Form Of Chronic Disease Research Articles

Strategies for General Practitioners to Enhance Cancer Care: Insights from a Patient-Centered Questionnaire Survey in Southern China.

The incidence of cancer is increasing, and cancer survivors are also growing exponentially. Cancer is defined as a new chronic disease. Nevertheless, the management of cancer in the form of chronic diseases in China is still in its infancy, without a standardized care model. This study aimed to explore the current status of management of cancer care from the patient's perspective. This cross-sectional study was a questionnaire survey of patients diagnosed with cancer, including information of the current situation of daily medical consultation, status of comorbidity, and expectations of seeking cancer care in future. Chi-square test and logistic regression analysis were used to explore the factors influencing patients' choice of cancer management mode. A total of 200 cancer patients were included in the study. The majority (n = 150) of cancer patients chose an oncologist in a tertiary hospital for cancer care. Difficulty in registration (45%), time-consuming (34.5%), repeated examinations (34.5%) and different treatment opinions (12.0%) were the main difficulties they encountered currently during tertiary hospital visits. In community hospital, lack of trust in general practitioners (n = 33) and the necessary drugs or testing items in community hospitals (n = 47) were the main difficulties during their visits. Logistic regression analysis showed that male (OR = 2.737, 95% CI, 1.332-5.627, p = 0.006) and elderly patients (OR = 3.186, 95% CI, 1.172-8.661, p = 0.023) were more likely to choose general practitioners (GPs) in community hospitals. Twenty-nine (14.5%) patients hope to have an integrated multidisciplinary management in tertiary and community hospitals with the active participation of GPs for cancer care. Improving drug availability, equipment and quality of cancer care services can help to increase cancer patients' recognition of community hospital. In addition, the multidisciplinary management integrated tertiary hospitals and communities with the participation of GPs is a worth exploring mode that improves the management of cancer care.

Nanomaterials in Drug Delivery: Strengths and Opportunities in Medicine.

There is a myriad of diseases that plague the world ranging from infectious, cancer and other chronic diseases with varying interventions. However, the dynamism of causative agents of infectious diseases and incessant mutations accompanying other forms of chronic diseases like cancer, have worsened the treatment outcomes. These factors often lead to treatment failure via different drug resistance mechanisms. More so, the cost of developing newer drugs is huge. This underscores the need for a paradigm shift in the drug delivery approach in order to achieve desired treatment outcomes. There is intensified research in nanomedicine, which has shown promises in improving the therapeutic outcome of drugs at preclinical stages with increased efficacy and reduced toxicity. Regardless of the huge benefits of nanotechnology in drug delivery, challenges such as regulatory approval, scalability, cost implication and potential toxicity must be addressed via streamlining of regulatory hurdles and increased research funding. In conclusion, the idea of nanotechnology in drug delivery holds immense promise for optimizing therapeutic outcomes. This work presents opportunities to revolutionize treatment strategies, providing expert opinions on translating the huge amount of research in nanomedicine into clinical benefits for patients with resistant infections and cancer.

The venereal morbidity in Russia in 1914-1924

It is accepted to explain increasing of venereal diseases during years of the Revolution by degradation of morality and general disorder of system of state administration and sanitary services in Russia. The cross-verification of information presented in scientific publications and primary information sources makes it possible to look into following issues: degree of venereal (syphilitic) contamination of population of pre-revolutionary Russia; influence on sanitary statistics by erroneous diagnostics and convictions of Zemstvo medicine about predominantly non-sexual path of transmission of syphilis pathogen in Russian countryside; dynamics and sources of venereal morbidity in wartime. The high indicators of pre-revolutionary statistics of venereal infections could be affected by diagnostic errors. The "village syphilis" encountered in public milieu could be completely different disease not sexually transmitted and not chronic form of disease. The primary documents allow to discuss increasing of the number of venereal patients during war years, that however, does not reach catastrophic numbers that can be found even in scientific publications. This is also confirmed by data of Chief Military Sanitary Board of the Red Army for 1920s and statistical materials of People's Commissariat of Health Care of the RSFSR. The high morbidity was demonstrated by same Gubernias that were problematic before the Revolution and only later by those ones through which during the war years passed army masses. In Russia, total level of syphilis morbidity after the end of Civil War occurred to be more than twice lower than in pre-war 1913 and continued to decrease under impact of sanitary measures of Soviet public health.

Vaccination-based immunotherapy to target profibrotic cells in liver and lung.

Fibrosis is the final path of nearly every form of chronic disease, regardless of the pathogenesis. Upon chronic injury, activated, fibrogenic fibroblasts deposit excess extracellular matrix, and severe tissue fibrosis can occur in virtually any organ. However, antifibrotic therapies that target fibrogenic cells, while sparing homeostatic fibroblasts in healthy tissues, are limited. We tested whether specific immunization against endogenous proteins, strongly expressed in fibrogenic cells but highly restricted in quiescent fibroblasts, can elicit an antigen-specific cytotoxic Tcell response to ameliorate organ fibrosis. In silico epitope prediction revealed that activation of the genes Adam12 and Gli1 in profibrotic cells and the resulting "self-peptides" can be exploited for Tcell vaccines to ablate fibrogenic cells. We demonstrate the efficacy of a vaccination approach to mount CD8+ Tcell responses that reduce fibroblasts and fibrosis in the liver and lungs in mice. These results provide proof of principle for vaccination-based immunotherapies to treat fibrosis.

Mean Blood Glucose Level and Basal Metabolic Index of Adult Residents of a Semi-Urban Community in Rivers State, Nigeria

This study was carried out on an adult population in Semi urban communities of Rivers State, Nigeria. The aim of the study is to determine if any relationship exist between blood glucose level and basal metabolic index. The subjects were randomly selected among the population and those who met the inclusion criteria were recruited and used for the study. They were apparently healthy subjects with no known history of a metabolic or any other form of chronic diseases. The sample size included a total of 168 subjects [108 males and 60 females] aged between 18 to 55 years. Clinical history and clinical examination methods were employed for sample/data collection. The height (m) and weight (kg) were measured using a stadiometer. The basal metabolic index (BMI) was calculated using the formula: (weight (kg) / height (m2). Random blood glucose (mg/dl) was obtained using a glucometer. The Statistical Program for Social Sciences (SPSS version 21.0) was used for the analysis. The significance of differences between and among group means was tested using analysis of variance (ANOVA) and multiple group means were compared using the post hoc test. To determine the link between variables, Pearson correlation analysis was used. Statistical significance was defined as a P- value of less than 0.05. In females, there was non-significant very low positive correlation between the blood glucose and the BMI. In addition, the mean level of glucose in blood for the different BMI categories did not show any significant difference when compared to normal BMI. In males, the mean blood glucose levels for all groups including overweight and obesed were not statistically significant when compared to the normal BMI. A Pearson correlation between blood glucose level and BMI indicated a non-significant markedly low positive correlation. In conclusion, it was discovered that there was a positive correlation between BMI and blood glucose levels in adult males and females in this study.

Frequency of extra articular manifestations in ankylosing spondylitis patients presented at independent university hospital Faisalabad.

Objective: To determine the frequency of extra articular manifestations in Ankylosing spondylitis patients at Independent University Hospital Faisalabad. Study Design: Cross-sectional study. Setting: Rheumatology Division of Internal Medicine Independent University Hospital, Faisalabad. Period: June 2020 to June 2021. Material & Methods: Consecutive one hundred and thirty-nine adult patients with baseline Ankylosing Spondylitis fulfilling the Assessment of spondyloarthropathy society criteria at early stage and Modified New York criteria in chronic form of disease, and fulfilling the selection criteria, were selected through Non-Probability Convenient Sampling technique for this study. Chi square test was used to compare the frequency of extra articular manifestations among disease duration, age groups and treatment group. A p-value ≤ 0.05 was considered statistically significant. Results: In this study, 139 number of patients were selected with confirmed diagnosis of ankylosing spondylitis. Mean age of patients was 32.60 ± 8.5 years with age range of 18 to 50 years. Extra articular manifestations were assessed in all selected patients of ankylosing spondylitis. Enthesitis and dactylitis were found in 8.6% (12) of patients. Uveitis was found in 5% (7) of patients. Similarly, psoriasis was found in 4.3% (6) of patients. Lung fibrosis was found in 3.6% (5) of patients. Inflammatory bowel disease was found in 2.9% (4) of patients. Conclusion: Assessment of extraarticular manifestations in AS was very important. Timely intervention with specific therapy decreases morbidity and mortality related to disease.

Methylation of the AIM2 gene: An epigenetic mediator of PTSD-related inflammation and neuropathology plasma biomarkers.

Posttraumatic stress disorder (PTSD) is associated with inflammation and various forms of chronic disease. The Absent in Melanoma 2 (AIM2) gene has been implicated in mechanisms of inflammation and anxiety, and methylation at a particular locus in this gene (cg10636246) has previously been shown to influence the association between PTSD and elevated C-reactive protein levels in blood. We tested if this association might extend to other indicators of inflammation and to plasma-based measures of neuropathology in a cohort of post-9/11 US military veterans. Using a Bayesian approach, mediation models were tested cross-sectionally (n = 478) and longitudinally (n = 298). Peripheral markers of inflammation and neuropathology were measured with ultra-sensitive Single Molecule Array (Simoa®) technology. Analyses revealed indirect effects of PTSD symptom severity on peripheral indices of both inflammation (interleukin [IL]6, IL-10, tumor necrosis factor-α; indirect standardized [std.] ß range = 0.018-0.023, all p-values adjusted for multiple testing [padj ] < 0.05) and neuropathology (neurofilament light [NFL]; indirect std. ß = -0.018, padj = 0.02) via AIM2 methylation. This indirect effect was also evident when predicting IL-10 at a follow-up assessment (indirect std. ß = -0.018, padj = 0.04) controlling for baseline IL-10. Given that AIM2 methylation mediated the association between PTSD symptoms and multiple inflammatory and neuropathology markers, our results suggest that AIM2 methylation may offer clinical utility for indexing risk for adverse health outcomes associated with these peripheral indices of inflammation and neuropathology. Results also suggest a possible shared etiology underlying the frequent co-occurrence of inflammation and neuropathology.

The active grandparent hypothesis: Physical activity and the evolution of extended human healthspans and lifespans

The proximate mechanisms by which physical activity (PA) slows senescence and decreases morbidity and mortality have been extensively documented. However, we lack an ultimate, evolutionary explanation for why lifelong PA, particularly during middle and older age, promotes health. As the growing worldwide epidemic of physical inactivity accelerates the prevalence of noncommunicable diseases among aging populations, integrating evolutionary and biomedical perspectives can foster new insights into how and why lifelong PA helps preserve health and extend lifespans. Building on previous life-history research, we assess the evidence that humans were selected not just to live several decades after they cease reproducing but also to be moderately physically active during those postreproductive years. We next review the longstanding hypothesis that PA promotes health by allocating energy away from potentially harmful overinvestments in fat storage and reproductive tissues and propose the novel hypothesis that PA also stimulates energy allocation toward repair and maintenance processes. We hypothesize that selection in humans for lifelong PA, including during postreproductive years to provision offspring, promoted selection for both energy allocation pathways which synergistically slow senescence and reduce vulnerability to many forms of chronic diseases. As a result, extended human healthspans and lifespans are both a cause and an effect of habitual PA, helping explain why lack of lifelong PA in humans can increase disease risk and reduce longevity.

Sleep disorders in children with rheumatic diseases

Rheumatic diseases (RD) are often diagnosed in childhood. Sleep disorders are commonly associated with RD in children. It is stressed that sleep disorders found in this type of clinical pathology cannot be exceptionally considered as an epiphenomenon typical to any form of chronic disease; rather, sleep disorders should be regarded as a part of the clinical manifestations of RD. An important role in the origins of this association is played by specific inflammatory mediators involved in the pathogenesis of various RD, which simultaneously affect the structure of sleep and contribute to sleep disorders. There are both nonspecific and characteristic variants of sleep disorders detected in some leading clinical forms of RD in children, in particular in juvenile rheumatoid (idiopathic) arthritis, systemic lupus erythematosus, systemic scleroderma, seronegative spondyloarthropathies, fibromyalgia. There is a relationship between the severity of sleep disorders, the activity of RD, the degree of emotional disorders and pain symptoms in children. Approaches to the correction of sleep disorders in children in the context of the treatment of RD are substantiated.

Generational Medicine in Singapore: A National Biobank for a Greying Nation

The United Nations’ projections for the period between 2019 and 2050 anticipate a rapid rise in population aging in Eastern and South-Eastern Asia. With such population aging often comes a disease burden in the form of chronic diseases, such as diabetes and cardiovascular diseases. In the context of Singapore, we examine the role of a national biobank called Health for Life in Singapore (HELIOS), which positions itself as aiming to improve the health and lives of future generations of Singapore. HELIOS’ aims and actions inform on the anxieties, desires and ambitions of the Singapore state and its healthcare system in the context of its changing population demography. We argue that HELIOS propagates a “sociotechnical imaginary” of what we call “generational medicine,” that posits a crucial role for biobanks in tackling the societal challenge of an aging population.

Manifestation of oxidative stress during pregnancy in women with chronic diseases of hepatobiliary system against the background of reproductive losses

In the early stages of gestation the changes in the lipid peroxidation can lead to violations of regulatory and protective functions of biomembranes in pregnant women. The objective: to study the changes in the concentration of intermediate and final products of LPO during the first trimester of gestation in patients with early miscarriage against the background of chronic diseases of the hepatobiliary system. Materials and methods. 118 pregnant women in the first trimester of gestation (7-10 weeks), aged 22 - 39 y. o. (mean age 29.4 ± 2.7 years) have been examined.64 women (54.2%) were diagnosed with a risk of miscarriage, and 17 patients were diagnosed with involuntary miscarriage within 10-12 days. All women were diagnosed with non-viral and non-alcoholic chronic HBS paathology: hepatic steatosis had 38 patients (32.2%), 80 patients (67.8%) had non-alcoholic steatohepatitis; in 97 patients (82.2%) chronic non-calculous cholecystitis was diagnosed. The state of lipid peroxidation was assessed by the content of malonic dialdehyde spectrophotometrically, as well as diene conjugates in the blood The indicator of erythrocyte peroxide hemolysis was examined by the level of erythrocyte peroxide resistance. Results. A significant increase in intermediate and final products of lipid peroxidation in pregnant women with an unfavorable premorbid background in the form of chronic diseases of the hepatobiliary system and a history of reproductive losses. A significant increase of MDA and DC concentration was found at the risk of premature termination of pregnancy. The degree of PLO processes activation makes these parameters integrative criteria for the detection of systemic metabolic disorders during gestation in women with GBS extragenital pathology. Conclusion. During physiological pregnancy there is an accumulation of metabolites of lipid peroxidation, which is associated with an increase in basic metabolism in women and an increase in oxygen consumption from the blood.

Peculiar features of arterial hypertension state on the background of atherosclerosis (clinical and instrumental comparisons)

A comparative analysis of the clinical and functional state of patients with arterial hypertension (AH), depending on the presence or absence of arterial sclerotic disease of the arterial bed is represented. 2 groups of 110 and 60 patients respectively were formed. The 1st group included persons with arterial hypertension (AH) and atherosclerotic changes in the arterial bed, the 2nd — with hypertension and without any atherosclerotic changes. It is shown that patients with hypertension and stenotic changes of the vascular bed are characterized by an increase in the levels of diastolic blood pressure and indicators of systolic and diastolic pressure load during the day. They have signs of structural changes in the cardiovascular system, as proved by indicators of arterial stiff ness, myocardium remodeling, circadian rhythms of blood pressure abnormalities, and, in addition, kidney damage in a chronic form of disease, stage 2–3.On the contrary, hypertension without atherosclerotic changes of the vascular bed is characterized by higher values of systolic blood pressure, increased variability of systolic and diastolic blood pressure during the day, and, in addition, atherogenic dislipoproteinemia and hyperuricemy within the metabolic syndrome are present. As a clinical sign of atherosclerotic vascular changes in patients with hypertension, more “severe” blood pressure is observed. It requires combined antihypertensive therapy, consisting of 3 or more groups of medications.

Depression in Chronically ill Patients of Railway General Hospital, Pakistan.

According to the World Health Organization (WHO), chronic diseases are the leading cause of death and disability worldwide and estimated to contribute to 73% of all deaths by 2020. In addition to the difficulty in effectively managing chronic diseases, they are often complicated further by the co-morbid depression stemming from the original disease. Depression has the highest burden of disease affecting more than 264 million people worldwide and worsens the burden of co-existing chronic medical diseases as well. A bidirectional relation exists between depression and chronic medical diseases. Statistical mapping of chronically ill patients of Pakistan suggests that 50% of its population suffers from some form of chronic disease. Little data exists for the prevalence of depression in chronically ill patients from most of Pakistan.Our objectives were to observe the patterns of depression in chronically ill patients and outline the need for intervention (if any) on a population of Railway General Hospital (RGH - a tertiary healthcare hospital in Rawalpindi, Pakistan). We also aimed at finding out the relation (if any) of age, gender, number of hospital admissions, education and effectiveness of medical disease management with depression. A cross sectional study was conducted on patients admitted due to their chronic medical diseases out of a population of 11,000 presenting at the medical OPD of RGH over a period of three months using Patient Health Questionnaire-9 (PHQ -9) Urdu version. About 50% of the patients suffered from moderate to severe forms of depression. A significant positive correlation was found between age and past psychiatric history of illnesses other than depression with depression while no significance was found with number of hospital admissions, gender or education level; 35% had suicidal ideation.Depression is quite often dismissed, underdiagnosed and leads to a poor quality of life and decrease in cost effectiveness in our population. Pakistan needs to use more resources on managing depression and medical professionals need to change their attitudes in holistically managing the patients. Treating depression is just as important as managing other symptoms of chronic medical diseases.

Development of asmartphone app for neuromuscular facial training.

Several studies have demonstrated asignificant benefit of neuromuscular facial training in the rehabilitation of patients with facial palsy. However, printed instructions for home training are often not of optimum quality and associated with low adherence to therapy. Professional guidance, e.g., by occupational therapists, is regarded as being of high quality, but is associated with ahigh cost burden, particularly in chronic forms of disease. The idea to develop asmartphone app for facial training arose from the above-described situation. The aim was to provide structured exercises for the mimic muscles in the sense of neuromuscular training with visual feedback via the front camera of the device. Anative app architecture in iOS was chosen to implement the graphical and content-related concept. In the Apple Xcode (Apple, Cupertino, CA, US) development environment, the app's code was written in the Swift programming language (Apple) and the graphical user interface was created. An app prototype was implemented that provides step-by-step instructions on selected mimic exercises via animated smileys. The duration and speed of the exercise can be varied within alimited range. In the development environment, the correct functionality of both physical and virtual devices was successfully tested. App-based facial training offers attractive opportunities to motivate patients for improved adherence to treatment, which could hypothetically lead to abetter outcome. Evaluation of this question is planned in aclinical trial after completion of the development.

ENDOCRINOLOGICAL INTERRELATED DISEASES: CELIAC DISEASE AND DIABETES MELLITUS

The results of the analytical review of scientific material presented in the article are devoted to the problem of intolerance of wheat protein gliadin in people with a predisposition to this food Allergy, as well as materials related to modern means against diabetes, based on the study of the endocrine system. The DPP-4 enzyme (dipeptidylpeptidase 4), which breaks down gluten protein in the human body, and the consequences of deficiency and excessive production of this enzyme in the form of chronic diseases (celiac disease and type II diabetes), were considered as one of the probable causes that combine these diseases. During the evaluation of the scientific material, the principle of determinism was applied to DPP-4, since this enzyme is the only one specifically interacting in the small intestine with gliadin and casein, and violations of the production and activity of this enzyme cause the appearance of gluten enteropathy. The review also presents data from foreign and Russian sources on the means for controlling diabetes based on substances that suppress the production of the enzyme DPP-4, hypersynthesis of which suppresses the production of insulin, which is one of the endocrinological causes of diabetes. Based on the studied data, it can be argued that the most positive and progressive solution to the problem of both chronic diseases is the method proposed by Japanese scientists, based on a special treatment of ginger root protease a, since, having the ability to break down gluten, this drug also leads to the suppression of dipeptidylpeptidase 4, while being a relatively affordable drug.

Development of asmartphone app for neuromuscular facial training. German Version

Several studies have demonstrated asignificant benefit of neuromuscular facial training in the rehabilitation of patients with facial palsy. However, printed instructions for home training are often not of optimum quality and associated with low adherence to therapy. Professional guidance, e.g., by occupational therapists, is regarded as being of high quality, but is associated with ahigh cost burden, particularly in chronic forms of disease. The idea to develop asmartphone app for facial training arose from the above-described situation. The aim was to provide structured exercises for the mimic muscles in the sense of neuromuscular training with visual feedback via the front camera of the device. Anative app architecture in iOS was chosen to implement the graphical and content-related concept. In the Apple Xcode (Apple, Cupertino, California, US) development environment, the app's code was written in the Swift programming language (Apple) and the graphical user interface was created. An app prototype was implemented that provides step-by-step instructions on selected mimic exercises via animated smileys. The duration and speed of the exercise can be varied within alimited range. In the development environment, the correct functionality of both physical and virtual devices was successfully tested. App-based facial training offers attractive opportunities to motivate patients for improved adherence to treatment, which could hypothetically lead to abetter outcome. Evaluation of this question is planned in aclinical trial after completion of the development.

Innate immune receptors in development of Mycobacterium tuberculosis infection

According to the World Health Organization, over 10 million new tuberculosis cases are reported annually worldwide. According to the 2017 Federal State Statistics Service Report, incidence rate for active TB infection in the Russian Federation was 109.8 cases per 100,000 population, of which 41.3% accounted for chronic disease form. Regardless of climatic conditions, high prevalence of TB infection, is not only due to high Mycobacterium tuberculosis viability, but also its ability for long persistence in human body and reactivation after an unlimited period of dormancy. The outcome of infection is largely determined by host immunoreactivity and its ability to develop protective immune response. In addition, status of immune system also underlies tuberculosis course after the onset: either as a localized form, or as a form with extensive damage to the lungs and even other organs observed in generalized infection. In recent decades, a great attention was paid to examining mechanisms of adaptive cell immunity played in pathogenesis of TB infection. No doubt, adaptive immunity is a powerful defense system providing a targeted specific immune response, but now it is becoming clear that it represents solely an effector arm of innate immunity. Innate immunity is a phylogenetically more ancient, inherited system largely aimed at ensuring rapid pathogen elimination and preventing development of infection at early stages when adaptive immunity ongoing antigen-specific maturation. Mechanisms of innate immunity mediated by cells, diverse receptors, molecules and their complexes, found on various cells. Activation of innate immunity begins with recognition of conserved molecular groups present in various pathogens called pathogen-associated molecular patterns (PAMPs), which are sensed by pathogen recognition receptors (PRRs). Here, we review current data on the role of innate receptors in recognizing M. tuberculosis-derived PAMPs, production of immunoregulatory cytokines and activation of signaling pathways playing a crucial role in the regulation of necroptosis, apoptosis and autophagy of infected macrophages. Significance of innate mucosal factors in implementing immune response to M. tuberculosis is discussed. In particular, Toll-like receptors, scavenger-receptors, mannose receptor, DC-SIGN etc. were described to participate in development of M. tuberculosis immunity. The data on single nucleotide polymorphic variants for innate genes are shown, which predispose to developing tuberculosis and affecting its course.

Opioid and benzodiazepine prescription among patients with cirrhosis compared to other forms of chronic disease

ObjectiveData on patterns and correlates of opioid and benzodiazepines prescriptions among patients with chronic conditions are limited. Given a diminished capacity for hepatic clearance, patients with cirrhosis represent a high...

Abstract B121: Checkpoint inhibitor vaccine stimulates antitumor T-cells that block tumor growth

Abstract Checkpoint inhibitor therapy augments pre-existing T-cell responses to tumor antigens, resulting in tumor control in 20-40% of patients with melanoma and other cancers. As a means to increase the effectiveness of this approach, we developed a dendritic cell (DC)-based vaccine strategy that specifically induces anti-tumor T-cell responses and prevents checkpoint activation. The approach is based on lentiviral vectors that express checkpoint inhibitor and tumor antigen and transduce DCs at high efficiency as a result of virion-packaging of the lentiviral accessory protein Vpx. In addition, the vectors express CD40 ligand (CD40L), a cell surface protein that strongly activates DCs, causing the cells to mature and secrete immunostimulatory cytokines, including TNFα, IL-6, and IL-12, that potentiate T-cell responses. The therapy harnesses the ability of DCs to prime T-cell responses against tumors, resulting in long-term antigen expression and continuous, localized release of checkpoint inhibitor during antigen-presentation. In the lymphocytic choriomeningitis virus (LCMV) mouse model, immunization with DCs transduced with lentiviral vectors that express soluble programmed cell death protein 1 (PD-1), CD40L and LCMV epitopes induced a 10-fold expansion of LCMV-specific CD8 T-cells and protected the mice against high-titer LCMV and a lethal intracranial LCMV challenge. Protection was 100-fold greater than that achieved by vaccination with LCMV peptide epitope-pulsed DCs. The strategy also appeared to cure mice infected with clone 13 LCMV, a chronic form of disease that results from T-cell exhaustion induced by checkpoint activation. In the B16-OVA mouse melanoma model, immunization with DCs transduced with vectors that express soluble PD-1, CD40L and OVA epitopes or a tumor antigen epitope from tyrosinase-related protein (TRP-1) protected mice from tumor formation. DC vaccination post-B16 challenge reduced tumor growth and prolonged survival. Mice immunized four days after intravenous injection of B16 cells showed no evidence of lung melanoma nodules three weeks later. Remarkably, immunization by direct injection of lentiviral vector, a method that obviates the need to harvest patient DCs, proved equally effective as ex vivo DC transduction in suppressing tumor growth. In addition, direct injection resulted in a much longer half-life of transduced cells. These studies demonstrate the ability of this approach to induce antigen-specific responses and overcome CTL exhaustion. Moreover, the lentiviral vector approach provides a means to express tumor neoantigens for the development of personalized immunotherapies that stimulate tumor-specific T-cell responses by clones present at low level or to antigens that the host has not responded. Citation Format: Takuya Tada, Nathaniel R. Landau, Thomas David Norton. Checkpoint inhibitor vaccine stimulates antitumor T-cells that block tumor growth [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B121.

Surgical Hip Dislocation Technique in Treatment of Patients with Slipped Capital Femoral Epiphysis

Purpose: to evaluate the efficiency of modified Dunn procedure for treatment of severe slipped capital femoral epiphysis.Material and Methods. The authors used the modified Duim procedure for treatment of 6 patients with SCFE aged from 10 to 13 years and displacement degree over 55°. Chronic disease form was reported in one patient, acute displacement along the chronic process was reported in 5 patients. All patients had a stable form of SCFE by Loder classification. Surgical procedure was performed within 6 to 12 months from the onset of disease.Results. Normal anatomical relations in the hip joint were restored in all patients. During follow up from 18 until 48 months the patients did not demonstrate aseptic femoral head necrosis or chondrolysis. Adolescents did not complain on pain or hip motion limitations. Treatment outcomes assessment by Harris hip score was 97 points.Conclusion. Based on outcomes of the modified Durm procedure the authors conclude that the method provides for complete restoration of the anatomical relations between femoral neck and epiphysis and, thus, the hip joint biomechanics. Femur dislocation allows to form an extended flap to ensure epiphysis perfusion which improves overall blood supply in the femoral head and consequently decreases the risk of aseptic necrosis and chondrolysis