Genetic and therapeutic landscapes in cohort of pancreatic adenocarcinomas: next-generation sequencing and machine learning for full tumor exome analysis.

About 7% of all cancer deaths are caused by pancreatic cancer (PCa). PCa is known for its lowest survival rates among all oncological diseases and heterogenic molecular profile. Enormous amount of genetic changes, including somatic mutations, exceeds the limits of routine clinical genetic laboratory tests and further stagnates the development of personalized treatments. We aimed to build a mutational landscape of PCa in the Russian population based on full exome next-generation sequencing (NGS) of the limited group of patients. Applying a machine learning model on full exome individual data we received personalized recommendations for targeted treatment options for each clinical case and summarized them in the unique therapeutic landscape.

[The effect of applying clinical organizational telemedicine technology management of anti-tuberculous care on dynamics of tuberculosis morbidity and mortality].

The tuberculosis is the most important medical and social problem among globally dangerous epidemiological phenomena. the tuberculosis ranks 9th place in the structure of mortality and disability of population and 1st place among causes of death from single infectious agent.The purpose of the study was to analyze dynamics of total morbidity and mortality because of tuberculosis against the background of the implementation of telemedicine clinical organizational technology in phthisiology care 2007-2021.The official Regional and Federal data of Rosstat for 2007-2021 were used. The indicators of total morbidity and mortality of population caused by tuberculosis in the Sverdlovsk Oblast were established. The research methods were content analysis, dynamic series analysis, graphical analysis, statistical differences analysis.In the Sverdlovsk Oblast, the morbidity and mortality of tuberculosis exceeded national average indicators by 1.2-1.5 times. In 2007-2021, as a result of implementation of clinical organizational telemedicine technology in managing phthisiology care, total morbidity and mortality of population caused by tuberculosis decreased up to 2.275 and 2.97 times respectively. The rate of decrease of analyzed epidemiological indicators generally correlated with national average data with statistical validity of difference t≥2.In regions with unfavorable epidemiological indicators of tuberculosis, application of innovative technologies in management of clinical organizational processes is required. The development and implementation of clinical organizational telemedicine technology for managing regional phthisiology care contributes to significant reduction of morbidity and mortality of tuberculosis and optimizes sanitary and epidemiological well-being.

[Long-term follow-up study of post-COVID-19 patients].

AIM: To evaluate dynamic changes in the lungs, hemostasis system, immune system in different terms after coronavirus pneumonia. MATERIALS AND METHODS: Ventilation-perfusion single-photon emission computed tomography/computed tomography (CT), functional methods of lung investigation, evaluation of hemostasis system, immune status and specific humoral immune response were performed and evaluated in different terms after coronavirus pneumonia. A total of 71 patients were examined according to this protocol. We examined patients with the lesion volume not less than 50% according to chest CT. All patients were divided into 2 groups depending on the distance from the acute stage of coronavirus pneumonia. Group 1 included patients who were examined early (3060 days after hospital discharge), group 2 included patients who were examined later (61180 days after hospital discharge). RESULTS: We obtained gradual regression of pathologically-modified tissue from 67.3% during the inpatient phase to 30.9% during the early period and to 19.7% during the late period of examination, according to CT scan of the chest organs. The same tendency was demonstrated by diffusion capacity of the lungs. Perfusion scintigraphy data showed a decrease in perfusion deficit from 26.012.8% during the early period of examination to 19.46.2% during the late period of examination. On the contrary, ventilatory scintigraphy demonstrates the increase of isotope passage time through the alveolar-capillary membrane over time (from 48.231.3 minutes in the early period to 83.637.2 minutes in the late period). An increase in D-dimer was detected in 24% of patients in the early group. The levels of inflammatory markers, indices of immune status, and specific humoral immune response did not differ in the two described groups. CONCLUSION: The results demonstrate gradual regression of pathological changes caused by coronavirus infection.

Specific features of T- and NK-cellular immunity in chronic lymphocytic leukemia.

Profound immunological dysfunction is the key factor determining the development of infectious complications in chronic lymphocytic leukemia (CLL). The aim of this work is to assess the features of the subpopulation composition of T-lymphocytes (T-helpers (Th), cytotoxic T-lymphocytes (Tcyt), T regulatory cells (Treg), T-NK cells, naive Th, Th-memory, activated T-lymphocytes, TCRγδ cells) and NK cells in peripheral blood of patients with newly diagnosed chronic lymphocytic leukemia (CLL) and receiving ibrutinib therapy. Hematological and immunophenotypic studies have been performed in 30 patients with previously untreated CLL, 122 patients on ibrutinib therapy and 20 healthy donors. The subpopulation composition of T-lymphocytes (Th, Tcyt, Treg, T-NK, naive T-helpers, memory T-helpers, TCRγδ cells, activated T-lymphocytes) and NK cells has been assessed on flow cytometer (FACSCanto II (BD)) using the following panel of monoclonal antibodies: CD45, CD19, CD3, CD4, CD5, CD8, TCRγδ, CD127, CD16, CD56, CD57 CD45RA, CD45R0, HLA-DR, CD25. Compared to controls all CLL samples were found to have higher the absolute number of T-lymphocytes, NK cells and their subpopulations, T-helpers (especially of memory T-cells), cytotoxic T-cells, regulatory T-cells, TCRγδ T-cells, activated T-lymphocytes, increased cytotoxic potential of NK cells in previously untreated CLL patients. Patients who received ibrutinib therapy have registered a positive trend towards recovery of the subpopulation composition of T-lymphocytes and NK-cells. CLL patients have been found to have quantitative and functional changes in the subpopulations of T-lymphocytes and NK cells, indicating dysregulation of the immune response, and a high risk of developing infections. Monitoring of immunological parameters for ibrutinib therapy make possible to estimate impact of ibrutinib on the adaptive anti-CLL immune response.

Case Report of an Acute Myocardial Infarction as a Result of Spontaneous Coronary Artery Dissection in a Patient with Fibromuscular Dysplasia.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an underdiagnosed and rare cause of myocardial infarction (MI). SCAD is defined as the separation of the coronary artery wall by hemorrhage with or without intimal tear. It causes acute coronary syndrome in 1.7% to 4% of cases. CASE SUMMARY: We report a case of a patient with acute MI caused by SCAD with marked progression of dissection within 4 days and spontaneous healing in 2 months. Fibromuscular dysplasia (FMD) of the arteries is an associated condition of SCAD that was found in our patient. CONCLUSION: In young women admitted to the clinic with signs of acute myocardial infarction, SCAD should be suspected. FMD as an associated condition that should be ruled out in every SCAD patient. Conservative treatment of SCAD is the most preferable strategy.

Magnetic field-induced pair density wave state in the cuprate vortex halo.

High magnetic fields suppress cuprate superconductivity to reveal an unusual density wave (DW) state coexisting with unexplained quantum oscillations. Although routinely labeled a charge density wave (CDW), this DW state could actually be an electron-pair density wave (PDW). To search for evidence of a field-induced PDW, we visualized modulations in the density of electronic states N(r) within the halo surrounding Bi2Sr2CaCu2O8 vortex cores. We detected numerous phenomena predicted for a field-induced PDW, including two sets of particle-hole symmetric N(r) modulations with wave vectors QP and 2Q P , with the latter decaying twice as rapidly from the core as the former. These data imply that the primary field-induced state in underdoped superconducting cuprates is a PDW, with approximately eight CuO2 unit-cell periodicity and coexisting with its secondary CDWs.

[Morphologic structure and immunohistochemical analysis of vaginal wall in women with pelvic organ prolapse].

AIM: to study a correlation between clinical stage of pelvic organ prolapse (POP), a histological structure and results of immunohistochemical study of the vaginal wall were evaluated. MATERIALS AND METHODS: A total of 60 peri- and postmenopausal women (average age 61.9+/-8.4 years) with POP of stage II-IV, according to the POP-Q classification, or with stress urinary incontinence and cystocele of stage I-II, who undergone to surgical treatment, were included in the study. During a procedure, a biopsy from the anterior vaginal wall was taken. Depending on the stage of POP, patients was divided into two groups. In the group 1, 30 patients with stage I and II of POP were included, while group 2 included 30 women with POP of stage III and more. The control group (group 3) consisted of 20 patients without POP (mean age 63.4+/-11.0 years) who underwent a hysterectomy due to to other indications. A histological and immunohistochemical studies of vaginal wall tissue was performed in order to determine the tissue content of collagen type I and III; matrix metalloproteinases 1 and 2 (MMP-1 and MMP-2), a tissue inhibitor of metalloproteinases 1 (TIMP-1), vimentin and smooth muscle actin. RESULTS: In contrast to two other groups, in group 2 there were significant changes in the connective tissue. Collagen has a form of fibrous mass with areas of reduced content. In addition, scarring areas with an increase in the content of type III collagen, a decrease in the amount of type I collagen and elastic fibers with significant fragmentation, were seen. Moreover, in patients with severe POP (III-IV), degradation of collagen fibers with a decrease in connective tissue strength and elasticity was detected. Women with POP had a low ratio of type I:III collagen. Analysis of the collagen content in the vaginal wall in patients with mild POP (I-II) revealed a significant increase in the level of collagen type I (p=0.0003) and a decrease in the content of type III (p=0.045), compared to patients with more severe POP (III-IV). The level of MMP-1 and MMP-2 in women with POP was higher, than in control group by 1.7 times (p<0.05). The content of TIMP-1 in the group 1 was significantly lower by 1.5 and 2.2 times, compared to group 2 and 3, respectively. An analysis of MMP-1 and MMP-2 concentration in patients of groups 1 and 2 revealed a significant (p=0.04) decrease in their activity in severe POP (III-IV). In women of the group 2, biopsy of the vaginal wall showed that expression of vimentin and smooth muscle actin in the connective tissue was significantly higher, than in group 1 and 3 (p<0.05). Vimentin expression in the group 2 was 1.4 and 2.6 times higher than in the group 1 and 3, respectively. In the control group, the expression of these markers in the vaginal wall was minimal and focal. CONCLUSION: Our data indicate that fibrosis and degradation of the connective tissue in the vaginal wall predominate in POP, and these changes are a consequence, but not a cause of PG. The aggravation of degenerative changes in the connective tissue leads to the progression of POP.

Imaging orbital-selective quasiparticles in the Hund's metal state of FeSe.

Strong electronic correlations, emerging from the parent Mott insulator phase, are key to copper-based high-temperature superconductivity. By contrast, the parent phase of an iron-based high-temperature superconductor is never a correlated insulator. However, this distinction may be deceptive because Fe has five actived d orbitals while Cu has only one. In theory, such orbital multiplicity can generate a Hund's metal state, in which alignment of the Fe spins suppresses inter-orbital fluctuations, producing orbitally selective strong correlations. The spectral weights Zm of quasiparticles associated with different Fe orbitals m should then be radically different. Here we use quasiparticle scattering interference resolved by orbital content to explore these predictions in FeSe. Signatures of strong, orbitally selective differences of quasiparticle Zm appear on all detectable bands over a wide energy range. Further, the quasiparticle interference amplitudes reveal that [Formula: see text], consistent with earlier orbital-selective Cooper pairing studies. Thus, orbital-selective strong correlations dominate the parent state of iron-based high-temperature superconductivity in FeSe.

[Adenoid cystic carcinoma of the larynx: a case report]. / Nabliudenie adenokistoznogo raka gortani.

Adenoid cystic carcinoma is one of the rare pathological conditions affecting the larynx. It is known to develop from the glandula elements present in this organ. The authors report a clinical observation of adenoid cystic carcinoma in the form of an exophytic tumour of the pale pink colour having a smooth surface and the well-pronounced vascular patterns at the base. The neoplasm is localized in the arytenoid and retroarytenoid cartilage regions. Being of 3.5-4 cm in size, the tumour causes the narrowing of the larynx in its posterior portions and restricts its mobility. Bearing in mind the considerable extension of the neoplastic process, we undertook laryngectomy including the resection of the orolaryngopharynx and the cervical portion of the oesophagus, the subtotal resection of the thyroid gland and the simultaneous reconstruction of the orolaryngopharynx.

[Pancreatoduodenectomy: learning curve within single multi-field center]. / Pankreatoduodenal'naia rezektsiia: krivaia obucheniia na primere odnogo mnogoprofil'nogo tsentra.

AIM: To analyze learning curve by using of immediate results of pancreatoduodenectomy at multi-field oncology institute. MATERIAL AND METHODS: For the period 2010-2016 at Abdominal Oncology Department of Herzen Moscow Oncology Research Institute 120 pancreatoduodenal resections were consistently performed. All patients were divided into two groups: the first 60 procedures (group A) and subsequent 60 operations (group B). Herewith, first 60 operations were performed within the first 4.5 years of study period, the next 60 operations - within remaining 2.5 years. RESULTS: Learning curves showed significantly variable intraoperative blood loss (1100 ml and 725 ml), surgery time (589 min and 513 min) and postoperative hospital-stay (15 days and 13 days) in group A followed by gradual improvement of these values in group B. Incidence of negative resection margin (R0) was also significantly improved in the last 60 operations (70 and 92%, respectively). CONCLUSION: Despite pancreatoduodenectomy is one of the most difficult surgical interventions in abdominal surgery learning curve will differ from one surgeon to another.

Discovery of orbital-selective Cooper pairing in FeSe.

The superconductor iron selenide (FeSe) is of intense interest owing to its unusual nonmagnetic nematic state and potential for high-temperature superconductivity. But its Cooper pairing mechanism has not been determined. We used Bogoliubov quasiparticle interference imaging to determine the Fermi surface geometry of the electronic bands surrounding the Γ = (0, 0) and X = (π/aFe, 0) points of FeSe and to measure the corresponding superconducting energy gaps. We show that both gaps are extremely anisotropic but nodeless and that they exhibit gap maxima oriented orthogonally in momentum space. Moreover, by implementing a novel technique, we demonstrate that these gaps have opposite sign with respect to each other. This complex gap configuration reveals the existence of orbital-selective Cooper pairing that, in FeSe, is based preferentially on electrons from the d yz orbitals of the iron atoms.

[Female genital prolapse surgery using ultra lightweight polypropylene mesh].

AIM: To compare the results of female genital prolapse (FGP) surgery via vaginal access using lightweight and ultra-lightweight polypropylene mesh. MATERIALS AND METHODS: From 2007 to 2011, 93 women aged from 46 to 71 years with II-IV stage FGP (POP-Q classification) were examined and underwent the vaginal extra-peritoneal colpopexy using polypropylene implants in the Department of Urology. Patients were divided into 2 groups. In patients of group 1 (n=50) the surgery was performed according to a newly developed technique using perforated ultra-lightweight (surface density 19 g/m2) domestically manufactured polypropylene implant. In group 2, a standard trocar set with light (surface density of 42.7 g/m2) foreign-made polypropylene implants was used. RESULTS AND DISCUSSION: Long-term follow-up was from 1 to 5 years. General surgical complications (urinary bladder injury, blood loss over 300 ml, perineal and vaginal hematomas) were detected in 2 (4%) patients of group 1 and in 7 (16.3%) patients of group 2. The most common specific mesh-related complication was the vaginal wall erosion, which was observed in 4 (9.3%) patients of group 2 and in 1 (2%) patient of group 1. FGP recurrence was diagnosed in 5 (10%) patients of group 1 in the non-treated part and in 8 (18.6%) patients of group 2. Three patients (7%) in group 2 developed recurrent cystocele due to the shrinkage of the mesh implant which was not observed in group 1. At 12 month follow-up, the results of FGP surgical treatment were estimated as good (full functional recovery and no FGP recurrence) in 41 (82%) and 32 (74.4%) patients of groups 1 and 2, respectively. CONCLUSION: We have developed a method of vaginal extra-peritoneal colpopexy using a perforated ultra-lightweight polypropylene implant. This technique has resulted in the absence of recurrence in the treated part of FGP, and 4.1, 4.2 and 4.7 fold reductions in the incidence of general surgical complications, vaginal wall erosions and perineal and vaginal hematomas, respectively, compared with FGP patients undergoing the placement of the lightweight polypropylene implant using the standard trocar set.

[Radical nephrectomy in a left pelvic dystopic kidney in a patient with renal cell carcinoma].

The incidence of the renal cell carcinoma in Russia and worldwide remains high. Current literature reports isolated cases of patients who were diagnosed and treated for malignant neoplasms of dystopic kidneys. In addition, the absence of patient complaints and the paucity of non-specific symptoms of pelvic dystopic kidneys lead to late diagnosis of this anomaly and the kidney diseases. This article presents a case study of a radical nephrectomy in a patient with renal cell carcinoma of the left pelvic dystopic kidney.

Detection of a Cooper-pair density wave in Bi2Sr2CaCu2O8+x.

The quantum condensate of Cooper pairs forming a superconductor was originally conceived as being translationally invariant. In theory, however, pairs can exist with finite momentum Q, thus generating a state with a spatially modulated Cooper-pair density. Such a state has been created in ultracold (6)Li gas but never observed directly in any superconductor. It is now widely hypothesized that the pseudogap phase of the copper oxide superconductors contains such a 'pair density wave' state. Here we report the use of nanometre-resolution scanned Josephson tunnelling microscopy to image Cooper pair tunnelling from a d-wave superconducting microscope tip to the condensate of the superconductor Bi2Sr2CaCu2O8+x. We demonstrate condensate visualization capabilities directly by using the Cooper-pair density variations surrounding zinc impurity atoms and at the Bi2Sr2CaCu2O8+x crystal supermodulation. Then, by using Fourier analysis of scanned Josephson tunnelling images, we discover the direct signature of a Cooper-pair density modulation at wavevectors QP ≈ (0.25, 0)2π/a0 and (0, 0.25)2π/a0 in Bi2Sr2CaCu2O8+x. The amplitude of these modulations is about five per cent of the background condensate density and their form factor exhibits primarily s or s' symmetry. This phenomenology is consistent with Ginzburg-Landau theory when a charge density wave with d-symmetry form factor and wavevector QC = QP coexists with a d-symmetry superconductor; it is also predicted by several contemporary microscopic theories for the pseudogap phase.

[Intravascular leiomyomatosis].

Intravenous leiomyomatosis is a rare disease from a group of tumors with the indefinite grading potential. The paper describes two cases of intravenous leiomyomatosis with its detailed morphological pattern, molecular genetic findings, and a brief literature review. Losses of heterozygosity of microsatellite repeats thatwere located on chromosome 10 in 10q22.1 and common in uterine leiomyosarcomas were found in both cases. Investigations of the morphological and biological characteristics of leimyomatosis are important to clarify the key molecular mechanisms underlying the development of this nosological entity and to determine etiopathogenetic relationships between intravenous leiomyomatosis and other uterine smooth muscle neoplasms.

Disorders in the Morphology and Nanostructure of Erythrocyte Membranes after Long-term Storage of Erythrocyte Suspension: Atomic Force Microscopy Study.

Disorders in the erythrocyte morphology and structure of their membranes during long-term storage of erythrocyte suspension (30 days at 4°C) were studied by atomic force microscopy. The morphology and nanostructure of erythrocyte membranes, biochemical parameters, ion exchange parameters, and hemoglobin spectra were recorded. The transformation of erythrocyte morphology and destruction of their membranes were observed throughout the storage period. Irreversible forms of spheroechinocytes and their fragments formed by the end of storage. The concentrations of potassium ions and lactate in solution of the blood preservatiive increased, while pH value decreased. Hemolysis detected by the erythrocyte "leakage" effect was observed starting from days 16-23 of storage.

[TREATMENT OF AGE-RELATED ANDROGEN DEFICIENCY IN PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA].

This paper reports the results of a comparative study evaluating the safety and efficacy of testosterone therapy in 44 patients with BPH and age-related androgen deficiency. All patients received α-blockers. The findings of the study showed a substantial improvement in the quality of life of patients in the study group that received testosterone therapy, compared with the control group treated with only α-blockers.