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The review presents the methodological recommendations of the Federation of Anesthesiologists and Resuscitators for the management of patients receiving long-term antithrombotic therapy, revised in 2021. The classification of complications and the degree of hemorrhagic risk, stratification of perioperative thromboembolic risk are presented. Taking into account modern concepts, the principles of interruption and resumption of antithrombotic, anticoagulant and antiplatelet therapy are described. Approaches to the emergency interruption of antithrombotic therapy during urgent surgical interventions, including emergency reversion of the effects of drugs received by the patient, are presented. The features of the appointment and changes in the tactics of antithrombotic therapy depending on the thromboembolic and hemorrhagic risk in such concomitant diseases and conditions as the presence of artificial heart valves, atrial fibrillation, ischemic stroke, myocardial infarction, coronary stenting are described. A separate section is devoted to thrombohemorrhagic safety when performing regional anesthesia against the background of antithrombotic therapy. Indications, contraindications and limitations for regional anesthesia in the context of antithrombotic therapy are given. Criteria for the quality of the provided medical care are given.

Endothelial dysfunction is a valued part in the pathogenesis of many diseases and conditions including the active phase of COVID-19 and postcovid syndrome. The review presents both the viral and autoimmune pathways for endothelial and glycocalyx lesions and the clinical impacts of such a lesion in comorbid patients. Both endothelium and glycocalyx affected by the SARS-CoV-2 virus are considered as the main goal for therapy in outpatient patients and patients with postcovid syndrome. The glycosaminoglycans belonged natural components of vascular wall seem appropriate pathogenetically in order to recovery the endothelial barrier. The review demonstrates the advantages and limitations of using sulodexide in patients with COVID-19. This article presents a clinical case of a patient with confirmed COVID-19 of moderate severity, with the presence of risk factors for thrombosis, who developed a post-covid syndrome, a heterogeneous symptom complex that developed after the acute phase of COVID-19 infection. The post-covid period was marked by symptoms of rapid fatigue, tachycardia, shortness of breath. By day 25-26, itching and red rash appeared, and there was moderate swelling of the shins and feet of both lower extremities. Taking into account the clinical picture and laboratory findings, a decision was made to cancel the previously prescribed low-molecular-weight heparin and prescribe sulodexide at a dose of 500 LU 2 times a day for a course of 28 days. On the 4th-5th day after the start of treatment there was a decrease in the area of skin rash, cessation of itching, almost complete disappearance of the cutaneous vascular pattern and reduction in the severity of edema. This clinical case demonstrates endothelial damage caused by COVID-19, which makes it advisable to use angioprotective drugs. © 2021, Remedium Group Ltd. All rights reserved.

The acceptability and effectiveness of low-molecular-weight heparin (LMWH) use in paediatrics has been confirmed by established Russian and foreign clinical practice. However, at present, the only LMWHs that are legally allowable for children are those with the international nonproprietary name of «dalteparin sodium», since this is directly stated in it’s Package Insert Leaflet (PIL). Prescribing the rest of the LMWHs for children will, in fact, be an off-label prescription. In addition, there are currently no standards of medical care, procedures for its delivery and regulations on the organization of medical care that would allow for the possibility of assigning LMWHs to children. This situation makes it difficult to introduce into the Russian pediatric practice the choice of administration of LMWHs in children where necessary. The use of LMWH in pediatrics may become available even without making changes to PIL, but subject to the establishment of such a recommendation in the new clinical guidelines. The latter is the only legal mechanism in force allowing legal and legally secure off-label appointment.

Summary Background Severe muscle mass (MM) loss is a defining feature of cancer observed across all types and stages of disease and is an independent predictor of poor clinical outcomes including higher incidences of chemotherapy toxicity and decreased survival. Protein is essential to build MM, yet the optimal amount for preventing or treating muscle loss in patients with cancer remains undefined. Methods The Protein Recommendation to Increase Muscle (PRIMe) study is a single-center, two-armed, parallel, randomized, controlled pilot trial that assesses the feasibility of utilizing a high protein (HP) diet to positively impact clinical outcomes in people undergoing chemotherapy to treat colorectal cancer. Forty patients with newly diagnosed stage II-IV colorectal cancer who are scheduled to receive chemotherapy will be included. Participants are randomly assigned to a HP or normal protein (NP) diet for twelve weeks. The HP and NP groups receive nutrition recommendations to achieve 2.0 g of protein per kilogram of body weight per day (g∙kg−1∙d−1) and 1.0 g⋅kg−1⋅d−1, respectively. These values refer to the upper and lower recommended range of protein intake for people with cancer. Energy recommendations are based on measured energy expenditure. Assessments are completed within two weeks of starting chemotherapy (baseline), at week 6, and at week 12. Changes to skeletal MM, physical function, anthropometrics, body composition, muscle strength, physical activity, energy metabolism, metabolic markers, nutritional status, quality of life, readiness to change and psychosocial determinants of behavioural change are assessed between the HP and NP groups. Feasibility of the nutritional intervention is assessed by change in MM as a surrogate marker. Conclusions This evidence-based study investigates the feasibility of increasing protein intake following a diagnosis of cancer on clinical outcomes during treatment for colorectal cancer. This study will inform larger trials assessing the impact of increasing protein intake in cancer to determine their importance and integration into standard clinical care for people with cancer.

Introduction. Thrombosis diagnosis and prevention in patients with Polycythemia vera (PV) suffered an ischemic stroke (IS) are still open. The aim was to find the reasons for systemic thrombogenicity and to compare the applicability of the main scales assessing thrombosis risk in patients with PV suffered IS.Materials and methods. We followed up 127 people (42-75 y.o.), of which 68 were patients with PV suffered IS (group I) and 59 non-PV-patients with ischemic stroke (group II). Clinical study included common blood analysis, rheological properties of erythrocytes, coagulation and endothelial parameters, cytokines, inflammation markers, angiogenesis markers, and testing for the V617F mutation in the JAK2 gene. The follow up included common and neurological examinations as well, and the assesment of thrombosis risk factors with both Caprini scale and CHA2DS2-VASc scale. All patients were examined twice as in the acute period of IS as well as in 16-18 months.Results. Between the groups no significant differences were found for the NIHSS average score and for Bartel index as well.The Caprini score belonged to the “very high risk” (score > 6) in both groups in the acute period of IS. At the same time, the score “8-10 points” prevailed in group II (68%) whereas the score “11-12 points” prevailed in group I.In the acute time of IS the CHA2DS2-VASc score revealed 12% of patients from both groups who had a score of “3-4 points” (moderate risk of thrombosis).In group I thrombotic complications rate correlated significantly with the JAK2V617F gene allelicloading (r = 0.236; p < 0.05), and the development of recurrence cerebrovascular disorders correlated significantly with Caprini score (r = 0.241; p < 0.05), but not with CHA2DS2-VASc score.Aiming to predict thrombotic complications in PV-patients the threshold (cut off) points were established for those markers as factor VIII, factor VII, red blood cell deformability, thrombin activated fibrinolysis inhibitor (TAFI), red blood cell count, white blood cell count, t-PA, VEGF-A, p-thrombomodulin, and ADAMTS-13.This pattern of parameters showed the odds ratio of thrombotic complications 10.3 (95% CI 7.6-13.8) in PV-patients in thelong-term period.At the end of the follow up the Caprini score showed a trend towards a decreasing in total while the CHA2DS2-VASc score remained virtually unchanged.Conclusion. We assume the accurate assessment of thrombotic risk in patients with Polycythemia vera suffered an ischemic stroke requires a proposed pattern of parameters including the test for JAK2V617F allelicloading and the calculation of Caprini score but not CHA2DS2-VASc score. Final results may provoke to change standard antithrombotic therapy in those patients towards its intensification due to pathogenetic featues of cancer-associated thrombosis.

The medical scientific community is constantly looking for possible ways to successfully treat the new coronavirus infection COVID-19. With the accumulation of experience and knowledge on this issue, the Russian Federation of Anesthesiologists and Reanimatologists regularly updates recommendations on anesthesia and intensive care for patients with COVID-19. The current, 4th edition, like the previous ones, has undergone significant changes and clarifications. Important updates have been made in the sections on respiratory therapy, drug therapy, thromboprophylaxis, and the managing patients with concomitant diseases. Optimization vectors for the next edition of the recommendations on anesthesia and intensive care for patients with COVID-19 have been formulated and substantiated.

Thrombogenicity and its causes in patients with ischemic stroke (IS) and pre-existing polycythemia vera (PV) is a significant clinical concern. The aim of this study was to identify the range of factors associated with increased thrombogenicity in patients with IS and pre-existing PV. We performed a physical examination and laboratory tests on 127 patients in the hyperacute stroke stage and 16-18 months after. Of them, 68 patients had PV (the main group) and 59 did not have this condition (the comparison group). Laboratory tests were conducted to evaluate blood rheology, hemostasis, endothelial function, angiogenesis, proinflammatory cytokine levels; we also tested patients for the presence of the V617F mutation in the JAK2 gene and analyzed the contribution of all studied parameters to the development of thrombotic and hemorrhagic complications. We found that the neurological picture did not differ between the groups: mean NIHSS scores were 12 and 13 points, respectively. Morphological and functional characteristics of red blood cells and platelets, hemostasis and cytokine profiles were compared between patients with IS and pre-existing PV and the comparison group. One of the key elements in potentiating thrombotic complications in patients with IS and PV was JAK2 V617F allele burden. The obtained data suggest the cumulative effect of the identified factors promoting thrombus formation in post-stroke patients with PV and overpowering the effect of antiplatelet therapy.

OBJECTIVES: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19) METHODS: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed. RESULTS: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for >12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11% versus 0%, p=0.030), lymphopenia (42% versus 18%, p=0.020), C-reactive protein level of >30 mg/L (35% versus 0%, p=0.0001), and D-dimer level of >1000 ng/mL (43% versus 6%, p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11% versus 2%, p=0.178) and cardiac alterations on echocardiogram (33% versus 22%, p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100] versus 81 [34-100], p=0.012), and school score (60 [15-100] versus 70 [15-95], p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls. CONCLUSIONS: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19.

In 2017 a new criteria for sepsis-induced coagulopathy (SIC) were issued following the revised sepsis definition in 2016. They aimed to the earliest detection of the sepsis-specific thrombotic phenotype of disseminated intravascular coagulation (DIC) in order to improve outcomes with early anticoagulant treatment in critically ill patients with sepsis. The following validation of SIC score demonstrated higher forecast value of that and revealed higher correlation with mortality compared to DIC score by the International Society on Thrombosis and Haemostasis (ISTH). In the future the ISTH plans to offer a simplified two-step scoring system for early DIC syndrome revealing in which SIC scale is as the first step, and the next step is the assessing of overt-DIC in patients who meet the criteria of SIC. The main goal of that should become the opportunity of timely therapeutic effects to the hemocoagulation in order to improve the treatment effectiveness of a sepsis.

The review presents the clinical guidelines of the Federation of Anaesthesiology and Resuscitation specialists of Russia, revised in 2018. The recommendations are based on a review of publications and modern international guidelines of the British Hematology Standards Committee (BSH, 2016), the European Society of Cardiology in partnership with the European Society of Cardiothoracic Surgeons (ESC and EACTS, 2018), the American Society of Regional Anesthesia and Pain (ASRA, 2018), The European Society of Anesthesiologists (ESA, 2010), as well as a consensus document of an interdisciplinary group of experts of the Russian Federation. Perioperative management of patients receiving long-term antithrombotic (antiplatelet and / or anticoagulant) therapy may be problematic, as they often need to interrupt antithrombotic therapy before surgery. In this, it is necessary to maintain a balance between the effectiveness of antithrombotic therapy and its safety by minimizing the frequency of both hemorrhagic and thrombotic complications. The recommendations presented in the review are aimed at achieving the strategic goal of perioperative antithrombotic therapy — minimizing the risk of bleeding subject to the minimum necessary antithrombotic potential.

Anemia is a known complication of diabetes mellitus (DM); however, its prevalence and prognostic relevance in patients with DM and pre-DM with normal kidney function have not been well defined. This study assessed the prevalence of anemia in patients with DM and pre-DM and evaluated its association with clinical outcomes during a 4-year follow-up period.This retrospective analysis included patients with DM and pre-DM referred to the Meir Medical Center Endocrine Institute in 2015. Patients with an estimated glomerular filtration rate (eGFR) of60 mL/min or any other recognized cause of anemia were excluded. The risk of developing microvascular or macrovascular complications or of death during the 4-year follow-up period was determined.A total of 622 patients (408 with DM and 214 with pre-DM) were included. The mean age of the patients was 64 ± 10.6 years, and 70% were women. The baseline hemoglobin A1C level was 7.1% ± 1.7% (54 mmol/mol), and the eGFR was 86.1 ± 15.3 mL/min. At the time of inclusion, 77 patients (19%) with DM and 23 (11%) with pre-DM had anemia (hemoglobin level 11.9 ± 0.8 and 11.8 ± 0.8 g/dL, respectively), compared with normal hemoglobin levels of 13.8 ± 0.9 and 13.7± 0.9 g/dL, respectively, in the others. A multivariable analysis demonstrated an inverse correlation between baseline hemoglobin (as a continuous variable) and mortality (P = .035), microvascular complications (P = .003), and eGFR decline (P.001) but not between baseline hemoglobin and macrovascular complications (P = .567).This study found a significant prevalence of anemia unrelated to renal failure, both in patients with DM and pre-DM. Anemia in these patients is associated with the development of microvascular complications, eGFR decline, and mortality. These results underscore the need for intensive lifestyle and pharmacologic interventions in these patients.

Anti-NMDA receptor (NMDAR) encephalitis is a recently identified autoimmune disorder with prominent psychiatric symptoms. Patients usually present with acute behavioral change, psychosis, catatonic symptoms, memory deficits, seizures, dyskinesias and autonomic instability. In female patients an ovarian teratoma is often identified. We describe a 32-year-old woman who presented with acute psychosis. Shortly after admission, she developed generalized seizures and deteriorated into a catatonic state. Although ancillary tests including MRI, electroencephalogram and cerebrospinal fluid (CSF) analysis were unremarkable, the presentation of acute psychosis in combination with recurrent seizures and a relentless course suggested autoimmune encephalitis. The patient underwent pelvic ultrasound which disclosed an ovarian tumor, leading to an urgent cystectomy with pathological confirmation of a mature cystic ovarian teratoma. Plasmapheresis was then initiated, yielding partial response over the next two weeks. Following the detection of high titers of anti-NMDAR antibodies in the CSF, the patient ultimately received second line immunosuppressive treatment with rituximab. Over several months of cognitive rehabilitation, a profound improvement was eventually noted, although minor anterograde memory deficits remained. In this report we call attention to the inclusion of anti-NMDAR encephalitis in the differential diagnosis of acute psychosis. The inclusion of this disorder in the differential diagnosis is critical, as prompt initiation of immunotherapy and tumor removal, if appropriate, could dramatically affect outcome.

Введение. Поступление вируса SARS-CoV-2 в организм человека сопровождается развитием COVID-19-ассоциированной коагулопатии, часто реализующейся в различных тромботических осложнениях. Актуальные клинические рекомендации описывают основные подходы к лечению и профилактике венозных тромбоэмболических осложнений (ВТЭО), однако реализация их не всегда представляется возможной. В реальной практике встречается значительное количество отклонений и нарушений, в том числе носящих системный характер, связанных как с ограниченностью представлений клиницистов о патогенетических аспектах развития инфекционного процесса, так и с избыточным желанием предотвратить отдельные из них. Цель исследования: изучение состояния реальной клинической практики в области лечения и профилактики развития тромботических осложнений у пациентов c новой коронавирусной инфекцией COVID-19 (НКИ COVID-19). Материалы и методы. В основе работы лежит анонимный опрос 223 врачей-специалистов, занимающихся лечением пациентов с хроническими и острыми заболеваниями сосудов. В опросник включено 18 вопросов, описывающих отношение врачей к проблеме в целом, а также касающихся выбора тактики лечения, применения антикоагулянтных препаратов и методов контроля системы гемостаза. Результаты. Подавляющее большинство участников опроса информированы и озадачены увеличением риска тромботических осложнений при НКИ COVID-19. При этом приоритетной целью антикоагулянтной терапии (АКТ) в острой фазе заболевания участники назвали лечение COVID-19-ассоциированной коагулопатии, а в стадии реконвалесценции — профилактику ВТЭО. Максимальную степень доверия при назначении АКТ имеют низкомолекулярные гепарины. Прямые оральные антикоагулянты, несмотря на отсутствие качественных рандомизированных исследований, подтверждающих их эффективность, большая часть врачей использует на амбулаторном этапе. Вызывает озабоченность значительный разброс вариантов и невысокий процент корректных ответов в вопросах, посвященных лабораторному контролю за системой гемостаза при АКТ. Заключение. Выполненный нами анализ свидетельствует о существенном расхождении реального применения антикоагулянтных препаратов у пациентов с НКИ COVID-19 с действующими клиническими рекомендациями. Кроме того, полученные результаты свидетельствуют о необходимости повышения уровня образованности практикующих специалистов в вопросах свертывания крови. Background. The SARS-CoV-2 virus invasion lead to COVID-19-associated coagulopathy accompanied with increased incidence of thrombotic complications. Current clinical guidelines give the main approaches to the treatment and prevention of them; however their implementation is not always possible in practice. In fact, there are a lot of violations including with a systemic genesis and associated either with the low understanding of infectious process pathogenesis aspects by clinicians or with their excessive desire to prevent coagulation disturbances. the revealing of real clinical practice conditions in the treatment and prevention of thrombotic complications in patients with coronavirus infection COVID-19. Materials/Methods. We provided an anonymous poll for 223 experts treating patients with chronic and acute vascular diseases. The questionnaire included 18 questions to identify as the experts attitude to this challenge as a whole as well as to their choice of treatment tactics, and anticoagulant drugs, and methods of laboratory monitoring of blood coagulation. Results. Most participants know the increased risk of thrombotic complications in COVID-19 and they are puzzled by it The treatment of COVID-19-associated coagulopathy is considered as the priority goal of anticoagulant therapy in the acute phase of COVID-19 whereas the prevention of venous thromboembolic complications is noted as main goal in convalescences. Low molecular weight heparins have gotten the highest confidence in the administration among anticoagulants. In turn, the most of experts use direct oral anticoagulants in outpatients even despite no confirmation is for DOAC’s effectiveness from randomized trials in this time. Besides it was revealed wide spread of opinions and low count of correct responses about laboratory control of the hemostatic system and anticoagulants. Conclusion. The analysis showed a serious inconsistency between the real anticoagulants administration in patients with COVID-19 and the recommendations of clinical guidelines. This circumstance obviates the need to raise educational level of physicians and surgeons in the field of blood coagulation.

Healthcare maintenance in inflammatory bowel disease refers to the ongoing health promotion and preventive care that are implemented while managing patients with this chronic illness. In addition to consolidating information about ongoing conventional treatments, queries should involve the domains of complementary medicine and quality of life given the complex nature of this disease. These patients are particularly at increased risk for infection, malignancy, malnutrition, mental illness, and bone disease. Despite its importance, these services are not delivered at the same rates when compared to the general population. Uncertainty around “ownership” of the patient by the primary care provider, anxiety surrounding safety of health maintenance interventions such as vaccination among immunosuppressed populations, and reimbursement concerns contribute to this gap in care. This chapter aims to be a useful primer, for primary care physicians and gastroenterologists, on the value of healthcare maintenance interventions. In addition, we will highlight practical strategies to enable implementation into practice.

To evaluate perinatal outcomes and long-term neurological morbidity of offspring to mothers with a history of ectopic pregnancy. In this retrospective study, perinatal outcomes and long-term neurological morbidity of offspring were assessed among mothers with a history of ectopic pregnancy, either medically or surgically treated. The study groups were followed until 18 years of age for neurological-related morbidity. For perinatal outcomes, generalized estimated equation (GEE) models were used to control for confounders. A Kaplan–Meier survival curve was used to compare cumulative neurological morbidity incidence and Cox proportional hazards model was conducted to control for confounders. A total of 243,682 mothers were included; 1424 mothers (0.58%) had a previous ectopic pregnancy, of which 25.6% (n = 365) were treated medically, and 74.3% (n = 1059) were treated surgically. Using GEE models, controlling for confounders, both surgically and medically treated ectopic pregnancies were noted as independent risk factors for preterm delivery in the subsequent pregnancies. Maternal history of surgically treated ectopic pregnancy was also independently associated with cesarean delivery. Offspring to mothers with previous ectopic pregnancy had comparable rates of long-term neurological morbidity. In the Cox proportional hazards model, controlling for confounders, being born to a mother with a history of previous ectopic pregnancy was not found to be independently associated with long-term neurological morbidity of offspring. Maternal history of ectopic pregnancy is independently associated with preterm delivery. However, offspring of mothers with a history of ectopic pregnancy are not at an increased risk for long-term neurological morbidity.

Hypoglycaemia is common in patients with type 1 diabetes and type 2 diabetes and constitutes a major limiting factor in achieving glycaemic control among people with diabetes. While hypoglycaemia is defined as a blood glucose level under 70 mg/dL (3.9 mmol/L), symptoms may occur at higher blood glucose levels in individuals with poor glycaemic control. Severe hypoglycaemia is defined as an episode requiring the assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions to assure neurologic recovery. Hypoglycaemia is the most important safety outcome in clinical studies of glucose lowering agents. The American Diabetes Association Standards of Medical Care recommends that a management protocol for hypoglycaemia should be designed and implemented by every hospital, along with a clear prevention and treatment plan. A tailored approach, using clinical and pathophysiologic disease stratification, can help individualize glycaemic goals and promote new therapies to improve quality of life of patients. Data from recent large clinical trials reported low risk of hypoglycaemic events with the use of newer anti-diabetic drugs. Increased hypoglycaemia risk is observed with the use of insulin and/or sulphonylureas. Vulnerable patients with T2D at dual risk of severe hypoglycaemia and cardiovascular outcomes show features of “frailty.” Many of such patients may be better treated by the use of GLP-1 receptor agonists or SGLT2 inhibitors rather than insulin. Continuous glucose monitoring (CGM) should be considered for all individuals with increased risk for hypoglycaemia, impaired hypoglycaemia awareness, frequent nocturnal hypoglycaemia and with history of severe hypoglycaemia. Patients with impaired awareness of hypoglycaemia benefit from real-time CGM. The diabetes educator is an invaluable resource and can devote the time needed to thoroughly educate the individual to reduce the risk of hypoglycaemia and integrate the information within the entire construct of diabetes self-management. Conversations about hypoglycaemia facilitated by a healthcare professional may reduce the burden and fear of hypoglycaemia among patients with diabetes and their family members. Optimizing insulin doses and carbohydrate intake, in addition to a short warm up before or after the physical activity sessions may help avoiding hypoglycaemia. Several therapeutic considerations are important to reduce hypoglycaemia risk during pregnancy including administration of rapid-acting insulin analogues rather than human insulin, pre-conception initiation of insulin analogues, and immediate postpartum insulin dose reduction.

Introduction Antenatal corticosteroids (ACS) are frequently used to reduce neonatal morbidity in preterm births (PTBs). A ‘rescue’ dose of ACS can be administer, if the risk of PTB remains. Some reports indicated that repeated doses of ACS might impact placental histology and possibly its function. We aimed to study whether repeated doses of ACS effect placental histopathology and pregnancy outcome. Methods The medical files and placental reports of all PTB, at 24-336/7 weeks, between Nov 2008–Dec 2019, were reviewed. The study population was divided into three groups; no-ACS (PTBs without ACS treatment), one-ACS (PTBs after a full or partial ACS course), and rescue-ACS (PTBs after a ‘rescue’ course of ACS). Placental lesions were classified according to “Amsterdam” criteria into maternal and fetal vascular malperfusion lesions, maternal and fetal inflammatory responses and chronic villitis. Placental lesions and pregnancy outcome were compared between the study groups. Results The no-ACS group (n = 58) was characterized by increased rates of PTB Discussion Rescue course of ACS is associated with increased rate of placental maternal inflammatory response. These findings probably result from maternal stress stimuli without an adverse impact on early neonatal outcome.

Background En bloc resection of benign tumors is only indicated in aggressive lesions with substantial destruction of the affected bone. Few reports have evaluated the long-term outcome of Grade 3 giant cell tumor of bone (GCTB; defined as severe bone destruction and soft tissue extension) treated with en bloc resection and reconstruction with a massive allograft. We recently reported that patients with benign tumors achieved better allograft reconstruction survivorship compared with those treated for a malignant bone tumor. In light of that finding, we wondered whether osteoarticular allografts would be a viable long-term alternative for Grade 3 GCTB, which could be important in some countries because of greater availability and lower costs compared with endoprostheses. Questions/purposes We analyzed a group of patients with Grade 3 GCTBs treated with en bloc resection and osteoarticular allograft reconstruction in terms of (1) survivorship free from allograft removal at 10 years; (2) survivorship free from reoperation for any reason at 10 years, (3) functional results as measured by the Musculoskeletal Tumor Society (MSTS) score, (4) assessment of arthrosis at the knee. Methods We retrospectively analyzed all patients with a Grade 3 GCTB treated between 1980 and 2007. Only patients treated with en bloc resection and reconstruction with massive osteoarticular allografts were included in the analysis. The indication for osteoarticular reconstruction during that time included severe bone destruction with intraarticular compromise of the tumor, intraarticular fracture because of tumor growth, the presence of inadequate remaining subchondral bone to resist normal loading (for the distal femur or proximal tibia), and the preservation of a soft-tissue component (ligaments or meniscus) for articular stability. During the period, 75 patients were treated with en bloc resection. Patients treated with intralesional curettage (n = 7), reconstruction with an endoprosthesis (n = 2), intercalary arthrodesis (n = 13), or unicondylar reconstruction (n = 14) were excluded. Of the original 75 treated with en bloc resection, 52% (39) were treated with osteoarticular allograft reconstruction, and no patient was lost to follow-up before 2 years or had substantial missing data. However, of the 39 patients, another 21% (8) have not been seen in the last 5 years, but these were included here because they reached the 10-year minimum surveillance period before being lost. Twenty-three of those 39 patients were previously reported by our group and 16 new patients (treated between 1980-1985) were included in this series (eight distal radius, six distal femur, two proximal tibias), extending the follow-up period and including more patients for analysis. The median (range) follow-up duration was 26 years (10 to 34). We assessed survivorship using a Kaplan-Meier analysis, we drew MSTS scores retrospectively from patients´ medical records, and we graded arthrosis using the Ahlback scale for the knee (which was by far the most common joint involved, n = 31, and so it was the joint we assessed for the presence of arthrosis). Results The survivorship free from allograft removal was 85% at 10 years (95% CI 74 to 96). The allograft survivorship free from reoperation for any reason at 10 years was 72% (95% CI 59 to 87). The median (range) MSTS score was 28 points (19 to 30). The grade of arthrosis in the knee at last follow-up was analyzed in 20 patients and classified in nine as Ahlback Type 4, in six as Type 3, in three as Type 2 and in two as Type 5. Conclusions Osteoarticular allograft reconstruction after a Grade 3 GCTB en bloc resection showed excellent long-term survivorship. We believe these results compare favorably with other studies on endoprosthetic reconstruction and head-to-head studies of these approaches should be performed; these would need to be multicenter trials. In the meantime, in locations where endoprostheses are unavailable or too expensive, we believe our results support the use of osteoarticular allografts. Level of evidence Level IV, therapeutic study.

Aim.To find out the relationship of particular blood cells (BC) and their ratios with lipid metabolism in patients with essential hypertension (EH), with (EH-1) and without kinesiotherapy (EH-2).Material and methods.The study included 30 healthy women (control group) and 72 women with EH, which were divided into 2 groups: group 1 (EH-1) — 37 women with stage II (target organ damage classification) hypertension who receive antihypertensive therapy; group 2 (EH-2) — 35 women who underwent antihypertensive therapy and kinesiotherapy (3-4 courses for 2-3 years).Results.Correlation analysis revealed that the studied relationships in healthy women, EH-1 and EH-2 women can be either direct or inverse. In healthy women, we observed negative association of monocytes (MON) with atherogenic index (AI), a positive association of basophils (BAS) with high density lipoproteins (HDL) and its negative association with low density lipoproteins (LDL), very low density lipoproteins (VLDL) and AI and red blood cells/platelets (RBC/PLT ratio) with HDL. Negative associations of lymphocytes (LYM)/BAS ratio with triglyceride (TG) and eosinophils (EOS)/BAS ratio with LDL were also detected. Patients with EH-1 had a direct relationship between LYM/EOS ratio and TG. In patients with EH-2, a negative relationship was found between PLT and HDL, MON and HDL, neutrophils (NEU)/MON ratio and TAG, and a positive — between white blood cells (WBC), NEU, MON and AI, LYM and TAG, MON and TAG, as well as AI.Conclusion.The obtained data indicate that all BC and their ratios in women with/without EH and with/without kinesiotherapy affect the lipid metabolism.

Digital technologies are gaining an important role in the management of patients with diabetes. We assessed clinical outcomes and user satisfaction of incorporating a digital diabetes care system in diabetes clinics of a developing country. The system integrated a wireless blood glucose monitor that communicates data to any smartphone utilizing a patented acoustic data transfer method, a mobile-app, and cloud-based software that stores, analyzes, and presents data. Five hospital endocrinology clinics in Vietnam sequentially recruited all patients willing to join the study, providing they had a smartphone and access to internet connectivity. Face-to-face visits were conducted at baseline and at 12 weeks, with monthly digital visits scheduled in the interim and additional digital visits performed as needed. HbA1c levels were measured at baseline and at 12 weeks (&plusmn, 20 days). The study included 300 patients of whom 279 completed the evaluation. Average glucose levels declined from 170.4 &plusmn, 64.6 mg/dL in the first 2 weeks to 150.8 &plusmn, 53.2 mg/dL in the last 2 weeks (n = 221, p &lt, 0.001). HbA1c levels at baseline and 12 weeks declined from 8.3% &plusmn, 1.9% to 7.6% &plusmn, 1.3% (n = 126, 0.001). The digital solution was broadly accepted by both patients and healthcare professionals and improved glycemic outcomes. The durability, scalability, and cost-effectiveness of this approach merits further study.

The article presents the results of long-term clinical, molecular-biological and laboratory studies on combined poly-stage treatment of patients with colon cancer with liver metastases. The cytotoxicity of various chemotherapeutic agents for colorectal carcinoma in the lines of HT 29 and NMG 64/84 cells was studied by analysis of human colony-forming tumor (HTCA). In vitro studies on the suspension of tumor cells from remote liver metastases were carried out to determine the most effective chemotherapeutic agents for intra-arterial hepatic infusion (HAI). Individual choice of the scheme of systemic chemotherapy depends on the level of thymidylate synthetase (TS) in the tumor tissue. Long-term own clinical experience and analysis of world literature allow authors to state that stage resection of the liver (STR) in combination with regional (HAI) and systemic chemotherapy is the method of choice in the treatment of patients with colorectal cancer with unresectable liver metastases. In comparison with other treatment methods (ALPPS and TSH), STR has the least negative consequences and is beneficial from the tumor-biological point of view.

The peculiarities of primary and secondary infective endocarditis (IE) were studied in 62 patients with primary and secondary IE, uncomplicated and complicated disease treated in S. P. Botkin city clinical hospital including analysis of dynamics of tumor necrosis factor α (TNF α), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF) within 3 weeks after the onset of antibiotic therapy. A rise in TNF α and IL-6 levels was shown to correlate with the severity of the disease and the development of infectious-toxic syndrome. Most patients had an increased level of VEGF, a mediator involved in the regulation of inflammation. It was shown that combination of high TNF-α and IL-6 levels with the initially low or gradually increasing VEGF levelsuggests the unfavourable prognosis characteristic of the most heavily diseased anddeceased patients.

Giant cell tumor (GCT) of bone is a locally aggressive, rarely metastasizing primary bone neoplasm that occurs most frequently in the epiphysis of long bones of young adults. It is composed of round, oval, or elongated mononuclear cells admixed with osteoclast-like giant cells that express receptor activator of nuclear factor κB (RANK). The mononuclear stromal cells express RANK ligand, a mediator of osteoclast activation. Denosumab, a monoclonal antibody that reduces tumor associated bone lysis by inhibiting the action of RANK ligand, has been used to treat selected cases of GCT. We reviewed the clinical records and histologic slides of 9 patients with GCT who had received denosumab therapy and were subsequently surgically treated. There were 5 men and 4 women aged 20 to 66 years (mean, 36 years). Duration of treatment varied from 2.5 to 13months (mean, 5.9 months). In all cases, different degrees of ossification, fibrosis, depletion of giant cells, and proliferation of mononuclear cells were seen. With this combination of changes, denosumab-treated GCT may mimic other lesions such as fibrous dysplasia, juvenile ossifying fibroma, nonossifying fibroma, and osteoblastoma. Less frequent but more relevant is the presence of cellular atypia or patterns of ossification that resemble an undifferentiated pleomorphic sarcoma, a conventional osteosarcoma, or a low-grade central osteosarcoma. The presence of clinical and radiologic response to denosumab, along with the lack of high mitotic activity, atypical mitotic figures, extensive necrosis, or a permeative pattern of growth, represents clues to achieve a correct diagnosis.

Central chondrosarcoma of bone is graded on a scale of 1 to 3 according to histological criteria. Clinically, these tumors can be divided into low-grade (Grade 1) and high-grade (Grade 2, Grade 3, and dedifferentiated) chondrosarcomas. Although en bloc resection has been the most widely used treatment, it has become generally accepted that in selected patients with low-grade chondrosarcomas of long bones, curettage is safe and effective. This approach requires an accurate preoperative estimation of grade to avoid under- or overtreatment, but prior reports have indicated that both imaging and biopsy do not always give an accurate prediction of grade.(1) What is the concordance of image-guided needle preoperative biopsy and postoperative grading in central (intramedullary) chondrosarcomas of long bones, and how does this compare with the concordance of image-guided needle preoperative biopsy and postoperative grading in central pelvic chondrosarcomas? (2) What is the concordance of preoperative image-guided needle biopsy and postoperative findings in differentiating low-grade from high-grade central chondrosarcomas of long bones, and how does this compare with the concordance in central pelvic chondrosarcomas?Between 1997 and 2014, in our institution, we treated 126 patients for central chondrosarcomas located in long bones and the pelvis. Of these 126 cases, 41 were located in the pelvis and the remaining 85 cases were located in long bones. This study considers 39 (95%) and 40 (47%) of them, respectively. We included all cases in which histological information was complete regarding preoperative and postoperative tumor grading. We excluded all cases with incomplete data sets or nondiagnostic preoperative biopsies. To evaluate the needle biopsy accuracy, we compared the histological tumor grade, obtained from the preoperative biopsy, with the final histological grade obtained from the postoperative surgical specimen. The weighted and nonweighted kappa statistics were used to evaluate the agreement.Concordance between the preoperative biopsy and the final pathological analysis in terms of histological grade was much higher in long-bone chondrosarcoma than in pelvic chondrosarcoma (83% [33 of 40] versus 36% [14 of 39]; odds ratio, 8, 48). Likewise, the weighted kappa coefficients were higher in long-bone chondrosarcoma than in pelvic chondrosarcoma for the determination of histological grade (0.63; 95% confidence interval [CI], 0.34-0.91 versus 0.12; -0.32 to 0.57; p0.001). When categorizing the lesions as low grade or high grade, concordance between the preoperative biopsy and the final pathological analysis was much higher in long-bone chondrosarcoma than in pelvic chondrosarcoma (90% [36 of 40] versus 67% [26 of 39]; odds ratio, 4, 5). Likewise, the weighted kappa coefficients were higher in long-bone chondrosarcoma than in pelvic chondrosarcoma (0.73; 95% CI, 0.51-0.94 versus 0.26; 0.04-0.48; p0.001).Image-guided needle biopsy, when performed by a specialist radiologist and evaluated by an experienced bone pathologist, is a useful tool in determining the histological grade of long-bone chondrosarcomas allowing identification of true low-grade tumors. The histological grade should be correlated with imaging and the clinical presentation, but under these circumstances, experienced tumor surgeons may use this information in planning surgical treatment. The same appears not to be true for pelvic lesions, in which histological grade established by needle biopsy should be interpreted with caution.Level III, diagnostic study.

Hunger resulting from food deprivation is associated with negative affect. This is supported by recent evidence showing that hunger-sensitive neurons drive feeding through a negative valence teaching signal. However, the complementary hypothesis that hormonal signals of energy surfeit counteract this negative valence, or even transmit positive valence, has received less attention. The adipose-derived hormone leptin signals in proportion to fat mass, is an indicator of energy surplus, and reduces food intake. Here, we showed that centrally-delivered leptin reduced food intake and conditioned a place preference in food-restricted as well as ad libitum fed rats. In contrast, leptin did not reduce food intake nor condition a place preference in obese rats, likely due to leptin resistance. Despite a well-known role for hindbrain leptin receptor signaling in energy balance control, hindbrain leptin delivery did not condition a place preference in food-restricted rats, suggesting that leptin acting in midbrain or forebrain sites mediates place preference conditioning. Supporting the hypothesis that leptin signaling induces a positive affective state, leptin also decreased the threshold for ventral tegmental area brain stimulation reward. Together, these data suggest that leptin signaling is intrinsically preferred, and support the view that signals of energy surfeit are associated with positive affect. Harnessing the positive valence of signals such as leptin may attenuate the negative affect associated with hunger, providing a compelling new approach for weight loss maintenance.

Pseudomyogenic hemangioendothelioma (PMH) is a rare vascular tumor that presents more frequently in young adults and has a male predominance. It is usually located in the superficial or deep soft tissues of the extremities, but concurrent bone involvement can be present. In approximately two-thirds of patients this disease is multifocal, often involving multiple tissue planes. It is a relapsing lesion with low metastatic potential. Given its clinical and morphologic characteristics (multifocality, epithelioid morphology, absence of clearly evident vascular differentiation on hematoxylin-eosin slides), PMH can be easily misinterpreted as other lesions, often with radically different treatment and prognosis. For this reason, we think it is important to recognize this entity, which has some unique features. Here, we will briefly describe the clinical and pathologic features of PMH, detailing its more relevant differential diagnoses.

Supplemental Digital Content is Available in the Text., Introduction: Seizure-related protein 6 (Sez6) contributes to chronic pain development as sez6 knockout mice show attenuated pain behaviours after peripheral nerve injury, compared with control mice. The type I transmembrane isoform of Sez6 is cleaved by the β-amyloid precursor protein cleavage enzyme 1 (BACE1), resulting in Sez6 extracellular domain shedding from the neuron surface. Objectives: To determine whether this BACE1-shed form of Sez6 can be detected in the cerebrospinal fluid (CSF) and whether Sez6 levels in the CSF are altered in neuropathic pain or chronic inflammatory pain (IP). Methods: We analysed the CSF samples collected during surgery from patients with chronic neuropathic pain (n = 8) or IP (n = 33), comparing them to the CSF samples from patients with suspected subarachnoid haemorrhage that was subsequently excluded (nonsurgical group, n = 5). Western blots were used to determine the relative Sez6 levels in the CSF from the different patient and nonsurgical comparison groups. Results: The results show that BACE1-shed Sez6 can be readily detected in the CSF by Western blot and that the levels of Sez6 are significantly higher in the IP group than in the nonsurgical comparison group. Conclusion: The association between elevated Sez6 levels in the CSF and IP is further evidence for persistent alterations in central nervous system activity in chronic IP conditions.

Environmental stimuli that signal food availability hold powerful sway over motivated behavior and promote feeding, in part, by activating the mesolimbic system. These food-predictive cues evoke brief (phasic) changes in nucleus accumbens (NAc) dopamine concentration and in the activity of individual NAc neurons. Phasic fluctuations in mesolimbic signaling have been directly linked to goal-directed behaviors, including behaviors elicited by food-predictive cues. Food-seeking behavior is also strongly influenced by physiological state (i.e., hunger vs. satiety). Ghrelin, a stomach hormone that crosses the blood-brain barrier, is linked to the perception of hunger and drives food intake, including intake potentiated by environmental cues. Notwithstanding, whether ghrelin regulates phasic mesolimbic signaling evoked by food-predictive stimuli is unknown. Here, rats underwent Pavlovian conditioning in which one cue predicted the delivery of rewarding food (CS+) and a second cue predicted nothing (CS-). After training, we measured the effect of ghrelin infused into the lateral ventricle (LV) on sub-second fluctuations in NAc dopamine using fast-scan cyclic voltammetry and individual NAc neuron activity using in vivo electrophysiology in separate groups of rats. LV ghrelin augmented both phasic dopamine and phasic increases in the activity of NAc neurons evoked by the CS+. Importantly, ghrelin did not affect the dopamine nor NAc neuron response to the CS-, suggesting that ghrelin selectively modulated mesolimbic signaling evoked by motivationally significant stimuli. These data demonstrate that ghrelin, a hunger signal linked to physiological state, can regulate cue-evoked mesolimbic signals that underlie food-directed behaviors. Cues that predict food availability powerfully regulate food-seeking behavior. Here we show that cue-evoked changes in both nucleus accumbens (NAc) dopamine (DA) and NAc cell activity are modulated by intra-cranial infusions of the stomach hormone ghrelin--a hormone known to act centrally to promote food intake. These data demonstrate that hormones associated with physiological state (i.e., hunger) can affect encoding of food-predictive cues in brain regions that drive food-motivated behavior.

Aim. To study the effect of triple combination therapy on oxidative stress and arterial remodeling in hypertensive patients with heart failure with preserved ejection fraction (HFpEF).Material and methods. The study involved 76 people with diagnosed HFpEF. After a comprehensive examination, patients were randomized into two equal groups: first group — patients who received perindopril 10 mg, indapamide 2,5mg and amlodipine 5 mg; second — patients who received losartan 100 mg, indapamide 2,5 mg, amlodipine 5 mg. Before and 16 weeks after the therapy initiation, cardiac ultrasound, assessment of endothelial function with estimating endothelium-dependent vasodilation, assessment of vascular stiffness by photoplethysmography and compression oscillometry were carried out. The plasma concentration of oxidative stress marker 8-isoprostane was studied.Results. During the follow-up period, a significant improvement in endothelial function was noted: in the first group — from 8,1% to 11,4% (p=0,001), in the second — from 5,8% to 8,3% (p=0,0007). In both groups, there was an improvement in microvessel elasticity: a significant decrease in specific peripheral vascular resistance, as well as a significant decrease in total peripheral resistance in the first group (p0,05). There was a significant increase in the stiffness of the aorta and muscular arteries in both groupsю In the first group, a stiffness index decreased from 10,38 m/s to 8,33 m/s (pConclusion. Oxidative stress, which develops due to chronic systemic inflammation, plays a key role in the pathogenesis of HFpEF. The results obtained show an improved endothelial function as a result of decrease in oxidative stress, which is accompanied by an improvement in vessel wall elasticity, thereby slowing down the heart failure progression.

Der einzig kurative Ansatz beim duktalen Adenokarzinom des Pankreas ist die Resektion des Tumors, die nur bei 15 – 30 % der Patienten moglich ist. Die lokale Tumorausbreitung oder Fernmetastasen machen in den meisten Fallen eine Operation obsolet. Die chirurgisch-onkologische Behandlungsqualitat mit Kurz- und Langzeitergebnissen zeigt eine erhebliche Variationsbreite, sodass „Expertise/Qualitat“ mit Mindestmengen und Zentrierung assoziiert werden. Ziel unserer retrospektiven Studie war es, die Ergebnisqualitat der Behandlung von Patienten mit Pankreaskarzinomen auf der Basis einer ausfuhrlichen praoperativen Diagnostik an einer Klinik mit GI-Schwerpunkt und der Kooperation mit einem Viszeralchirurgen bzw. Team mit chirurgisch-onkologischer Expertise in der Pankreaschirurgie an einer nicht universitaren Versorgungsklinik zu untersuchen und mit Resultaten der Spitzenzentren zu vergleichen. 53 Patienten mit duktalem Pankreasadenokarzinom wurden von 1/2002 – 12/2009 operiert. Die 30-Tage-Krankenhausmortalitat betrug 3,8 %, die mediane Uberlebenszeit der operierten Patienten nach Entlassung aus dem Krankenhaus 23,1 Monate. Die 5-Jahres-Uberlebensrate R0-resezierter Patienten, die alle adjuvant chemotherapiert wurden, war mit 31 % hoch. Die Uberlebenszeiten und die auserordentlich hohe Resektionsquote von 98,1 % bei Patienten, deren Tumoren uberwiegend als T3 (81 %) eingestuft wurden, zeigen die besonders erfolgreiche Zusammenarbeit zwischen gastroenterologischer Diagnostik, viszeraler Pankreaschirurgie und onkologischer Nachbehandlung. Die Ergebnisse sind mit denen von sog. „High-Volume-Zentren“ vergleichbar. Die verantwortlichen Arzte beider Abteilungen wurden an universitaren Spitzenzentren ausgebildet. Expertise ist bei entsprechender Team-Konstellation von einem Spitzenzentrum an ein nicht universitares Versorgungskrankenhaus ubertragbar.

The development of hypertrophic scars and keloids is a relatively common complication of different otologic procedures involving incision of the skin behind the ear. This case report aims to describe the successful treatment of keloids that developed following ear surgeries that have been performed via a retro-auricular approach (cochlear implantation and the removal of cholesteatoma) by an intralesional cryosurgery method. Two patients who were previously operated for an extensive pediatric cholesteatoma and one patient who underwent a cochlear implant surgery have developed large keloids at the radix helix. The keloids were treated under local anesthesia by the intralesional cryosurgery method. Over a 6-month period, the scars gradually flattened and became paler and the clinical symptoms of itchiness, pain, and tenderness have significantly been reduced. No complications were documented, and there were no recurrences in a follow-up period of 30 months. This case report demonstrates that intralesional cryosurgery provides the surgeon with an effective method to treat keloid scars following the removal of cholesteatoma or cochlear implantation, thus improving the quality of life and body image and enabling the patients to use the implanted device in an adequate and satisfactory way. Level of Evidence: Level V, therapeutic study.

Ouabain (OUA) is a steroid hormone capable of inhibiting the protein Na+K+ATPase present in the plasma membrane of cells. Ouabain was initially extracted from the roots of African trees such as Acocanthera ouabaio and Strophantus gratus seeds and later described as an endogenous component found in higher mammals. The adrenal gland is the main site of synthesis of ouabain and it is released in stressful situations, conditions similar to those where there is secretion of corticosteroids. Immunological functions have been shown to be regulated by ouabain. In order to understand the effects of ouabain on B lymphocyte populations in different lymphoid organs, mice received intraperitoneal injections of ouabain for 3 consecutive days. Twenty-four hours after the last injection, cells were analyzed by flow cytometry. In the spleen, ouabain modulated especially follicular B cells, inducing a significant decrease in the percentage and absolute numbers of those cells. Ouabain also reduced the absolute number of marginal zone B lymphocytes. No difference in the percentage or absolute number of B lymphocytes in the spleen forty-eight hours after the last injection was observed. An increase in the number of B cells was seen in mesenteric lymph nodes and this retention appears to be directly related to increased expression of CXCR5 chemokine receptor and reduction of CD62L, which also explains the observed reduction of B cells in the spleen. Our results indicate that ouabain regulates the dynamics of B lymphocytes in peripheral organs but production of total IgM and IgG in the serum of animals treated in vivo with ouabain was not affected.

Methylmercury (MeHg) is known to be a chemical that poses a risk to public health. Exposure to MeHg and vitamin A (VitA) occurs through the ingestion of fish, present in the diet of most pregnant women. The absorption of these elements generates oxidative stress and can generate adaptations for future stressful events. Here, we assessed how exposure to VitA and/or MeHg during the fetal and breastfeeding period modulates the toxicity of MeHg reexposure in adulthood. We focus on redox systems and repairing DNA damage. Male rats (n = 50), were divided into 5 groups. Control received mineral oil; The VitA group received VitA during pregnancy, during breastfeeding and was exposed to MeHg in adulthood; VitA + MeHg received VitA and MeHg during pregnancy and breastfeeding and was exposed to MeHg in adulthood. The single exposure group (SE) was exposed to MeHg only in adulthood; and the MeHg group was pre-exposed to MeHg during pregnancy and breastfeeding and re-exposed to MeHg in adulthood. After treating the animals, we evaluated the redox status and the level of DNA damage in all rats. The results revealed that MeHg significantly decreased the activity of glutathione peroxidase (GPx) and sulfhydryl levels and increased the activity of superoxide dismutase (SOD), glutathione transferase, glutathione and carbonyl in all exposed groups. These results suggest that the second exposure to MeHg directly altered the effects of oxidation and that there were no specific effects associated with exposure during the fetal and breastfeeding periods. In addition, our findings indicate that MDA levels increased in MeHg and SE levels and no differences in MDA levels were observed between the VitA and MeHg + VitA groups. We also observed that animals pretreated exclusively with VitA showed residual damage similar to the control's DNA, while the other groups showed statistically higher levels of damage. In conclusion, low doses of MeHg and VitA during fetal and breastfeeding periods were unable to condition an adaptive response to subsequent exposure to MeHg in adulthood in relation to the observed levels of oxidative damage assessed after exposure.

The neuropeptide dynorphin (DYN) activates kappa opioid receptors (KORs) in the brain to produce depressive-like states and decrease motivation. KOR-mediated suppression of dopamine release in the nucleus accumbens (NAc) is considered one underlying mechanism. We previously showed that, regardless of estrous cycle stage, female rats are less sensitive than males to KOR agonist-mediated decreases in motivation to respond for brain stimulation reward, measured with intracranial self-stimulation (ICSS). However, the explicit roles of KORs, circulating gonadal hormones, and their interaction with dopamine signaling in motivated behavior are not known. As such, we measured the effects of the KOR agonist U50,488 on ICSS stimulation thresholds before and after gonadectomy (or sham surgery). We found that ovariectomized females remained less sensitive than sham or castrated males to KOR-mediated decreases in brain stimulation reward, indicating that circulating gonadal hormones do not play a role. We used qRT-PCR to examine whether sex differences in gene expression in limbic brain regions are associated with behavioral sex differences. We found no sex differences in Pdyn or Oprk1 mRNA in the NAc and ventral tegmental area (VTA), but tyrosine hydroxylase (Th) mRNA was significantly higher in female compared to male VTA. To further explore sex-differences in KOR-mediated suppression of dopamine, we used fast scan cyclic voltammetry (FSCV) and demonstrated that U50,488 was less effective in suppressing evoked NAc dopamine release in females compared to males. These data raise the possibility that females are protected from KOR-mediated decreases in motivation by an increased capacity to produce and release dopamine.

Patients with peritoneal metastases of gastric cancer have a poor prognosis with a median survival of 7 months. A benefit of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) could be shown in several selected patient cohorts but remains controversial. The aim of this study was, to reflect the results of a national German HIPEC registry initiated by the German Society of General and Visceral Surgery (DGAV). The DGAV HIPEC registry StuDoQ|Peritoneum documents patients with peritoneal malignancy contributed from 52 hospitals. All consecutive documented patients from 2011 until 2016 (n = 3078) were treated with CRS and HIPEC and were analysed. A total of 315 (10%) suffered from gastric cancer and were analysed. A complete data set of 235 patients was available for this study, including 113 male (48.1%) and 122 female (51.9%) patients with a median age of 53.4 years (SD ± 11.9). The median PCI was 8.0 (range 1–30). A complete cytoreduction was achieved in 121 patients (71.6%). Postoperative complications (Clavien–Dindo grades 3–4) occurred in 40 patients (17%). The median overall survival (OS) time was 13 months. The 5-year survival rate was 6%. According to the PCI from 0–6 (n = 74); 7–15 (n = 70) and 16–39 (n = 24) the median OS differs significantly (18 months vs. 12 months vs. 5 months; p = 0.002). CRS and HIPEC in selected patients with gastric cancer and peritoneal spread can improve survival when they are treated in centers. An accurate staging and patient selection are of major importance to achieve long-term survival.

Colon cancer (CC) and rectal cancer (RC) are synonymously called colorectal cancer (CRC). Based on our experience in basic and clinical research as well as routine work in the field, the term CRC should be abandoned. We analyzed the available data from the literature and results from our multicenter Research Group Oncology of Gastrointestinal Tumors termed FOGT to confirm or reject this hypothesis. Anatomically, the risk of developing RC is four times higher than CC, while physical activity helps to prevent CC but not RC. Obvious differences exist in molecular carcinogenesis, pathology, surgical topography and procedures, and multimodal treatment. Therefore, we conclude that CC is not the same as RC. The term “CRC” should no longer be used as a single entity in basic and clinical research as well as other areas of classification., publishedVersion

Objective: To determine the satisfaction from treatment and effectiveness of flash glucose monitoring system (FGM) in patients with type 2 diabetes. Design and Methods: 101 individuals with type 2 diabetes on multiple daily insulin injection (MDI) therapy for ≥1 year (mean duration 21.81±7.65 years) and HbA1c 7.4-10.2% (57-88 mmol/mol) were randomized to the intervention (n=53) or the standard care group (n=48). Those in the intervention group were instructed to use FGM and once a week 7-points BG assessment to confirm any a symptomatic hypoglycemia. The control group continued the routine BG measurement as before the study and add once a week 7-points BG measurement at constant day. For 12 weeks, both groups were instructed to adjust insulin dose in the frequent face-to-face and telephone visits. Satisfaction from treatment, quality of life, comfort using FGM, HbA1c and hypoglycemia events were evaluated. Results: The mean age was 66.75 ± 7.55; 64.35% were male. Total treatment satisfaction increased in the intervention group (p=0.053). At the 12 week of the study, subjects in the intervention group found treatment significantly more flexible (p=0.019), convenient (p=0.052), and would recommend it more to their counterparts (p=0.023). The mean HbA1c was 8.51 ± 0.81%. After 10 weeks, HbA1c changes were -0.82% in the intervention group and -0.29% in the control (p=0.0013). 67.9% subjects from the intervention study and 27.1% from the control group reduced HbA1c ≥0.5% HbA1c (p Conclusion: FGM potentially produces a modification of behavior/life style and improves treatment satisfaction. It improves glycemic control in subjects with type 2 diabetes treated by MDI without increased frequency of hypoglycemia. Disclosure M. Yaron: None. E. Roitman: Speaker's Bureau; Self; Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; GlucoMe. Stock/Shareholder; Self; GlucoMe. G. Aharon-Hananel: None. Z. Landau: None. T. Ganz: None. M. Karp: None. M. Ish-Shalom: None. J. Singer: None. J. Wainstein: None. I. Raz: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Stock/Shareholder; Self; DarioHealth. Advisory Panel; Self; Merck Sharp & Dohme Corp., Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Orgenesis Inc., Pfizer Inc., Sanofi R&D, SmartZyme Biopharma. Consultant; Self; Bristol-Myers Squibb Company. Speaker's Bureau; Self; Bristol-Myers Squibb Company, Johnson & Johnson Diabetes Institute, LLC., Merck Sharp & Dohme Corp., Novartis Pharma K.K., Sanofi-Aventis. Consultant; Self; FuturRx Ltd, Insuline Medical,Camereyes Ltd, Exscopia, Medial EarlySign Ltd. Stock/Shareholder; Self; Glucome Ltd, InsuLine Medical Ltd.. Consultant; Self; Dermal Biomics Inc. Stock/Shareholder; Self; Orgenesis Inc.. Speaker's Bureau; Self; Teva Pharmaceutical Industries Ltd.. Advisory Panel; Self; Concenter BioPharma/Silkim Ltd, Camereyes Ltd. Stock/Shareholder; Self; CameraEyes Ltd. Advisory Panel; Self; Breath of Life PharmaLtd, Panaxia.