LONG-TERM RESULTS OF DIFFERENT UV-CROSSLINKING TECHNIQUES IN PATIENTS WITH PROGRESSIVE KERATOCONUS

Purpose. To compare a clinical effectiveness of different UV-crosslinking techniques in patients with progressive keratoconus.Material and methods. Randomized prospective clinical trial included 130 eyes of 117 keratoconic patients. There were created 2 equal groups of 65 eyes. In the group I patients underwent a classical UV-crosslinking technique with a complete central corneal deepithelialization, in the group II a UV-crosslinking with dosed corneal epithelium scarification was performed using a new device. The postoperative follow-up period was 24 months. Preoperatively in the group I the uncorrected visual acuity (UCVA) was 0.21±0.11, the best corrected visual acuity (BCVA) was 0.49±0.14, the central corneal pachymetry (CCP) – 469.1±23/4μm, the mean keratometry (Kave) – 46.1±1.7D, in the group II: UCVA was 0.22±0.09, BCVA – 0.48±0.12, CCP – 475.2±28.5μm, Кave – 46.7±1.4D.Results. The mean postoperative pain score was 6.9±1.3, relief on the 3-rd ±1.2 day post-op. in the group I, and 2.8±1.1 relief on the 1-st±0.4 day post-op. in the group II. All patients had a 0.1 to 0.12 visual acuity loss 7 days after the surgery that was due to a mild corneal opacification. At 3 months after operation in both groups the UCVA and the BCVA were back to their preoperative values. In the group I the UCVA increased by 0.07±0.03 (р<0.05) 2 years after the treatment, the BCVA increased by 0.11±0.04 (р<0.05). At that time in the group II the similar values were obtained: 0.08±0.02 (р<0.05), 0.1±0.04 (р<0.05) respectively. The Kave index in both groups gradually decreased during first 12 months after operation and then stabilized. At the end of the follow up it was lower by 2.6±0.5D (р<0.05) in the group I and by 2.4±0.3D (р<0.05) in the group II. According to the anterior OCT, the depth of demarcation line was 327±11μm in the group I and 318±13μm in the group II. The demarcation line was absent in all cases 12 months after surgery. In the early postoperative period 3 months after operation the CCP gradually decreased. It reduced by 3.77±0.83% (р<0.05) in the group I and by 3.17±0.88% (р<0.05) in the group II. After that the CCP slowly increased during the entire follow-up, but 24 months later it was still lower by 2.36±0.57% (р<0.05) in the group I and by 1.68%±0.75 (р<0.05) in the group II. Confocal microscopy 1 month after surgery revealed typical changes of corneal structure at the depth up to 310±9μm (290 to 335) in the group I and 300±8μm (280 to 330) in the group II. A full reinnervation and the repopulation of the cornea with keratocytes was seen 6 months after operation. The only complication (delayed corneal epithelization) was in the group with classical UV-crosslinking technique.Conclusions. The trial revealed similar clinical outcomes after classical UV-crosslinking technique and UV-crosslinking with dosed corneal epithelium scarification, however in the latter case during the postoperative period the severity and duration of pain were significantly reduced

Monocyte migration to the synovium in rheumatoid arthritis patients treated with adalimumab

Objectives The mechanism of action of treatment with tumour necrosis factor (TNF) blockers in rheumatoid arthritis (RA) is still not completely understood. The aim of this study was to test if adalimumab treatment could affect the influx of monocytes into the synovium. Methods A novel technique was used to analyse the migration of labelled autologous monocytes before and 14 days after initiation of adalimumab treatment using scintigraphy. CD14 monocytes were isolated from patients with RA, using a positive selection procedure with magnetic-activated cell sorting, and labelled with technetium-99m-hexamethylpropylene-amino-oxime. Scintigraphic scans were made 1, 2 and 3 h after re-infusion. Results As early as 14 days after the start of treatment with adalimumab a significant decrease in disease activity score evaluated in 28 joints was shown. There was no significant decrease in the influx of monocytes into the joint at this time. Conclusions This study indicates that adalimumab treatment does not reduce the influx of monocytes into the synovium early after initiation of treatment. As previous studies showed a rapid decrease in macrophage infiltration after TNF-antibody therapy, which could not be explained by increased cell death, this points to an important role for enhanced efflux of inflammatory cells from the synoviu

Fit‐for‐Purpose Biometric Monitoring Technologies: Leveraging the Laboratory Biomarker Experience

Biometric Monitoring Technologies (BioMeTs) are becoming increasingly common to aid data collection in clinical trials and practice. The state of BioMeTs, and associated digitally measured biomarkers, is highly reminiscent of the field of laboratory biomarkers two decades ago. In this review, we have summarized and leveraged historical perspectives, and lessons learned from laboratory biomarkers as they apply to BioMeTs. Both categories share common features, including goals and roles in biomedical research, definitions, and many elements of the biomarker qualification framework. They can also be classified based on the underlying technology, each with distinct features and performance characteristics, which require bench and human experimentation testing phases. In contrast to laboratory biomarkers, digitally measured biomarkers require prospective data collection for purposes of analytical validation in human subjects, lack well-established and widely accepted performance characteristics, require human factor testing and, for many applications, access to raw (sample-level) data. Novel methods to handle large volumes of data, as well as security and data rights requirements add to the complexity of this emerging field. Our review highlights the need for a common framework with appropriate vocabulary and standardized approaches to evaluate digitally measured biomarkers, including defining performance characteristics and acceptance criteria. Additionally, the need for human factor testing drives early patient engagement during technology development. Finally, the use of BioMeTs requires a relatively high degree of technology literacy among both study participants and healthcare professionals. Transparency of data generation and the need for novel analytical and statistical tools creates opportunities for precompetitive collaborations

Тромботическая окклюзия у пациентов с острым ишемическим инсультом

Currently, reperfusion therapy is the main method of treating patients with ischemic stroke (IS). The safety and efficacy of systemic thrombolytic therapy with a recombinant tissue plasminogen activator in patients with IS within 3 hours, and then 4.5 hours after the onset of symptoms of the disease was demonstrated in the NINDS (1995) and ECASS III (2008) studies. In 2018, based on the results of five studies, clear indications were formulated for performing thrombectomy (TE) in patients with IS, which involve the detection of thrombosis of a large stroke-associated artery. Given the continuous growth in the number of the adult population, which constitutes the bulk of patients with IS, information on the prevalence of patients with thrombotic occlusion of cerebral arteries, who are potential candidates for TE, may be important for regional vascular centers.Aim of study. To describe IS patients admitted within the 6-hour “therapeutic window”.Materials and methods. The study included 145 patients with cerebral IS who were admitted within the first 6 hours after the onset of symptoms of the disease. All patients underwent computed tomographic (CT) angiography in order to verify the occlusion of the cerebral artery.Results. In our study, a correlation was established between the NIHSS severity of IS and the likelihood of verification of stroke-related artery thrombosis by CT angiography, but in 32.6% of patients with severe stroke (NIHSS at least score 14), no thrombotic occlusion was detected, and in 13% of patients with a clinic of mild acute cerebrovascular accident (NIHSS no more than 6), on the contrary, thrombotic occlusion was detected. Mortality in patients with verified thrombotic occlusion of the cerebral artery was higher than in patients without it (38% versus 10.5%, p<0.001). Such a significant difference in the mortality rate was due to the initially more severe stroke (NIHSS at admission 17 [10; 23] versus 5 [2; 10], p><0.001) in patients with thrombotic occlusion of a stroke-related artery, as well as a higher incidence of severe swallowing disorders (30% versus 9.5%, p ><0.002), which are a risk factor for pneumonia, as well as a higher frequency of such a comorbid background as chronic kidney disease and atrial fibrillation (30% versus 13.7%, p=0.018% and 58% versus 29.5%, p=0.001, respectively). CONCLUSION 1. Thrombosis of the cerebral stroke-associated artery was detected in 34.5% of patients with ischemic stroke who were admitted within the first 6 hours from the onset of the disease. 2. The main reason for the failure to perform thrombectomy in patients with ischemic stroke admitted within the 6-hour therapeutic window is the lack of verification of stroke-related artery thrombosis using computed tomographic angiography. Due to thrombosis at a different location (other than thrombosis of the internal carotid artery and / or M1 segment of the middle cerebral artery), 10% of patients with verified thrombosis did not meet the currently existing selection criteria for thrombectomy. Keywords: ischemic stroke, reperfusion therapy, cerebral artery thrombosis, cryptogenic stroke>˂0.001). Such a significant difference in the mortality rate was due to the initially more severe stroke (NIHSS at admission 17 [10; 23] versus 5 [2; 10], p˂0.001) in patients with thrombotic occlusion of a stroke-related artery, as well as a higher incidence of severe swallowing disorders (30% versus 9.5%, p˂0.002), which are a risk factor for pneumonia, as well as a higher frequency of such a comorbid background as chronic kidney disease and atrial fibrillation (30% versus 13.7%, p=0.018% and 58% versus 29.5%, p=0.001, respectively).Conclusion. 1. Thrombosis of the cerebral stroke-associated artery was detected in 34.5% of patients with ischemic stroke who were admitted within the first 6 hours from the onset of the disease. 2. The main reason for the failure to perform thrombectomy in patients with ischemic stroke admitted within the 6-hour therapeutic window is the lack of verification of stroke-related artery thrombosis using computed tomographic angiography. Due to thrombosis at a different location (other than thrombosis of the internal carotid artery and / or M1 segment of the middle cerebral artery), 10% of patients with verified thrombosis did not meet the currently existing selection criteria for thrombectomy. В настоящее время реперфузионная терапия является основным методом лечения пациентов с ишемическим инсультом (ИИ). Безопасность и эффективность системной тромболитической терапии при помощи рекомбинантного тканевого активатора плазминогена у пациентов с ИИ в пределах 3 часов, а в последующем 4,5 часа от начала симптомов заболевания была продемонстрирована в исследованиях NINDS (1995) и ECASS III (2008). В 2018 году, основываясь на результатах пяти исследований, были сформулированы четкие показания для выполнения тромбэктомии (ТЭ) у пациентов с ИИ, которые подразумевают выявление тромбоза крупной инсульт-связанной артерии. В условиях непрерывного роста числа взрослого населения, составляющего основную массу пациентов с ИИ, информация о распространенности больных с тромботической окклюзией церебральных артерий, являющихся потенциальными претендентами для выполнения ТЭ, может быть важной для региональных сосудистых центров.Цель исследования. Охарактеризовать пациентов с ИИ, поступающих в 6-часовом «терапевтическом окне».Материал и методы. В исследование включены 145 пациентов с церебральным ИИ, поступивших в первые 6 часов от начала развития симптомов заболевания. Всем пациентам с целью верификации окклюзии церебральной артерии выполняли компьютерную томографическую (КТ) ангиографию.Результаты. В нашем исследовании была установлена корреляция между тяжестью ИИ по шкале NIHSS и вероятностью верификации при помощи КТ-ангиографии тромбоза инсульт-связанной артерии, но у 32,6% пациентов с клиникой тяжелого инсульта (NIHSS не менее 14 баллов) не было выявлено тромботической окклюзии, а у 13% пациентов с клиникой легко протекающего острого нарушения мозгового кровообращения (NIHSS не более 6 баллов), напротив, тромботическая окклюзия была выявлена. Летальность у пациентов с верифицированной тромботической окклюзией церебральной артерии была статистически значимо выше, чем у пациентов без таковой (38% против 10,5%, р<0,001). Столь значительная разница между показателями летальности была обусловлена исходно более тяжелым инсультом (оценка по NIHSS при поступлении 17 [10; 23] против 5 [2; 10], p><0,001, статистически значимо) у больных с тромботической окклюзией инсульт-связанной артерии, а также большей частотой статистически значимых грубых расстройств глотания (30% против 9,5%, p><0,002, статистически значимо), являющихся фактором риска развития пневмонии и такого коморбидного фона, как хроническая болезнь почек и фибрилляция предсердий (30% против 13,7%, р=0,018 и 58% против 29,5%, р=0,001 соответственно). Выводы 1. Тромбоз церебральной инсульт-связанной артерии выявлен у 34,5% пациентов с ишемическим инсультом, поступающих в первые 6 часов от начала заболевания. 2. Основной причиной невыполнения тромбэктомии у пациентов с ишемическим инсультом, поступивших в 6-часовом «терапевтическом окне», является отсутствие верификации тромбоза инсульт-связанной артерии при помощи компьютерной томографической ангиографии. По причине тромбоза другой локализации (отличной от тромбоза внутренней сонной артерии и/или М1 сегмента средней мозговой артерии) 10% пациентов с верифицированным тромбозом не соответствовали существующим в настоящее время критериям отбора для выполнения тромбэктомии. Ключевые слова: ишемический инсульт, реперфузионная терапия, тромбоз мозговой артерии, криптогенный инсульт>˂ 0,001). Столь значительная разница между показателями летальности была обусловлена исходно более тяжелым инсультом (оценка по NIHSS при поступлении 17 [10; 23] против 5 [2; 10], p˂ 0,001, статистически значимо) у больных с тромботической окклюзией инсульт-связанной артерии, а также большей частотой статистически значимых грубых расстройств глотания (30% против 9,5%, p˂ 0,002, статистически значимо), являющихся фактором риска развития пневмонии и такого коморбидного фона, как хроническая болезнь почек и фибрилляция предсердий (30% против 13,7%, р=0,018 и 58% против 29,5%, р=0,001 соответственно).Выводы. 1. Тромбоз церебральной инсульт-связанной артерии выявлен у 34,5% пациентов с ишемическим инсультом, поступающих в первые 6 часов от начала заболевания. 2. Основной причиной невыполнения тромбэктомии у пациентов с ишемическим инсультом, поступивших в 6-часовом «терапевтическом окне», является отсутствие верификации тромбоза инсульт-связанной артерии при помощи компьютерной томографической ангиографии. По причине тромбоза другой локализации (отличной от тромбоза внутренней сонной артерии и/или М1 сегмента средней мозговой артерии) 10% пациентов с верифицированным тромбозом не соответствовали существующим в настоящее время критериям отбора для выполнения тромбэктомии.

Overweight in young people contributes to the expression of STAT1 and STAT6 genes in the peripheral blood monocytes, stimulated by IL-4

Overweight and obesity lead to the formation of a pro-inflammatory phenotype of the adipose tissue macrophages, but it is not known how exactly the balance of STAT1 and STAT6 transcription factors is implemented in the peripheral blood monocytes and how this affects the further polarization process in overweight. The article examines the level and ratio of expression of the STAT1 and STAT6 transcription factors in the polarization of the peripheral blood monocytes depending on the body weight. The study enrolled 20 women and men aged from 18 to 25 years. In terms of BMI, the subjects were divided into the following groups: individuals with normal body weight (BMI 18.50-24.99 kg/m2), represented by 5 women and 5 men; overweight individuals (BMI 25.00-29.99 kg/m2), including 5 men and 5 women. Using standard methods peripheral blood monocytes stimulated by LPS and yIFN, IL-4 was isolated and incubated for 3 and 7 days. PCR method was used to determine the expression level of the stat1 and stat6 genes in incubated cells. The concentration of IL-6 and TGF/31 was measured in the supernatant on the 7th day of incubation, and TGF/31 and hs-CRP in the serum of the subjects. The obtained results revealed a significant increase in the level of IL-6 in the supernatant of macrophages stimulated by LPS and yIFN in overweight individuals. The level of hs-CRP in the serum was also significantly higher in overweight individuals. It has been shown that under the conditions of overweight development, there is a significant increase in the level of expression of stat1 and stat6 genes in cells stimulated by IL-4. The obtained data indicate the presence of a preconditioning state of the peripheral blood monocytes with activation of signaling networks mainly in macrophages stimulated by the M2 phenotype under conditions of increased nutrients intake.Підвищення маси тіла та ожиріння призводить до формування прозапального фенотипу макрофагів жирової тканини, але достеменно не відомо, яким чином реалізується баланс транскрипційних факторів STAT1 та STAT6 в моноцитах периферичної крові і як це впливає на подальший процес поляризації за умов підвищення маси. Досліджено рівень та співвідношення експресії транскрипційних факторів STAT1 та STAT6 при поляризації моноцитів периферичної крові в залежності від маси тіла. Дослідження проведено за участі 20 осіб жіночої та чоловічої статі віком від 18 до 25 років. За ІМТ проведено розподіл по групам: особи з нормальною масою тіла ІМТ 18,50-24,99 кг/м2 із 5 жінок та 5 чоловіків, особи з підвищеною масою ІМТ25,00-29,99 кг/м2 із 5 чоловіків та 5 жінок. За стандартними методиками були виділені моноцити периферичної крові, стимульовані LPS, yFN, та IL-4 і проведена інкубація на 3 і 7 добу. В інкубованих клітинах визначали рівень експресії генів statl та stat6 методом ПЛР. У су-пернатанті клітин на 7 добу інкубації визначали рівень IL-6 і TGFf31, у сироватці крові рівень TGF/31 і вчСРБ методом ІФА. Одержані результати виявили достовірне підвищення рівня IL-6 в супернатанті макрофагів, стимульованих LPS та yIFN у осіб з підвищеною масою тіла. Рівень вчСРБ у сироватці крові був також достовірно вищий у осіб з підвищеною масою тіла. Показано, що за умов формування підвищеної маси тіла відбувається достовірне підвищення рівня експресії генів statl і stat6 у клітинах, стимульованих IL-4. Отримані дані свідчать про наявність стану прекондиціювання моноцитів периферичної крові з активацією сигнальних мереж переважно у макрофагах, стимульованих за М2 фенотипом за умов підвищеного надходження нутрієнтів

Orbital complications of rhinogenic etiology in children: some aspects

The aim of the study was to study the features of the nature of the course, diagnosis and tactics of managing children with RSOC according to the children’s ENT department of the OKB No. 2, Tyumen.Цель работы – выявить особенности течения, микробиологического пейзажа и объема оказания медицинской помощи детям с РСОО

High viral load of Merkel cell polyomavirus DNA sequences in Langerhans cell sarcoma tissues.

International audienceBACKGROUND: Langerhans cell (LC) sarcoma (LCS) is a high-grade neoplasm with overtly malignant cytologic features and an LC phenotype. We very recently suggested that LC behaves as a reservoir for common dermotropic Merkel cell polyomavirus (MCPyV) and determined the relationship between LC histiocytosis (LCH), which has an underlining oncogenic capacity, and MCPyV as a trigger for a reactive process rather than a neoplastic process. We propose LC to be a reservoir for MCPyV and hypothesize that some LCS subtypes may be related to the MCPyV agent. FINDINGS: We examined seven LCS tissues using multiplex quantitative PCR (Q-PCR) and immunohistochemistry with anti MCPyV large-T (LT) antigen antibody. High viral loads of MCPyV DNA sequences (viral load = relative levels of MCPyV) were detected (0.328-0.772 copies/cell (Merkel cell carcinoma (MCC) = 1.0)) using Q-PCR in 43% (3/7) tissues, but LT antigen expression was not observed (0/7). CONCLUSIONS: Frequent MCPyV-DNA amplification suggests that LCS in some patients may be related to MCPyV infection. Moreover, the higher viral load of LCS (median, 0.453 copies/cell) than low load of LCH (0.003, median of 12 cases) (P < 0.01) may suggest a virally induced tumorigenic process in some LCS. Although the absence of LT antigen expression may indicate a different role for MCPyV in this pathology, some subtypes of LCS may develop in the background of MCPyV-infected LC. To the best of our knowledge, this is the first report on the relationship between MCPyV and LCS. The recent discovery of MCPyV opened new therapeutic avenues for MCC. These data open novel possibilities for therapeutic interventions against LCS

Monocyte Scintigraphy in Rheumatoid Arthritis: The Dynamics of Monocyte Migration in Immune-Mediated Inflammatory Disease

Background: Macrophages are principal drivers of synovial inflammation in rheumatoid arthritis (RA), a prototype immune-mediated inflammatory disease. Conceivably, synovial macrophages are continuously replaced by circulating monocytes in RA. Animal studies from the 1960s suggested that macrophage replacement by monocytes is a slow process in chronic inflammatory lesions. Translation of these data into the human condition has been hampered by the lack of available techniques to analyze monocyte migration in man. Methods/Principal Findings: We developed a technique that enabled us to analyze the migration of labelled autologous monocytes in RA patients using single photon emission computer tomography (SPECT). We isolated CD14+ monocytes by CliniMACS in 8 patients and labeled these with technetium-99m (99m-Tc-HMPAO). Monocytes were re-infused into the same patient. Using SPECT we calculated that a very small but specific fraction of 3.4x10(-3) (0.95-5.1x10(-3)) % of re-infused monocytes migrated to the inflamed joints, being detectable within one hour after re-infusion. Conclusions/Significance: The results indicate monocytes migrate continuously into the inflamed synovial tissue of RA patients, but at a slow macrophage-replacement rate. This suggests that the rapid decrease in synovial macrophages that occurs after antirheumatic treatment might rather be explained by an alteration in macrophage retention than in monocyte influx and that RA might be particularly sensitive to treatments targeting inflammatory cell retention