Triple combination of vemurafenib, cobimetinib, and atezolizumab in real clinical practice in the Russian Federation: results of the A1 cohort of the ISABELLA study.

Background: Among several treatment options for BRAF-mutant metastatic melanoma, a combination of BRAF inhibitor, MEK inhibitor, and anti-PDL1 antibody seems to be a new emergent approach recently registered in the Russian Federation. It is still not clear which patient population benefits more from this simultaneous use of three drugs instead of its sequencing.

Aim: This study aimed to evaluate patients' characteristics treated in real practice in 14 Russian regions by triple combination and to analyze their outcomes depending on biomarkers (PD-L1 expression).

Exposure of volunteers to microgravity by dry immersion bed over 21 days results in gene expression changes and adaptation of T cells.

The next steps of deep space exploration are manned missions to Moon and Mars. For safe space missions for crew members, it is important to understand the impact of space flight on the immune system. We studied the effects of 21 days dry immersion (DI) exposure on the transcriptomes of T cells isolated from blood samples of eight healthy volunteers.

The impact of short-term confinement on human innate immunity.

During space missions cosmonauts are exposed to a myriad of distinct stressors such as radiation, overloads, weightlessness, radiation, isolation in artificial environmental conditions, which causes changes in immune system. During space flights it is very difficult to determine the particular factor associated with the observed immunological responses. This makes ground-based experiments examining the effect of each space flight associated factor along of particular value.

Epileptiform GluN2B-driven excitation in hippocampus as a therapeutic target against temporal lobe epilepsy.

GluN2B is an NMDAR subunit that displays restricted expression in the mature hippocampus - a structure playing a major role in temporal lobe epilepsy. However, the contribution of GluN2B to the pathophysiology of the condition has not been fully explored. Here we combined status epilepticus models of temporal lobe epilepsy, protein expression studies, and patch-clamp experiments to demonstrate the profound change in the nature of glutamatergic transmission mediated in the epileptiform hippocampus by a subpopulation of GluN2B-containing NMDAR receptors.

New Hybrid Compounds Combining Fragments of Usnic Acid and Thioether Are Inhibitors of Human Enzymes TDP1, TDP2 and PARP1.

Tyrosyl-DNA phosphodiesterase 1 (TDP1) catalyzes the cleavage of the phosphodiester bond between the tyrosine residue of topoisomerase 1 (TOP1) and the 3' phosphate of DNA in the single-strand break generated by TOP1. TDP1 promotes the cleavage of the stable DNA-TOP1 complexes with the TOP1 inhibitor topotecan, which is a clinically used anticancer drug. This article reports the synthesis and study of usnic acid thioether and sulfoxide derivatives that efficiently suppress TDP1 activity, with IC values in the 1.

Use of the «BCR/ABL - multitest» kit in the algorithm of laboratory diagnostics of oncohematological diseases: economic aspects.

Abnormal mRNAs of the hybrid BCR-ABL gene in the majority of cases initiate the synthesis of proteins with a mass of 210 kDa (p210), 190 kDa (p190), and 230 kDa (p230). Expression of the p210 variant is most common in CML (95% of cases), while the p190 and p230 variants are less common (1-4%). On the contrary, p190 predominates in ALL.

The combined use of thoracic and abdominal aortic stent grafts for endovascular repair of wide neck abdominal aortic aneurysms in high risk patients.

Introduction: Treatment of abdominal aortic aneurysms (AAA) with large (28 mm to 34 mm) and wide diameter (> 35 mm) necks remains a challenge in patients who are high-risk candidates for open repair. While several case reports describe the use of a thoracic stent graft in conjunction with a traditional modular bifurcated stent graft, most patients do not have the aortic length to accommodate such a configuration. We present our experience utilizing a distal unibody bifurcated aortic stent graft (Endologix, Irvine, CA) in conjunction with a proximal thoracic aortic stent graft (Medtronic, Minneapolis, MN) to treat wide-necked non-ruptured AAAs in patients who were otherwise poor candidates for open or fenestrated repair.

Avelumab expanded access program in metastatic Merkel cell carcinoma: Efficacy and safety findings from patients in Europe and the Middle East.

Incidence rates of Merkel cell carcinoma (MCC), an uncommon skin cancer with an aggressive disease course, have increased in recent decades. Limited treatment options are available for patients with metastatic MCC (mMCC). Avelumab, an anti-programmed cell death-ligand 1 monoclonal antibody, became the first approved treatment for mMCC after the results of the phase 2 JAVELIN Merkel 200 study.

Immunological Aspects of Isolation and Confinement.

Beyond all doubts, the exploration of outer space is a strategically important and priority sector of the national economy, scientific and technological development of every and particular country, and of all human civilization in general. A number of stress factors, including a prolonged confinement in a limited hermetically sealed space, influence the human body in space on board the spaceship and during the orbital flight. All these factors predominantly negatively affect various functional systems of the organism, in particular, the astronaut's immunity.

Real-World Experience with Targeted Therapy in BRAF Mutant Advanced Melanoma Patients: Results from a Multicenter Retrospective Observational Study Advanced Melanoma in Russia (Experience) (ADMIRE).

Clinical trials of targeted therapy (TT) and immunotherapy (IT) for highly aggressive advanced melanoma have shown marked improvements in response and survival rates. However, real-world data on treatment patterns and clinical outcomes for patients with advanced BRAF V600 mutant melanoma are ultimately scarce. The study was designed as an observational retrospective chart review study, which included 382 patients with advanced BRAF V600 mutant melanoma, who received TT in a real-world setting and were not involved in clinical trials.

Microarray-based analysis of the BRAF V600 mutations in circulating tumor DNA in melanoma patients.

Background: Circulating tumor DNA (ctDNA) holds great potential for cancer therapy and can provide diagnostic and prognostic information before and during treatment.

Methods: Plasma DNA samples from 97 melanoma patients, 20 healthy donors and 3 patients with benign skin tumors were analyzed by microarray analysis and droplet digital PCR (ddPCR).

Results: A microarray for simultaneous detection of six BRAF V600 mutations in ctDNA has been developed.

[Chromato-mass spectrometric analysis of urine proteins associated with the functions of Toll-receptors in a healthy person under conditions of 17-day isolation.].

Under controlled conditions of 17-day isolation (Sirius-17 experiment), the protein composition of urine was studied in 6 healthy test volunteers-3 women and 3 men. Collection of samples in the form of a second freely separated morning urine fraction was carried out in the background (seven days before the experiment), as well as 1 day after the end of exposure. Chromatographic-mass-spectrometric semi-quantitative analysis of the protein composition of samples was performed on a system consisting of an Agilent 1100 chromatograph and an LTQ-FT Ultra hybrid mass spectrometer using bioinformatics resources UniProtKB, GeneOntology.

Outcome of rectus femoris muscle flaps performed by vascular surgeons for the management of complex groin wounds after femoral artery reconstructions.

Objective: Groin wound complications after femoral artery reconstructions are highly morbid and notoriously difficult to treat. Successful techniques include long-term antibiotic therapy, operative débridement, and muscle flap coverage. Historically, more complex muscle flap coverage, such as a rectus femoris muscle flap (RFF), has been performed by plastic and reconstructive surgeons.

Lack of Response to Imatinib in Melanoma Carrying Rare Mutation p.T632I.

Approximately 15% of acral and mucous melanomas carry activating mutations in oncogene. There is a diversity of spectrum of mutations, with some of them rendering tumors responsive to imatinib, while others being imatinib-resistant or not studied yet. Here we present an acral melanoma patient with р.

Y-chromosomal analysis of clan structure of Kalmyks, the only European Mongol people, and their relationship to Oirat-Mongols of Inner Asia.

Kalmyks, the only Mongolic-speaking population in Europe, live in the southeast of the European Plain, in Russia. They adhere to Buddhism and speak a dialect of the Mongolian language. Historical and linguistic evidence, as well a shared clan names, suggests a common origin with Oirats of western Mongolia; yet, only a limited number of genetic studies have focused on this topic.

Melanoma arising in a Giant congenital melanocytic nevus: two case reports.

Background: A giant congenital melanocytic nevus (GCMN) is found in 0.1% of live-born infants. If present, the lesion has a chance of about 6% to develop into malignant melanoma.

Therapeutic potential of phosphodiesterase type 5 inhibitors in heart failure with preserved ejection fraction and combined post- and pre-capillary pulmonary hypertension.

Objective: Heart failure with preserved ejection fraction (HFpEF) is frequently associated with pulmonary hypertension (PH), which substantially impacts survival. Based on pulmonary vascular resistance (PVR) and the diastolic pressure gradient (DPG), current guidelines distinguish between isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH). However, the therapeutic consequences of this sub-classification remain entirely unclear.

Outcomes of endovascular treatments for in-stent restenosis in patients with mesenteric atherosclerotic disease.

Objective: Mesenteric angioplasty and stenting (MAS) has surpassed open revascularization as the treatment of choice for mesenteric ischemia. Despite the lower perioperative mortality associated with MAS, the need for reintervention is not infrequent. The purpose of this study was to review the outcomes of patients treated for mesenteric artery in-stent restenosis (MAISR).

Outcomes of familial abdominal aortic aneurysm repair in the Vascular Quality Initiative.

Objective: Recent investigations have reported increased rates of aneurysm-related complications after endovascular aneurysm repair (EVAR) in familial abdominal aortic aneurysm (fAAA) patients. The purpose of this study was to evaluate the outcomes of open aortic repair (OAR) and EVAR in sporadic AAA (spAAA) and fAAA patients in the Society for Vascular Surgery Vascular Quality Initiative.

Methods: This was a retrospective review of all AAA repairs in the Vascular Quality Initiative from 2003 to 2017.

[Neurodevelopmental disorders in children with epilepsy].

Neurodevelopmental disorders, including intellectual disability, autistic-spectrum disorders, speech disorders, attention deficit hyperactivity disorder (ADHD), learning disabilities, are more prevalent in children with epilepsy compared with the general population. Marked developmental delay and regression of acquired skills are characteristic of epileptic encephalopathies. Conditions, in which neurodevelopmental disorders are associated with the marked epileptiform EEG activity, while clinical epileptic seizures are absent, represent a serious problem.

Advanced Endovascular Approaches in the Management of Challenging Proximal Aortic Neck Anatomy: Traditional Endografts and the Snorkel Technique.

Advances in endovascular technology, and access to this technology, have significantly changed the field of vascular surgery. Nowhere is this more apparent than in the treatment of abdominal aortic aneurysms (AAAs), in which endovascular aneurysm repair (EVAR) has replaced the traditional open surgical approach in patients with suitable anatomy. However, approximately one-third of patients presenting with AAAs are deemed ineligible for standard EVAR because of anatomic constraints, the majority of which involve the proximal aneurysmal neck.

A genome-wide screen for bacterial envelope biogenesis mutants identifies a novel factor involved in cell wall precursor metabolism.

The cell envelope of Gram-negative bacteria is a formidable barrier that is difficult for antimicrobial drugs to penetrate. Thus, the list of treatments effective against these organisms is small and with the rise of new resistance mechanisms is shrinking rapidly. New therapies to treat Gram-negative bacterial infections are therefore sorely needed.

Results of carotid angioplasty and stenting are equivalent for critical versus high-grade lesions in patients deemed high risk for carotid endarterectomy.

Background: To examine outcomes of carotid angioplasty and stenting (CAS) in patients with critical carotid stenosis who are deemed high risk for carotid endarterectomy.

Methods: Medical records were retrospectively analyzed for patients undergoing CAS between September 2002 and March 2011 at a single institution. Patients were classified as having either critical (≥ 90%) or high-grade (70%-89%) carotid stenosis based on angiography.

Rapamycin prevents seizures after depletion of STRADA in a rare neurodevelopmental disorder.

A rare neurodevelopmental disorder in the Old Order Mennonite population called PMSE (polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome; also called Pretzel syndrome) is characterized by infantile-onset epilepsy, neurocognitive delay, craniofacial dysmorphism, and histopathological evidence of heterotopic neurons in subcortical white matter and subependymal regions. PMSE is caused by a homozygous deletion of exons 9 to 13 of the LYK5/STRADA gene, which encodes the pseudokinase STRADA, an upstream inhibitor of mammalian target of rapamycin complex 1 (mTORC1). We show that disrupted pathfinding in migrating mouse neural progenitor cells in vitro caused by STRADA depletion is prevented by mTORC1 inhibition with rapamycin or inhibition of its downstream effector p70 S6 kinase (p70S6K) with the drug PF-4708671 (p70S6Ki).