Integrated approach to radiodiagnosis of follicular thyroid neoplasia: a retrospective cohort trial

Background. An evidence-based diagnostic tactics for follicular thyroid gland neoplasia is lacking to date. First-line priority are radiography diagnostic techniques, which vary in capacities and therefore must be regulated in use.Objectives. An efficacy evaluation of multiparametric ultrasound (US), sonoelastography (SEG) and radionuclide scintigraphy (RS) in diagnosis of follicular thyroid neoplasms (FTN).Methods. Preoperative examination was interpreted in 222 FTN patients (86 with follicular thyroid adenoma, FTA, and 136 with follicular thyroid cancer, FTC) with subsequent surgery. A retrospective statistical data analysis was performed for B-mode US, colour Doppler imaging (CDI), power Doppler imaging (PDI), sonoelastography and Tc-99m pertechnetate scintigraphy.Results. Novel FTN descriptive evidence has been obtained. Particularly, an FTA vs. FTC trait comparison showed no reliable US marker of a node assignment to FTA or FTC. Trials of the national-manufactured TI-RADS system showed its good diagnostic potential: FTN sensitivity 89.55, specificity 77.58 and accuracy 83.52%. A SEG picture of FTN was typically motley-colour and mosaic. Young’s modulus in FTA was 27.5 ± 7.1 kPa, a higher stiffness (62.1 ± 12.1 kPa) in FTC indicated a higher likelihood of malignancy. Scintigraphy exhibited a modest capacity for FTN diagnosis (sensitivity 86.67, specificity 48.08 and accuracy 56.72%). AUC values (0.617) indicate its limited use for differential FTN diagnosis, mainly in hyperfunctioning nodules. Our experience elaborated an original algorithm for radiographic techniques application in FTN diagnosis.Conclusion. Several radiographic methods are warranted in suspected FTN. First-line is multiparametric US B-mode imaging to detect FTN priority markers and US symptom complexes. Sonoelastography is second-line in ambiguous cases to further clarify structure (stiffness) of the thyroid nodule examined. Unlike SEG, scintigraphy assesses the functional traits of thyroid nodule and so has limited indications, an important factor to consider in FTN

Comparative evaluation of empagliflozin, canagliflozin and sitagliptin cardioprotective properties in rats with experimental type 2 diabetes mellitus

Background: Myocardial infarction (MI) is one of the leading causes of mortality in patients with type 2 diabetes mellitus (DM), therefore it is essential to give preference to a glucose-lowering drug having optimal cardioprotective properties. A comparative study of the various sodium-glucose co-transporter inhibitors representatives’ protective effects in experimental MI was not carried out within the framework of one study.Aim: To evaluate the influence of empagliflozin (EMPA) and canagliflozin (CANA), in comparison with sitagliptin (SITA), on hemodynamic parameters and myocardial damage area in rats with diabetes type 2 model in experimental MI.Materials and methods: Type 2 DM was modelled in Wistar rats by means of 4-week high-fat diet followed by nicotinamide 230 mg/kg and streptozotocin 60 mg/kg administration. 4 weeks after DM induction the following groups were made: «DM+SITA» — treatment with SITA 50 mg/kg, «DM+EMPA» — treatment with EMPA 2 mg/kg, «DM+CANA» — treatment with CANA 25 mg/kg per os once daily for 8 weeks. Animals in «DM» group remained untreated for the following 8 weeks. Rats in control group were fed with standard chow. 16 weeks after the experiment beginning transient global myocardial ischemia was modelled in all rats. Hemodynamic parameters and myocardium necrosis area were evaluated.Results: The necrosis area was larger in «DM» group, than in control one (p=0.018). Infarction size in «DM+SITA» did not differ from that in «DM» group (62.92(41.29;75.84) and 57.26(45.51;70.08)%, р=0.554). Necrosis area in «DM+EMPA» and «DM+CANA» groups was smaller than in «DM» group (37.90(20.76;54.66)%, 46.15(29.77;50.55) vs 57.26(45.51;70.08)%, р=0.008 and р=0.009, respectively). Necrosis size did not differ between «DM+EMPA» and «DM+CANA» groups (p=0.630). Ischemic contracture in «DM+CANA» group was less prominent than under the use of all other glucose-lowering drugs. We observed increase of coronary blood flow in «DM+EMPA» group, in comparison with «DM», «DM+CANA» and «DM+SITA» groups.Conclusions: SITA does not have cardioprotective effect in ischemia-reperfusion injury in diabetic rats. EMPA and CANA have similarly prominent infarct-limiting properties. EMPA is able to increase coronary blood flow, whereas cardioprotective action of CANA is associated with ischemic contracture diminishing

Протектор микрографтов кожи в ожоговой ране: аллодерма или гидрогелевое покрытие?

AIM OF STUDY Was to compare the dynamics of engraftment of skin micrographs in a burn wound when using protectors from an allodermal graft and from a hydrogel coating.MATERIAL AND METHODS The experimental study was conducted on 18 rats with a scab formed 3 days after modeling a deep burn with an area of 20% of the body surface. Partial fascial necrectomy was performed: two rounded sections of the sling with a diameter of 25 mm were excised. 6 automicrographs of skin 4x4 mm, 0.3 mm thick, were applied to each surface freed from the scab. In each animal, micrographs on one of the wounds were covered with a hydrogel protector, on the other with an allodermotransplant from another animal of the group. A secondary aseptic dressing was applied to the protectors. On the 5th and 20th days after the operation, the state of micrographs was studied: blood circulation — according to laser Doppler flowmetry, microstructure in vivo — using optical coherence tomography, microstructure ex vivo — according to histological examination of biopsies.ReSUlTS Differences in the rate of restoration of blood circulation of micrographs in the early stages of the postoperative period were found. In the first 5 days, the perfusion of micrographs under an allodermal protector exceeded the indicator in micrographs under a hydrogel coating by 44 [21; 51] % (p=0.031) due to the contribution of endothelial and neurogenic mechanisms of blood flow modulation. Starting from day 10, the differences in perfusion were levelled, but there were signs of more active endothelial regulation of blood flow under the skin (p=0.028). Histologically, the appearance of full-blooded capillaries was revealed earlier in micrographs under the alloderm than when using a hydrogel protector. By 20 days, under the condition of regular change of hydrogel coatings, the area of wound healing under the studied coatings did not significantly differ. However, the structure of the integumentary tissue under the alloderm according to the optical coherence tomography data was closer to normal skin than when using a hydrogel protector.CONClUSIONS From the point of view of the physiology of the wound process, alloderm is the preferred option of an autograft protector in comparison with a hydrogel coating, which is probably due to the paracrine biological activity of the alloderm. However, hydrogel coatings can provide a comparable level of efficiency, provided they are regularly changed and, potentially, given the properties of cytokine activity.ЦЕЛЬ ИССЛЕДОВАНИЯ Сравнить динамику приживления микрографтов кожи в ожоговой ране при использовании протекторов из аллодермального трансплантата и из гидрогелевого покрытия.МАТЕРИАЛ И МЕТОДЫ Экспериментальное исследование проведено на 18 крысах, имеющих струп, сформировавшийся через 3 суток после моделирования глубокого ожога площадью 20% поверхности тела. Выполнялась частичная фасциальная некрэктомия: иссечение двух округлых участков струпа диаметром по 25 мм. На каждую поверхность, освобожденную от струпа, наносились 6 ауто­микрографтов кожи 4х4 мм толщиной 0,3 мм. У каждого животного микрографты на одной из ран закрывались гидрогелевым протектором, на другой — аллодермотрансплантатом от другого животного группы. На протекторы накладывалась вторичная асептическая повязка. На 5-е и на 20-е сутки после операции исследовалось состояние микрографтов: кровообращение — по данным лазерной допплеровской флоуметрии, микроструктура in vivo — с помощью оптической когерентной томографии, микроструктура ex vivo — по данным гистологического исследования биоптатов.РЕЗУЛЬТАТЫ Обнаружены различия в скорости восстановления кровообращения аутомикрографтов на ранних этапах послеоперационного периода. В первые 5 суток перфузия микрографтов под аллодермальным протектором превысила показатель в микрографтах под гидрогелевым покрытием на 44 [21; 51] % (р=0,031) за счет вклада эндотелиального и нейрогенного механизмов модуляции кровотока. Начиная с 10-х суток различия в перфузии нивелировались, однако сохранялись признаки более активной эндотелиальной модуляции кровотока под аллокожей (p=0,028). Гисто­логически в микрографтах под аллокожей выявлено более раннее появление полнокровных капилляров, чем при использовании гидрогелевого протектора. К 20-м суткам, при условии регулярной смены гидрогелевых покрытий, площадь заживления ран под исследуемыми покрытиями значимо не различалась. Однако структура покровной ткани под аллодермой, по данным оптической когерентной томографии, была ближе к нормальной коже, чем при использовании гидрогелевого протектора.ЗАКЛЮЧЕНИЕ С точки зрения физиологии раневого процесса аллокожа является предпочтительным вариантом протектора аутотрансплантата в сравнении с гидрогелевым покрытием, что, вероятно, обусловлено паракринной биологической активностью аллодермы.Однако гидрогелевые покрытия могут обеспечить сопоставимый уровень эффективности при условии их регулярной смены и, потенциально, придания им свойств цитокиновой активности

Recurrent, low-frequency coding variants contributing to colorectal cancer in the Swedish population

<div><p>Genome-wide association studies (GWAS) have identified dozens of common genetic variants associated with risk of colorectal cancer (CRC). However, the majority of CRC heritability remains unclear. In order to discover low-frequency, high-risk CRC susceptibility variants in Swedish population, we genotyped 1 515 CRC patients enriched for familial cases, and 12 108 controls. Case/control association analysis suggested eight novel variants associated with CRC risk (OR 2.0–17.6, p-value < 2.0E-07), comprised of seven coding variants in genes <i>RAB11FIP5</i>, <i>POTEA</i>, <i>COL27A1</i>, <i>MUC5B</i>, <i>PSMA8</i>, <i>MYH7B</i>, and <i>PABPC1L</i> as well as one variant downstream of <i>NEU1</i> gene. We also confirmed 27 out of 30 risk variants previously reported from GWAS in CRC with a mixed European population background. This study identified rare, coding sequence variants associated with CRC risk through analysis in a relatively homogeneous population. The segregation data suggest a complex mode of inheritance in seemingly dominant pedigrees.</p></div

Epidemiological and clinical features of lymphoproliferative diseases in the head and neck region

Background. Lymphomas are a heterogeneous group of the lymphoid and hematopoietic system tumors. Neoplastic process often develops in head and neck area, including the integumentary tissues, orbit, nasal cavity, paranasal sinuses, oral cavity, pharynx, salivary glands, thyroid gland, as well as neck lymph nodes. The difficulties of head and neck lymphomas diagnosis are significant, since very often there is a combined non-tumor pathology. The high heterogeneity of lymphomas in the head and neck area requires structuring knowledge about their epidemiology and clinical manifestations.Objective: to study the epidemiological and clinical features of the head and neck lymphoproliferative diseases, which will lead to an improvement in diagnostic quality of this nosology's.Materials and methods. The frequency of head and neck lymphoproliferative diseases detection was estimated based on the study of epicrisis and clinical data of 174 patients hospitalized at the N.N. Blokhin National Medical Research Center of Oncology in the period from 2000 to 2020.Results. Taking into account the modern clinical and morphological classification of lymphomas of the World Health Organization (2017), information about the features of localization, characteristic signs of extranodal foci and lymph nodes is presented. Detection frequency of various subtypes non-Hodgkin's and Hodgkin's lymphomas were determined on a sufficient cohort of patients.Conclusion. Based on the analysis of clinical and morphological features of head and neck lymphomas, epidemiological and clinical features are described in detail, and differences in the symptoms and clinical manifestations of non-Hodgkin's and Hodgkin's lymphomas with a predominant head and neck involvement are revealed

The 12p13.33/RAD52 locus and genetic susceptibility to squamous cell cancers of upper aerodigestive tract

Acknowledgments: The authors thank all of the participants who took part in this research and the funders and support and technical staff who made this study possible. We also acknowledge and thank The Cancer Genome Atlas initiative whose data contributed heavily to this study. Funding: Funding for study coordination, genotyping of replication studies and statistical analysis was provided by the US National Institutes of Health (R01 CA092039 05/05S1) and the National Institute of Dental and Craniofacial Research (1R03DE020116). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Stat1 Phosphorylation Determines Ras Oncogenicity by Regulating p27Kip1

Inactivation of p27Kip1 is implicated in tumorigenesis and has both prognostic and treatment-predictive values for many types of human cancer. The transcription factor Stat1 is essential for innate immunity and tumor immunosurveillance through its ability to act downstream of interferons. Herein, we demonstrate that Stat1 functions as a suppressor of Ras transformation independently of an interferon response. Inhibition of Ras transformation and tumorigenesis requires the phosphorylation of Stat1 at tyrosine 701 but is independent of Stat1 phosphorylation at serine 727. Stat1 induces p27Kip1 expression in Ras transformed cells at the transcriptional level through mechanisms that depend on Stat1 phosphorylation at tyrosine 701 and activation of Stat3. The tumor suppressor properties of Stat1 in Ras transformation are reversed by the inactivation of p27Kip1. Our work reveals a novel functional link between Stat1 and p27Kip1, which act in coordination to suppress the oncogenic properties of activated Ras. It also supports the notion that evaluation of Stat1 phosphorylation in human tumors may prove a reliable prognostic factor for patient outcome and a predictor of treatment response to anticancer therapies aimed at activating Stat1 and its downstream effectors

Effect of Gas Atmosphere on Catalytic Behaviour of Zirconia, Ceria and Ceria Zirconia Catalysts in Valeric Acid Ketonization

[EN] Ketonization of valeric acid, which can be obtained by lignocellulosic biomass conversion, was carried out in a fixed bed flow reactor over ZrO2, 5-20 % CeO2/ZrO2 and CeO2 both under hydrogen and nitrogen stream at 628 K and atmospheric pressure. Regardless gas-carrier 10 wt% CeO2/ZrO2 was found to show higher catalytic activity compared to zirconia per se as well as other ceria modified zirconia while ceria per se exhibited very low catalytic activity. All catalysts provided higher acid conversion in H-2 than in N-2 whereas selectivity to 5-nonanone was insensitive to gas atmosphere. XRD, FTIR, UV-Vis DRS, XPS, HRTEM methods were applied to characterize catalysts in reduced and unreduced states simulating corresponding reaction conditions during acid ketonization. XRD did not reveal any changes in zirconia and ceria/zirconia lattice parameters as well as crystalline phase depending on gas atmosphere while insertion of ceria in zirconia caused notable increase in lattice parameter indicating some distortion of crystalline structure. According to XPS, FTIR and UV-Vis methods, the carrier gas was found to affect catalyst surface composition leading to alteration in Lewis acid sites ratio. Appearance of Zr3+ cations was observed on the ZrO2 surface after hydrogen pretreatment whereas only Zr4+ cations were determined using nitrogen as a gas-carrier. These changes of catalyst's surface cation composition affected corresponding activity in ketonization probably being crucial for reaction mechanism involving metal cations catalytic centers for acid adsorption and COO- stabilization at the initial step.Financial support from the Russian Foundation of Basic Research (RFBR Grant No 11-03-94001-CSIC) is gratefully acknowledged. This work was supported by the Federal Program "Scientific and Educational Cadres of Russia'' (Grant No 2012-1.5-12-000-1013-002). The authors also wish to thank Dr. Evgeniy Gerasimov, Dr. Igor Prosvirin, Dr. Demid Demidov from the Department of Physicochemical Methods at the Boreskov Institute of Catalysis for TEM and XPS measurements.Zaytseva, YA.; Panchenko, VN.; Simonov, MN.; Shutilov, AA.; Zenkovets, GA.; Renz, M.; Simakova, IL.... (2013). Effect of Gas Atmosphere on Catalytic Behaviour of Zirconia, Ceria and Ceria Zirconia Catalysts in Valeric Acid Ketonization. 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Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.

Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer

Проспективное исследование выявляемости рака предстательной железы при выполнении мультипараметрической магнитно-резонансной/ ультразвуковой fusion, стандартной и сатурационной биопсии

Background. Currently, about 80 % of men with low-grade prostate cancer (per ISUP 1 (International Society of Urological Pathology)) have indications for radical treatment. Overdiagnosis of low-grade cancer is associated with the use of systematic biopsy methods (standard transrectal, saturation) under ultrasound control for diagnosis verification. To improve prostate cancer diagnosis, the European Association of Urology (2019) recommended multiparametric magnetic resonance imaging before biopsy, and in case of detection of a suspicious lesion magnetic resonance imaging (MRI)-targeted biopsy. In clinical practice, the most common method of MRI-targeted biopsy is multiparametric MRI ultrasound-guided (mpMRI/US) fusion biopsy. However, some studies show contradictory results in detection of prostate cancer using systematic and MRI-targeted biopsy techniques.Aim. To compare detection of clinically significant prostate cancer (ISUP ≥2) using mpMRI/US fusion, standard, and saturation biopsy.Materials and methods. The study included 96 patients. The following inclusion criteria were applied: prostate-specific antigen &gt;2 ng/mL and/or detection of a suspicious lesion during digital rectal and/or transrectal ultrasound examination, and PI-RADS (Prostate Imaging Reporting and Data System) v.2.1 score ≥3. At the first stage, “unblinded” urologist performed a transperineal mpMRI/US fusion and saturation biopsies. At the second stage, “blinded” urologist performed standard transrectal biopsy. Clinically significant cancer was defined as ISUP ≥2.Results. Median age was 63 years, prostate volume – 47 cm3, prostate-specific antigen – 6.82 ng/mL. MpMRI/US fusion, standard, and saturation biopsies were comparable in regard to the rate of detection of clinically significant (29, 24, 28 %; p = 0.81) and clinically insignificant (25, 26, 35 %; p = 0.43) cancer. Overall prostate cancer detection rates were also similar: 54, 50, 63 %, respectively (p = 0.59). The percentages of positive cores in mpMRI/US fusion, standard, and saturation biopsies were 33, 10 and 13 %, respectively (p &lt;0.01). The maximal core length in mpMRI/US was 6.4 mm, in standard biopsy – 6.35 mm, in saturation biopsy – 5.1 mm (p = 0.7).Conclusion. Detection rates of clinically significant, clinically insignificant prostate cancer and overall detection rate are comparable between systematic biopsy techniques and mpMRI/US fusion biopsy.Введение. В настоящее время до 80 % мужчин с раком предстательной железы (РПЖ) низкой степени злокачественности (ISUP 1 (по классификации Международного общества урологических патологов)) подлежат радикальному лечению. Гипердиагностика РПЖ низкой степени злокачественности обусловлена использованием для верифиации диагноза так называемых систематических методов биопсии предстательной железы, выполняемых под ультразвуковым (УЗ) контролем (стандартная трансректальная, сатурационная). В целях улучшения диагностики РПЖ Европейской ассоциацией урологов рекомендовано (2019) перед биопсией всем пациентам проводить мультипараметрическую магнитно-резонансную томографию, в случае обнаружения подозрительного очага выполнять магнитно-резонансную (МР) прицельную биопсию. Наибольшее распространение получила мультипараметрическая МР/УЗ (мпМР/УЗ) fusion-биопсия. Однако в ряде исследований представлены противоречивые результаты выявляемости РПЖ при сравнении систематических и МР-прицельных методов биопсии.Цель исследования – сравнение выявляемости клинически значимого РПЖ (ISUP ≥2) при проведении мпМР/УЗ fusion, стандартной и сатурационной биопсии.Материалы и методы. В исследование были включены 96 пациентов. Критерии включения: уровень простатического специфического антигена &gt;2 нг/мл, и/или обнаружение подозрительного очага при проведении пальцевого ректального и/или трансректального ультразвукового исследования, и ≥3 баллов по критериям PI-RADS (Prostate Imaging Reporting and Data System) v.2.1. Первым этапом «расслепленный» уролог выполнял трансперинеальную мпМР/УЗ fusion и сатурационную биопсию, вторым этапом «ослепленный» уролог проводил стандартную трансректальную биопсию. Клинически значимый РПЖ определяли как ISUP ≥2.Результаты. Медиана возраста пациентов составила 63 года, объема предстательной железы – 47 см3, уровня простатического специфического антигена – 6,82 нг/мл. При сравнении результатов мпМР/УЗ fusion, стандартной и сатурационной биопсии не обнаружены статистически достоверные различия в отношении выявляемости клинически значимого (29, 24 и 28 % соответственно; p = 0,81) и клинически незначимого (25, 26 и 35 % соответственно; p = 0,43) рака. Общая выявляемость РПЖ также сопоставима – 54, 50 и 63 % соответственно (p = 0,59). Доля положительных биоптатов составила 33, 10 и 13 % соответственно (p &lt;0,01). Максимальная длина биоптата, пораженного раком, при мпМР/УЗ fusion-биопсии – 6,4 мм, при стандартной – 6,35 мм, при сатурационной – 5,1 мм (p = 0,7).Заключение. Выявляемость клинически значимого, клинически незначимого и общая выявляемость РПЖ сопоставимы при проведении как систематических методов биопсии, так и мпМР/УЗ fusion-биопсии.ps