Terminal Stage Of Disease Research Articles

NEURONAL INJURY DRIVES GLIOBLASTOMA INITIATION

Abstract AIMS Glioblastoma (GBM), the most common primary brain malignancy in adults, remains incurable. Pervasive heterogeneity and plasticity underpin therapy resistance and lethal recurrence, suggesting that prevention or earlier intervention may be required. Improved understanding of GBM initiation is a prerequisite for achieving this goal. GBM frequently originates from neural stem cells (NSCs) of the subventricular zone, which, upon acquisition of mutations, migrate away from their niche and form tumours at distal sites through unknown mechanisms. Here, we explored GBM initiation and its microenvironment. METHOD We combined a murine somatic GBM model which faithfully recapitulates the human disease with PDX models and patient tissue datasets. We used immunohistochemistry, scRNA-sequencing, immuno-phenotyping, behavioural and survival studies and in vivo gain- and loss-of-function experiments in Sarm1-/- lines. RESULTS Time-course analysis of tumour development identified neuronal degeneration as an early event in GBM tumourigenesis, occurring preferentially in white matter, where we find mutated NSCs are immediately rerouted. Axonal loss was accompanied by a robust inflammatory response, marked by microglial and astrocytic activation. Neuronal degeneration played a causative role, in that transection injury of corpus callosum axons accelerated tumourigenesis and, conversely, GBM development was delayed in Sarm1-/- mice with impaired Wallerian degeneration, a major mode of neuronal death following injury. Consistently, terminal Sarm1-/- tumours were more diffuse, contained more immature tumour cells and were less immune-infiltrated than their WT counterparts. Strikingly, behavioural studies revealed that Sarm1-/- tumour-bearing mice also retained improved motor performance compared to WT mice, even at terminal disease stages. CONCLUSION Our work provides important insights into GBM development, identifying white matter injury as a key initiating event, elicited by early tumour cells and orchestrated by neuronal degeneration. It identifies Wallerian degeneration, a druggable pathway already in clinical trials for neurodegenerative diseases, as a therapeutic target for GBM, with the potential to extend survival and ameliorate cognition.

Exploring the Experience of Guo Yi Master Lei Zhongyi in Dialectical Treatment of Heart Failure Based on the Theory of "Yang Wei Yin Xian"

The term "heart failure" first appeared in Wang Shuhe's "Meridian: Spleen and Stomach Diseases". The related description of heart failure is recorded in the "Huangdi Neijing", which is a disease mainly characterized by palpitations, asthma, and edema. It is often the terminal stage of chronic heart disease that cannot be cured. Its basic pathogenesis is prolonged illness with deficiency of heart qi, loss of nourishment in the heart, weakness in blood circulation, prolonged stagnation of the heart meridians, cessation of water consumption, and the generation of phlegm and dampness, resulting in heart failure. The theory of "Yang Wei Yin Xian" is a highly summarized understanding by Zhang Zhongjing of the etiology and pathogenesis of chest pain and heartache. Chinese medical master Lei Zhongyi has been practicing medicine for more than 60 years and has unique insights in the prevention and treatment of heart failure, with considerable clinical efficacy. He believes that heart failure belongs to the principle of deficiency and excess, and the theory of "yang micro yin string" is also applicable to this disease. Its onset is closely related to the pathological changes of substances such as qi, blood, and body fluids. The method of treating phlegm and blood stasis together should run through the treatment process, especially for patients who consume qi and yin in the later stage. Emphasis should be placed on promoting blood circulation and nourishing qi and yin, and the treatment should focus on both attacking and tonifying, with Qi and blood regulating simultaneously. Based on clinical experience, the original Yangxin Huoxue Tang has achieved significant clinical efficacy.

Amyotrophic Lateral Sclerosis and swim training affect copper metabolism in skeletal muscle in a mouse model of disease.

Swim training and regulation of copper metabolism result in clinical benefits in amyotrophic lateral sclerosis (ALS) mice. Therefore, the study aimed to determine whether swim training improves copper metabolism by modifying copper metabolism in the skeletal muscles of ALS mice. SOD1G93A mice (n = 6 per group) were used as the ALS model, and wild-type B6SJL (WT) mice as controls (n = 6). Mice with ALS were analyzed before the onset of ALS (ALS BEFORE), at baseline ALS (first disease symptoms, trained and untrained, ALS ONSET), and at the end of ALS (last stage disease, trained and untrained, ALS TERMINAL). Copper concentrations and the level of copper metabolism proteins in the skeletal muscles of the lower leg were determined. ALS disease caused a reduction in the copper concentration in ALS TERMINAL untrained mice compared with the ALS BEFORE (10.43 ± 1.81 and 38.67 ± 11.50 μg/mg, respectively, p = .0213). The copper chaperon for SOD1 protein, which supplies copper to SOD1, and ATPase7a protein (copper exporter), increased at the terminal stage of disease by 57% (p = .0021) and 34% (p = .0372), while the CTR1 protein (copper importer) decreased by 45% (p = .002). Swim training moderately affected the copper concentration and the concentrations of proteins responsible for copper metabolism in skeletal muscles. The results show disturbances in skeletal muscle copper metabolism associated with ALS progression, which is moderately affected by swim training. From a clinical point of view, exercise in water for ALS patients should be an essential element of rehabilitation for maintaining quality of life.

Research Progress of Traditional Chinese Medicine Based on TGF-β/Smad Signal Pathway in Preventing and Treating Myocardial Fibrosis in Heart Failure

Heart failure is the terminal stage of cardiovascular disease, and its pathological mechanism is ventricular remodeling. Therefore, the fundamental of preventing and treating heart failure is to inhibit ventricular remodeling. The important link of ventricular remodeling is myocardial fibrosis. It can prevent and cure heart failure by inhibiting the occurrence of myocardial fibrosis. By querying relevant domestic and foreign literatures in recent years, it was found that TGF-β/Smad signaling pathway plays an important role in the development of myocardial fibrosis, it may reduce cell damage through anti-inflammatory, antioxidant stress, anti-apoptosis, etc., Maintaining extracellular matrix stability, alleviate the degree of myocardial fibrosis, Chinese medicine in the prevention and treatment of fibrosis has high efficacy, multi-target, improve long-term prognosis and other advantages. To explore a more accurate target drug for preventing and treating myocardial fibrosis in heart failure, reduce the rate of readmission of patients with heart failure, and provide a greater possibility for promoting the prevention and treatment of myocardial fibrosis in heart failure by traditional Chinese medicine.

Aerobic exercise-induced HIF-1α upregulation in heart failure: exploring potential impacts on MCT1 and MPC1 regulation

BackgroundThe terminal stage of ischemic heart disease develops into heart failure (HF), which is characterized by hypoxia and metabolic disturbances in cardiomyocytes. The hypoxic failing heart triggers hypoxia-inducible factor-1α (HIF-1α) actions in the cells sensitized to hypoxia and induces metabolic adaptation by accumulating HIF-1α. Furthermore, soluble monocarboxylic acid transporter protein 1 (MCT1) and mitochondrial pyruvate carrier 1 (MPC1), as key nodes of metabolic adaptation, affect metabolic homeostasis in the failing rat heart. Aerobic exercise training has been reported to retard the progression of HF due to enhancing HIF-1α levels as well as MCT1 expressions, whereas the effects of exercise on MCT1 and MPC1 in HF (hypoxia) remain elusive. This research aimed to investigate the action of exercise associated with MCT1 and MPC1 on HF under hypoxia.MethodsThe experimental rat models are composed of four study groups: sham stented (SHAM), HF sedentary (HF), HF short-term exercise trained (HF-E1), HF long-term exercise trained (HF-E2). HF was initiated via left anterior descending coronary artery ligation, the effects of exercise on the progression of HF were analyzed by ventricular ultrasound (ejection fraction, fractional shortening) and histological staining. The regulatory effects of HIF-1α on cell growth, MCT1 and MPC1 protein expression in hypoxic H9c2 cells were evaluated by HIF-1α activatort/inhibitor treatment and plasmid transfection.ResultsOur results indicate the presence of severe pathological remodelling (as evidenced by deep myocardial fibrosis, increased infarct size and abnormal hypertrophy of the myocardium, etc.) and reduced cardiac function in the failing hearts of rats in the HF group compared to the SHAM group. Treadmill exercise training ameliorated myocardial infarction (MI)-induced cardiac pathological remodelling and enhanced cardiac function in HF exercise group rats, and significantly increased the expression of HIF-1α (p < 0.05), MCT1 (p < 0.01) and MPC1 (p < 0.05) proteins compared to HF group rats. Moreover, pharmacological inhibition of HIF-1α in hypoxic H9c2 cells dramatically downregulated MCT1 and MPC1 protein expression. This phenomenon is consistent with knockdown of HIF-1α at the gene level.ConclusionThe findings propose that long-term aerobic exercise training, as a non- pharmacological treatment, is efficient enough to debilitate the disease process, improve the pathological phenotype, and reinstate cardiac function in HF rats. This benefit is most likely due to activation of myocardial HIF-1α and upregulation of MCT1 and MPC1.

Bacterial outer membrane vesicle-cancer cell hybrid membrane-coated nanoparticles for sonodynamic therapy in the treatment of breast cancer bone metastasis

Breast cancer bone metastasis is a terminal-stage disease and is typically treated with radiotherapy and chemotherapy, which causes severe side effects and limited effectiveness. To improve this, Sonodynamic therapy may be a more safe and effective approach in the future. Bacterial outer membrane vesicles (OMV) have excellent immune-regulating properties, including modulating macrophage polarization, promoting DC cell maturation, and enhancing anti-tumor effects. Combining OMV with Sonodynamic therapy can result in synergetic anti-tumor effects. Therefore, we constructed multifunctional nanoparticles for treating breast cancer bone metastasis. We fused breast cancer cell membranes and bacterial outer membrane vesicles to form a hybrid membrane (HM) and then encapsulated IR780-loaded PLGA with HM to produce the nanoparticles, IR780@PLGA@HM, which had tumor targeting, immune regulating, and Sonodynamic abilities. Experiments showed that the IR780@PLGA@HM nanoparticles had good biocompatibility, effectively targeted to 4T1 tumors, promoted macrophage type I polarization and DC cells activation, strengthened anti-tumor inflammatory factors expression, and presented the ability to effectively kill tumors both in vitro and in vivo, which showed a promising therapeutic effect on breast cancer bone metastasis. Therefore, the nanoparticles we constructed provided a new strategy for effectively treating breast cancer bone metastasis.Graphical

#2125 Endotypes of kidney injury in patients with acute decompensation of heart failure and their impact on long-term mortality

Abstract Background and Aims Renal dysfunction with and without albuminuria is common in patients with heart failure and associated with poorer outcomes. However, the prevalence and long-term influence of increased urine albumin creatinine ratio (uACR) and/or isolated decreased glomerular filtration rate (GFR &amp;lt; 60 ml/min/1,73 m2) have not been well studied in patients with acute decompensation of heart failure (ADHF). The aim was to investigate the prevalence of different variants of kidney injury and their impact on the mortality in patients with ADHF within 1 year of follow-up. Method This prospective, observational study included 140 patients who were discharged after ADHF. We excluded patients with terminal stage of chronic kidney disease, end-stage heart failure, malignancy. Patients were divided according to the kidney function (the maximum level of GFR) and albuminuria level taken at hospitalization into four groups: normal renal function (GFR&amp;gt;60 ml/min/1,73 m2, uACR&amp;lt;30 mg/gCr), isolated decreased GFR (GFR&amp;lt;60 ml/min/1,73 m2, uACR&amp;lt;30 mg/gCr), isolated albuminuria (GFR&amp;gt;60 ml/min/1,73 m2, uACR&amp;gt;30 mg/gCr), combined changes (GFR&amp;lt;60 ml/min/1,73 m2, uACR&amp;gt;30 mg/gCr). The observation period was 365 days. Results During hospitalization 25% (n = 35) patients had GFR&amp;gt;60 ml/min/1,73 m2, uACR&amp;lt;30 mg/gCr, 19.3% (n = 27) patients had isolated decreased GFR, 22.8% (n = 32) patients had isolated uACR&amp;gt;30 mg/gCr, and 32.9% (n = 46) patients had both. The baseline and admission characteristics are presented in the table (Fig. 1). 34 (24,3%) patients died during follow-up. Mortality was remarkably higher in groups with registered albuminuria during hospitalization regardless of GFR level (25% (n = 8) patients with isolated increased uACR, 39.1% (n = 18) patients with combined changes; with non-albuminuria: (11.4% (n = 4) patients with GFR&amp;gt;60 ml/min/1,73 m2, uACR&amp;lt;30 mg/gCr, 14.8% (n = 4) patients with isolated decreased GFR, p = 0.019 for trend). Kaplan-Meier plots revealed worse outcomes for these groups after adjusting for ejection fraction (EF) (Log-Rank p = 0.0057) (Fig. 2). In the multivariate Cox regression, in which age, gender, reduced EF and three categories of kidney damage were included, only combination of decreased GFR and albuminuria was an independent predictor of long-term mortality (hazard ratio: 3.71 95% confidential interval 1.59 to 8.67, p = 0.002). Conclusion Albuminuria is frequently observed in patients with ADHF and, especially with combination with decreased GFR, associated with higher mortality rate during 1 year of follow-up. Albuminuria with decreased GFR during hospitalization with ADHF was an independent risk factor for mortality during one year.

Formulation and application of the "hospital-to-home + online-to-offline" treatment scheme in caring for and supporting vulnerable patients with chronic heart failure.

Chronic heart failure (CHF) is the terminal stage of cardiovascular disease. In this study, the "hospital-to-home + online-to-offline" (H2H + O2O) care scheme was implemented for patients with CHF during vulnerable periods, and its effect was evaluated. Patients with CHF in the cardiovascular department of a Class III/Grade A hospital in Jiangxi Province from January to December 2020 were selected using a convenience sampling method and randomly divided into a control and intervention group (n= 100 each). The patients in the control group received routine in-hospital treatment and out-of-hospital follow-up, while in the intervention group, a multi-disciplinary cooperation team with CHF specialist nurses evaluated and stratified the patients before discharge and formulated individualized prescriptions and care plans. Based on the "Health & Happiness" chronic disease follow-up application designed for this study, the specialist nurses provided patients with one-to-one guidance. After three months, the cardiac function, heart failure knowledge, self-care behavior, and re-hospitalization rate of the patients were compared between the two groups. Cardiac function was evaluated by the serum B-type natriuretic peptide (BNP), the left ventricular ejection fraction (LVEF), and a six-minute walking test (6MWT). Heart failure knowledge and self-care behavior was assessed using specific questionaries. The level of cardiac function in the intervention group was significantly higher than that in the control group, and the difference was statistically significant (P< 0.001). The mastery of heart failure knowledge and self-care behavior in the intervention group were significantly higher than those in the control group, and the differences were statistically significant (P< 0.05). The re-hospitalization rate due to CHF in the intervention group was 21.0%, which was lower than that in the control group (35.0%), and the difference was statistically significant (P< 0.05). The H2H + O2O care scheme can be used for the transition of vulnerable patients with CHF from the hospital to family care to improve the patients' level of cardiac function, elevate their knowledge level and self-care abilities, and improve their overall health outcomes.

End-of-life decisions in the intensive care unit-exploring the knowledge and attitude of nurses and doctors: a national survey

Aim: In our country, there is a growing awareness regarding end-of-life practices. It has become evident that treatments in intensive care to end-stage patients, instead of honoring their previously made end-of-life decisions, significantly diminishes patients’ overall quality of life. The aim of study is drawing attention to end-of-life decision practices and to evaluate the knowledge and attitudes of intensive care physicians and nurses, who are decisive in end-of-life decision-making practices. Methods: The study was planned as a multi-center, cross-sectional, descriptive questionnaire. There were 21 questions about demographic data, definitions, and end-of-life decisions. 259 of 760 intensive care physicians and nurses who filled out the questionnaire were included. Results: Two hundred and fifty-nine participants were included. The rate of decision for terminal sedation and euthanasia was differentiating according to intensive care experience. Participants’ knowledge was insufficient regarding withholding and withdrawal approaches. Intensive care physicians, and patients at the terminal stage of chronic disease were recommended as decision makers with the highest rate. Conclusion: In this study, it was determined that the participants' knowledge about end-of-life decision concepts was not sufficient, and their approaches were differentiating due to experience. It is considered that there is a need for education and standardization about end-of-life decision-making process.

Immune profile of patients with peritoneal carcinomatosis selected for CRS-HIPEC therapy.

Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option for peritoneal carcinomatosis (PC) from colorectal cancer (CRC), which is otherwise a terminal stage of disease. Nevertheless, survival outcomes are only marginally superior to other treatments. This fact highlights the need for better strategies to control intra-abdominal disease recurrence after CRS-HIPEC, including the complementary use of immunotherapies. The aim of this study was therefore to investigate the immune phenotype of T cells in patients with PC. Fifty three patients with CRC (34 patients with PC and 19 patients without PC) were enrolled in a prospective study (clinicaltrials.gov: NCT04108936). Peripheral blood and omental fat were collected to isolate peripheral blood mononuclear cells (PBMCs) and adipose tissue mononuclear cells (ATMCs). These cells were analysed by flow cytometry using a panel focused upon T cell memory differentiation and exhaustion markers. We found a more naïve profile for CD8+ T cells in peripheral blood and intra-abdominal fat of PC patients compared to comparator group (CG) patients. Furthermore, there was an over-representation of CD4+ T cells expressing inhibitory receptors in adipose tissue of PC patients, but not in blood. Our description of intraperitoneal T cell subsets gives us a better understanding of how peritoneal carcinomatosis shapes local immune responses.

Longitudinal changes in patient reported outcome measures in patients with cancer six months prior to death: A case-control study.

1585 Background: Provider assessments consistently fall short in determining when cancer patients enter into the terminal phase of their disease. Despite prior desires to spend their last days outside an institution, patients often seek emergency room care and most report never having a palliative consultation at the time of their terminal admission. Patient reported outcome measures (PROMs) are derived directly from the patient and may provide insight into the experience near the end of life to facilitate earlier involvement of supportive oncology. This study aims to compare PROMs in the 6 months prior to death to those not dying among patients with cancer. Methods: This study uses a routine PROMs program implemented since September 2020 for all patients with a cancer diagnosis at a tertiary care hospital. This study focused on PROMs using 3 domains of the Patient Reported Outcomes Measurement Information System (PROMIS): physical function, pain interference, and fatigue; PROMs frequency mirrored patients’ oncologic visits. Using a retrospective case-control study, patients who had died within 6 months of a PROMs response (cases) were compared to controls who were alive at the time of the case’s death. Cases were matched 1:2 to controls by age at PROMs completion, gender, cancer disease site, and stage. Generalized estimating equation (GEE) models adjusted for age at PROMs completion, gender, cancer disease site, stage, and correlations between individual patient encounters were used to compare mean PROMs scores between cases and controls in each domain. Results: In total, 274 cases were compared to 270 unique controls. Univariate comparisons between cases and controls demonstrated significant differences only in Charlson Comorbidity Index (CCI), with cases demonstrating worse CCI (3.3 ± 2.5) compared to controls (2.3 ±2.2; p &lt; 0.001). Time from diagnosis to PROMs completion was not different between groups (4.08 versus 4.10 years, p = 0.798). Over the 6 months prior to death, 10.5%/15.0%/32.0% cases had severe pain/fatigue/physical function scores compared to 3.3%/3.7%.8.7% in controls (p &lt; 0.001). GEE models demonstrated that cases had a higher mean fatigue score of 5.34 points (95% CI = 3.81 to 6.88), higher mean pain interference score of 4.92 points (95% CI = 3.42 to 6.43), and lower mean physical function score of 7.39 points (95% CI = -8.84 to -5.93) indicating more severe symptom scores for cases in all three domains. Conclusions: On average, patients experiencing death within 6 months of PROMs completion demonstrated worse physical functioning, pain interference, and fatigue scores compared to their age, gender, cancer disease site, and stage matched controls. The differences in PROMs scores represent a first step to improving understanding of PROMs during the terminal stage of disease and may guide indicators for earlier need of supportive oncology support.

Myeloid sarcoma of the larynx as manifestation of the terminal stage of myeloproliferative disease

A rare clinical observation of advanced myeloid sarcoma developed through blast transformation of post-polycythemia vera myelofibrosis as extramedullary manifestation of acute myeloid leukemia affecting larynx, laryngopharynx, trachea, soft tissues of the neck, pleura, and skeletal bones is presented.

Билатеральное стентирование почечных артерий как метод лечения вазоренальной гипертензии и хронической болезни почек. Клинический случай и обзор литературы

The purpose — to analyze current data on renal artery stenting in vasorenal hypertension, ischemic nephropathy, and end-stage renal failure; to consider a clinical case. Material and methods. A clinical case is presented of bilateral stenting of the renal arteries in a patient with vasorenal hypertension, chronic kidney disease of the fifth degree in a multidisciplinary hospital with a favorable course. The article describes the clinical results after endovascular intervention, a literature review on the management and selection of patients with renal artery stenosis for revascularization. Results. After simultaneous bilateral stenting of the renal arteries in a patient with end-stage renal insufficiency, renal function returned to normal; the patient stopped the sessions of programmed hemodialysis. Conclusions. Stenting of renal arteries can normalize the kidney function even in the terminal stage of chronic kidney disease. There are no clear clinical recommendations for the selection of patients for renal arteries endovascular stenting in the terminal stage of chronic kidney disease. The tactic of simultaneous bilateral stenting was obviously justified in this clinical case.

Morphological changes in the brain in liver cirrhosis of alcoholic and viral etiology

Background. Hepatic encephalopathy is an actual problem of modern medicine. However, its pathogenesis and histological picture are currently insufficiently studied. Less is known about the impact of the nature of primary liver disease on pathogenesis and histological picture of hepatic encephalopathy. This determines the relevance of further morphological studies of the brain in the late stages of liver cirrhosis of various etiologies.The aim. To establish and compare the morphological changes in the brain in alcoholic liver cirrhosis and viral (hepatitis C virus (HCV)) cirrhosis.Materials and methods. The morphological study of the brain of 40 deceased in outcome of HCV-associated cirrhosis and 23 patients died in outcome of chronic alcoholism was carried out. Histological changes in various parts of the brain were studied using survey and elective stains. The immunohistochemical study of HCV NS3 and CD68 expression in different brain regions was performed in cases of HCV-infection.Results. The changes of neurons, glial cells and cerebral microvessels underlie in the basis of morphological picture of brain damage in both studied groups underlie that corresponds to the “classical” model of hepatic encephalopathy pathogenesis. At the same time, a number of morphological features were observed. The most prominent differences concerned the manifestations of the glial reaction. The productive changes of macroglial cells with the appearance of multiple Alzheimer’s astrocytes type 2 as well as spongious changes in subcortical white matter dominated in the observations of alcoholic cirrhosis. In contrast, microglia cells reaction (microgliosis) in white matter was noticed in HCV-associated cirrhosis.Conclusions. The differences in histological signs of brain in the terminal stages of liver disease of viral and alcoholic etiology are shown. They broaden current idea of morphological picture of hepatic encephalopathy, and may be used to study its pathogenesis.

Liver cirrhosis in children

Liver cirrhosis in children and adolescents is a consequence of a variety of chronic liver diseases, metabolic disorders, and genetic diseases. In infants, cirrhosis is most often due to biliary atresia and genetic-metabolic diseases, while in older children it usually occurs as a result of autoimmune hepatitis, Wilson’s disease, alpha-1 antitrypsin deficiency, and primary sclerosing cholangitis. Symptoms of cirrhosis in children and adolescents are not specific. In pediatric patients, the first sign of cirrhosis may more often be low weight gain, weakness, loss of appetite, low-grade fever, as well as more specific signs: transient jaundice, mild pruritus, epistaxis, heaviness in the right hypochondrium, changes in liver density on palpation, hyperbilirubinemia, hyperenzymemia, etc. Complications of pediatric cirrhosis are similar to those observed in adult patients and include gastrointestinal bleeding caused by esophageal varices, ascites, and spontaneous bacterial peritonitis. In pediatric practice, special attention should be paid to nutritional correction in liver cirrhosis since children have higher requirements for protein and micronutrients for growth and development. Treatment of cirrhosis-induced portal hypertension in children and adolescents is mainly based on methods developed for adults. The article deals with diagnostic and differential diagnostic aspects of the terminal stage of liver disease in children. The therapeutic management of patients with cirrhosis of the liver and acute renal failure is based on support of various organ functions. Hemodialysis/ plasmapheresis may serve in some patients as an interim therapy before liver transplantation. The indications for liver transplantation and problems arising after surgery are considered.

Actualization of Positions of Gliflozins in Treatment Algorithms for Patients with Heart Failure: Chronology of Success

INTRODUCTION: Despite the efforts of the cardiologic communities to introduce approaches to treatment of heart failure (HF) based on the highest level of evidence, HF remains one of the least satisfied demands in the therapy of cardiovascular diseases due to high prevalence, poor prognosis and insufficient use of treatment methods with clinically proven effectiveness. The article considers chronology of study and introduction of sodium-glucose cotransporter 2 inhibitors (syn.: gliflozins; SGLT2is) in clinical practice from the moment of creation of the first drug of this group ― florizin ― and further, stepwise with the change of the therapeutic paradigm as the result of performed clinical trials. Thus, EMPAREG OUTCOME, CANVAS, DECLARE-TIMI 58 studies demonstrated that SGLT2is not only produce a glucosuric effect, but also reduce the development and progression of HF and increase the life expectancy of patients with type 2 diabetes mellitus (DM2) and with reduced left ventricular ejection fraction (LFEF). DAPA-HF, EMPEROR-Reduced studies proved a possibility of improving the outcomes for patients with HF with reduced LVEF irrespective of the presence or absence of DM2, thereby significantly expanding the potential target group for SGLT2is. EMPEROR-Preserved study is the only study of SGLT2is to date (the study drug ― empagliflozin) that has demonstrated high effectiveness of the drug in prevention of cardiovascular mortality and hospitalizations for HF, probably irrespective of LVEF and the existence of DM2. In result, on September 9, 2021, FDA (Food and Drug Administration, USА) assigned the breakthrough therapy status to Jardiance (empagliflozin) drug for treatment of HF with preserved LFEF. EMPA-REG OUTCOME, DAPA-HF, EMPEROR-Reduced, EMPEROR-Preserved, DAPA-CKD studies have shown SGLT2is to slow down the development of the terminal stage of chronic kidney disease. Finally, the main result of EMPULSE study completed in 2022, was the proven clinical benefit of empagliflozin in hospitalized and stabilized patients with acute HF decompensation irrespective of HF status and existence of DM2.&#x0D; CONCLUSION: From the moment SGLT2is have been introduced in the clinical practice, they rapidly and successfully passed the way from the second-line antidiabetic drugs for which it was just enough not to worsen the prognosis for serious cardiovascular complications, to independent and effective class of drugs for treatment of HF (with class I and IIa recommendations). The totality of clinical trials of empagliflozin showed that empaflorizin is so far the only drug of the SGLT2is group with the proven safety and clinical effectiveness including the influence on the prognosis, in patients with HF irrespective of the LVEF status, presence or absence of DM2, for use in outpatient treatment and in stabilized patients in hospital.

Preoperative care for patients in terminal stage of disease from the perspective of nurses

Objective: to understand the meanings attributed by nurses to preoperative care provided to terminal disease patients. Methods: qualitative research that used the Grounded Theory as methodological reference and was conducted in the surgical wards of a university hospital. Results: eleven nurses participated in the research. A theory was elaborated for the central phenomenon: Nurses caring for terminal disease patients in the preoperative period in the context of a surgical ward. Conclusion: nurses attribute meanings to this care that has its own particularities, that requires professional preparation and that demands, even more, an effective communication within the multidisciplinary team and in the relationship with the patient and family. Contributions to practice: the theory presented allows professionals to reflect on their praxis, understand the intervening conditions for ethical dilemmas and conflicts involved and consequences, as well as strategies to improve care in this scenario.

Immune disorders in dogs with chronic kidney disease: Review

The aim of this literature review was to identify the stages of chronic kidney disease in dogs that have greater immune dysfunction and which cellular components of the innate and humoral immune system are most affected by the retention of uremic toxins. Chronic kidney disease is characterized by being a serious and irreversible disease, but common in the practice of medical clinic for dogs and cats and usually affects those of advanced age. The consequences of chronic kidney disease can expand to other systems as the disease progresses; systemic arterial hypertension, hypertensive retinopathies and secondary renal hyperparathyroidism are examples of extra-renal impairment caused by chronic kidney disease. The Interest Renal Society (IRIS), established degrees of progression of renal impairment according to serum concentrations of symmetrical creatinine and dimethylarginine, biomarkers of kidney injury, which allows aid in diagnosis, classification of the degree of nephrological and systemic impairment and treatment affected patient. Studies in human patients demonstrate that, in the terminal stages of kidney disease, there is an impairment of the immune function of these patients, which contributes to the increase in the rate of deaths related to secondary infections, cancers caused by viruses and low responsiveness to vaccines. In Veterinary Medicine, despite the scarcity of research on immunosuppression in dogs with chronic kidney disease, some have observed, in vitro and in vivo environments, dysfunction in the innate and humoral immune system of dogs with advanced chronic kidney disease, due to the proinflammatory environment resulting from the retention of uremic toxins that had their clearance affected by impaired kidney excretory function. Stage III of chronic kidney disease in dogs requires greater care, not only to prevent the disease from progressing to stage IV, but also to prevent immune disorders that may result in death. The adoption of intervention criteria and measures aimed at preventing and / or minimizing these immunological disorders depends on the expansion of research on this topic to establish better clinical management for dogs with nephrological disorder.

Malignant tracheoesophageal fistula: diagnosis and management

: Tracheoesophageal fistula (TEF) refers to a pathological connection between the tracheo-bronchial tree and esophagus, and may be found in 5–15% of esophageal and 1% of tracheo-bronchial malignancies. Individuals with such advanced malignancy resulting in TEF, are usually at terminal stages of disease. They are often burdened with intolerance to feeding and are subject to frequent pulmonary infections secondary to respiratory contamination. Presentation varies from mild coughing to florid sepsis due to aspiration pneumonia. Diagnosis can usually be made by bronchoscopy and esophagoscopy. In cases where the TEF is small and cannot be visualized by these methods, fluoroscopic swallow evaluation may be useful. The primary aims of treatment are to initiate broad spectrum antibiotics when sepsis is present, to separate the esophagus from the respiratory tree preventing soilage, and to ensure enteral nutrition. In order to determine the approach to management, patients may be categorized into those who present with TEF without a diagnosis of a malignancy, those who present with TEF during oncological treatment with chemotherapy and/or radiation, and those in remission after treatment with definitive chemotherapy and/or radiation, and have developed TEF as a complication. The mainstay of therapy is endoscopic stenting of the esophagus and/or airway. Definitive surgical intervention is usually reserved for patients who are tumor free and involves take-down of the fistula with interposition of a muscle flap. Although therapy is mainly palliative in most circumstances, a systematic approach to this disease may provide patients with a better quality of life.

MO358: Analysis of Acute Kidney Injury Incidence in Patients After Left Ventricle Assist Device Implantation

Abstract BACKGROUND AND AIMS Chronic heart failure (CHF) in the terminal stage is a crucial issue of medicine. Heart transplantation is still the best treatment option. Lack of donors, long waiting time make heart transplantation almost impossible. Implantation of left ventricular assist device—LVAD) in patients with CHF is a bridge to transplantation. Nevertheless, the LVAD implantation procedure is time-consuming, requires significant material costs, and leads to numerous complications in the postoperative period. Acute kidney injury (AKI) is one of the most common and dangerous complications. Issues of AKI in patients with LVAD should be carefully taught. The aim of the study is to examine the incidence of postoperative renal failure after the implantation of LVAD and its relationship to outcomes. In addition, we want to share with our experience of AKI management in patients with LVAD. METHOD A retrospective analysis of 265 medical records of patients after surgical implantation of LVAD who were hospitalized to the National Research Cardiac Surgery Center, Nur-Sultan city, Kazakhstan. Period of hospitalization from 01.2015 to 10.2021 year. The Kidney Disease Improving Global Outcome (KDIGO) criteria were used to define AKI. RESULTS Total number of patients 265 after LVAD implantation. Male—85.66% and female—14.34%. Mean ICU stay of patient without severe AKI—7.17±5.47 days. Mean ICU stay of patient with severe AKI—11.82±7.47 days. Patients with severe AKI and blood purification—59 patients (24.9%), male—61–92.4%, femal—-5–7.6%. Total number of LVAD patients—265. ICU Mortality rate of patients after LVAD implantation—11 patients (4.15%). Severe AKI—59 patients (22.3%). Recovery of AKI—47 patients (79.66%). Transformation to terminal stage of chronic renal disease (CRD) with chronic dialysis—1 patient (1.69%). ICU Mortality rate of patients with severe AKI—11 (18.64%). CONCLUSION AKI is a common complication in the immediate postoperative period after LVAD implantation. AKI negatively affects the outcome of the disease. The mortality rate of LVAD patients with renal insufficiency exceeds by 14% the mortality of patients with renal insufficiency. Blood purification is the effective method of severe AKI therapy.