[Approximation analysis in the study of the epidemiology of the epistaxis]. / Approksimatsionnyi analiz v izuchenii epidemiologii nosovykh krovotechenii.

Epistaxis or nosebleeds (NB) are the most common emergency pathology that otorhinolaryngologists have to deal with. Purpose of the work: to study the prevalence of patients with NB in the otorhinolaryngological departments of hospitals in Moscow from 2003 to 2019. The reports of the heads of the ENT departments of the city clinical hospitals in Moscow were studied. Inclusion criteria were hospitals working with an adult contingent of patients. An approximation analysis was carried out and trend indicators of the prevalence of NB were studied. RESULTS: 2003 to 2019 the total number of patients treated in ENT hospitals was 563 189 people, 20 623 (3.7%) patients were treated with NB, of which 52 (0.25%) died. The average age of the deceased was 64.7 years, men are 73.7% more prevalent than women. In 96.2% of patients, epistaxis was a complication of the underlying disease, and in 3.8%, it was regarded as a concomitant condition. In 30.8% of the deceased, NB recurred with the background of malignant lesions of the nose and nasopharynx, in 69.2% - posthemorrhagic anemia aggravated diseases of other organs and systems. Over the past 17 years, there has been a tendency for the growth of treated patients with diseases of ENT organs and patients with nosebleeds by 58.5% and 51.1%, respectively. The studied approximation of the relative prevalence and mortality rates in patients with NB showed that for the period from 2003 to 2019. trend values are practically at the same level with the minimum multidirectional linear dynamics - -0.24% and +0.04%, respectively.

Oral vitamin D supplementation induces transcriptomic changes in rectal mucosa that are linked to anti-tumour effects.

BACKGROUND: The risk for several common cancers is influenced by the transcriptomic landscape of the respective tissue-of-origin. Vitamin D influences in vitro gene expression and cancer cell growth. We sought to determine whether oral vitamin D induces beneficial gene expression effects in human rectal epithelium and identify biomarkers of response. METHODS: Blood and rectal mucosa was sampled from 191 human subjects and mucosa gene expression (HT12) correlated with plasma vitamin D (25-OHD) to identify differentially expressed genes. Fifty subjects were then administered 3200IU/day oral vitamin D3 and matched blood/mucosa resampled after 12 weeks. Transcriptomic changes (HT12/RNAseq) after supplementation were tested against the prioritised genes for gene-set and GO-process enrichment. To identify blood biomarkers of mucosal response, we derived receiver-operator curves and C-statistic (AUC) and tested biomarker reproducibility in an independent Supplementation Trial (BEST-D). RESULTS: Six hundred twenty-nine genes were associated with 25-OHD level (P < 0.01), highlighting 453 GO-term processes (FDR<0.05). In the whole intervention cohort, vitamin D supplementation enriched the prioritised mucosal gene-set (upregulated gene-set P < 1.0E-07; downregulated gene-set P < 2.6E-05) and corresponding GO terms (P = 2.90E-02), highlighting gene expression patterns consistent with anti-tumour effects. However, only 9 individual participants (18%) showed a significant response (NM gene-set enrichment P < 0.001) to supplementation. Expression changes in HIPK2 and PPP1CC expression served as blood biomarkers of mucosal transcriptomic response (AUC=0.84 [95%CI 0.66-1.00]) and replicated in BEST-D trial subjects (HIPK2 AUC=0.83 [95%CI 0.77-0.89]; PPP1CC AUC=0.91 [95%CI 0.86-0.95]). CONCLUSIONS: Higher plasma 25-OHD correlates with rectal mucosa gene expression patterns consistent with anti-tumour effects, and this beneficial signature is induced by short-term vitamin D supplementation. Heterogenous gene expression responses to vitamin D may limit the ability of randomised trials to identify beneficial effects of supplementation on CRC risk. However, in the current study blood expression changes in HIPK2 and PPP1CC identify those participants with significant anti-tumour transcriptomic responses to supplementation in the rectum. These data provide compelling rationale for a trial of vitamin D and CRC prevention using easily assayed blood gene expression signatures as intermediate biomarkers of response.

[ENT care in the context of the new coronavirus infection COVID-19]. / Aktual'nye voprosy okazaniya spetsializirovannoi lor-pomoshchi v usloviyakh novoi koronavirusnoi infektsii COVID-19.

The spread of the pandemic of the new coronavirus infection COVID-19 inevitably makes adjustments to the medical care. Given that the main route of transmission is airborne, otorhinolaryngologists are at increased risk of infection. Based on the literature data of leading otorhinolaryngologists, as well as their own experience working with patients with the new coronavirus infection COVID-19, the authors present relevant recommendations on the organization of specialized otorhinolaryngological care in the context of the COVID-19 pandemic. The authors consider the etiology, pathogenesis, and clinical manifestations of COVID-19. The features of the examination of ENT, diagnostic and therapeutic procedures, including the use of silicone hydrotamps to stop the front and rear nose bleeds, developed in L.I. Sverzhevskiy OHRIM, and indications for hospitalization in the ENT hospital. Features of operations on the otorhinolaryngological profile during a COVID pandemic are also described. Summing up, the authors indicate that during the pandemic of the new coronavirus infection COVID-19, otorhinolaryngologists need to adhere to two fundamental principles aimed at preventing the spread of infection: the use of modern effective personal protective equipment and the use of examination methods (surgical treatment methods) that prevent the formation of biological aerosols.

Low plasma vitamin D is associated with adverse colorectal cancer survival after surgical resection, independent of systemic inflammatory response.

OBJECTIVE: We assessed the effect of surgical resection of colorectal cancer (CRC) on perioperative plasma vitamin D (25OHD) and C-reactive protein (CRP) level. We investigated the relationship between circulating vitamin D level and CRC survival. DESIGN: We sequentially sampled 92 patients undergoing CRC resection, and measured plasma 25OHD and CRP. For survival analyses, we assayed 25OHD and CRP in two temporally distinct CRC patient cohorts (n=2006, n=2100) and investigated the association between survival outcome, circulating vitamin D and systemic inflammatory response. RESULTS: Serial sampling revealed a postoperative fall (mean 17.3 nmol/L; p=3.6e-9) in plasma 25OHD (nadir days 1-2). CRP peaked 3-5 days postoperatively (143.1 mg/L; p=1.4e-12), yet the postoperative fall in 25OHD was independent of CRP. In cohort analyses, 25OHD was lower in the 12 months following operation (mean=48.8 nmol/L) than preoperatively (54.8 nmol/L; p=1.2e-5) recovering after 24 months (52.2 nmol/L; p=0.002). Survival analysis in American Joint Committee on Cancer stages I-III demonstrated associations between 25OHD tertile and CRC mortality (HR=0.69; 95% CI 0.46 to 0.91) and all-cause mortality (HR=0.68; 95% CI 0.50 to 0.85), and was independent of CRP. We observed interaction effects between plasma 25OHD and rs11568820 genotype (functional VDR polymorphism) with a strong protective effect of higher 25OHD only in patients with GG genotype (HR=0.51; 95% CI 0.21 to 0.81). We developed an online tool for predicted survival (https://apps.igmm.ed.ac.uk/mortalityCalculator/) that incorporates 25OHD with clinically useful predictive performance (area under the curve 0.77). CONCLUSIONS: CRC surgery induces a fall in circulating 25OHD. Plasma 25OHD level is a prognostic biomarker with low 25OHD associated with poorer survival, particularly in those with rs11568820 GG genotype. A randomised trial of vitamin D supplementation after CRC surgery has compelling rationale.

Phase 3 study of recombinant von Willebrand factor in patients with severe von Willebrand disease who are undergoing elective surgery.

Essentials Recombinant von Willebrand factor (rVWF) is effective in von Willebrand disease (VWD). A phase 3 study of rVWF, with/without recombinant factor VIII (rFVIII) before surgery in VWD. Overall rVWF's efficacy was rated excellent/good; rVWF was administered alone in most patients. rVWF was well-tolerated and hemostasis was achieved in patients with severe VWD undergoing surgery. SUMMARY: Background Recombinant von Willebrand factor (rVWF) has demonstrated efficacy for on-demand treatment of bleeding in severe von Willebrand disease (VWD), warranting evaluation in the surgical setting. Objectives This study (NCT02283268) evaluated the hemostatic efficacy/safety profile of rVWF, with/without recombinant factor VIII (rFVIII), in patients with severe VWD undergoing surgery. Patients/Methods Patients received rVWF 40-60 IU kg-1 , VWF ristocetin cofactor activity was measured 12-24 h before surgery. If endogenous FVIII activity (FVIII:C) target levels were achieved 3 h before surgery, rVWF was administered alone 1 h before surgery; rVWF was co-administered with rFVIII if target endogenous FVIII levels were not achieved. rVWF was infused postoperatively to maintain target trough levels. Overall and intraoperative hemostatic efficacy, the pharmacodynamics of rVWF administration and the incidence of adverse events (AEs) were assessed. Results All patients treated with rVWF for major (n = 10), minor (n = 4) and oral (n = 1) surgery had overall and intraoperative hemostatic efficacy ratings of excellent (73.3% and 86.7%) or good (26.7% and 13.3%). Most rVWF infusions (89.4%) were administered alone, resulting in hemostatically effective levels of endogenous FVIII within 6 h, which were sustained for 72-96 h; 70% (n = 7/10) of major surgeries were performed without rFVIII co-administration. Six patients reported 12 treatment-emergent AEs. Two patients each had one serious AE: diverticulitis (not treatment related) and deep vein thrombosis (sponsor-assessed as possibly treatment related). No severe allergic reactions or inhibitory antibodies were reported. Conclusions These data support the efficacy and safety profile of rVWF in patients with severe VWD undergoing elective surgery.

A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus.

Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed by replication in an independent set of 1,281 cases and 3,218 controls to find novel risk loci. We identify a novel variant at 19p13.3 associated with HL (rs1860661; odds ratio (OR)=0.81, 95% confidence interval (95% CI) = 0.76-0.86, P(combined) = 3.5 × 10(-10)), located in intron 2 of TCF3 (also known as E2A), a regulator of B- and T-cell lineage commitment known to be involved in HL pathogenesis. This meta-analysis also notes associations between previously published loci at 2p16, 5q31, 6p31, 8q24 and 10p14 and HL subtypes. We conclude that our data suggest a link between the 19p13.3 locus, including TCF3, and HL risk.

[The effectiveness of propranolol therapy of subfold hemangioma in the children during the first year of life].

The objective of the present study was to estimate the effectiveness and tolerance of propranolol therapy prescribed to the children presenting with vascular hyperplasia of the larynx. The experience with propranolol therapy of 12 patients suffering vascular hyperplasia of the larynx (subfold hemangioma) is analysed. Nine of these children had been given systemic glucocorticoid therapy prior to the present study that failed to produce a clinically significant effect. On the contrary, the treatment with propranolol resulted in a well apparent clinical effect in the form of the marked decrease in the size of subfold hemangioma and the reduction in the degree of laryngeal stenosis from grade 2-3 to 0-1 as early as 10-14 days after the onset of propranolol therapy at a daily dose of 2 mg/kg. None of the patients developed adverse reactions related to the treatment with propranolol. The results of the study indicate that the treatment of vascular hyperplasia, such as subfold hemangioma with the non-selective beta-blocker propranolol is both efficacious and safe for the patients. This gives reason to recommend this therapeutic modality as the first-line treatment of the children starting from the first weeks of life.

Changes in parameters of laser-induced potentials after transcutaneous electroneurostimulation.

Changes in nerve conduction after 10-min electroneurostimulation of the posterior surface of the neck were studied. Changes in the parameters of laser-induced potentials obtained during stimulation of C7 dermatome on hands and posterior surface of the neck were found. Decrease in the amplitude and shortening of the component latency were shown. Method of laser-induced potentials was concluded to provide unbiased estimation of the level and peculiarities of analgesic effects of physical factors.

Cytogenetic study of professional rescue rangers of Russian Ministry of Emergencies.

Cytogenetic studies in rescue rangers of the Russian Ministry of Emergencies has shown that this category of specialists are exposed to genotoxic factors during their professional activity. The level of induction of cytogenetic injuries of rescue team members depended on labor conditions, genotype (glutathione-S-transferase M1 and T1 xenobiotic detoxication genes), and tobacco smoking.

[Chromosomal aberrations and parameters of oxidative stress in Chernobyl clean-up workers in a remote period after ionizing radiation]. / Khromosomnye aberratsii i pokazateli okislitel'nogo stressa u likvidatorov posledstvii avarii na Chernobyl'skoi AES v otdalennom periode posle deistviia ioniziruiushchei radiatsii.

This investigation was performed to test a supposition about the influence of disturbances in antioxidative system on cytogenetical parameters in Chernobyl' clean-up workers. It was shown that some cytogenetical parameters straightly correlated with the parameters of oxidative stress, while other cytogenetical parameters show just reverse correlations. Apparently, these relationships are not of cause-and-effect type, but they reflect a complex processes occurring in humans for a long period after radiation exposure.

Enteroviruses identifications and differentiation on the basis of the selective group--specific inhibitory effect of chemical compounds.

Two new enteroviruses (EV) inhibitors with the selective group-specific effect were detected and studied representing the products of the original chemical synthesis. One of them--nifan (arylfuran derivative) inhibits poliomyelitis virus replication, the other one--belvtazide (synchonic acid derivative) blocks non-poliomyelitis EV (ECHO and Coxsackie B) replication. The study of the reference strains of poliomyelitis virus type 1-3, twenty-three ECHO virus types (from the 1st to the 33rd), Coxsackie B virus type 1-6 and 288 primary EV isolates did not reveal type or strain specific variability in the inhibitors effect. Nifan and belvtazide supress the replication of both EV monostrains and their mixtures. The isolates of mixed nature are inhibited by the mixture nifan + belvtazide. At the same time neither separate chemicals nor their blend affects viruses from other families (Adenoviridae, Orthomyxoviridae, Herpesviridae etc.). The mechanism of nifan and belvtazide action is intracellular EV replication inhibition (they do not affect the process of virus adsorption and penetration into the cell), suppression of de novo virus synthesis by 7.0-2.25 lg (tissue culture infective dose 50 per cent) TCID50/ml and of virus-induced RNA synthesis. The drugs feature is high selectivity (90-91%) regarding RNA polioviruses (nifan) and RNA non-poliomyelitis EV (belvtazide). Nifan and belvtazide antiviral effect selectivity allows unknown cytopathic agents (CPA) belonging to the EV to be established with the high degree (over 98%) of reproducibility at the stage of primary identification with the differentiation of poliomyelitis and non-poliomyelitis viruses.

[An analysis of the DNA synthesized in adenovirus-infected cells under exposure to nucleoside analogs]. / Analiz DNK, sinteziruemoi v infitsirovannykh adenovirusom kletkakh pri vozdeistvii analogov nukleozidov.

The method of dot DNA-DNA hybridization was used to reveal the inhibition of the synthesis of the adenoviral DNA by 6-azacytidine, cyclocytidine and ribamidyl in the adenovirus-infected cells Hep-2, a degree of which depended on the preparation concentration.

[Outcome of decompression operations in the treatment of Legg-Perthes disease]. / Iskhody dekompressivnykh operatsii v lechenii bolezni Pertesa.

The authors evaluate the results of 90 decompression operations in 68 patients with Perthes' disease at stages I-IV; the mean age of the children was 8.3 +/- 1.2 years and the follow-up period after the surgery was from 6 months to 10 years. Decompression operations made in the clinic have been protected by author's certificates No. 942712 and No. 1050672. The results were excellent and good in 87.8% and satisfactory in 12.2%. Decompression operations are substantiated from the pathogenetic viewpoint. They interrupt the pathologic process in the epiphysis, contribute to a rapid restoration of the femoral head, are characterized by low traumatism and may be performed simultaneously on both sides which precipitate the children's rehabilitation. The best results have been observed in the children aged 5 to 7 years and at stages I and II of the disease. The surgical treatment has allowed to reduce the terms of the treatment of the children 3 to 4-fold as compared with the conservative method.

[Etiology of diseases of the hip joint in children]. / K etiologii zabolevanii tazobedrennogo sustava u detei.

The rentgenometric examination of the hip joint in 165 children with a high degree of reliability of the coxitis syndrome has revealed a displastic nature of the disease in 49,5% of them. It was mainly due to non-correct orientation of the proximal end of the femur. The overstrain of such joint causes its functional incompetence, pain, restricted functioning and lameness. The investigation performed enabled the author to establish the etiology of the disease, to assess the degree of maldevelopment of the hip joint and to find new ways of pathogenetic therapy.

[Comparative study of the repeated nucleotide sequences in DNA from differentiated tissues and tumors]. / Sravnitel'noe issledovanie povtoriaiushchikhsia nukleotidnykh posledovatel'nosv v DNK differentsirovannykh tkanei i pri malignizatsii

DNA renaturation kinetics was measured for the genomes of normal (spleen) and malignant (plasmacytoma) mouse tissues and for DNA from liver, sperm and developing embryos of the loach. It has been shown that the measuring of DNA renaturation kinetics makes it possible to reveal differences in the content of certain fractions of the repetitions in the genomes of different species. Moreover, differences in the distribution of the repetitions between hetero- and euchromatine can be identified. Loach embryo DNA (blastula stage) was shown to contain larger amount of the fraction renaturing at Cot less than 10(-2) as compared to liver and sperm DNAs (by 5%). An enrichment with respect to the intermediate repetitions (10(-2) less than Cot less than 10(2)) was found in the mouse plasmacytoma DNA as compared to the spleen DNA. The nature of these distinctions is discussed.