Introduction The number of individuals worldwide with Alzheimer's disease (AD) is growing at a rapid rate. New treatments are urgently needed. We review the current pipeline of drugs in clinical trials for the treatment of AD. Methods We interrogated ClinicalTrials.gov, the federal registry of clinical trials to identify drugs in trials. Results There are 126 agents in 152 trials assessing new therapies for AD: 28 treatments in Phase 3 trials, 74 in Phase 2, and 24 in Phase 1. The majority of drugs in trials (82.5%) target the underlying biology of AD with the intent of disease modification; 10.3% are putative cognitive enhancing agents; and 7.1% are drugs being developed to reduce neuropsychiatric symptoms. Discussion This pipeline analysis shows that target biological processes are more diversified, biomarkers are more regularly used, and repurposed agents are being explored to determine their utility for the treatment of AD.

Following algorithms based on point of care tests or on structured clinical practice with standard laboratory tests does not decrease blood loss, but reduces the transfusion of PRBCs and blood components after routine cardiac surgery, when compared with clinician discretion. Cardiac surgery services should use transfusion guidelines based on laboratory-guided algorithms, and the possible benefits of point of care testing should be tested against this standard.

Introduction: Alzheimer's disease (AD) represents a global health crisis. Treatments are needed to prevent, delay the onset, slow the progression, improve cognition, and reduce behavioral disturbances of AD. We review the current clinical trials and drugs in development for the treatment of AD. Methods: We searched the governmental website clinicaltrials.gov where are all clinical trials conducted in the United States must be registered. We used artificial intelligence (AI) and machine learning (ML) approaches to ensure comprehensive detection and characterization of trials and drugs in development. We use the Common Alzheimer's Disease Research Ontology (CADRO) to classify drug targets and mechanisms of action of drugs in the pipeline. Results: As of January 25, 2022 (index date for this study) there were 143 agents in 172 clinical trials for AD. The pipeline included 31 agents in 47 trials in Phase 3, 82 agents in 94 trials in Phase 2, and 30 agents in 31 trials in Phase 1. Disease-modifying therapies represent 83.2% of the total number of agents in trials; symptomatic cognitive enhancing treatments represent 9.8% of agents in trials; and drugs for the treatment of neuropsychiatric symptoms comprise 6.9%. There is a diverse array of drug targets represented by agents in trials including nearly all CADRO categories. Thirtyseven percent of the candidate agents in the pipeline are repurposed drugs approved for other indications. A total of 50,575 participants are needed to fulfill recruitment requirements for all currently active clinical trials. Discussion: The AD drug development pipeline has agents representing a substantial array of treatment mechanisms and targets. Advances in drug design, outcome measures, use of biomarkers, and trial conduct promise to accelerate the delivery of new and better treatments for patients with AD.

We present the clinicopathological features of 56 cases of the nested variant of urothelial bladder carcinoma. This is an uncommon variant of bladder cancer, recognized by the current WHO classification of urologic tumors. The nested component represented 100 % of the tumor in 24 cases. The architectural pattern of the tumor varied from solid expansile to infiltrative nests characterized by deceptively bland histologic features resembling von Brunn nests. Typical features of high-grade conventional urothelial carcinoma were present in 32 cases. Most neoplastic cells had nuclei of low to intermediate nuclear grade with occasional nuclear enlargement, most frequently seen in deep areas of tumor. The nested component expressed cytokeratins 7, 20, CAM5.2, and high molecular weight (34ßE12), p63, Ki67, p53, p27, and GATA3. Tumor extension was T1 (n = 9), minimally T2 (n = 10), T2a (n = 1), T2b (n = 4), T3a (n = 8), T3b (n = 13), and T4a (n = 11). On follow-up, 36 of patients died of or were alive with disease from 2 to 80 months (mean 21 months). Four patients died of other causes. Eleven other patients remained disease free. Univariate survival analysis showed no differences for nested carcinoma compared with conventional urothelial carcinoma. As in conventional urothelial carcinoma, in nested carcinoma of the bladder pT category defined different survival groups. In summary, nested variant of urothelial bladder carcinoma is typically associated with advanced stage. In samples of limited volume, it may be misdiagnosed as proliferation of von Brunn nests or other nested-like bladder lesions, delaying definitive therapy.

SUMMARY Background

Oral mucosa's lesions and oral symptoms were positively associated with Inflammatory Bowel Disease, mainly during disease activity periods and conceivably, associated with corticosteroid and immunosuppressant therapy.

Background and aims: Acute-on-chronic liver failure (ACLF) is a frequent syndrome associated with high mortality. The aims of the present study are: a) comparing the Chronic Liver Failure Consortium (CLIF-C) ACLF Model for End-Stage Liver Disease (MELD), MELD Sodium (MELD-Na) and Child-TurcottePugh (CTP) scores for prediction of short/medium term mortality; b) identifying ACLF prevalence in patients admitted to the ward; and c) comparing mortality between non-ACLF/ACLF.Methods: Retrospective cohort study of 177 patients admitted to the Gastroenterology ward for acute decompensation of cirrhosis.Results: We included 132 males. Alcohol was the cirrhosis cause/co-factor in 79.7% of cases. Infection was present in 40.7%. At admission, 19.8% of patients presented ACLF and 7.9% developed it during hospitalization (overall prevalence was 27.7%). ACLF grade 1 was diagnosed in 55.1% of the ACLF patients; grade 2, in 42.8%, and grade 3, in 2.0%. Infection (p < 0.001) and hepatic encephalopathy (p = 0.004) were more prevalent and C-reactive protein and leukocyte counts were higher in ACLF patients. ACLF 28 and 90-day mortality was 45.8% and 60.4%, respectively. The CLIF-C ACLF score was significantly superior to CTP, MELD, MELD-Na in predicting 28-day (AUROC 0.799 ± 0.078, 95% CI 0.637-0.891) and 90-day mortality (AUROC 0.828 ± 0.063, 95% CI 0.705-0.952).Conclusion: ACLF is highly prevalent in the ward. The new CLIF scores identify high mortality cirrhotic patients admitted to the ward and are better than their predecessors to predict ACLF patients' short/medium term mortality.

The thromboelastography trace is altered in the presence of aprotinin when celite and kaolin are used as activators but not when tissue factor is the activator.