Average Life Expectancy Of Patients Research Articles

Obesity and diabetes, the pandemic of our time: the difficult to manage complication of diabetes, diabetic foot

Overweight and obesity are major problems worldwide, affecting more than half of the adult population. With wrong eating habits, the rise of fast-food culture and sedentary lifestyles, obesity continues to spread almost all over the world. In addition to the many physical problems obesity causes, it also significantly affects mental health. One of the most feared conditions caused by obesity is type 2 diabetes, a systemic disease that negatively affects every part of the body. In addition to the many problems it causes, diabetes causes foot problems in one out of every 6-7 patients throughout their lives, some of which may lead to limb loss and even death. The average life expectancy of patients with diabetic foot is significantly shortened. Treatment of these patients is also very costly. In this case report, we tried to explain the relationship between obesity and diabetes and diabetic foot problems that can lead to serious financial and moral losses.

Clinical and morphological features of Osler-Weber-Randu disease with signs of visceral injury

Randu-Osler-Weber disease or hereditary hemorrhagic telangiectasia is an autosomal dominant disorder characterized by dilated capillaries and veins, which are usually localized on the skin and mucous membranes of the oral cavity, as well as in the respiratory, urinary and digestive tracts. The anatomical basis of the disease is damage to blood vessels with degeneration and hypoplasia of the muscle and elastic layers, resulting in focal thinning of the vessel walls with further expansion of their lumen. Violation of angiogenesis persists throughout the patient's life, and is manifested by the formation of aneurysms, telangiectasias, and arteriovenous shunts. The average life expectancy of patients with burdened heredity is 63.2 years. The peak of mortality occurs at the age of 50, which is mainly associated with acute complications of the disease. However, among people suffering from Randu-Osler-Weber disease there are also long-lived people who die at the age of 70-79 years, and the cause of death is the complication of the main disease and the addition of chronic diseases. The purpose of this article is to consider in more detail possible manifestations and complications, methods of treatment of Randu-Osler-Weber disease for timely recognition of the disease and provision of timely medical assistance. This article describes a case of an abdominal form of hereditary hemorrhagic telangiectasia in an 82-year-old patient. The results of the postmortem pathomorphological examination of damaged tissues due to Randu-Osler-Weber disease are presented. During the study of micropreparations of the mucous lip, small intestine, mesentery of the small intestine and liver, groups of vessels were found, the wall of which is thinned in places and thickened in places, in the wall of these vessels there is a decrease or complete absence of muscle and elastic fibers, only endothelium is present, surrounded by loose connective tissue, postcapillary venules expand and anastomose with arterioles. In the lumen of these falsely developed vessels, mixed thrombi are determined. An elderly patient suffered from a combined pathology: hereditary hemorrhagic telangiectasia with arterio-venous malformations in the liver, heart, mesentery, small intestine, and coronary heart disease. These processes were complicated by the development of congestive heart failure, which disturbed the hemodynamic and rheological properties of blood and contributed to the occurrence of thrombosis of arterio-venous malformations in the mesentery and the wall of the small intestine. In the following, necrosis of the loops of the small intestine occurred with the development of diffuse purulent-fibrinous peritonitis and endogenous intoxication. Patients with hereditary hemorrhagic telangiectasia have a higher risk of bleeding and neurological complications, including anemia, cerebral abscess, stroke, venous thrombosis, and heart failure, because of late diagnosis of this hereditary disease. Early diagnosis is based on clinical data and careful collection of family history. In 90% of patients under the age of 40, the diagnosis of hereditary hemorrhagic telangiectasia can be established using the Curaçao criteria. This disease brings a significant amount of suffering in everyday life for both patients and their families, and requires significant attention of a multidisciplinary team of doctors at every stage of medical care.

The possibilities of using PET on a mouse model of parkinsonism

Parkinson's disease is a chronic degenerative progressive disease associated primarily with the death of neurons in the substantia nigra and other brain structures. The main symptoms are hypokinesia, rigidity, rest tremor, postural instability, as well as other autonomic and mental disorders. The prevalence of Parkinson's disease is 0.15 %; this figure reaches 1 % for people over 60 years of age. Ten years after the onset of the disease, 65 % of patients become disabled. The average life expectancy of patients is 9 years. Diagnosis of Parkinson's disease is carried out mainly by clinical manifestations, which begin when more than half of the dopaminergic neurons are already damaged. Before that, various compensatory mechanisms are still working, but over time their action ceases to be sufficient. Therefore, a crucial area in medicine is the early diagnosis of Parkinson»s disease. This is possible using functional imaging methods such as PET, SPECT, CT, and MRS. These methods allow detecting even the slightest changes in the structure and functioning of the brain and assessing the integrity of neurons and dopaminergic pathways. The paper presents the possibility of using PET imaging to determine the degree of degeneration of brain structures in a mouse model of MPTP-induced parkinsonian syndrome.

Photodynamic therapy of malignant brain tumors (literature review

Primary brain malignancies are among the 17 most common tumor types worldwide, and about 77 % of them are glial tumors. An integrated approach to the treatment of these pathologies, including total resection of tumor tissue and postoperative chemotherapy and radiation therapy, is aimed at prolonging the patient’s life as much as possible. However, even when using the «gold standard» in treatment, the average life expectancy of patients with glioblastoma is 14.6 months, and of patients with diffuse astrocytoma — 50.5 months. The use of selective methods of influencing tumor cells, including photodynamic therapy, is a current trend in neuro-oncology. Several controlled studies have demonstrated a statistically significant effect of photodynamic therapy in increasing the life expectancy of patients with high-grade gliomas compared with conventional treatment. This review is devoted to the analysis of the effectiveness of photodynamic therapy and fluorescence-guided resection in the treatment of high-grade glial tumors for further search for ways to improve these treatment methods in order to enhance the radicality of tumor removal and increase the duration and quality of life of patients.

The predictive role of CA- 125 value in early stage endometrioid endometrial cancer

Objective: We aimed to evaluate the prognostic role of preoperative serum cancer antigen 125 (CA-125) in endometrioid endometrial cancer for determining the cut-off values for clinicopathological factors.
 Study design: 161 patients were included in the study. The inclusion criteria were histopathological confirmation of endometrioid endometrial cancer and patients with CA-125 levels measured at most ten days before surgery. The association between CA-125 value and clinicopathological variables were analyzed. Receiver operating characteristic curve statistical tests with clinicopathological factors were used to determine the cut-off values and the prognostic role of CA-125.
 Results: The median value of CA-125 level was 15.4 (3, 2-577) IU/L. These CA-125 cut-off values ranged from 14.30 to 18.67 IU/L (sensitivity 53%– 100%, specificity 30%–59%). The statistical analysis showed a significant relation between CA-125 value and stage and pelvic-paraaortic lymph nodes metastasis. The average life expectancy of patients with CA-125 ≥15.4 was 102.8±5.9 months, whereas that of patients with CA-125

Parole chiave. Appropriatezza prescrittiva, consumi farmaceutici, emofilia, fattori della coagulazione, malattia di von Willebrand, malattie emorragiche congenite.

Therapeutic strategies for the treatment of congenital bleeding disorders. Congenital hemorrhagic diseases (CHDs) are a group of rare disorders caused by quantitative or qualitative deficiency of one or more coagulation factors. Haemophilia A, Haemophilia B, and von Willebrand disease are the most common congenital bleeding disorders. Over the past decades, the evolution of CHDs treatments has resulted in an increase in the average life expectancy of patients and in an improvement in their quality of life; it has also enabled the prevention of bleeding complications much more effectively than in the past. This has been possible, especially for haemophilia, mainly because of earlier diagnosis, introduction of recombinant factors, especially long-acting factors, and availability of new non-substitutive therapies. In 2021, there was an increase in the overall expenditure and consumption of coagulation factors in Italy; the increase concerned especially the long-acting recombinant factors used in the treatment of Haemophilia A and B and the monoclonal antibody emicizumab. Waiting for innovative therapies that can enable individually tailored therapies, special attention must be paid to prescriptive appropriateness and to identify the best diagnostic and therapeutic care pathways for patients.

Clinical features of the course of cystic fibrosis during pregnancy and childbirth

Cystic fibrosis is one of the urgent medical and social problems of health care systems in most countries due to fairly high prevalence, development of multi-organ lesions, and poor outcomes.Due to modern advances in the diagnosis and treatment of cystic fibrosis, not only has the average life expectancy of patients increased, but their quality of life has also improved, and it has become possible to maintain pregnancy and childbearing. Since cystic fibrosis can adversely affect the course of pregnancy, childbirth, and health of both mother and child, proper management of women with cystic fibrosis during pregnancy and childbirth is of particular relevance. The presented clinical case is an example of competent supervision at all stages of monitoring of a patient with cystic fibrosis during pregnancy and childbirth.

Cost-effectiveness analysis of autogenous arteriovenous fistula, arteriovenous graft, and tunneled-cuffed catheter for hemodialysis in patients with end-stage kidney disease in Southern China.

To evaluate the cost-effectiveness of three permanent vascular accesses for maintenance hemodialysis patients from a hospital perspective throughout 5 years, which is the average life expectancy of patients with end-stage kidney disease. We conducted a EuroQol(EQ-5D) questionnaire survey between January 2021 and March 2021 with 250 patients to estimate the health utility of various states in patients under different hemodialysis vascular access. We designed a Markov model and conducted a cost-effectiveness analysis to compare the cost-effectiveness of three hemodialysis vascular access in Guangzhou throughout 5 years. The mean costs were US$44,481 with tunneled-cuffed catheter (TCC), and US$68,952 and US$59,247 with arteriovenous graft (AVG) and autogenous arteriovenous fistula (AVF), respectively. The mean quality-adjusted life-years (QALYs) was 1.41 with TCC, and 2.37 and 2.73 with AVG and AVF, respectively. AVG had an incremental cost-effectiveness ratio (ICER) of US$25,491 per QALY over TCC; AVF had an ICER of -US$26,958 per QALY over AVG. At a willingness to pay below US$10,633.8 per QALY, TCC is likely the most cost-effective vascular access. At any willingness to pay between US$10,633.8 and US$30,901.4 per QALY, AVF is likely the most cost-effective vascular access. These findings illustrate the value of AVF given its relative cost-effectiveness to other hemodialysis modalities. Although AVG costs much more than TCC for slightly higher QALYs than TCC, AVG still has a greater advantage over TCC for patients with longer life expectancy due to its lower probability of death.

О ЦЕЛЕСООБРАЗНОСТИ ПРОВЕДЕНИЯ ПОВТОРНОЙ РАДИОТЕРАПИИ ПРИ РЕЦИДИВАХ И ПРОДОЛЖЕННОМ РОСТЕ РАНЕЕ ОБЛУЧЕННЫХ ОПУХОЛЕЙ РАЗЛИЧНОЙ ЛОКАЛИЗАЦИИ

Introduction: The development of a recurrence or a second tumor in previously irradiated patients requires, in some cases, repeated radiotherapy (reirradiation) of the previously irradiated tissue volume. In the past decades, it was widely believed that it was possible to irradiate one anatomical zone in curative doses only once (taking into account the tolerance of healthy tissues) and the issue of repeated irradiation was practically not discussed (there are only a few studies). This approach was due to the fact that the use of old technologies did not allow sufficient protection of healthy tissues surrounding the tumor, which led to severe complications. Due to the development of radiotherapy technologies and new advances in radiobiology, the number of studies on the re-irradiation of recurrent tumors has recently increased significantly, however, they are mainly retrospective in nature and do not have a sufficient evidence compared to indications for primary radiotherapy. However, reirradiation can be used not only for palliative purposes, but also to achieve long-term local control. Modern medical approaches and technical capabilities make it possible to re-irradiate tumors of any localization, up to the second curative dose. Purpose: To investigate the expediency of repeated irradiation of patients with different tumor localizations, taking into account the survival rates of patients, possible complications and subsequent quality of life. Materials and methods: For the first time in Armenia, an analysis of the results of reirradiation is carried out on the basis of the experience of one clinic. The results of treatment of 1300 patients, who received radiotherapy at the IRA MEDICAL Group Radiotherapy Center from March 2019 to March 2022 were studied. The study included 52 patients, who received the second course of RT, which accounted for 4% of the total number of patients. The median age of patients was 60.5 years (22 - 81), including 22 men, 30 women, based on pathologies: CNS tumors - 17 patients, brain metastasis - 10, gynecology - 6, head and neck tumors - 6, metastatic skeletal bone lesions - 4, breast cancer - 3, other localizations - 6. Stage of the disease: III - 7 patients, IV - 37, unclassified - 8. The mean interval between two courses of radiotherapy was 34.5 months (1.5 - 252). The median total equivalent dose from two irradiation courses is 99 Gy (56-121). Except of the patients, who received reirradiation for metastatic relapse, the total equivalent dose was 102 Gy (84–121), and the median follow-up time after reirradiation was 9 months (4–29.5). Results: The average life expectancy of patients, who died during the observation period was 6.5 months (1-23). In 7 out of 52 patients, who initially had low KPS (60%), survival was up to 3.5 months or less. After excluding these patients from further statistical analysis, the median survival of the remaining patients was 10 months (4 – 23). As of March 31, 2022, 31 patients (59.6%) are alive, with an average follow-up of 13 months (5 – 29.5). The number of post-radiation complications and the quality of life of patients were also assessed. There were no treatment related deaths or reduced quality of life in the early stages. The results of this prospective study demonstrate that the use of the latest technologies in repeat radiotherapy can improve survival and quality of life in these patients. Thanks to new technologies, it is possible to conduct a repeated course of radiotherapy even in curative doses. When planning the second therapeutic or palliative course of radiotherapy, it is necessary to carefully select patients, taking into account a number of factors related to the previous treatment and the individual characteristics of the patient. After completion of the study, we plan to create recommendations on the criteria for selecting candidates for re-irradiation.

INVESTIGATIONS OF CHRONIC HEPATITIS B and C IN HIV-INFECTION

Relevance. Today, there are controversies regarding the influence of hepatitis B and C viruses on the course of HIV infection.
 Objective assess the course and outcomes of chronic hepatitis B and C in HIV-infected patients, as well as to analyze the causes of death of such patients.
 Materials and methods. A retrospective pseudorandomized study was conducted with a depth of 5 years. 114 medical records of inpatients (HIV infection in association with hepatitis B and C) were selected. The analysis of the causes of death in patients with HIV infection was carried out based on the study of autopsy materials of 21 patients.
 Results. It was established that the frequency of CHV exacerbation in III-IV clinical stages of HIV infection is significantly higher, and remission is lower than in I-II stages - (36.8±4.5) versus (7.0±2.4)% and (35.1±4.5) and (7.9±2.5)%, respectively (p<0.001). The frequency of liver cirrhosis was characterized by a clear tendency to increase with the deepening of immunodeficiency.
 The calculation of the frequency of findings in liver cirrhosis showed that in the I-II clinical stage of HIV infection, this value was equal to 0.17, and in the III-IV stage - 0.33. The relative risk of developing liver cirrhosis in HIV-infected patients was 0.52. Moreover, the probability of a fatal outcome in cirrhosis of the liver in HIV-infected patients in the I-II clinical stage was equal to 0.16, and in the III-IV stage - 0.29, with a relative risk of 0.63. The reduction in the relative risk of a fatal outcome taking into account the stage of HIV infection is 0.32.
 The average life expectancy of patients from the moment of detection of HIV antibodies was (3.4±0.6) years (from 4 months to 9 years). Such a short average life expectancy of HIV-infected patients was caused by a large number of patients diagnosed for the first time already in the IV clinical stage. In more than half (13 out of 21) the causes of death were AIDS-related diseases (61.9 %).
 Conclusions. A retrospective pseudorandomized study showed that cirrhosis of the liver in the early stages of HIV infection was registered 2.7 times less often than in patients with HIV infection in the stage of secondary diseases.
 Exacerbation of chronic hepatitis B and C is significantly more often established in the III-IV clinical stage of concomitant HIV infection. Under the same circumstances, signs of cirrhosis of the liver are more often registered, and fatal outcomes occupy one of the leading places in patients with HIV infection. This indicates the need to revise the tactics of clinical management of this category of patients.
 In 61.9 % of cases, the causes of death were AIDS-indicative diseases. Tuberculosis turned out to be the leading cause of death (46.1 %) of HIV-infected patients and was mainly in a generalized form. Toxoplasmosis (30.8 %) with damage to the brain and other organs takes the second place in terms of the frequency of fatal AIDS-indicative diseases. Meningoencephalitis of unspecified (probably herpetic) etiology was found in 23.1 % of the deceased. An important place in the structure of fatal outcomes in HIV-infected patients is occupied by the terminal stage of cirrhosis of the liver of mixed etiology - viral and alcoholic (38.1 %).

Serum leptin and neuropeptide Y in patients with cystic fibrosis-A single center study.

Along with the significant elongation in the average life expectancy of patients with cystic fibrosis (CF), there are still significant discrepancies in the height, weight, and body mass index (BMI) of patients compared to controls without CF. The correlation between hormones that regulate appetite and body fat mass may be an additional factor in weight loss or poor weight gain in CF patients. Our objective was to estimate serum concentrations of leptin and neuropeptide Y in patients with CF as well as to assess correlations between studied hormones and the clinical parameters of CF. Leptin and neuropeptide Y serum concentrations after an overnight fast were measured using an enzyme-linked immunosorbent assay. All study participants had anthropometric tests and spirometry. In addition, fasting serum lipid profile was also analyzed. Fasting leptin levels in CF were significantly higher in patients with CF patients (13.9 ± 6.9 vs. 6.5 ± 2.6 ng/mL, p < 0.001) compared to controls. There were no differences in leptin concentration between female and male CF participants (15.7 ± 7.8 vs. 12.2 ± 5.6 ng/mL, p = 0.13). Leptin was correlated with age (R = 0.64, p < 0.001), BMI (R = 0.65, p < 0.001), spirometry results (R = −0.49, p < 0.01), and body fat (R = 0.5, p < 0.05). There were no differences in neuropeptide Y concentration between participants with CF and controls as well as neuropeptide Y was not correlated with any studied parameters. The results of our study suggest that weight loss may be associated with a decreased level of leptin, while reduced pulmonary function in CF may be related to an elevated level of leptin.

Analysis of the health status of patients with type 1 and type 2 diabetes mellitus living in urban and rural areas of the Saratov region (according to the data of the federal register of patients with diabetes mellitus)

BACKGROUND: The World Health Organization considers diabetes mellitus as a significant public health problem, including this disease as one of the four priority noncommunicable diseases. Over the past few decades, the prevalence of diabetes has been steadily increasing and represents a significant threat to the public health of the world’s population. In connection with the territorial features of residence and the availability of medical care to residents of urban and rural areas, studies that include an analysis of the incidence of diabetes mellitus, disability and mortality of the urban and rural population from complications of this disease are one of the important mechanisms for monitoring the health status of the population, which predetermines the improvement and implementation strategies aimed at improving the demographic situation.AIM: To conduct a comparative retrospective analysis of the health indicators of patients with type 1 and type 2 diabetes mellitus living in urban and rural areas of the Saratov region.MATERIALS AND METHODS: Information on life expectancy, morbidity, complications, causes of disability, direct causes of death in patients with type 1 and type 2 diabetes mellitus living in the Saratov region in urban and rural areas was obtained from the Federal Register of Patients with Diabetes; information on the urban and rural population of the Saratov region was obtained from official statistical sources published on the website of the Federal State Statistics Service. Mathematical, statistical and analytical research methods were used. Statistical data processing was carried out using the Microsoft Excel 2019 program. The significance of the difference between the average and relative values was assessed using the Student’s t-test. The presence of a relationship between the signs was determined using the Pearson coefficient. The Mann-Whitney U-test was used to compare populations by quantitative characteristics. The significance level was determined at t&gt;2 and p&lt;005. Data were presented as P ± m, where P is the relative value and m is its standard error, and M ± m, where M is the mean value and m is its standard error.RESULTS: A higher average life expectancy was noted for people with type 2 diabetes, regardless of place of residence, in comparison with the same indicator in the Saratov region. The average life expectancy of patients with type 1 diabetes is 18 years lower than in the Saratov region for those living in urban areas and 17 years for rural residents. There is an excess of the levels of primary and general morbidity in people suffering from type 1 and 2 diabetes and living in rural areas over the same indicators of urban residents. The main causes of death in both urban and rural patients with type 1 and 2 diabetes are: chronic cardiovascular insufficiency, cerebrovascular accident and acute cardiovascular diseases. Disability rates in patients with type 2 diabetes living in urban areas are lower than in rural areas.CONCLUSION: Analysis of data from the Federal Register of Patients with Diabetes Mellitus in the Saratov Region showed high levels of primary and general morbidity, disability and mortality in patients with type 1 and 2 diabetes living in rural areas. Also, frequently occurring complications from the cardiovascular system were identified in all patients with type 1 and type 2 diabetes, regardless of the place of residence. The relationship between the levels of morbidity, mortality, disability, the incidence of complications and the place of residence of patients with type 1 and type 2 diabetes is not statistically significant.

Pancreatic Cancer and Microenvironments: Implications of Anesthesia.

Simple SummaryPancreatic cancer is a lethal malignant neoplasm with less than 10% 5-year relative survival after the initial diagnosis. Several factors may be related to the poor prognosis of pancreatic cancer, including the rapid tumor progression, increased metastatic propensity, insignificant symptoms, shortage of early diagnostic biomarkers, and its tendency toward resistance to both chemotherapy and radiotherapy. Pancreatic neoplastic cells interact intimately with a complicated microenvironment that can foster drug resistance, metastasis, or relapse in pancreatic cancer. In addition, evidence shows that perioperative factors, including surgical manipulation, anesthetics, or analgesics, might alter the tumor microenvironment and cancer progression. This review outlines the up-to-date knowledge of anesthesia implications in the pancreatic microenvironment and provides future anesthetic strategies for improving pancreatic cancer survival. Pancreatic malignancy is a lethal neoplasm, as well as one of the leading causes of cancer-associated mortality, having a 5-year overall survival rate of less than 10%. The average life expectancy of patients with advanced pancreatic cancer does not exceed six months. Although surgical excision is a favorable modality for long-term survival of pancreatic neoplasm, metastasis is initially identified in nearly 80% of the patients by the time of diagnosis, making the development of therapeutic policy for pancreatic cancer extremely daunting. Emerging evidence shows that pancreatic neoplastic cells interact intimately with a complicated microenvironment that can foster drug resistance, metastasis, or relapse in pancreatic cancer. As a result, the necessity of gaining further insight should be focused on the pancreatic microenvironment contributing to cancer progression. Numerous evidence reveals that perioperative factors, including surgical manipulation and anesthetics (e.g., propofol, volatile anesthetics, local anesthetics, epidural anesthesia/analgesia, midazolam), analgesics (e.g., opioids, non-steroidal anti-inflammatory drugs, tramadol), and anesthetic adjuvants (such as ketamine and dexmedetomidine), might alter the tumor microenvironment and cancer progression by affecting perioperative inflammatory or immune responses during cancer surgery. Therefore, the anesthesiologist plays an important role in perioperative management and may affect surgical outcomes. However, the literature on the impact of anesthesia on the pancreatic cancer microenvironment and progression is limited. This review summarizes the current knowledge of the implications of anesthesia in the pancreatic microenvironment and provides future anesthetic strategies for improving pancreatic cancer survival rates.

Residual changes in patients with cavernous pulmonary tuberculosis in the treatment of chemotherapy drugs

In the pre-antibiotic period, the average life expectancy of patients since the development of the cavern usually did not exceed 5 years. A modern clinic accumulates materials for the treatment of cavernous tuberculosis. However, the nature and dynamics of residual changes formed at the site of former cavernous processes, especially after chemotherapy, in the long-term follow-up, are still insufficiently elucidated.

Deciphering Biomarkers for Leptomeningeal Metastasis in Malignant Hemopathies (Lymphoma/Leukemia) Patients by Comprehensive Multipronged Proteomics Characterization of Cerebrospinal Fluid.

Simple SummaryThe early diagnosis of leptomeningeal disease is a challenge because it is asymptomatic in the early stages. Consequently, it is important to identify a panel of biomarkers to help in its diagnosis and/or prognosis. For this purpose, we explored a multipronged proteomics approach in cerebrospinal fluid (CSF) to determine a potential panel of biomarkers. Thus, a systematic and exhaustive characterization of more than 300 CSF samples was performed by an integrated approach by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) and functional proteomics analysis to establish protein profiles, which were useful for developing a panel of biomarkers validated by in silico approaches. In the present work, leptomeningeal disease, a very destructive form of systemic cancer, was characterized from several proteomics points of view. This pathology involves the invasion of the leptomeninges by malignant tumor cells. The tumor spreads to the central nervous system through the cerebrospinal fluid (CSF) and has a very grim prognosis; the average life expectancy of patients who suffer it does not exceed 3 months. The early diagnosis of leptomeningeal disease is a challenge because, in most of the cases, it is an asymptomatic pathology. When the symptoms are clear, the disease is already in the very advanced stages and life expectancy is low. Consequently, there is a pressing need to determine useful CSF proteins to help in the diagnosis and/or prognosis of this disease. For this purpose, a systematic and exhaustive proteomics characterization of CSF by multipronged proteomics approaches was performed to determine different protein profiles as potential biomarkers. Proteins such as PTPRC, SERPINC1, sCD44, sCD14, ANPEP, SPP1, FCGR1A, C9, sCD19, and sCD34, among others, and their functional analysis, reveals that most of them are linked to the pathology and are not detected on normal CSF. Finally, a panel of biomarkers was verified by a prediction model for leptomeningeal disease, showing new insights into the research for potential biomarkers that are easy to translate into the clinic for the diagnosis of this devastating disease.

Imaging manifestations of von Hippel-Lindau disease: an illustrated guide focusing on the central nervous system.

Von Hippel-Lindau (VHL) disease is a rare, autosomal dominant inherited syndrome that affects the germline of the VHL gene, a tumor suppressor gene. VHL disease is characterized by the multisystemic development of a variety of benign and malignant tumors, especially in the central nervous system (CNS). Such tumors include retinal and CNS hemangioblastomas, as well as endolymphatic sac tumors. The various tumor sites are responsible for the diversity of signs and symptoms related to the disease. The mean age at symptom onset is 33 years. Despite medical advances, the average life expectancy of patients with VHL disease is 49 years. Imaging plays a pivotal role in the clinical diagnosis and is essential to the follow-up of patients with VHL disease. This pictorial essay describes characteristic CNS manifestations of VHL disease-related tumors that all radiology residents should be aware of.

Gedunin, A Novel HSP90 Inhibitor, Decreases Cellular Growth and Induces Apoptosis In Glioblastoma Cell Lines

Glioblastoma multiforme (GBM) is an aggressive neoplasm characterized by an elevated, aberrant, proliferative capacity accompanied by diffuse patterns of brain invasion. It has been estimated that in 2018 there were 17,000 deaths out of 24,000 newly diagnosed cases of GBM. The average life expectancy of patients with GBM is only slightly over one year. Current guideline-recommended therapy consisting of tumor resection followed by chemotherapy with temozolomide and radiation has shown limited efficacy due to resistance and high recurrence rates. There is a critical need for the development of new drugs and combination treatment modalities that will considerably increase patient survival and improve the poor prognosis of the disease. Natural products have long served as a source of chemotherapeutic agents. Gedunin is a naturally occurring molecule with clinical potential as an HSP90 inhibitor. Gedunin was isolated from the neem tree, Azadirachta indica A. Juss. (Meliaceae). A. Indica, traditionally used for the treatment of malaria, has been shown to possess some anticancer activity. Our primary objective was to determine the antiproliferative and apoptotic effects of gedunin in glioblastoma cell lines, with the goal of also determining the key signaling pathways affected by gedunin. The antiproliferative effects of gedunin were assessed using the MTT and LDH assays. Protein immunoblots were carried out to test the effects of gedunin on survival signaling pathways such as Akt, mTOR, NF kappa B, and apoptotic markers such as PARP, caspases, and Bcl-xL. Differences between the treated and the untreated groups were analyzed using a one-way ANOVA followed by a Bonferroni post-hoc test. Our data revealed that gedunin (0-20 µM) induced a concentration-dependent and time-dependent decrease in glioma cell proliferation. In addition, gedunin attenuated signaling of downstream targets such as Akt/mTOR and NF kappa B. These protein expressions were downregulated in the presence of gedunin. Furthermore, gedunin induced both PARP and caspase cleavages and decreased the expression of Bcl-xL, an antiapoptotic protein. In conclusion, gedunin decreases cell proliferation and induces apoptosis in glioma cell lines by attenuating key survival signaling pathways and could serve as a therapeutic molecule in the management of gliomas.

Pharmacoeconomic analysis of pertuzumab in treatment of HER2-positive breast cancer in Ukraine

Background. The incidence of breast cancer tends to be increasing worldwide in recent years. It is characterized by various clinical manifestations and potential treatment approaches. The choice of treatment strategy, its sequence as well as the efficiency of administered chemotherapy is quite relevant these days.&#x0D; Purpose – assessing economic feasibility of targeted therapy with pertuzumab (Perjeta®) in patients with metastatic HER2+ BC from the perspective of the health care system of Ukraine.&#x0D; Materials and methods. The treatment outcomes as well as related costs were determined by means of Markov analytical modelling based on a randomized multicenter open clinical study of CLEOPATRA phase III [2]. The model time horizon was 20 years. The alternative schemes of frontline therapy of metastatic HER2+ breast cancer were compared: PTD regimen pertuzumab + trastuzumab + docetaxel and TD regimen trastuzumab + docetaxel. Based on Markov modelling, pharmacoeconomic analysis by means of cost-effectiveness and cost-utility methods was carried out. As an efficiency criterion, LYG amount was used, as a utility criterion − QALY indicator. Direct medical costs were counted, the structure of which had been determined according to the current Protocol. The cost of drugs was calculated in accordance with the Register of wholesale prices for pharmaceuticals of the Ministry of Health of Ukraine; the cost of treatment procedures was determined in accordance with the available price lists of paid medical services provided by licensed medical institutions. Discounting at the level of 3 % per year was applied. Sensitivity analysis of the outcomes was carried out before pertuzumab price changed.&#x0D; Results. According to the modelling, the average life expectancy of patients with HER2+ BC, receiving PTD scheme is 15.69 years compared to 13.95 years in the TD group. Along with prolonging life, associated with PTD scheme, its quality increases. Patients in the TD group gain 7.8 QALY on average, while in the PTD group it is 9.24. The total expenses for the simulated (involved into modeling) study period in the PTD group averaged UAH 1 970 369.6 per patient, in the TD group − UAH 732 517.7. ICER (cost of 1 additional life year) and ICUR (cost of 1 additional qualityadjusted life year) incremental coefficients amounted to UAH 710924.6 and UAH 861175.4 respectively.&#x0D; Conclusions. 1. Pertuzumab target drug is an effective pharmaceutical when administered to patients with metastatic HER2 + breast cancer. 2. The frontline therapy regimen for patients with metastatic HER2 + breast cancer with pertuzumab being included is more expensive in comparison with trastuzumab + docetaxel regimen; at the same time it makes it possible to achieve better results, i. e. to provide on average extra 1.74 life years and 1.44 QALY in 20-year perspective. 3. Pharmacoeconomic analysis based on Markov model and cost-effectiveness and cost-benefit calculations make it possible to consider pertuzumab (Perjeta®), included into frontline targeted therapy regimen of trastuzumab + docetaxel in patients with metastatic HER2+ breast cancer, as an economically feasible medical technology under current health care conditions in Ukraine.

Clinical case of a patient with subungual melanoma

Subungual melanoma is a rare malignant tumor, little known to practitioners. Its location makes diagnosis difficult and requires differentiation with conditions such as onychomycosis, panaritium, hematoma, etc. Unsymptomatic onset brings more problems, the error level during visual examination even among experienced oncologists reaches 25–40%, and the average life expectancy of patients with fully manifested melanoma is limited to 3–4 years.So we present a clinical case to emphasize the need for oncological alertness during an outpatient examination of the subungual lesions. A 32-year-old woman came to the reception complaining of a non-healing bleeding, relatively painless wound of the left little toe. The condition was associated with trauma, for about a month she treated the wound herself, “cauterizing” it with antiseptics.After outpatient treatment of a granulating wound, the material was sent for histological diagnosis, which showed the presence of pigmentless melanoma in the stage of active growth. The woman was urgently hospitalized in the oncology department, where 5th finger exarticulation and inguinal-iliac lymphadenectomy were performed successfully. After this, the condition remained stable, but 14 months later there was a formation in the area of the postoperative scar. A study of a new surgical material confirmed the recurrence of malignant melanoma with Clark invasion level 2.In our opinion, outpatient surgeons should not delay histological examination for all ulcerative and granulomatous lesions of the feet, which will improve the differential diagnosis.

Managing Cystic Fibrosis in Polish Healthcare.

The quality and length of life of patients with cystic fibrosis (CF) are determined by a number of factors including the quality of healthcare received by patients, as well as access to drug programs dedicated to this particular disease. The purpose of this paper is to present an overview of changes in the average life expectancy and mortality rate of the CF population in Poland between 2000 and 2018. Furthermore, we would like to evaluate access to healthcare services, including the drug program, guaranteed by public healthcare system, and funded by National Health Fund (NHF). The average life expectancy of patients with CF increased in the period in question from ca. 14.5 ± 7.6–24.5 ± 8.9 years (mean ± SD, p = 0.0001). We have observed a drop in the number of deaths in paediatric age during that period. Despite the increase in life expectancy, the use of health resources in patients with CF, especially the drug program, is dramatically low. Considering the fact that in Poland there was no active countrywide CF registry, now it is possible to estimate the frequency of use of CF healthcare services in various provinces exclusively on the basis of database maintained by the Polish NHF.