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Trazodone is a serotonin antagonist/reuptake inhibitor, approved for treating major depressive disorder (MDD). Oral formulations are widely studied and marketed in several countries worldwide while there is little evidence to support use of parenteral formulation. Our narrative review summarizes pharmacological properties and clinical data concerning use of parenteral trazodone in mood disorders. PubMed and Web of Science were used to identify the most relevant literature. The main evidence concerns four studies evaluating efficacy in major depressive disorder and indicates that trazodone was well tolerated and effective. Off-label use in agitation associated with bipolar disorder is also reported in three studies, although prescription of concomitant treatment, as a confounding factor, may have influenced outcome measures. The limited available evidence supports parenteral trazodone use in major depressive disorder and suggests that trazodone is a suitable option in patients at high risk of treatment-emergent mania (TEM).

Objective: : Intramuscular medications are widely used to treat psychomotor agitation (PMA) in uncooperative patients. We evaluated knowledge and attitude towards guidelines and the prescribing patterns in a sample of Italian psychiatrists., Methods: : A structured 28-item questionnaire was submitted to psychiatrists of Italian Departments of Mental Health. We considered 8 clinical scenarios of PMA. For comparing two qualitative variables Chi-square tests were performed., Results: : One hundred thirty-four psychiatrists completed the survey. The use of a monotherapy is significatively higher ( p ＜ 0.05) over a dual therapy in all clinical scenarios except PMA due to Mood Disorder and Psychotic Disorders, whereas the use of a polytherapy is significatively higher ( p ＜ 0.05) in PMA due to Mood Disorders and Psychotic Disorders. The use of second-generation antipsychotic (SGAs) as monotherapy over first-generation antipsychotics (FGAs) is significantly higher ( p ＜ 0.05) in PMA due to Central Nervous System (CNS) stimulants. The use of SGAs over FGAs in polytherapy is significantly higher ( p ＜ 0.05) in PMA due to CNS stimulants. Knowledge of guidelines results 67.1% and significatively higher ( p ＜ 0.05) among those who prefer SGAs as monotherapy rather than FGAs in PMA due to Intellectual Disability, CNS depressants and Delirium. Knowledge of guidelines results significatively higher ( p ＜ 0.05) among those who prefer SGAs rather than FGAs in polytherapy in PMA due to Mood disorders., Conclusion: : This survey reports variation in prescribing patterns for medication used to treat PMA. While SGAs are often prescribed as first choice following the more recent guidelines, FGAs and multi-drug solutions seem to be still a popular solution.

Paroxetine and Sertraline are the only medications approved in posttraumatic stress disorder (PTSD). However, about 60% of traumatized patients fail to show an adequate clinical response. Second generation antipsychotics are recommended as second-line monotherapy or third-line augmentation strategies and quetiapine appears as one of the most used and promising agents. Up to date, no reviews assessed the efficacy of quetiapine in the treatment of PTSD. We aimed to assess the effectiveness and general safety of quetiapine on PTSD. A systematic review was conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and Cochrane guidelines, selecting studies that evaluated the efficacy of quetiapine on global or specific PTSD symptomatology. Ten studies (n = 894) were considered eligible for qualitative synthesis: one case report, one case series, one prospective cohort study, 3 open-label trials, 3 retrospective studies, one randomized controlled trial. Quetiapine was effective on global PTSD symptomatology assessed in 6 studies as well as on re-experiencing (4/4 studies), avoidance (4/3 studies) and hyperarousal (4/4 studies), flashbacks (2/2 studies), depressive (4/4 studies), anxiety (1/1 studies), psychotic (3/3 studies), insomnia (4/5 studies), nightmares (3/3 studies) specific symptoms and PTSD domains. Sedation was among the most frequently observed adverse effects and the main cause of drug discontinuation. Preliminary findings support the efficacy of quetiapine in ameliorating symptoms relative to PTSD and its overall safety. However, quetiapine use in PTSD cannot be recommended yet as studies mainly rely on open-label, retrospective studies or case series.

Anxiety symptoms and anxiety disorders are frequent in patients with schizophrenia and are associated with greater severity of both positive and negative symptoms, cognitive impairment, poorer functioning and quality of life. Accumulating evidence suggests that atypical antipsychotics may have a role in treating comorbid anxiety symptoms. A systematic review was conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and Cochrane guidelines, selecting randomized control trials (RCTs) that evaluated efficacy of olanzapine on anxiety symptoms in patients diagnosed with schizophrenia and included anxiety evaluation scales. We searched PubMed and Web of Science databases for articles in English language available until September 2021. We selected 7 studies (3 with primary data analysis, 4 with secondary data analysis) regarding the use of olanzapine in patients with schizophrenia. In fours studies olanzapine was superior to haloperidol in improving anxiety symptoms. Four studies compared olanzapine versus risperidone: in two of them risperidone was superior to olanzapine, although one study was limited by a relatively small sample size. In the other two there were no significant differences between olanzapine and risperidone-treated patients. One study found that olanzapine and clozapine were comparable in terms of efficacy. Although olanzapine was superior to haloperidol in treating anxiety, this symptom was a secondary outcome measure in most of the considered studies. Future RCTs comparing different antipsychotics and larger sample sizes may allow to develop more solid treatment strategies.

Since decades, lithium and valproate remain the pharmacological cornerstone to treat bipolar disorder. Different response patterns occur according to the phases of illness. At same time, individual pretreatment variables may concur to determine a specific drug-response. Our narrative review focuses on these two key clinical aspects to summarize the state of art. Information from i) clinical trials and ii) the most relevant international guidelines is collected to assess the clinical and preclinical factors that may guide the use of lithium rather than valproate. Lithium may be effective in treating acute mania, and lithium efficacy is maximized when used to prevent both manic and depressive episodes. Lithium may be a better treatment choice in patients with: positive family history for bipolar disorder, mania-depression-interval pattern, few previous affective episodes/hospitalizations, high risk for suicide, no comorbidities. Valproate may be more effective as antimanic rather than prophylactic agent. Valproate might be a better choice in patients with many previous affective episodes/hospitalizations and psychiatric comorbidities. Finally, neither lithium nor valproate are suggested for the treatment of acute mixed states or bipolar depression. To consider clinical and preclinical factors may thus be useful to select the best treatment strategy.

Kawasaki disease (KD) is rare in infants less than 3 months of age, and its recurrence is exceptional. Infants with KD are at higher risk of severe clinical presentation, therapy failure, complications and coronary aneurysms (CAAs), and this is the reason they deserve more aggressive therapy and a strict clinical follow-up. We report a 2-month-old male with KD, complicated by Macrophage Activation Syndrome (MAS). Despite timely and aggressive therapy with immunoglobulins, steroids and aspirin, multiple CAAs developed. Two-month therapy with anakinra completely reverted all the aneurysms. After six months, the infant experienced KD relapse and was successfully re-treated with immunoglobulins, steroids and aspirin. A strict echocardiographic follow-up did not show recurrence of aneurysms. Two years later, the child is healthy, without cardiac sequelae. In our experience, anakinra was effective in reverting multiple aneurysms and its effect proved to be long-lasting, even in front of KD recurrence. Based on this evidence, it seems reasonable to hypothesize not to limit the use of anakinra as rescue therapy for complicated or refractory KD, but to consider the possibility of adding it to first-line therapies for some subgroups of very-high-risk patients, in order to strengthen the prevention of CAAs.

Purpose/background: Bipolar disorder and major depressive disorder are heterogeneous conditions characterized by marked variations in mood. High levels of anxiety are often present in these conditions and are associated with increased suicidal risk, increased disease duration, and treatment resistance. Mood stabilizers or antipsychotics are recommended for the treatment of bipolar disorder in comorbidity with anxiety disorders. This study examines current knowledge to evaluate the efficacy of quetiapine in the treatment of anxiety in mood disorders., Methods/procedures: A systematic review was conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and Cochrane guidelines, selecting randomized control trials that evaluated the efficacy of quetiapine on anxiety symptoms in patients diagnosed with bipolar disorder or major depressive disorder and included anxiety evaluation scales., Findings/results: We collected 27 studies (19 with primary data analysis, 8 with secondary data analysis) regarding the use of quetiapine in mood disorders. Quetiapine was more effective than placebo and active comparators in reducing anxiety in unipolar and bipolar patients in 20 of these studies. In 7 studies, quetiapine was not superior to psychoactive comparators or placebo on the anxiety dimension., Implications/conclusions: Statistical power might be limited by small sample size in 5 of the studies included in our review. Moreover, data on anxiety were a secondary outcome in most studies. Nevertheless, the reported studies show with good levels of concordance that quetiapine is effective in controlling anxiety symptoms in patients with mood disorders. This evidence supports current guidelines and recommendations concerning the use of quetiapine in clinical practice., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Magnesium is a fundamental cation that regulates neuronal transmission, protein synthesis, energy metabolism. Magnesium deficiency mostly affects nervous and cardiovascular systems determining weakness, tremors, seizure and arrhythmias. This condition retains also a role in memory function and neuronal plasticity. Importantly magnesium deficiency could remain latent and asymptomatic resulting a risk factor for cardiovascular disease. In this sense we aim to determine magnesium status in patient presenting cognitive impairment of vascular origin., Methods: 21 healthy subjects and 27 patients presenting vascular cognitive impairment were included in this study. Both plasma and intraerythrocitary magnesium level were measured to detect magnesium deficiency and cognitive performance was evaluated trough Mini Mental State Evaluation (MMSE)., Results: Here we showed that patients presenting vascular cognitive impairment present intraerythrocitary magnesium level lower than age-matched healthy subjects. To note their plasma magnesium resulted within reference limit., Conclusion: We suggest that intracellular magnesium laboratory measurement is needed to detect occult magnesium deficiency in population at risk. Magnesium supplementation could represent an adjuvant for healthy aging in high risk population.

Objectives: Trazodone is a multifunctional triazolopyridine drug with antidepressant, anxiolytic, sedative, and hypnotic properties. The current retrospective study was designed to investigate the effectiveness of trazodone for reducing acute psychomotor activation (PA) in patients with bipolar disorder (BD). We specifically reasoned that a parenteral route of administration could offer potential advantages in this clinical setting., Methods: We assessed the effectiveness and safety of parenteral trazodone in a retrospective study conducted in 64 inpatients with BD and acute PA. The effectiveness assessment was the Clinical Global Impression Scale - Severity Of Illness (CGI-S) rated before the administration of parenteral trazodone (baseline) and at the end of treatment. A post-treatment reduction in CGI-S score ≥ 20% compared with baseline was considered as the primary outcome measure., Results: Administration of parenteral trazodone was associated with significant improvements in CGI-S scores from baseline (5.4 ± 0.9) to the end of the study (4.2 ± 1.0; p < 0.001, Wilcoxon matched-pairs signed-ranks test). A total of 34 patients (53.1%) showed a post-treatment reduction in CGI-S score ≥ 20% compared to baseline. Multivariable binary logistic regression analysis using a forward selection procedure identified treatment duration (in days) as the only independent predictor of post-treatment reduction in CGI-S score ≥ 20% (odds ratio: 1.28; 95% confidence interval: 1.02-1.60, p <0.05). Adverse effects occurred in 13 (20.3%) patients., Conclusions: Parenteral trazodone is well-tolerated and effective in 53.1% of patients with BP and acute PA. Treatment duration was identified as an independent predictor of response in our sample.

There is still no "gold standard" for the diagnosis and prognosis of post-operative periprosthetic joint infection (PJI). Among serum biomarkers, an emerging molecule is presepsin, the soluble fraction of CD14, recently described in other settings as a powerful diagnostic tool to detect sepsis at different degrees of severity. The aim of this study was to investigate the diagnostic and prognostic value of presepsin in PJI. A total of 30 patients with PJI and 30 patients without PJI were enrolled. Presepsin, C-reactive protein (CRP), serum interleukin (IL)-6, triggering receptor expressed on myeloid cells 1 (TREM-1), CCL2, matrix metalloproteinase 9 (MMP-9), CD163, osteopontin (OPN), and toll-like receptor 2 (TLR2) were measured at different times after surgery. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were analyzed for each biomarker. Presepsin showed greater diagnostic value than CRP and IL-6; CD163, TREM-1, and MMP-9 had very low diagnostic potential. Presepsin, OPN, CCL2, suPAR, and TLR2 all decreased significantly with increasing time of recovery after surgery in PJI patients. Presepsin can be considered a useful tool for the diagnosis and clinical monitoring of PJI and can be backed by a panel of new inflammatory markers involved in monocyte-/macrophage-mediated inflammatory responses, such as OPN, CCL2, TLR2, and suPAR.

Background: This randomized, double-blind, parallel-group clinical trial aims to assess the equivalence of intra-articular polynucleotides compared to standard hyaluronic acid (HA) viscosupplementation in the treatment of knee osteoarthritis (OA)., Methods: 75 patients affected by knee OA were assessed for eligibility and 72 were enrolled and randomized to receive either intra-articular polynucleotides (Condrotide-36 patients) or hyaluronic acid (Hyalubrix-36 patients) at the Orthopedic Institute "Gaetano Pini" (Milan). All patients underwent three intra-articular injections of Condrotide or Hyalubrix with an interval of 1week. Participants, care givers, and investigators responsible for outcome assessment were all blinded to group assignment. Primary outcome measurements (KOOS and pain level (1) at rest, (2) at weight-bearing and (3) during physical activity) were evaluated at baseline (T0) and after one (T1), two (T2), six (T6), ten (T10), and 26 (T26)weeks. Secondary measurements included the determination of COMP serum levels at T0, T6 and T26., Results: The reduction of pain and the increase of KOOS values from baseline were statistically significant for both treatments; nevertheless, for parameter KOOS "symptoms" the treatment with Condrotide showed significant results already after twoweeks (at T2 p=0.003) while the results obtained with Hyalubrix became significant only after 18 weeks (at T18 p=0.01). No significant adverse events were reported., Conclusions: Condrotide is as effective as Hyalubrix in reducing knee OA symptoms but showed an earlier response on pain reduction and can therefore be considered a valid alternative to the use of HA in the treatment of OA, avoiding the adverse events of NSAIDs and of intra-articular corticosteroids., (Copyright © 2014 Elsevier B.V. All rights reserved.)

An adequate intake of magnesium (Mg) is important for bone cell activity and contributes to the prevention of osteoporosis. Because (a) Mg is mitogenic for osteoblasts and (b) reduction of osteoblast proliferation is detected in osteoporosis, we investigated the influence of different concentrations of extracellular Mg on osteoblast-like SaOS-2 cell behavior. We found that low Mg inhibited SaOS-2 cell proliferation by increasing the release of nitric oxide through the up-regulation of inducible nitric oxide synthase (iNOS). Indeed, both pharmacological inhibition with the iNOS inhibitor l-N(6)-(iminoethyl)-lysine-HCl and genetic silencing of iNOS by small interfering RNA restored the normal proliferation rate of the cells. Because a moderate induction of nitric oxide is sufficient to potentiate bone resorption and a relative deficiency in osteoblast proliferation can result in their inadequate activity, we conclude that maintaining Mg homeostasis is relevant to ensure osteoblast function and, therefore, to prevent osteoporosis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To determine the prevalence of anti-cyclic citrullinated peptide (CCP) antibodies in systemic sclerosis (SSc) and to assess any association between the presence of anti-CCP, radiographic features, and clinical manifestations., Materials and Methods: Anti-CCP antibodies and rheumatoid factor (RF) were tested in serum samples from 75 patients with SSc (64 women and 11 men), with a mean age of 59.4 years (range 24-85) with either diffuse (dcSSc) and limited (lcSSc) cutaneous involvement. As a control group, 22 age- and sex-matched healthy controls (HCs) were examined. Standard radiographs of the hands and wrists were examined in each patient., Results: The presence of anti-CCP was found in sera of 10.6% (8/75) patients with SSc (lcSSc 3 of 44, 6.8%; dcSSc 5 of 31, 16.1%). None of the HCs was positive for anti-CCP. The positivity of RF was observed in 19 of 75 (25.3%) SSc patients (lcSSc 10 of 44, 22.7%; dcSSc 9 of 31, 29%). Statistically significant association was found between anti-CCP positivity and the presence of arthritis (p<0.0001) and marginal erosions (p=0.001)., Conclusion: Our data show that joint involvement is a common presenting feature of SSc. In this report, we show that anti-CCP antibodies can be detected also in patients with SSc, but they are generally less commonly present than in adults with rheumatoid arthritis (RA). Thus, the finding of high titers of anti-CCP antibodies may help to define the diagnosis of overlap syndrome SSc/RA and facilitate diagnosis and appropriate treatment.

We have developed a new method of screening for hemophilia A in families at risk for the disease. A DNA probe (St14) that detects a very polymorphic region on the human X chromosome has been shown to be closely linked to hemophilia A. We observed no recombination between the St14 locus and hemophilia A in 12 families studied. The odds in favor of linkage are 4.4 X 10(9) to 1 (lod score, 9.65). The 95 per cent confidence interval for the probability of a recombination between St14 and hemophilia A is 0 to 6.5 per cent. This DNA probe, which is informative in more than 90 per cent of families at risk of hemophilia A, can be used in conjunction with classic biologic assays to identify carriers with an accuracy of 96 per cent or more. If a small risk of misclassification due to crossover between the test and the disease loci is accepted, this DNA marker should allow first-trimester prenatal diagnosis of hemophilia A. Segregation analysis with St14 may thus represent a major improvement in genetic counseling for hemophilia A.