Ultrasound-based deep learning radiomics model for differentiating benign, borderline, and malignant ovarian tumours: a multi-class classification exploratory study.

Background: Accurate preoperative identification of ovarian tumour subtypes is imperative for patients as it enables physicians to custom-tailor precise and individualized management strategies. So, we have developed an ultrasound (US)-based multiclass prediction algorithm for differentiating between benign, borderline, and malignant ovarian tumours.

Methods: We randomised data from 849 patients with ovarian tumours into training and testing sets in a ratio of 8:2.

Development and validation of an ultrasound-based deep learning radiomics nomogram for predicting the malignant risk of ovarian tumours.

Background: The timely identification and management of ovarian cancer are critical determinants of patient prognosis. In this study, we developed and validated a deep learning radiomics nomogram (DLR_Nomogram) based on ultrasound (US) imaging to accurately predict the malignant risk of ovarian tumours and compared the diagnostic performance of the DLR_Nomogram to that of the ovarian-adnexal reporting and data system (O-RADS).

Methods: This study encompasses two research tasks.

Predicting the Severity of Esophageal Varices in Patients with Hepatic Cirrhosis Using Non-Invasive Markers.

Background: The presence and extent of severity of esophageal varices (EV) in patients with liver cirrhosis (LC) are predicted using noninvasive clinical, biochemical, and imaging parameters. The aim of this study was to investigate the accuracy of noninvasive predictors of EV, such as the platelet count-to-spleen diameter ratio (PSR), platelet count-to-spleen volume ratio (PSVR), spleen size (SZ), and a combination of these markers in determining the severity of EV in patients with cirrhosis.

Methods: We recruited 82 inpatients with LC from the Department of Gastroenterology at the First Affiliated Hospital of Guangxi Medical University between January 2018 and December 2019 for this diagnostic investigation.

Identifying 2PHDO as a SOCE inhibitor from Chinese herbal extracts.

STIM- and Orai-mediated store operated calcium entry (SOCE) is a ubiquitous Ca2+ signaling process, crucial for the proper function of immune, muscle and neuronal systems. To treat SOCE-related disorder or diseases of these systems, and to mechanistically dissect activation and function of SOCE, specific SOCE inhibitors are needed. However, strategies for developing new SOCE modifiers are still limited.

Identification of a STIM1 Splicing Variant that Promotes Glioblastoma Growth.

Deregulated store-operated calcium entry (SOCE) mediated by aberrant STIM1-ORAI1 signaling is closely implicated in cancer initiation and progression. Here the authors report the identification of an alternatively spliced variant of STIM1, designated STIM1β, that harbors an extra exon to encode 31 additional amino acids in the cytoplasmic domain. STIM1β, highly conserved in mammals, is aberrantly upregulated in glioma tissues to perturb Ca signaling.

Aripiprazole lauroxil 2-month formulation with 1-day initiation in patients hospitalized for an acute exacerbation of schizophrenia: exploratory efficacy and patient-reported outcomes in the randomized controlled ALPINE study.

Background: A randomized, controlled, phase 3b study (ALPINE) evaluated efficacy and safety of a 2-month formulation of aripiprazole lauroxil (AL) using a 1-day initiation regimen in patients hospitalized for an acute exacerbation of schizophrenia. Paliperidone palmitate (PP) was used as an active control. Exploratory endpoint assessments included severity of illness, positive and negative symptoms, quality of life, caregiver burden, and satisfaction with medication.

Comparison of mesenchymal stromal cells from peritoneal dialysis effluent with those from umbilical cords: characteristics and therapeutic effects on chronic peritoneal dialysis in uremic rats.

Background: A long-term of peritoneal dialysis (PD) using a hypertonic PD solution (PDS) leads to patient's peritoneal membrane (PM) injury, resulting in ultrafiltration failure (UFF) and PD drop-out. Our previous study shows that PD effluent-derived mesenchymal stromal cells (pMSCs) prevent the PM injury in normal rats after repeated exposure of the peritoneal cavity to a PDS. This study was designed to compare the cytoprotection between pMSCs and umbilical cord-derived MSCs (UC-MSCs) in the treatment of both PM and kidney injury in uremic rats with chronic PD.

Analysis of prolactin and sexual side effects in patients with schizophrenia who switched from paliperidone palmitate to aripiprazole lauroxil.

One strategy to address hyperprolactinemia and associated sexual side effects in patients receiving antipsychotics is switching to an antipsychotic not associated with prolactin elevation (eg, aripiprazole). This post hoc analysis assessed prolactin concentrations and sexual side effects in an open-label prospective study of switching long-acting injectable antipsychotics from paliperidone palmitate (PP) to aripiprazole lauroxil (AL). Serum prolactin was measured throughout the study.

Aripiprazole Lauroxil Dosing Regimens: Understanding Dosage Strengths and Injection Intervals.

Aripiprazole lauroxil (AL) is a long-acting atypical antipsychotic approved for the treatment of schizophrenia in adults. AL has five regimen options that offer three different injection intervals using four different dosage strengths. The relationship between dosage strength (milligram injected), injection interval (time between injection visits), and expected steady-state plasma aripiprazole concentrations may not be readily apparent.

Beyond 52-Week Long-Term Safety: Long-Term Outcomes of Aripiprazole Lauroxil for Patients With Schizophrenia Continuing in an Extension Study.

Objective: To describe the long-term safety, tolerability, and symptom trajectory with the long-acting injectable antipsychotic aripiprazole lauroxil (AL) in patients with DSM-5-diagnosed schizophrenia followed for up to 180 weeks (3.5 years).

Methods: Long-term safety of 2 fixed doses of AL (441 or 882 mg every 4 weeks) was assessed during up to 180 weeks (3.

Effects of Olanzapine Combined With Samidorphan on Weight Gain in Schizophrenia: A 24-Week Phase 3 Study.

Objective: A combination of olanzapine and the opioid receptor antagonist samidorphan is under development for the treatment of schizophrenia and bipolar I disorder. The single-tablet combination treatment is intended to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. In this phase 3 double-blind trial, the authors evaluated the weight profile of combined olanzapine/samidorphan compared with olanzapine in patients with schizophrenia.

Efficacy and Safety of a 2-Month Formulation of Aripiprazole Lauroxil With 1-Day Initiation in Patients Hospitalized for Acute Schizophrenia Transitioned to Outpatient Care: Phase 3, Randomized, Double-Blind, Active-Control ALPINE Study.

Objective: Evaluate efficacy and safety of a 2-month formulation of aripiprazole lauroxil (AL) with 1-day initiation during hospitalization for acute exacerbation of schizophrenia followed by transition to outpatient care.

Methods: The phase 3b double-blind Aripiprazole Lauroxil and Paliperidone palmitate: INitiation Effectiveness (ALPINE) study was conducted from November 2017 to March 2019. Adults with acute schizophrenia according to DSM-5 criteria were randomized (1:1) to AL (AL NanoCrystal Dispersion + oral aripiprazole 30 mg, day 1; AL 1,064 mg, day 8 and every 8 weeks [q8wk]) or paliperidone palmitate (PP 234 mg, day 1; PP 156 mg, day 8 and then q4wk) for 25 weeks.

Type 3 Inositol 1,4,5-Trisphosphate Receptor is a Crucial Regulator of Calcium Dynamics Mediated by Endoplasmic Reticulum in HEK Cells.

Being the largest the Ca store in mammalian cells, endoplasmic reticulum (ER)-mediated Ca signalling often involves both Ca release via inositol 1, 4, 5-trisphosphate receptors (IPR) and store operated Ca entries (SOCE) through Ca release activated Ca (CRAC) channels on plasma membrane (PM). IPRs are functionally coupled with CRAC channels and other Ca handling proteins. However, it still remains less well defined as to whether IPRs could regulate ER-mediated Ca signals independent of their Ca releasing ability.

Assessing effectiveness of aripiprazole lauroxil vs placebo for the treatment of schizophrenia using number needed to treat and number needed to harm.

Objective: Schizophrenia clinical trials commonly measure observed changes in Positive and Negative Syndrome Scale (PANSS) total score. However, it is more intuitive to think of response vs nonresponse, a binary outcome. Assessing binary outcomes enables calculation of number needed to treat (NNT) for therapeutic outcomes, number needed to harm (NNH) for adverse outcomes, and likelihood to be helped or harmed (LHH) to demonstrate benefit/risk tradeoffs.

Effect of hepatic and renal impairment on the pharmacokinetics of olanzapine and samidorphan given in combination as a bilayer tablet.

Background: A combination of olanzapine and samidorphan (OLZ/SAM) is in development to provide the established antipsychotic efficacy of olanzapine while mitigating olanzapine-induced weight gain.

Methods: Two multicenter, open-label, parallel-cohort studies were performed to evaluate the effect of moderate hepatic impairment (Child-Pugh score 7-9 [class B]; study 1) and severe renal impairment (estimated glomerular filtration rate: 15-29 mL/min/1.73 m; study 2) on the pharmacokinetics, safety, and tolerability of a single dose of OLZ/SAM 5/10 mg.

Pharmacokinetics and safety of deltoid or gluteal injection of aripiprazole lauroxil NanoCrystal Dispersion used for initiation of the long-acting antipsychotic aripiprazole lauroxil.

Background: Aripiprazole lauroxil (AL), a long-acting injectable antipsychotic for the treatment of schizophrenia in adults, can be started with either 21 days of daily oral aripiprazole supplementation or a 1-day initiation regimen consisting of a single injection of a NanoCrystal Dispersion formulation of AL (AL) and a single dose of 30 mg oral aripiprazole. This phase I study assessed the pharmacokinetics and safety of deltoid gluteal AL injections.

Methods: Patients with schizophrenia or schizoaffective disorder ( = 47) were randomized 1:1 to receive a single intramuscular dose of AL in the deltoid or gluteal muscle.

Social and functional outcomes with two doses of aripiprazole lauroxil vs placebo in patients with schizophrenia: a post-hoc analysis of a 12-week phase 3 efficacy study.

To assess the effect of the long-acting antipsychotic aripiprazole lauroxil (AL) on social and functional outcomes compared with placebo in patients with acute schizophrenia, a post-hoc analysis was conducted. Patients with acute schizophrenia were enrolled in a 12-week, double-blind, placebo-controlled efficacy trial, and randomized 1:1:1 to receive AL 441 mg, AL 882 mg, or placebo every 4 weeks. Changes in social functioning using the 6- and 4-item Positive and Negative Syndrome Scale (PANSS) Prosocial subscales were evaluated.

Switching patients with schizophrenia from paliperidone palmitate to aripiprazole lauroxil: A 6-month, prospective, open-label study.

We assessed the effectiveness of switching from paliperidone palmitate (PP) or risperidone long-acting injection (RLAI) to aripiprazole lauroxil (AL). Prospective, 6-month study in patients with schizophrenia with residual symptoms or intolerance with PP/RLAI. Effectiveness assessed via all-cause and medication-related discontinuation; CGI-S/BPRS and adverse event monitoring assessed efficacy/tolerability, respectively.

Long-term safety and tolerability of aripiprazole lauroxil in patients with schizophrenia.

Objective: Safety and tolerability of long-term treatment with the long-acting antipsychotic aripiprazole lauroxil (AL) were evaluated in patients with schizophrenia.

Methods: This was an international, multicenter, phase 3, 52-week safety study of 2 fixed doses of AL (441 mg or 882 mg intramuscular every 4 weeks). Safety endpoints included adverse events (AEs) and extrapyramidal symptoms (EPS) including akathisia, injection-site reactions (ISRs), and clinically relevant changes in metabolic and endocrine values.

Effects of the Opioid System Modulator, Samidorphan, on Measures of Alcohol Consumption and Patient-Reported Outcomes in Adults with Alcohol Dependence.

Background: Demonstrating clinically meaningful benefits of alcohol use disorder treatments is challenging.

Methods: We report findings from a 12-week, phase 2, randomized, double-blind, placebo-controlled study of samidorphan (1, 2.5, or 10 mg/d) in adults with alcohol use disorder (NCT00981617).

Pharmacokinetic Evaluation of a 1-Day Treatment Initiation Option for Starting Long-Acting Aripiprazole Lauroxil for Schizophrenia.

Background: Aripiprazole lauroxil (AL), a long-acting injectable antipsychotic for the treatment of schizophrenia, requires 21 days of oral aripiprazole supplementation upon initiation. We report findings from a phase 1 study investigating a nanocrystalline milled dispersion of AL (ALNCD) as a potential 1-day initiation regimen. The 1-day initiation regimen is designed to enable rapid achievement of plasma aripiprazole concentrations that are comparable with the 21-day oral initiation regimen.

Switching stable patients with schizophrenia from their oral antipsychotics to aripiprazole lauroxil: a post hoc safety analysis of the initial 12-week crossover period.

Objective: Switching antipsychotic medications is common in patients with schizophrenia who are experiencing persistent symptoms or tolerability issues associated with their current drug regimen. This analysis assessed the safety of switching from an oral antipsychotic to the long-acting injectable antipsychotic aripiprazole lauroxil (AL).

Methods: This was a post hoc analysis of outpatients with schizophrenia who were prescribed an oral antipsychotic and who enrolled in an international, open-label, long-term (52-week) safety study of AL.

Durability of Therapeutic Response With Long-Term Aripiprazole Lauroxil Treatment Following Successful Resolution of an Acute Episode of Schizophrenia.

Objective: To evaluate durability of therapeutic effect of long-term treatment with aripiprazole lauroxil in patients with schizophrenia following successful treatment of an acute psychotic episode.

Methods: This post hoc analysis assessed long-term outcomes for a subgroup of patients who entered a 52-week extension study after being successfully stabilized with one of 2 doses of aripiprazole lauroxil (441 or 882 mg) in a pivotal 12-week, placebo-controlled, randomized clinical trial. Durability of therapeutic effect was measured by the proportion of patients completing the 1-year course of aripiprazole lauroxil, the trajectories of the Positive and Negative Syndrome Scale (PANSS) total and the Clinical Global Impression-Severity (CGI-S) item scores beyond the first 12 weeks, and the likelihood of remission at any follow-up point.