised centre in central Italy, by administering the Italian form of the Vineland Adaptive Behaviour Scales Second Edition (VABS-II), at baseline as well as 6 months and 1 year after the lockdown. Participants with ASD who were not able to access their normal, in-person care - they were only followed at a distance (i.e. telehealth) - declined dramatically in their adaptive behaviour during the first months after the lockdown for some VABS-II dimensions such as the socialisation and daily living domains. The effects of the lockdown on adaptive behaviour remained after 1 year. Our results emphasise the need for immediate, continuous and personal support for people with ASD during and after the restrictions caused by the COVID-19 pandemic, in order to ensure at least partial recovery of adaptive functioning.

Biologic therapies for plaque type psoriasis in patients with previous malignant cancer: long-term safety in a single- center real-life population.

INTRODUCTION: This is an Italian single-center retrospective study evaluating safety and efficacy of biologic agents in psoriatic patients with a previous diagnosis of malignant cancer. AIM: Management of moderate and severe psoriasis patients with a past medical history of malignancies could be difficult because biologic agents are historically associated with a presumptive increased risk of neoplastic reactivation or of a new incoming cancer. The aim of this study is to assess the safety of biologics in patients with a previous cancer diagnosis. MATERIAL AND METHODS: The study analyzed 16 moderate to severe psoriasis patients with a diagnosis of malignant cancer in the previous 10 years treated with biologic agents for up to at least 96 weeks. In five of these patients, cancer was diagnosed in the previous 5 years. RESULTS: We observed a rapid decrease in PASI (psoriasis area severity index) reaching a 90% improvement in 100% of patients. Oncologic follow up did not show any worsening or reactivation of cancer during the entire observation period. No new malignancies were observed in the analyzed sample. CONCLUSIONS: Biologic agents in our experience have demonstrated to be safe and effective in psoriatic patients with a past medical history of malignant cancer.