Plasma pentraxin 3 in idiopathic inflammatory myopathies: a possible new biomarker of disease activity.

Pentraxin-3 (PTX3) is a component of humoral innate immunity with essential functions both in promotion and resolution of inflammation. We aimed to study the PTX3 in the plasma and in the muscle of patients with idiopathic inflammatory myopathies (IIM) and whether PTX3 may correlate with disease activity. Plasma PTX3 levels were assessed in 20 patients with IIMs, 10 dermatomyositis (DM), and 10 polymyositis (PM), compared to 10 patients with rheumatoid arthritis (RA) and 10 healthy donors (HDs) aged, sex, and body mass index matched. Disease activity in IIMs was assessed by Myositis Disease Activity Assessment Visual Analog Scale (MYOACT), while disease activity score on 28 joints (DAS28) was used for RA patients. Muscle histopathology and immunohistochemical (IHC) analyses were also performed. Mean plasma PTX3 levels were significantly higher in IIM patients than HDs (518 ± 260 pg/ml vs. 275 ± 114 pg/ml, P = 0.009). Linear regression analysis adjusted for age, sex, and disease duration showed a direct correlation between PTX3 and CPK levels (ß: 0.590), MYOACT (ß: 0.759), and physician global assessment of disease activity (ß: 0.832) in IIMs. No association between PTX3 levels and DAS28 was found in RA. Global PTX3 pixel fraction was higher in IIM than HDs muscle, but a lower PTX3 expression was found in perifascicular areas of DM and in myofibers with sarcolemmal staining for membrane attack complement. PTX3 plasma levels were increased in IIMs and correlated with disease activity suggesting a possible role as biomarker of disease activity. PTX3 showed a different distribution in DM or PM muscle.

Antidepressant discontinuation syndrome: A state-of-the-art clinical review.

Antidepressant drugs are prescribed to patients with depressive, anxiety disorders, and other conditions. Evidence about antidepressant discontinuation syndrome (ADS) and related outcomes is sparse, although potentially burdensome in some patients. The present state-of-the-art review aims to appraise the most current evidence about ADS critically. ADS has been documented for most antidepressant drugs, although most literature focuses on selective serotonin reuptake inhibitors prescribed for depression. While down-titration cannot exclude the chance of ADS, it is nonetheless warranted in the clinical setting, especially for short half-life and sedative compounds such as paroxetine. Integrative management with concurrent pharmacotherapy and psychotherapy may minimize the eventual unpleasant effects arising within the discontinuation process. In addition, patient-tailored interventions and education should be part of the discontinuation strategy. Future research must rely on broadly accepted definitions for ADS and related phenomena such as antidepressant withdrawal and shed further light on the underpinning neurobiology. Discriminating between ADS-related phenomena and relapse of depression is likewise warranted, along with a neuroscience-based nomenclature instead of a class one.

Suicide associated with COVID-19 infection: an immunological point of view.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a pandemic and leading cause of death. Beyond the deaths directly caused by the virus and the suicides related to the psychological response to the dramatic changes as socioeconomic related to the pandemic, there might also be suicides related to the inflammatory responses of the infection. Infection induces inflammation as a cytokine storm, and there is an increasing number of studies that report a relationship between infection and suicide. MATERIALS AND METHODS: We searched the World Health Organization status report and the PubMed database for keywords (COVID-19, suicide, infection, inflammation, cytokines), and reviewed five cytokine pathways between suicide and inflammation using two meta-analyses and two observational studies starting from November 31, 2020, focusing on the relationship between suicide and inflammation by infection. First, we discussed existing evidence explaining the relationship between suicidal behaviors and inflammation. Second, we summarized the inflammatory features found in COVID-19 patients. Finally, we highlight the potential for these factors to affect the risk of suicide in COVID-19 patients. RESULTS: Patients infected with COVID-19 have high amounts of IL-1ß, IFN-γ, IP10, and MCP1, which may lead to Th1 cell response activation. Also, Th2 cytokines (e.g., IL-4 and IL-10) were increased in COVID-19 infection. In COVID-19 patients, neurological conditions, like headache, dizziness, ataxia, seizures, and others have been observed. CONCLUSIONS: COVID-19 pandemic can serve as a significant environmental factor contributing directly to increased suicide risk; the role of inflammation by an infection should not be overlooked.

High disease relapse after bDMARD spacing in psoriatic arthritis compared to rheumatoid arthritis and axial spondyloarthritis patients: real-life data from BIOPURE registry.

The objective is to evaluate the effectiveness of a spacing strategy of bDMARDs in a cohort of selected patients in disease remission or low-disease activity (LDA) without glucocorticoids affected with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). This was a single-centre study carried out on patients prospectively enrolled in the biologic Apulian registry. Patients whose disease was in remission or LDA without taking glucocorticoids during the previous 6 months and who had agreed to increase the time interval between bDMARD doses were included in this study. Demographic and clinical characteristics were recorded at baseline and at 3, 6 and 12 months of follow-up. Endpoint of the study was the survival of spacing doses in the time lag of the study. Failure of spacing was defined as the first flare of disease. Thirty-seven RA, 28 PsA and 20 axSpA patients underwent bDMARD spacing according to a local strategy. During the follow-up, 5 RA, 6 PsA and 4 axSpA patients had a joint flare, but further 5 PsA patients manifested a skin relapse. Global persistence was 86.5% for RA (MST = 41 (95% CI: 37-45) months) and 80% for axSpA patients (MST = 36 (95% CI: 31-42) months). PsA patients showed a lower persistence, being of 60.7% (MST = 30 (95% CI: 23-36) months) (log-rank test, p = 0.03). Dose reduction by spacing bDMARD doses may be a feasible approach in patients with persistent remission/LDA activity. However, PsA patients might have greater odds of spacing failure because of skin psoriasis relapse. Key Points • Spacing of bDMARDs may be a feasible strategy for some patients with rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis who achieve the target and withdrawn glucocorticoids. • Psoriatic arthritis patients showed lower persistence because of both articular and skin relapses.

Clinical features associated with early drop-out among outpatients with unipolar and bipolar depression.

Drop-out from follow-up visits carries significant burden for people diagnosed with depression. The present study assesses multiple clinical moderators of drop-out among depressed outpatients. We retrospectively followed-up 131 outpatients over 6 months: 78 major depressive disorder (MDD), and 53 bipolar disorder (BD-I = 24; BD-II = 29) patients diagnosed according to the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition. Participants were assessed with standard rating scales administered by experienced psychiatrists. Upon descriptive and Cox regression analyses, 17/53 BDs (32%) dropped-out; the overall survival time until drop-out was 57.94 ± 17.79 days. BD drop-outs were younger, had an earlier age at onset, shorter illness duration, lower rates of lifetime obsessive-compulsive disorder/suicidal behavior, higher rates of substance use disorder (SUD), anxious and mixed features of depression compared to BDs attending up to six months. Among MDD patients, 10/78 cases (13%) dropped-out by month-6 with an average survival of 42.40 ± 16.45 days. Earlier age of onset, younger age, positive family history for mood disorders, lower rates of lifetime generalized anxiety disorder were significantly more frequent among drop-outs than completers, as opposite to SUD, and lifetime recurrent depression. Older age predicted lower drop-out among BDs and MDDs, although with almost null hazard ratio (HR) = 0.928, p < 0.01 vs. HR = 0.941, p < 0.01, respectively. Higher rates of lifetime SUD predicted higher drop-out rates by month-6 among MDDs (HR = 5.477, p = 0.02). Limitations of the study: retrospective design, small sample size, lack of objective measures of treatment-adherence/mood rating during follow-up. Drop-out is common in the real-world setting, warranting specific interventions since the beginning of the treatment.

Occult HBV infection may negatively impact on drug survival in patients with rheumatoid arthritis on treatment with a first biologic drug. An appraisal from the Biologic Apulian Registry (BIOPURE).

We performed a retrospective analysis to evaluate the survival on first line biologic drug of rheumatoid arthritis (RA) patients with potential occult HBV infection (pOBI). We analysed longitudinal data of 486 consecutive RA patients starting a first biological drug in a time frame from 1st January 2008 to 31st December 2014. Demographic and disease related characteristics were collected at baseline and at the last observation visit. Baseline serological markers of HBV infection and causes of treatment discontinuation were also recorded. Primary endpoint was the influence of pOBI on drug survival, estimated by Kaplan-Meier life table analysis. Estimates hazard ratios (HRs) of drug discontinuation, adjusted for disease characteristics, biological drug class and HBcAb status were computed by Cox-regression models. The retention rate was significantly lower in pOBI positive patients (58.2%) when compared to pOBI negative ones (67.8%) and this data was confirmed also when only discontinuation due to ineffectiveness was considered (pOBI positive 66.4% vs pOBI negative 75.3%, long rank 7.93, p=0.005). Cox regression models showed a significant association between HBcAb-neg (HR 0.58, 0.41-0.84), higher ESR-DAS28 at baseline (HR 1.07, 1.03-1.11) or RF/ACPA-neg (HR 1.46, 1.04-2.06) and drug discontinuation. Occult HBV infection seems to influence negatively the effectiveness of biological therapies in RA patients.

Patrones de tratamiento, sobrevida y efectividad a largo plazo de agentes biológicos en pacientes con Artritis Psoriásica / Patterns of treatment, survival and long-term effectiveness of biological agents in patients with Psoriatic Arthritis

Objetivos: Evaluar los patrones de tratamiento de las DME-b (Drogas Modificadoras de la Enfermedad-biológicas), su sobrevida acumulada y su eficacia a largo plazo en pacientes con Artritis Psoriásica (APs) utilizando el índice LUNDEX. Materiales y métodos: Estudio multicéntrico retrospectivo. Se incluyeron pacientes con diagnóstico de APs que hayan iniciado tratamiento con DME-b. Se recolectaron datos sociodemográficos y clínicos. Se consignaron fechas de inicio de DME-b, tratamiento concomitante, suspensión o cambio de tratamiento, y razones de suspensión. La respuesta terapéutica se definió acorde a MDA (Minimal Disease Activity), a los 6, 12 meses y anualmente a partir del inicio de DME-b. Análisis estadístico: Test de Student y Chi². Curvas de Kaplan Meier y Log Rank. Análisis de regresión de Cox. Resultados: Se incluyeron 72 pacientes con APs, 39 (54,2%) de sexo masculino. La edad mediana fue de 54,5 años (RIC 45-61) y el tiempo mediano de evolución de la enfermedad de 11 años (RIC 6-15). 71,2% (n=42) presentaron comorbilidades. El primer DME-b fue en orden decreciente de frecuencia: Adalimumab (45,8%), Etanercept (36,1%), Certolizumab (5,6%), Infliximab (4,2%), Ustekinumab (4,2%), Abatacept (2,7%) y Golimumab (1,4%). 15 pacientes (25,4%) recibieron DME-b en monoterapia. La sobrevida media fue de 82 meses (DE±7,4). El LUNDEX del primer biológico fue 24,7% a los 6 meses y 44,3% al año. La sobrevida media de Adalimumab fue de 90 meses (DE±10,4) y de Etanercept 79 meses (DE±12). Los pacientes añosos presentaron menor sobrevida de la droga [≥55 años: X59,8 (DE±10,5) vs <55 años: X101,2 (DE±9,7), p=0,006]. Luego de ajustar por diferentes confundidores, la edad ≥55 años se mantuvo significativamente a menor sobrevida [HR=1,064 (IC=1,01-1,11) p=0,005]. El LUNDEX fue menor en obesos vs no obesos (16% vs 66% al año, p=0,89; 10,5 vs 74,9% a los 2 años, p=0,011 y 5,9 vs 81,8% a los 3 años, p=0,005). Conclusiones: La sobrevida promedio del primer DME-b fue de 6,8 años. La única variable asociada a menor sobrevida fue la mayor edad.

Objectives: To evaluate the treatment patterns of DME-b (Disease-Modifying Drugs-biological), their accumulated survival and their long-term efficacy in patients with psoriatic arthritis (PsA) using the LUNDEX index. Materials and methods: Retrospective multicentre study. We included patients diagnosed with PsA who started treatment with DME-b. Sociodemographic and clinical data were collected. BMI-D start dates, concomitant treatment, suspension or change of treatment, and reasons for suspension were recorded. The therapeutic response was defined according to MDA (Minimal Disease Activity), at 6, 12 months and annually from the beginning of DME-b. Statistical analysis: Student test and Chi². Curves of Kaplan Meier and Log Rank. Cox regression analysis. Results: We included 72 patients with PsA, 39 (54.2%) male. The median age was 54.5 years (IQR 45-61) and the median time of evolution of the disease was 11 years (IQR 6-15). 71.2% (n=42) presented comorbidities. The first DME-b was in decreasing order of frequency: Adalimumab (45.8%), Etanercept (36.1%), Certolizumab (5.6%), Infliximab (4.2%), Ustekinumab (4.2%), Abatacept (2.7%) and Golimumab (1.4%). 15 patients (25.4%) received DME-b monotherapy. The mean survival was 82 months (SD±7.4). The LUNDEX of the first biological was 24.7% at 6 months and 44.3% per year. The mean survival of Adalimumab was 90 months (SD±10.4) and Etanercept 79 months (SD±12). Older patients had a lower survival of the drug [≥55 years: X59.8 (SD±10.5) vs <55 years: X101.2 (SD±9.7), p=0.006]. After adjusting for different confounders, age ≥55 years was significantly maintained at lower survival [HR=1.064 (CI=1.01-1.11) p=0.005]. The LUNDEX was lower in obese vs. non-obese (16% vs. 66% per year, p=0.89, 10.5 vs 74.9% at 2 years, p=0.011 and 5.9 vs 81.8% at 3 years, p=0.005). Conclusions: The average survival of the first DME-b was 6.8 years. The only variable associated with lower survival was the older age.

Predictors of hospitalization length of stay among re-admitted treatment-resistant Bipolar Disorder inpatients.

BACKGROUND: Hospitalization accounts for significant health care resource utilization for treatment-resistant Bipolar Disorder (BD), especially among frequent users of acute inpatient psychiatric units. Appraisal of the clinical features and predictive role of selected variables is therefore crucial in such population, representing the aim of the present research. METHODS: A hundred and nineteen BD inpatients with an established history of pharmacological treatment resistance for either mania or bipolar depression were classified as long hospitalization cases (LOS+) and their controls and compared against each other for a number of demographic, clinical, and psychopathological features. RESULTS: Overall, female sex, current second-generation atypical antipsychotic (SGA)/mood stabilizer other than lithium as well as antidepressant treatment at the admission occurred statistically more frequently among LOS+ cases, concordant with higher scores at the Hamilton scales for depression and anxiety. Lithium utilization at the time of hospitalization did not differ between cases and controls (LOS-, n = 81/119), as predominant affective temperament and other psychopathological rating did not. Overall, the time of admission, use of SGA, anticonvulsant (other than lithium), antidepressant, lifetime alcohol dependence, and BD Type (-I or -II), but not current mood polarity at the time of hospitalization, correctly predicted LOS+ grouping 68.2% of the times: Exp(B) = 3.151, p042. LIMITATIONS: Post-hoc, cross-sectional study, relatively small sample size, recall and selection bias on some diagnoses. CONCLUSIONS: Overall, LOS+ treatment-resistant BD inpatients characterize for higher severity and greater pharmaco-utilization use, which warrants replication studies to include additional predictors to shed further light on the matter.

Depression and pain: primary data and meta-analysis among 237 952 people across 47 low- and middle-income countries.

BACKGROUND: Depression and pain are leading causes of global disability. However, there is a paucity of multinational population data assessing the association between depression and pain, particularly among low- and middle-income countries (LMICs) where both are common. Therefore, we investigated this association across 47 LMICs. METHODS: Community-based data on 273 952 individuals from 47 LMICs were analysed. Multivariable logistic and linear regression analyses were performed to assess the association between the International Classification of Diseases, 10th Revision depression/depression subtypes (over the past 12 months) and pain in the previous 30 days based on self-reported data. Country-wide meta-analysis adjusting for age and sex was also conducted. RESULTS: The prevalence of severe pain was 8.0, 28.2, 20.2, and 34.0% for no depression, subsyndromal depression, brief depressive episode, and depressive episode, respectively. Logistic regression adjusted for socio-demographic variables, anxiety and chronic medical conditions (arthritis, diabetes, angina, asthma) demonstrated that compared with no depression, subsyndromal depression, brief depressive episode, and depressive episode were associated with a 2.16 [95% confidence interval (CI) 1.83-2.55], 1.45 (95% CI 1.22-1.73), and 2.11 (95% CI 1.87-2.39) increase in odds of severe pain, respectively. Similar results were obtained when a continuous pain scale was used as the outcome. Depression was significantly associated with severe pain in 44/47 countries with a pooled odds ratio of 3.93 (95% CI 3.54-4.37). CONCLUSION: Depression and severe pain are highly comorbid across LMICs, independent of anxiety and chronic medical conditions. Whether depression treatment or pain management in patients with comorbid pain and depression leads to better clinical outcome is an area for future research.

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.

Somatopsychic correlates and quality of life of the dialyzed patient: a cross-sectional study.

BACKGROUND: The dialysis delivered after a chronic kidney disease (CDK) or any otherwise severe end-stage renal failure is a complex medical task, leading to major medical and psychopathological distress for the patient. The aim of the present study was to analyze the impact of the dialysis experience on the nephrologic patient's global quality of life. METHODS: In the present cross-sectional study, involving 96 patients with end-stage renal disease receiving hemodialysis, demographic, medical, and psychological differential features across different CDK diagnoses were accounted and were then correlated each other. RESULTS: Among other differential features, the "acknowledgement of dependence" (from the medical device delivering the dialysis) emerged as a factor correlated to "self-sufficiency" in CDK patients receiving hemodialysis. CONCLUSIONS: Although further, larger-sampled studies on the topic are needed, medical and psychological interventions are useful to ensure a better global quality of life and good therapeutic adherence in dialysis patients.

Matrix metalloproteinase (MMP)-2 and MMP-9 as inflammation markers of Trichinella spiralis and Trichinella pseudospiralis infections in mice.

Trichinella spiralis and Trichinella pseudospiralis exhibit differences in the host-parasite relationship such as the inflammatory response in parasitized muscles. Several studies indicate that matrix metalloproteinases (MMPs) represent a marker of inflammation since they regulate inflammation and immunity. The aim of this study was to evaluate the serum levels of gelatinases (MMP-9 and MMP-2) in mice experimentally infected with T. spiralis or T. pseudospiralis, to elucidate the involvement of these molecules during the inflammatory response to these parasites. Gelatin zymography on SDS polyacrilamide gels was used to assess the serum levels and in situ zymography on muscle histological sections to show the gelatinase-positive cells. In T. spiralis infected mice, the total MMP-9 serum level increased 6 days post-infection whereas, the total MMP-2 serum level increased onward. A similar trend was observed in T. pseudospiralis infected mice but the MMP-9 level was lower than that detected in T. spiralis infected mice. Significant differences were also observed in MMP-2 levels between the two experimental groups. The number of gelatinase positive cells was higher in T. spiralis than in T. pseudospiralis infected muscles. We conclude that MMP-9 and MMP-2 are markers of the inflammatory response for both T. spiralis and T. pseudospiralis infections.

Alexithymia and its relationships with acute phase proteins and cytokine release: an updated review.

The alexithymia construct is multidimensional and comprises several features: (a) difficulty in identifying and describing feelings, (b) difficulty in distinguishing feelings from the bodily sensations, (c) diminution of fantasy, and (d) concrete and poorly introspective thinking. Altered immune responses have been seen in some psychiatric disorders and several data suggest that analogous changes could also be observable in alexithymia. Hence, the aim of this review is to investigate the relationships between alexithymia and acute phase proteins and cytokines in psychiatric, psychosomatic and medical diseases. Several studies have reported an association between alexithymia and higher circulating levels of acute phase proteins, especially C-Reactive Protein. Moreover, in alexithymic subjects the pro-inflammatory and anti-inflammatory cytokine balance may be tuned toward a pro-inflammatory imbalance with a concomitant altered cell-mediated immunity. These findings may be consistent with the "“stress-alexithymia hypothesis"”. Therefore, the screening of alexithymic traits and the administration of appropriate psychological and psychotherapeutical interventions should be integral parts of disease management programs. Supplying such interventions will probably help with prevention of the development of the disease and/or its exacerbation by improving the quality of life of alexithymic individuals.

Is there a role for agomelatine in the treatment of anxiety disorders?A review of published data.

Anxiety disorders (Ads) are the most common type of psychiatric disorders, Pharmacologic options studied for treating ADs may include benzodiazepines, tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRIs), noradrenergic and specific serotonergic antidepressants (NaSSA) and serotonin and noradrenaline reuptake inhibitors (SNRIs). Agomelatine, a new melatonergic antidepressant, has been shown effective in various types of mood disorders. Moreover, some evidence points towards a possible efficacy of such a drug in the treatment of ADs. Therefore, the aim of this review was to elucidate current (facts and views) data on the role of agomelatine in the treatment of ADs. The trials evaluating agomelatine in the treatment of generalized anxiety disorder are few but, overall, encouraging in regards to its efficacy. However, further randomized, placebo-controlled studies on larger samples use are needed. Apart from some interesting case reports, no large studies are, to date, present in literature regarding agomelatine in the treatment of other ADs, such as panic disorder, social anxiety disorder, obsessive-compulsive disorder and post-traumatic stress disorder. Therefore, the clinical efficacy and the relative good tolerability of agomelatine in generalized anxiety (GAD) warrants further investigation in ADs.

The influence of affective temperaments and psychopathological traits on the definition of bipolar disorder subtypes: a study on bipolar I Italian national sample.

UNLABELLED: Affective temperament and psychopathological traits such as separation anxiety (SA) and interpersonal sensitivity (IPS) are supposed to impact on the clinical manifestation and on the course of Bipolar Disorder (BD); in the present study we investigated their influence on the definition of BD subtypes. METHOD: : Among 106 BD-I patients with DSM-IV depressive, manic or mixed episode included in a multi-centric Italian study and treated according to the routine clinical practice, 89 (84.0%) were in remission after a follow-up period ranging from 3 to 6 months (Clinical Global Impression-BP [CGI-BP] <2). Remitting patients underwent a comprehensive evaluation including self-report questionnaires such as the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-A) scale, Separation Anxiety Symptom Inventory (SASI), Interpersonal Sensitivity Measure (IPSM) and the Semi-structured interview for Mood Disorder (SIMD-R) administered by experienced clinicians. Correlation and factorial analyses were conducted on temperamental and psychopathological measures. Comparative analyses were conducted on different temperamental subtypes based on the TEMPS-A, SASI and IPSM profile. RESULTS: : Depressive, cyclothymic and irritable TEMPS-A score and SASI and IPSM total scores were positively and statistically correlated with each other. On the contrary, hyperthymic temperament score was negatively correlated with depressive temperament and not significantly correlated with the other temperamental and psychopathological dimensions. The factorial analysis of the TEMPS-A subscales and SASI and IPSM total scores allowed the extraction of 2 factors: the cyclothymic-sensitive (explaining 46% of the variance) that included, as positive components, depressive, cyclothymic, irritable temperaments and SASI and IPSM scores; the hyperthymic (explaining the 19% of the variance) included hyperthymic temperament as the only positive component and depressive temperament and IPSM, as negative components. Dominant cyclothymic-sensitive patients (n=49) were more frequently females and reported higher number of depressive, hypomanic and suicide attempts when compared to the dominant hyperthymic patients (n=40). On the contrary, these latter showed a higher number of manic episodes and hospitalizations than cyclothymic-sensitive patients. The rates of first-degree family history for both mood and anxiety disorders were higher in cyclothymic-sensitive than in hyperthymic patients. Cyclothymic sensitive patients also reported more axis I lifetime co-morbidities with Panic Disorder/Agoraphobia and Social Anxiety Disorder in comparison with hyperthymics. As concerns axis II co-morbidity the cyclothymic-sensitive patients met more frequently DSM-IV criteria 1, 5 and 7 for borderline personality disorder than the hyperthymics. On the contrary, antisocial personality disorder was more represented among hyperthymic than cyclothymic patients, in particular for DSM-IV criteria 1 and 6. LIMITATION: : No blind evaluation and uncertain validity of personality inventory. CONCLUSION: : Our results support the view that affective temperaments influence the clinical features of BD in terms of both clinical and course characteristics, family history and axis I and II co-morbidities. Hypothetical temperamental subtypes as measured by TEMPS-A presented important interrelationships that permit to reliably isolate two fundamental temperamental disposition: the first characterized by rapid fluctuations of mood and emotional instability, and the second by hyperactivity, high level of energy and emotional intensity. Dominant cyclothymic and hyperthymic bipolar I patients reported important differences in terms of gender distribution, number and polarity of previous episodes, hospitalizations, suicidality, rates of co-morbid anxiety and personality traits and disorders. Our data are consistent with the hypothesis that affective temperaments, and in particular cyclothymia, could be utilized as quantitative, intermediate phenotypes in order to identify BD susceptibility genes.

Phosphate glass fibres and their role in neuronal polarization and axonal growth direction.

Phosphate glass fibres with composition 50P(2)O(5)-30CaO-9Na(2)O-3SiO(2)-3MgO-(5-x)K(2)O-xTiO(2)mol.% (x=0, 2.5, 5, respectively coded as TiPS(0), TiPS(2.5) and TiPS(5)) were drawn following the preform drawing approach. A 20-day solubility test in bi-distilled water was carried out on glass fibres with different compositions and diameters ranging between 25 and 82 µm. The results show that the glass composition, the initial fibre diameter and the thermal treatment are the main factors influencing the dissolution kinetics and that the fibres maintain their structural integrity and composition during dissolution. Biological tests were carried out on aligned TiPS(2.5) glass fibres using Neonatal Olfactory Bulb Ensheathing Cell Line (NOBEC) and Dorsal Root Ganglia (DRG) neurons. The fibres showed to be permissive substrates for cell adhesion and proliferation. The aligned configuration of the fibres seemed to provide a directional cue for growing axons of DRG neurons, which showed to sprout and grow long neurites along the fibre axis direction. These promising findings encourages further studies to evaluate the potential use of resorbable glass fibres (e.g.in combination with a nerve guidance tube) for the enhancement of the peripheral nerve healing with the role of supporting and guiding the cells involved in the nerve regeneration.

Selective immunoglobulin A deficiency and celiac disease: let's give serology a chance.

Patients with selective immunoglobulin (Ig) A deficiency have a 10- to 20-fold increased risk of celiac disease. In these patients, serological diagnosis of celiac disease can be difficult, since specific IgA-based assays are usually negative and IgG-specific antibody tests are insufficiently reliable. We describe a girl with selective IgA deficiency who had a troublesome diagnosis of celiac disease that was established only after an unexpected positive test result for antitransglutaminase IgA and antiendomysium IgA. Our observation indicates that IgA-based serology should not be forgotten in patients with selective IgA deficiency, since positive results for antitransglutaminase IgA, antiendomysium IgA, or both can be observed at any time during diagnostic investigations.