Ablation of Paroxysmal Atrial Fibrillation: between Present and Future.

Pulmonary vein isolation (PVI) is the established cornerstone for atrial fibrillation (AF) ablation, indeed current guidelines recognize PVI as the gold standard for first-time AF ablation, regardless of if it is paroxysmal or persistent. Since 1998 when Haïssaguerre pioneered AF ablation demonstrating a burden reduction after segmental pulmonary vein (PV) ablation, our approach to PVI was superior in terms of methodology and technology. This review aims to describe how paroxysmal atrial fibrillation ablation has evolved over the last twenty years. We will focus on available techniques, a mechanistic understanding of paroxysmal AF genesis and the possibility of a tailored approach for the treatment of AF, before concluding with a future perspective.

Unfolding the Challenges To Prepare Single Crystalline Complex Oxide Membranes by Solution Processing.

The ability to prepare single crystalline complex oxide freestanding membranes has opened a new playground to access new phases and functionalities not available when they are epitaxially bound to the substrates. The water-soluble Sr3Al2O6 (SAO) sacrificial layer approach has proven to be one of the most promising pathways to prepare a wide variety of single crystalline complex oxide membranes, typically by high vacuum deposition techniques. Here, we present solution processing, also named chemical solution deposition (CSD), as a cost-effective alternative deposition technique to prepare freestanding membranes identifying the main processing challenges and how to overcome them. In particular, we compare three different strategies based on interface and cation engineering to prepare CSD (00l)-oriented BiFeO3 (BFO) membranes. First, BFO is deposited directly on SAO but forms a nanocomposite of Sr-Al-O rich nanoparticles embedded in an epitaxial BFO matrix because the Sr-O bonds react with the solvents of the BFO precursor solution. Second, the incorporation of a pulsed laser deposited La0.7Sr0.3MnO3 (LSMO) buffer layer on SAO prior to the BFO deposition prevents the massive interface reaction and subsequent formation of a nanocomposite but migration of cations from the upper layers to SAO occurs, making the sacrificial layer insoluble in water and withholding the membrane release. Finally, in the third scenario, a combination of LSMO with a more robust sacrificial layer composition, SrCa2Al2O6 (SC2AO), offers an ideal building block to obtain (001)-oriented BFO/LSMO bilayer membranes with a high-quality interface that can be successfully transferred to both flexible and rigid host substrates. Ferroelectric fingerprints are identified in the BFO film prior and after membrane release. These results show the feasibility to use CSD as alternative deposition technique to prepare single crystalline complex oxide membranes widening the range of available phases and functionalities for next-generation electronic devices.

Management of cerebral amyloid angiopathy and atrial fibrillation: We are still far from precision medicine.

The use of anticoagulation therapy could prove to be controversial when trying to balance ischemic stroke and intracranial bleeding risks in patients with concurrent cerebral amyloid angiopathy (CAA) and atrial fibrillation (AF). In fact, CAA is an age-related cerebral vasculopathy that predisposes patients to intracerebral hemorrhage. Nevertheless, many AF patients require oral systemic dose-adjusted warfarin, direct oral anticoagulants (such as factor Xa inhibitors) or direct thrombin inhibitors to control often associated with cardioembolic stroke risk. The prevalence of both CAA and AF is expected to rise, due to the aging of the population. This clinical dilemma is becoming increasingly common. In patients with coexisting AF and CAA, the risks/benefits profile of anticoagulant therapy must be assessed for each patient individually due to the lack of a clear-cut consensus with regard to its risks in scientific literature. This review aims to provide an overview of the management of patients with concomitant AF and CAA and proposes the implementation of a risk-based decision-making algorithm.

Machine learning approach for the development of a crucial tool in suicide prevention: The Suicide Crisis Inventory-2 (SCI-2) Short Form.

The Suicide Crisis Syndrome (SCS) describes a suicidal mental state marked by entrapment, affective disturbance, loss of cognitive control, hyperarousal, and social withdrawal that has predictive capacity for near-term suicidal behavior. The Suicide Crisis Inventory-2 (SCI-2), a reliable clinical tool that assesses SCS, lacks a short form for use in clinical settings which we sought to address with statistical analysis. To address this need, a community sample of 10,357 participants responded to an anonymous survey after which predictive performance for suicidal ideation (SI) and SI with preparatory behavior (SI-P) was measured using logistic regression, random forest, and gradient boosting algorithms. Four-fold cross-validation was used to split the dataset in 1,000 iterations. We compared rankings to the SCI-Short Form to inform the short form of the SCI-2. Logistic regression performed best in every analysis. The SI results were used to build the SCI-2-Short Form (SCI-2-SF) utilizing the two top ranking items from each SCS criterion. SHAP analysis of the SCI-2 resulted in meaningful rankings of its items. The SCI-2-SF, derived from these rankings, will be tested for predictive validity and utility in future studies.

Thromboembolic prevention in athletes: management of anticoagulation in sports players affected by atrial fibrillation.

Atrial fibrillation (AF) is a common cardiac arrhythmia that poses a significant risk of stroke and thromboembolic events. Anticoagulation therapy is essential for preventing stroke in patients with AF. An increasing number of people of all ages, including cardiac patients, approach physical activity as both a leisure-time exercise and a competitive sport. Therefore, patients at risk of AF are increasingly allowed to practice sports activities. Management of oral anticoagulant therapy (OAT) in these patients is extremely challenging because of the need to balance the risks and benefits of medications, considering both hemorrhagic (in case of trauma) and ischemic complications when the drugs are avoided. Official recommendations are limited for these patients and forbid sports that increase the risk of trauma and consequent bleeding in most cases. These recommendations are strongly influenced by the "traditional" management of OAT, which mainly involves coumarin derivatives. Non-vitamin K antagonist direct oral anticoagulants (DOACs), with their more favorable pharmacokinetic-pharmacodynamic profile than that of coumarin derivatives, may represent an opportunity to modify the approach to sports activity in patients with AF and indications for OAT. This study aimed to review the use of anticoagulants in athletes with AF, highlight their efficacy and safety, and provide practical considerations regarding their management.

Paucisymptomatic post COVID-19 myocarditis in a young athlete during return to play workflow: possible usefulness of global longitudinal strain analysis.

A young competitive athlete undergoes the diagnostic investigations protocol before returning to competitive practice (return to play protocol) after COVID-19 infection. Despite the paucisymptomatic presentation of COVID-19 infection and the absence of relevant anomalies in standard first-level diagnostic investigations, echocardiographic examination findings especially speckle tracking analysis (global longitudinal strain) along with some clinical aspects suggested further second-level investigations eventually allowing the identification of inflammatory myocardial damage.

MiR126-targeted-nanoparticles combined with PI3K/AKT inhibitor as a new strategy to overcome melanoma resistance.

Metastatic melanoma poses significant challenges as a highly lethal disease. Despite the success of molecular targeting using BRAFV600E inhibitors (BRAFis) and immunotherapy, the emergence of early recurrence remains an issue and there is the need for novel therapeutic approaches. This study aimed at creating a targeted delivery system for the oncosuppressor microRNA 126 (miR126) and testing its effectiveness in combination with a phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (AKT) inhibitor for treating metastatic melanoma resistant to BRAFis. To achieve this, we synthesized chitosan nanoparticles containing a chemically modified miR126 sequence. These nanoparticles were further functionalized with an antibody specific to the chondroitin sulfate proteoglycan 4 (CSPG4) melanoma marker. After evaluation in vitro, the efficacy of this treatment was evaluated through an in vivo experiment using mice bearing resistant human melanoma. The co-administration of miR126 and the PI3K/AKT inhibitor in these experiments significantly reduced tumor growth and inhibited the formation of liver and lung metastases. These results provide evidence for a strategy to target an oncosuppressive nucleic acid sequence to tumor cells while simultaneously protecting it from plasma degradation. The system described in this study exhibits encouraging potential for the effective treatment of therapy-resistant metastatic melanoma while also presenting a prospective approach for other forms of cancer.

Long-Term Follow-Up In Paroxysmal Atrial Fibrillation Patients With Documented Isolated Trigger.

Aims: Supraventricular tachycardias may trigger atrial fibrillation (AF). The aim of the study was to evaluate the prevalence of supraventricular tachycardia (SVT) inducibility in patients referred for AF ablation and to evaluate the effects of SVT ablation on AF recurrences. Methods and results: 249 patients (mean age: 54 ± 14 years) referred for paroxysmal AF ablation were studied. In all patients, only AF relapses had been documented in the clinical history. 47 patients (19%; mean age: 42 ± 11 years) had inducible SVT during the electrophysiological study and underwent an ablation targeted only at SVT suppression. Ablation was successful in all 47 patients. The ablative procedures were: 11 slow-pathway ablations for atrioventricular nodal re-entrant tachycardia; 6 concealed accessory pathway ablations for atrioventricular re-entrant tachycardia; 17 focal ectopic atrial tachycardia ablations; 13 with only one arrhythmogenic pulmonary vein. No recurrences of SVT were observed during the follow-up (32 ± 18 months). 4 patients (8.5%) showed recurrence of at least one episode of AF. Patients with inducible SVT had less structural heart disease and were younger than those without inducible SVT. Conclusion: A significant proportion of candidates for AF ablation are inducible for an SVT. SVT ablation showed a preventive effect on AF recurrences. Those patients should be selected for simpler ablation procedures tailored only to the triggering arrhythmia suppression.

Standford type A aortic dissection in a patient with situs inversus totalis, with critical clinical presentation: a case report.

The association of Standford type A acute aortic dissection with situs inversus totalis (SIT) is extremely rare and only a few cases are reported in the literature to date. Due to the particular rarity, this unusual condition, if not diagnosed quickly and correctly, can generate both clinical and surgical difficulties. Case presentation: We describe the case of a male Caucasian patient with SIT and aortic dissection type A, who occurred to our Emergency Department with a severe clinical condition of shock. Using the fast diagnostic approach with chest X-Ray and echocardiography followed by computed tomography investigation, a Standford type A acute aortic dissection and the presence of SIT were detected. The patient was subjected to surgical treatment with optimal results in a short time. Clinical discussion and conclusion: The event of aortic dissection is an extremely serious condition and the simultaneous presence of a critical clinical presentation with an unusual congenital anomaly could condition a correct and rapid diagnostic process. Only an accurate diagnostic investigation can give a quick diagnosis and useful elements for a correct therapeutic approach.

Candidate germline biomarkers of lenalidomide efficacy in mantle cell lymphoma: the Fondazione Italiana Linfomi MCL0208 trial.

In the Fondazione Italiana Linfomi MCL0208 phase 3 trial, lenalidomide maintenance (LEN) after autologous stem cell transplantation (ASCT) in mantle cell lymphoma (MCL) improved progression-free survival (PFS) vs observation (OBS). The host pharmacogenetic background was analyzed to decipher whether single-nucleotide polymorphisms (SNPs) of genes encoding transmembrane transporters, metabolic enzymes, or cell-surface receptors might predict drug efficacy. Genotypes were obtained via real-time polymerase chain reaction of the peripheral blood germ line DNA. Polymorphisms of ABCB1 and VEGF were found in 69% and 79% of 278 patients, respectively, and predicted favorable PFS vs homozygous wild-type (WT) in the LEN arm was 3-year PFS of 85% vs 70% (P < .05) and 85% vs 60% (P < .01), respectively. Patients carrying both ABCB1 and VEGF WT had the poorest 3-year PFS (46%) and overall survival (76%); in fact, in these patients, LEN did not improve PFS vs OBS (3-year PFS, 44% vs 60%; P = .62). Moreover, the CRBN polymorphism (n = 28) was associated with lenalidomide dose reduction or discontinuation. Finally, ABCB1, NCF4, and GSTP1 polymorphisms predicted lower hematological toxicity during induction, whereas ABCB1 and CRBN polymorphisms predicted lower risk of grade ≥3 infections. This study demonstrates that specific SNPs represent candidate predictive biomarkers of immunochemotherapy toxicity and LEN efficacy after ASCT in MCL.

Top-Layer Engineering Reshapes Charge Transfer at Polar Oxide Interfaces.

Charge-transfer phenomena at heterointerfaces are a promising pathway to engineer functionalities absent in bulk materials but can also lead to degraded properties in ultrathin films. Mitigating such undesired effects with an interlayer reshapes the interface architecture, restricting its operability. Therefore, developing less-invasive methods to control charge transfer will be beneficial. Here, an appropriate top-interface design allows for remote manipulation of the charge configuration of the buried interface and concurrent restoration of the ferromagnetic trait of the whole film. Double-perovskite insulating ferromagnetic La2 NiMnO6 (LNMO) thin films grown on perovskite oxide substrates are investigated as a model system. An oxygen-vacancy-assisted electronic reconstruction takes place initially at the LNMO polar interfaces. As a result, the magnetic properties of 2-5 unit cell LNMO films are affected beyond dimensionality effects. The introduction of a top electron-acceptor layer redistributes the electron excess and restores the ferromagnetic properties of the ultrathin LNMO films. Such a strategy can be extended to other interfaces and provides an advanced approach to fine-tune the electronic features of complex multilayered heterostructures.

MiR-378a-3p Acts as a Tumor Suppressor in Colorectal Cancer Stem-Like Cells and Affects the Expression of MALAT1 and NEAT1 lncRNAs.

MiR-378a-3p plays a critical role in carcinogenesis acting as a tumor suppressor, promoting apoptosis and cell cycle arrest and reducing invasion and drug resistance in several human cancers, including colorectal cancer (CRC), where its expression is significantly associated with histological classification and prognosis. In this study, we investigated the biological and cellular processes affected by miR-378a-3p in the context of CRC carcinogenesis. In agreement with the literature, miR-378a-3p is downregulated in our cohort of CRC patients as well as, in 15 patient-derived colorectal cancer stem-like cell (CRC-SC) lines and 8 CRC cell lines, compared to normal mucosae. Restoration of miR-378a-3p restrains tumorigenic properties of CRC and CRC-SC lines, as well as, significantly reduces tumor growth in two CRC-SC xenograft mouse models. We reported that miR-378a-3p modulates the expression of the lncRNAs MALAT1 and NEAT1. Their expression is inversely correlated with that of miR-378a-3p in patient-derived CRC-SC lines. Silencing of miR-378a-3p targets, MALAT1 and NEAT1, significantly impairs tumorigenic properties of CRC-SCs, supporting the critical role of miR-378a-3p in CRC carcinogenesis as a tumor-suppressor factor by establishing a finely tuned crosstalk with lncRNAs MALAT1 and NEAT1.

Punctual and kinetic MRD analysis from the Fondazione Italiana Linfomi MCL0208 phase 3 trial in mantle cell lymphoma.

Minimal residual disease (MRD) analysis is a known predictive tool in mantle cell lymphoma (MCL). We describe MRD results from the Fondazione Italiana Linfomi phase 3 MCL0208 prospective clinical trial assessing lenalidomide (LEN) maintenance vs observation after autologous stem cell transplantation (ASCT) in the first prospective comprehensive analysis of different techniques, molecular markers, and tissues (peripheral blood [PB] and bone marrow [BM]), taken at well-defined time points. Among the 300 patients enrolled, a molecular marker was identified in 250 (83%), allowing us to analyze 234 patients and 4351 analytical findings from 10 time points. ASCT induced high rates of molecular remission (91% in PB and 83% in BM, by quantitative real-time polymerase chain reaction [RQ-PCR]). Nevertheless, the number of patients with persistent clinical and molecular remission decreased over time in both arms (up to 30% after 36 months). MRD predicted early progression and long-term outcome, particularly from 6 months after ASCT (6-month time to progression [TTP] hazard ratio [HR], 3.83; P < .001). In single-timepoint analysis, BM outperformed PB, and RQ-PCR was more reliable, while nested PCR appeared applicable to a larger number of patients (234 vs 176). To improve MRD performance, we developed a time-varying kinetic model based on regularly updated MRD results and the MIPI (Mantle Cell Lymphoma International Prognostic Index), showing an area under the ROC (Receiver Operating Characteristic) curve (AUROC) of up to 0.87 using BM. Most notably, PB reached an AUROC of up to 0.81; with kinetic analysis, it was comparable to BM in performance. MRD is a powerful predictor over the entire natural history of MCL and is suitable for models with a continuous adaptation of patient risk. The study can be found in EudraCT N. 2009-012807-25 (https://eudract.ema.europa.eu/).

Young transgenic hMTH1 mice are protected against dietary fat-induced metabolic stress-implications for enhanced longevity.

hMTH1 protects against mutation during oxidative stress. It degrades 8-oxodGTP to exclude potentially mutagenic oxidized guanine from DNA. hMTH1 expression is linked to ageing. Its downregulation in cultured cells accelerates RAS-induced senescence, and its overexpression in hMTH1-Tg mice extends lifespan. In this study, we analysed the effects of a brief (5 weeks) high-fat diet challenge (HFD) in young (2 months old) and adult (7 months old) wild-type (WT) and hMTH1-Tg mice. We report that at 2 months, hMTH1 overexpression ameliorated HFD-induced weight gain, changes in liver metabolism related to mitochondrial dysfunction and oxidative stress. It prevented DNA damage as quantified by a comet assay. At 7 months old, these HFD-induced effects were less severe and hMTH1-Tg and WT mice responded similarly. hMTH1 overexpression conferred lifelong protection against micronucleus induction, however. Since the canonical activity of hMTH1 is mutation prevention, we conclude that hMTH1 protects young mice against HFD by reducing genome instability during the early period of rapid growth and maximal gene expression. hMTH1 protection is redundant in the largely non-growing, differentiated tissues of adult mice. In hMTH1-Tg mice, expression of a less heavily mutated genome throughout life provides a plausible explanation for their extended longevity.

Evaluating the feasibility of a real world pharmacovigilance study (OPTIMISE:MS).

BACKGROUND: Clinical trial populations do not fully reflect routine practice. The power of routinely collected data to inform clinical practice is increasingly recognised. METHODS: The OPTIMISE:MS pharmacovigilance study is a prospective, pragmatic observational study, conducted across 13 UK MS centres. Data were collected at the time of routine clinical visits. The first participant was recruited on 24th May 2019; data were extracted on 11th November 2021. RESULTS: 2112 participants were included (median age 44.0 years; 1570 (72%) female; 1981 (94%) relapsing-remitting MS). 639 (30%) were untreated at study entry, 205 (10%) taking interferon beta/copaxone, 1004 (47%) second/third generation DMT first line and 264 (13%) had escalated from a platform DMT. 342 clinical events were reported, of which 108 infections. There was an increased risk of adverse events in people taking second/third generation DMT (RR 3.45, 95%CI 1.57-7.60, p<0.01 vs no DMT). Unadjusted Poisson regression demonstrated increased incident adverse events in people taking natalizumab (IRR 5.28, 95%CI 1.41-19.74, p<0.05), ocrelizumab (IRR 3.24, 95%CI 1.22-8.62, p<0.05), and GA biosimilar (Brabio) (IRR 4.89, 95%CI 1.31-18.21, p<0.05) vs no DMT. CONCLUSIONS: Routinely collected healthcare data can be used to evaluate DMT safety in people with MS. These data highlight the potential of pragmatic studies to guide understanding of risks and benefits associated with DMT.

Grey Matter Volume Reductions of the Left Hippocampus and Amygdala in PTSD: A Coordinate-Based Meta-Analysis of Magnetic Resonance Imaging Studies.

INTRODUCTION: In recent years, research on posttraumatic stress disorder (PTSD) focused on the description of different biological correlates of illness. Morphological changes of different brain regions were involved in PTSD neurophysiopathology, being related to trauma or considered a resilience biomarker. In this meta-analysis, we aimed to investigate the grey matter changes reported in magnetic resonance imaging (MRI) studies on patients who have developed PTSD compared to exposed subjects who did not show a clinical PTSD onset. METHODS: We meta-analysed eight peer-reviewed MRI studies conducted on trauma-exposed patients and reported results corrected for false positives. We then conducted global and intergroup comparisons from neuroimaging data of two cohorts of included subjects. The included studies were conducted on 250 subjects, including 122 patients with PTSD and 128 non-PTSD subjects exposed to trauma. RESULTS: Applying a family-wise error correction, PTSD subjects compared to trauma-exposed non-PTSD individuals showed a significant volume reduction of a large left-sided grey matter cluster extended from the parahippocampal gyrus to the uncus, including the amygdala. CONCLUSIONS: These volumetric reductions are a major structural correlate of PTSD and can be related to the expression of symptoms. Future studies might consider these and other neural PTSD correlates, which may lead to the development of clinical applications for affected patients.

HBV Reactivation in Patients with Past Infection Affected by Non-Hodgkin Lymphoma and Treated with Anti-CD20 Antibody Based Immuno-Chemotherapy: A Multicenter Experience.

Hepatitis B virus reactivation (HBVr) can develop in HBV surface antigen (HBsAg) positive or HBsAg-negative and anti-hepatitis B core antigen antibodies (anti-HBc) positive (past HBV infection) patients receiving immuno-chemotherapy for hematological malignancies. A higher rate of HBVr is associated with the use of rituximab (R) in patients with past HBV infection, thus justifying an antiviral prophylaxis. In this study we evaluated the incidence of HBVr in a real-life cohort of 362 anti-HBc-positive subjects affected by non-Hodgkin lymphoma (NHL), mainly receiving lamivudine (LAM) prophylaxis (93%) and all undergoing a R-containing regimen. A retrospective, multicenter, observational study was conducted in 4 Italian Hematology Departments. The primary endpoint was the incidence of virologic (HBV DNA-positive), serologic (HBsAg-positive) and clinical (ALT increase > 3 × upper limit of normal) HBVr, which occurred in five, four and one patients, respectively, with a total HBVr rate of 1.4%. None of them had to discontinue the chemotherapy program, while two patients required a delay. Treatment-related adverse events (AEs) were reported during LAM prophylaxis in three patients (0.9%). In conclusion, this study confirms the efficacy and safety of LAM prophylaxis in anti-HBc-positive patients undergoing R-containing regimens.

Oxidative Stress, Mutations and Chromosomal Aberrations Induced by In Vitro and In Vivo Exposure to Furan.

Furan is a volatile compound that is formed in foods during thermal processing. It is classified as a possible human carcinogen by international authorities based on sufficient evidence of carcinogenicity from studies in experimental animals. Although a vast number of studies both in vitro and in vivo have been performed to investigate furan genotoxicity, the results are inconsistent, and its carcinogenic mode of action remains to be clarified. Here, we address the mutagenic and clastogenic activity of furan and its prime reactive metabolite cis-2 butene-1,4-dial (BDA) in mammalian cells in culture and in mouse animal models in a search for DNA lesions responsible of these effects. To this aim, Fanconi anemia-derived human cell lines defective in the repair of DNA inter-strand crosslinks (ICLs) and Ogg1-/- mice defective in the removal of 8-hydroxyguanine from DNA, were used. We show that both furan and BDA present a weak (if any) mutagenic activity but are clear inducers of clastogenic damage. ICLs are strongly indicated as key lesions for chromosomal damage whereas oxidized base lesions are unlikely to play a critical role.

Elesclomol-induced increase of mitochondrial reactive oxygen species impairs glioblastoma stem-like cell survival and tumor growth.

BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor in adults, characterized by a poor prognosis mainly due to recurrence and therapeutic resistance. It has been widely demonstrated that glioblastoma stem-like cells (GSCs), a subpopulation of tumor cells endowed with stem-like properties is responsible for tumor maintenance and progression. Moreover, it has been demonstrated that GSCs contribute to GBM-associated neovascularization processes, through different mechanisms including the transdifferentiation into GSC-derived endothelial cells (GdECs). METHODS: In order to identify druggable cancer-related pathways in GBM, we assessed the effect of a selection of 349 compounds on both GSCs and GdECs and we selected elesclomol (STA-4783) as the most effective agent in inducing cell death on both GSC and GdEC lines tested. RESULTS: Elesclomol has been already described to be a potent oxidative stress inducer. In depth investigation of the molecular mechanisms underlying GSC and GdEC response to elesclomol, confirmed that this compound induces a strong increase in mitochondrial reactive oxygen species (ROS) in both GSCs and GdECs ultimately leading to a non-apoptotic copper-dependent cell death. Moreover, combined in vitro treatment with elesclomol and the alkylating agent temozolomide (TMZ) enhanced the cytotoxicity compared to TMZ alone. Finally, we used our experimental model of mouse brain xenografts to test the combination of elesclomol and TMZ and confirmed their efficacy in vivo. CONCLUSIONS: Our results support further evaluation of therapeutics targeting oxidative stress such as elesclomol with the aim of satisfying the high unmet medical need in the management of GBM.

Effects on suicidal risk: Comparison of clozapine to other newer medicines indicated to treat schizophrenia or bipolar disorder.

BACKGROUND: Clozapine is the only treatment with regulatory-recognition of lowering suicidal risk, at least in schizophrenia patients. It remains uncertain whether such effects extend to other drugs for psychosis. METHODS: We searched for reports on rates of suicidal behavior during treatment with clozapine and other modern drugs for psychosis (aripiprazole, olanzapine, risperidone, quetiapine, and ziprasidone) versus comparison or control treatments and analyzed the contrasts by random-effect meta-analysis to obtain pooled odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: We identified 35 paired comparisons of modern drugs for psychosis versus comparison or control treatments in 18 reports. There was moderate overall superiority of all agents tested over alternatives (OR = 0.522, p = 0.004). With clozapine, this effect was large (OR = 0.229, p < 0.0001) and consistent (7/7 trials), but significant antisuicidal effects were not found with other drugs for psychosis in 28 other trials (OR = 0.941, p = 0.497). Apparent efficacy of specific agents ranked: risperidone ⩾ olanzapine ⩾ aripiprazole ⩾ ziprasidone ⩾ mixed drugs for psychosis ⩾ quetiapine, but none of these differences was significant. CONCLUSIONS: An ability of clozapine to reduce risk of suicides and attempts in schizophrenia patients appears to be a unique effect not shared with other modern medicines indicated for schizophrenia or bipolar disorder.