Duvelisib with docetaxel for patients with anti-PD-1 refractory, recurrent or metastatic head and neck squamous cell carcinoma.

Background: Treatments after anti-PD-1 therapy for patients with recurrent, metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) are limited. Blocking phosphatidylinositol 3-kinase (PI3K) signaling may lead to tumor immunomodulation and enhanced taxane sensitivity. This phase 2 trial evaluated dual, selective PI3Kδ/γ inhibition with docetaxel in patients with anti-PD-1 refractory R/M HNSCC.

Response-Adaptive Surgical Timing in neoadjuvant immunotherapy demonstrates enhanced pathologic treatment response in Head and Neck Squamous Cell Carcinoma.

Purpose: We evaluated whether IDO-inhibitor BMS986205 (IDOi) + PD-1 inhibitor nivolumab enhanced T-cell activity and augmented immune-mediated antitumor responses in untreated, resectable HNSCC. We employed response-adaptive surgical timing to identify responders to immunotherapy and enhance their response.

Patients And Methods: Patients with HNSCC were 3:1 randomized to receive nivolumab with or without BMS986205 PO daily (NCT03854032).

Genomics-driven derivatization of the bioactive fungal sesterterpenoid variecolin: Creation of an unnatural analogue with improved anticancer properties.

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin () and variecolactone () was identified in ATCC 16872. Heterologous production of and was achieved in by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues (-).

Coordination of Ru(II)-Arene Fragments to Dipyridophenazine Ligands Leads to the Modulation of Their In Vitro and In Vivo Anticancer Activity.

Despite extensive research on the anticancer properties of Ru complexes with dipyrido[3,2-:2',3'-]phenazine (dppz) ligands, their in vivo efficacy is rarely investigated. Aiming to understand whether the coordination of certain half-sandwich Ru(II)-arene fragments might improve the therapeutic potential of dppz ligands, we prepared a series of Ru(II)-arene complexes with the general formula [(η-arene)Ru(dppz-R)Cl]PF, where the arene fragment was benzene, toluene, or -cymene and R was -NO, -Me, or -COOMe. All compounds were fully characterized by H and C NMR spectroscopy and high-resolution ESI mass-spectrometry, and their purity was verified by elemental analysis.

Case Report: Multiple Causes of Cardiac Death After the First Infusion of Atezolizumab: Histopathological and Immunohistochemical Findings.

Immune checkpoint inhibitors are promising agents for anticancer therapy. But despite their high efficacy in the treatment of solid tumors, there is still a problem with immune-related adverse events, especially cardiovascular complications with a very high mortality rate. Myocarditis or ischemic heart disease progression is not the only possible cause of cardiovascular death in patients treated with checkpoint inhibitors.

Myocardial PD-L1 Expression in Patients With Ischemic and Non-ischemic Heart Failure.

Immune checkpoints inhibitors are promising and wide-spread agents in anti-cancer therapy. However, despite their efficacy, these agents could cause cardiotoxicity, a rare but life-threatening event. In addition, there are still no well-described predictive factors for the development of immune-related adverse events and information on high risk groups.

[The use of intralaboratory and external quality control of immunohistochemical studies to improve the detection of estrogen and progesterone receptors].

Immunohistochemical study of breast cancer has been practiced for several decades; however, the standardization of this process has not yet been achieved, despite substantial advances in methodology. The paper presents practical guidelines and standards for testing breast carcinomas, which can be used as day-to-day control of the work of an immunohistochemistry laboratory. It considers the concept of external quality control in the immunohistochemical detection of estrogen (ER) and progesterone (PR) receptors, as well as the problems of harmonization in the immunohistochemical analysis of breast carcinomas, by using the nuclear biomarkers, such as ER and PR, as an example.

Interfering with Metabolic Profile of Triple-Negative Breast Cancers Using Rationally Designed Metformin Prodrugs.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by an aberrant metabolic phenotype with high metastatic capacity, resulting in poor patient prognoses and low survival rates. We designed a series of novel Au cyclometalated prodrugs of energy-disrupting Type II antidiabetic drugs namely, metformin and phenformin. Prodrug activation and release of the metformin ligand was achieved by tuning the cyclometalated Au fragment.

[Assessment of PD-L1 expression using the neural network analysis algorithm in non-small cell lung carcinoma biopsy specimens].

Unlabelled: Neural network analysis of digital copies of histological micropreparations is one of the methods used to standardize quantitative continuous data. PD-L1 (22C3) biomarker expression in metastatic non-small cell lung carcinomas without mutations in the EGFR, ALK, and ROS1 genes serves as an indication for the use of pembrolizumab for the first-line therapy.

Objective: To quantify PD-L1 biomarker expression in non-small cell lung carcinomas using the neural network analysis of digital copies of histological micropreparations.

Impact of Oscillating Positive Expiratory Pressure Device Use on Post-Discharge Hospitalizations: A Retrospective Cohort Study Comparing Patients with COPD or Chronic Bronchitis Using the Aerobika and Acapella Devices.

Purpose: Managing and preventing disease exacerbations are key goals of COPD care. Oscillating positive expiratory pressure (OPEP) devices have been shown to improve clinical outcomes when added to COPD standard of care. This retrospective database study compared real-world resource use and disease exacerbation among patients with COPD or chronic bronchitis prescribed either of two commonly used OPEP devices.

A Functional Respiratory Imaging Approach to the Effect of an Oscillating Positive Expiratory Pressure Device in Chronic Obstructive Pulmonary Disease.

Purpose: Chronic obstructive pulmonary disease (COPD) patients are prone to suffer from chronic bronchitis, which ultimately affects their quality of life and overall prognosis. Oscillating positive expiratory pressure (oPEP) devices are designed to aid in the mucus clearance by generating positive pressure pulses in the airways. The main aim of this study was to analyze the impact of a specific oPEP device - Aerobika - on top of standard of care medication in COPD patients' lung dynamics and drug deposition.

A Real-World Evidence Study Assessing the Impact of Adding the Aerobika Oscillating Positive Expiratory Pressure Device to Standard of Care Upon Healthcare Resource Utilization and Costs in Post-Operative Patients.

Introduction: The aim of this real-world study was to measure the benefit of the Aerobika oscillating positive expiratory pressure (OPEP) device when added to standard of care (defined as incentive spirometry [IS]) for post-operative patients.

Methods: Adults aged ≥ 18 years who were hospitalized for cardiac, thoracic or upper abdominal surgery between 1 September 2013 and 30 April 2017 were identified from IQVIA's Hospital Charge Detail Master (CDM) database; the index date was the date of the first hospitalization for surgery. The control cohort (IS) included patients who had ≥ 1 CDM record within 12 months prior to the index date and ≥ 1 record after discharge, evidence of IS use during index hospitalization and no evidence of use of a PEP or OPEP device at any time during the study period.

[Comparison of digital and visual methods for Ki-67 assessment in invasive breast carcinomas].

Aim: to compare two methods for quantitative assessment of the proliferative activity index (PAI): a visual estimation method by several investigators and digital image analysis (DIA). The use of the Ki-67 index in the daily clinical practice of a Morbid Anatomy Department is associated with the problem of reproducibility of quantitative assessment of the Ki-67 PAI. Due to the development of digital imaging techniques in morphology, new methods for PAI evaluation using the DIA are proposed.

A Retrospective Study of the Effectiveness of the AeroChamber Plus Flow-Vu Antistatic Valved Holding Chamber for Asthma Control.

Introduction: Electrostatic charge in valved holding chambers (VHCs) may lead to inconsistent metered-dose inhaler (MDI) asthma drug delivery. We compared the AeroChamber Plus Flow Vu Antistatic Valved Holding Chamber (ACFV AVHC) with non-antistatic control VHCs in terms of asthma exacerbations, resource use, and cost in an asthma population.

Methods: Patients included in an adjudicated claims database with ACFV AVHC or non-antistatic VHC (control VHC) use between 1/2010 and 8/2015 (index) who were treated with an inhaled corticosteroid (ICS) or a combination of an ICS and a long-acting β2 agonist MDI within 60 days before or after the index date, were diagnosed with asthma, and had ≥12 months of pre- and ≥30 days of post-index health plan enrollment were included.

[Role of peripheral adrenergic links in the development of antidepressive effect in an experimental model of behavioral depression in rats].

The study was made on the reserpine model of behavioural depression in cats. The morphofunctional state of peripheral adrenergic nerves in control experiments and under action of antidepressants (befol and nialamid) was studied by fluorescent microscopic method. One definite correlation was shown between the state of somatovegetative changes and the level of neuromediator activity of the adrenergic structures.

[A comparative study of befol pharmacokinetics in experimental animals and man].

The pharmacokinetics of befol at different routes of administration to animals and humans was studied. The therapeutic level of the drug concentration was established.

[Immunochemical study of the meningococcal cell wall].

Meningococcus strains--standard and those isolated from the cerebrospinal fluid of patients suffering from the cerebrospinal meningitis were grown on fluid and solid protein-free nutrient media. Electron microscopic study showed that in the strains isolated from patients the wall was much thicker than in the standard strains. The cell wall preparations were obtained by its solution at pH 9.

[Changes in the surface structures of bacteria as a cause of weak immunogenicity of vaccines from several strains of Citrobacter].

The authors present the results of studying the weakly immunogenic Citrobacter strains; some O-antigens of Citrobacter (11, 14, 19, 21a, 21b, 26) caused in immunization of rabbits a weak immune response (antibody titre--1:400-1:800). An electron microscopic study of the vaccines (obtained from these strains) and their fragments showed that a partial desquamation and denaturing of the antigenic material occurred in the process of preparation of heated vaccines. Formalin-treated vaccine subjected to preliminary deflaggelation for 2 min at 3000 cps was used for obtaining the O-sera against the mentioned antigens.

[Preliminary electron microscopic and x-ray study of the crystalline protein of diphtheria toxin].

The authors present the results of the electron microscopic and roentgenological study of the crystalline protein of diphtheria toxin. On the basis of direct measurements of the crystal image and diffraction pictures it was possible to calculate the interplane distances of the placement of molecules in the crystal. Examination in polarization microscope showed that the crystals were optically uniaxial with a direct extinction and a positive character of elongation.