Principal Cause Of Death Research Articles

Diabetes induces modifications in costameric proteins and increases cardiomyocyte stiffness.

Several studies have demonstrated that diabetes mellitus can increase the risk of cardiovascular disease and remains the principal cause of death in these patients. Costameres connect the sarcolemma with the cytoskeleton and extracellular matrix, facilitating the transmission of mechanical forces and cell signaling. They are related to cardiac physiology because individual cardiac cells are connected by intercalated discs that synchronize muscle contraction. Diabetes impacts the nanomechanical properties of cardiomyocytes, resulting in increased cellular and left ventricular stiffness, as evidenced in clinical studies of these patients. The question of whether costameric proteins are affected by diabetes in the heart has not been studied. This work analyzes whether type 1 diabetes mellitus (T1DM) modifies the costameric proteins and coincidentally changes the cellular mechanics in the same cardiomyocytes. The samples were analyzed by immunotechniques using laser confocal microscopy. Significant statistical differences were found in the spatial arrangement of the costameric proteins. However, these differences are not due to their expression. Atomic force microscopy was used to compare intrinsic cellular stiffness between diabetic and normal cardiomyocytes and obtain the first elasticity map sections of diabetic living cardiomyocytes. Data obtained demonstrated that diabetic cardiomyocytes had higher stiffness than control. The present work shows experimental evidence that intracellular changes related to cell-cell and cell-extracellular matrix communication occur, which could be related to cardiac pathogenic mechanisms. These changes could contribute to alterations in the mechanical and electrical properties of cardiomyocytes and, consequently, to diabetic cardiomyopathy.NEW & NOTEWORTHY The structural organization of cardiomyocyte proteins is critical for their efficient functioning as a contractile unit in the heart. This work shows that diabetes mellitus induces significant changes in the spatial organization of costamere proteins, t tubules, and intercalated discs. We obtained the first elasticity map sections of living diabetic cardiomyocytes. The results show statistical differences in the map sections of diabetic and control cardiomyocytes, with diabetic cardiomyocytes being stiffer than normal ones.

Causes of death in Japanese patients with diabetes based on the results of a survey of 68,555 cases during 2011-2020: Committee report on causes of death in diabetes mellitus, Japan Diabetes Society (English version).

The principal causes of death among 68,555 patients with diabetes and 164,621 patients without diabetes who died in 208 hospitals throughout Japan between 2011 and 2020 were determined based on a survey of hospital records. The most frequent cause of death in patients with diabetes was malignant neoplasms (38.9%) (lung 7.8%, pancreas 6.5%, liver 4.1%), followed, in order of descending frequency, by infectious diseases (17.0%) and then vascular diseases (10.9%) (cerebrovascular diseases 5.2%, ischemic heart diseases 3.5%, renal failure 2.3%). The proportion of deaths from malignant neoplasms and vascular diseases has trended upward and downward, respectively. Almost all deaths from ischemic heart diseases were due to myocardial infarction, and the proportion of deaths from heart diseases other than ischemic heart diseases was relatively high (9.0%), with most cases due to heart failure. Diabetic coma associated with hyperglycemia accounted for only 0.3% of deaths. The proportion of deaths from malignant neoplasms, infectious diseases, renal failure, ischemic heart diseases, and heart failure was significantly higher in patients with diabetes than in those without diabetes, and the proportion of deaths from cerebrovascular diseases was significantly lower in patients with diabetes. With regard to the relationship between the age and cause of death in patients with diabetes, malignant neoplasms were the most frequent cause of death in all age groups, and the incidence was around 50% for those in their 50s and 60s. The incidence of death due to infectious diseases was highest in patients older than their 70s. The incidence of death due to vascular diseases for patients in their 40s and 50s was higher than that due to infectious diseases. The highest incidence of death due to ischemic heart diseases was observed for patients in their 40s, and that due to renal failure and heart failure in patients older than their 70s. Compared with patients without diabetes, patients with diabetes demonstrated a higher incidence of death due to pancreatic cancer, infectious diseases, renal failure, ischemic heart diseases, and heart failure, and a lower incidence of death due to cerebrovascular diseases in all age groups. The average age at death of patients with diabetes was 74.4 years old in men and 77.4 years old in women, which were lower than the average lifespan of the Japanese general population in 2020 by 7.2 and 10.3 years, respectively. However, these differences were smaller than in previous surveys. The average age at death due to all causes, especially due to ischemic heart diseases, cerebrovascular diseases, heart failure, infectious diseases, and diabetic coma, was lower in patients with 'poorer' glycemic control than in those with 'better' glycemic control. In the total survey population, the average age at death of patients with diabetes was significantly higher than that of patients without diabetes. The average age at death due to malignant neoplasms and cerebrovascular diseases was higher in patients with diabetes than in those without diabetes and that due to renal failure, ischemic heart diseases, and infectious diseases was lower in patients with diabetes than in those without diabetes.

Prevalence of Cardiotoxicity Secondary to Trastuzumab in Patients with HER-2-Positive Breast Cancer in Southeast Mexico

In Mexico, breast cancer (BC) is the principal cause of death in women over 30 years old, with an annual mortality rate of 14.61 deaths per a 100,000 population. Chemotherapy, in combination with trastuzumab (TTZ), improves the survival of cancer patients; however, cardiotoxicity (CT) is the principal consequence. CT prevalence occurs between 10% and 30% of patients; however, there are no data about the prevalence of CT in the Mexican population. This study aims to establish the prevalence of CT in patients treated with anti-HER-2 therapy among BC women in southeast Mexico. A retrospective cross-sectional study was carried out from January 2015 to July 2019. The records of 46 patients diagnosed with HER-2-positive BC who attended the Mexican Social Security Institute in the Ambulatory Care Medicine Unit were analyzed. The diagnostic criterion for CT was a decrease in LVEF > 10% from baseline or a final LVEF < 53%. CT prevalence was observed in 19 (41.3%) of women with cancer, with an average decrease in LVEF of 13%. In the population, we found an association between weight, surface area, and the loading dose of TTZ with CT. Nutritional follow-up and the administration of cardioprotective drugs are necessary to recover LVEF and avoid cardiovascular failure in women with BC and survivors.

Analysis of mortality in François' langurs (Trachypithecus francoisi) managed care in Trachypithecus francoisi rare animal breeding Center in Wuzhou, Guangxi, China: a 16-year review.

In managed care settings, primates are susceptible to a variety of health complications. A comprehensive understanding of the causes of mortality and their association with management practices is essential for enhancing the welfare of managed care populations such as François' langurs (Trachypithecus francoisi). However, literature addressing prevalent diseases or causes of death in such settings remains limited among François' langurs in managed care. To address this knowledge gap, we conducted an analysis of mortality causes in François' langurs (n = 97) who died of natural causes during a 16-year period (2007-2022) at the Trachypithecus francoisi Rare Animal Breeding Center in Wuzhou, Guangxi, China. Morphological diagnosis and organ system and etiological evaluations were performed. François' langurs were divided into six age-range groups, following previous studies: infant (≤ 1 year old), juvenile (1 to 2 years), sub-adult (2 to 4 years), adult (4 to 10 years), middle-aged (10 to 15 years), and geriatric (> 15 years). Results revealed that the primary causes of mortality in managed care François' langurs were pneumonia (n = 11, 12.22%), neoplasia (n = 7, 7.78%), ileus (n = 7, 7.78%), senility (n = 6, 6.67%), gastroenteritis (n = 6, 6.67%), cardiac disease (n = 5, 5.56%), hemorrhage (n = 5, 5.56%), intestinal adhesion (n = 4, 4.44%), and renal abscess (n = 4, 4.44%). The gastrointestinal system was most frequently implicated in deaths, followed by the respiratory system (n = 17, 18.89%), multisystem disease (n = 16, 17.78%), and cardiovascular system (n = 15, 16.67%). Regarding etiology, infectious or inflammatory (n = 32, 35.56%) and physiological factors (n = 17, 18.89%) were identified as the leading contributors to the high mortality rate. It is imperative for managers to recognize the distinct risk profiles associated with different age groups. Specifically, pneumonia was the principal cause of death in infant and juvenile langurs, while renal disease, neoplasia, gastroenteritis, and intestinal obstruction were the primary causes of death in adult and middle-aged François' langurs and advanced age and cardiac disease were the main causes of death in geriatric langurs.

Assessing Cardiovascular Knowledge Gaps in Iraq Nursing Students

Cardiovascular disease (CVD) is the principal cause of death globally, yet there is a noticeable gap in literature regarding the knowledge of nursing students about this critical health issue. This study aimed to assess the understanding of CVD among students at a nursing college and to explore the association between their knowledge levels and socio-demographic characteristics. Employing a descriptive cross-sectional design, the research involved a random sample of 100 nursing students, using a standardized questionnaire validated by experts and tested for reliability (alpha correlation coefficient of 0.70). Statistical analysis was conducted using SPSS version 26, revealing that 59% of participants had a moderate level of knowledge about CVD. Based on these findings, we recommend the incorporation of more frequent educational sessions on cardiovascular health in nursing curricula to enhance student knowledge. Future research should expand on these findings to foster a deeper understanding of educational impacts on healthcare outcomes. Highlights: Moderate Knowledge: 59% of students have moderate CVD knowledge, indicating room for educational improvements. Reliable Assessment: The study used a validated questionnaire ensuring accurate knowledge assessment. Educational Recommendations: Suggests more frequent lectures to enhance student understanding of cardiovascular health. Keywords: Nursing Education, Student Awareness, Health Outcomes, Cardiovascular Disease, Knowledge

Incidence of the Frequency of Lung cancer in Kurdistan Province During 2005-2016

Background: Cancer is one of the principal causes of death in most countries of the world. Lung cancer is the deadliest and most expensive cancer in the world. In this study, the incidence of lung cancer in Kurdistan province was investigated for the first time in a specific period. Methods: In this cross-sectional study, 815 cases of lung cancer were investigated in Kurdistan province between 2005 and 2016. Reported cases of lung cancer were extracted at the Cancer Registry Center by gender, age, and morphology. Considering the population of 2005 as the standard population, the expected incidence rate was calculated, and the standardized incidence rate was estimated directly. Results: The results showed that the highest incidence of lung cancer was observed in 2016 and 2014 with 153 and 136 cases, respectively, and the lowest in 2009 and 2005, with 11 and 18 cases, respectively. The frequency of cases was observed in the age groups of 75-79 years in 2012 with 23 cases (22.77%) and in the age group of 70-74 years with 28 cases (18.30%) in 2016. The highest crude incidence was observed in 1394 with 12.47 and the lowest in 2013 with 1.10. Conclusion: According to the results of the present study, the incidence of lung cancer was higher in men than women and the incidence of the disease was higher in older ages. Analytical studies are necessary to find the causes of the disease and solve the problems related to this disease.

Distinct Expression Profiles of Neuroblastoma-Associated mRNAs in Peripheral Blood and Bone Marrow of Non-High-Risk and High-Risk Neuroblastoma Patients.

Non-high-risk (non-HR) neuroblastoma (NB) patients have excellent outcomes, with more than a 90% survival rate, whereas HR NB patients expect less than a 50% survival rate. Metastatic disease is the principal cause of death among both non-HR and HR NB patients. Previous studies have reported the significant but limited prognostic value of quantitative PCR (qPCR)-based assays, measuring overlapping but different sets of neuroblastoma-associated mRNAs (NB-mRNAs), to detect metastatic disease in both non-HR and HR patient samples. A droplet digital PCR (ddPCR)-based assay measuring seven NB-mRNAs (CRMP1, DBH, DDC, GAP43, ISL1, PHOX2B, and TH mRNAs) was recently developed and exhibited a better prognostic value for HR patient samples than qPCR-based assays. However, it remained to be tested on non-HR patient samples. In the present study, we employed the ddPCR-based assay to study peripheral blood (PB) and bone marrow (BM) samples collected at diagnosis from eight non-HR and eleven HR cases and characterized the expression profiles of NB-mRNAs. The most highly expressed NB-mRNAs in PB and BM differed between non-HR and HR cases, with the CRMP1 mRNA being predominant in non-HR cases and the GAP43 mRNA in HR cases. The levels of NB-mRNAs in PB and BM were 5 to 1000 times lower in non-HR cases than in HR cases. The PB to BM ratio of NB-mRNAs was 10 to 100 times higher in non-HR cases compared to HR cases. The present case series suggests that non-HR and HR NB patients have the distinct expression profiles of NB-mRNAs in their PB and BM.

Management of Cardiovascular Risk in the Non-alcoholic Fatty Liver Disease Setting.

Non-alcoholic fatty liver disease (NAFLD) is an overlooked and undetected pathology, which affects more than 32% of adults worldwide. NAFLD is becoming more common in Western industrialised countries, particularly in patients with central obesity, type 2 diabetes, dyslipidaemia and metabolic syndrome. Although NAFLD has traditionally been interpreted as a liver disease with a high risk of liver-related complications, NAFLD is an underappreciated and independent risk factor for atherosclerotic cardiovascular disease, which is the principal cause of death in patients with NAFLD. Treatment options to counteract both the progression and development of cardiovascular disease and NAFLD include lifestyle interventions, such as weight loss, increased physical activity and dietary modification, and optimal medical therapy of comorbid conditions; nevertheless, further studies are needed to define optimal treatment strategies for the prevention of both hepatic and cardiovascular complications of NAFLD.

Quantitative Analysis of Innate Lymphoid Cells in Patients with ST-Segment Elevation Myocardial Infarction

ABSTRACT Background Acute myocardial infarction (AMI) is one of the principal causes of death in Mexico and worldwide. AMI triggers an acute inflammatory process that induces the activation of different populations of the innate immune system. Innate lymphoid cells (ILCs) are an innate immunity, highly pleiotropic population, which have been observed to participate in tissue repair and polarization of the adaptive immune response. Objective We aimed to analyze the levels of subsets of ILCs in patients with ST-segment elevation myocardial infarction (STEMI), immediately 3 and 6 months post-AMI, and analyze their correlation with clinical parameters. Results We evaluated 29 STEMI patients and 15 healthy controls and analyzed the different subsets of circulating ILCs, immediately 3 and 6 months post-AMI. We observed higher levels of circulating ILCs in STEMI patients compared to control subjects and a significant correlation between ILC levels and cardiac function. We also found increased production of the cytokines interleukin 5 (IL-5) and interleukin 17A (IL-17A), produced by ILC2 cells and by ILC3 cells, respectively, in the STEMI patients. Conclusion This study shows new evidence of the role of ILCs in the pathophysiology of AMI and their possible involvement in the maintenance of cardiac function.

Quality of palliative and end-of-life care: a quantitative study of temporal trends and differences according to illness trajectories in Quebec (Canada)

BackgroundOur aim was to assess temporal trends and compare quality indicators related to Palliative and End-of-Life Care (PEoLC) experienced by people dying of cancer (trajectory I), organ-failure (Trajectory II), and frailty/dementia (trajectory III) in Quebec (Canada) between 2002 and 2016.MethodsThis descriptive population-based study focused on the last month of life of decedents who, based on the principal cause of death, would have been likely to benefit from palliative care. Five PEoLC indicators were assessed: home deaths (1), deaths in acute care beds with no PEoLC services (2), at least one Emergency Room (ER) visit in the last 14 days of life (3), ER visits on the day of death (4) and at least one Intensive Care Unit (ICU) admission in the last month of life (5). Data were obtained from Quebec’s Integrated Chronic Disease Surveillance System (QICDSS).ResultsThe annual percentage of home deaths increased slightly between 2002 and 2016 in Quebec, rising from 7.7 to 9.1%, while the percentage of death during a hospitalization in acute care without palliative care decreased from 39.6% in 2002 to 21.4% in 2016. Patients with organ failure were more likely to visit the ER on the day of death (20.9%) than patients dying of cancer and dementia/frailty with percentages of 12.0% and 6.4% respectively. Similar discrepancies were observed for ICU visits in the last month and ER visits in the last 14 days.ConclusionPEoLC indicators showed more aggressiveness of care for patients with organ failure and highlight the need for more equitable access to quality PEoLC between malignant and non-malignant illness trajectories. These results underline the challenges of providing timely and optimal PEoLC.

Pulmonary manifestations and prognosis of a cohort of patients with interstitial lung disease and positive to anti-Th/To autoantibodies

IntroductionTh/To autoantibody may be relevant in evaluating patients with interstitial lung disease (ILD) because the clinical diagnosis of systemic sclerosis (SSc) may not be evident. The study's objective was to describe manifestations and evolution of pulmonary function in a cohort of ILD patients positive for Th/To autoantibodies. MethodsILD patients positive for anti-Th/To autoantibody were enrolled in this protocol. Baseline clinical features were registered, and survival analysis was performed to identify risk factors associated with worse survival. ResultsFifty-two patients positive for anti-Th/To autoantibodies with ILD were included. Only 21% of the patients fulfilled the ACR/EULAR 2013 systemic sclerosis classification criteria, and 63.4% fulfilled the IPAF ATS/ERS 2015 criteria. Twenty-five percent of the patients died during follow-up. Respiratory failure was the principal cause of death. Twenty-nine patients (56%) were positive for other hallmark SSc autoantibodies. The most frequent HRCT pattern was nonspecific interstitial pneumonia (NISP). Survival was strongly associated to the systolic pulmonary arterial pressure (sPAP), male sex and the extent of fibrosis in HRCT; besides, patients positive for other hallmark SSc autoantibodies had worse survival compared to those positive only to anti-Th/To. Seventy-six percent of them behaved as fibrotic progressive pulmonary disease, with an absolute decline of the FVC of at least 5%. ConclusionsOnly a small proportion of ILD patients positive for Th/To meet the criteria to be classified as SSc; however, most met criteria for IPAF. A high proportion of patients behave as progressive fibrotic pulmonary disease. Survival is associated with sPAP, the extent of lung disease, and the presence of other hallmark SSc autoantibodies.

Choking as Cause of Death Among the Mentally Ill: A Literature review

Introduction According to data, choking is one of the principal causes of death in mental health units. Specifically, research reveals that psychiatric patients -compared to the general population- are 43 times more likely to die due to choking. Nevertheless, only a limited number of studies has been focused on the risk factors of choking among this category of patients. Interestingly, dysphagia and choking on food are underdiagnosed and underreported in the UK psychiatry departments while there is an important insufficiency of provided information in national guidance archives as well as in regional clinical settings for adults with mental health diseases.ObjectivesTo explore the risk factors of choking among psychiatric patients and to highlight interventions of preventing choking-related incidents.MethodsA review of 36 articles -from 2010 to 2023- on PubMed and Google Scholar regarding choking-related incidents among inpatients of mental health units.Articles exploring choking suicide-related incidents or choking as cause of neurological illness, were excluded from the research. Keywords: choking, psychiatric patients, death.ResultsNumerous risk factors of choking have been identified, such as:Antipsychotics,Anxiolytics,Bradykinetic dysphagia (extra-pyramidal syndrome),Intellectual disabilities,Dementia,Anxiety,Coughing while eating,Fast paced eating and cramming food,Mealtime-related stressors such as willingness of avoiding peers.ConclusionsThere is an absolute need for a specialized training of nurses, caregivers, mental health clinicians to prevent incidents and injuries of inpatients due to choking. Close supervision, routine screening during the mealtime, and detailed information from relatives about the patient’s eating habits are essential for the safety and the ameliorated quality of hospitalization for the mentally ill.Disclosure of InterestNone Declared

Analytical Review on Newly Approved Antidiabetic and Antihypertensive Drugs

Diabetes and hypertension are the principal causes of death all over the world. Both diabetes and hypertension coexist frequently. Managing both is a multi-faced task requiring extensive care. Therapeutic intervention optimization and ensuring patient safety are the results of assessing medications in biological samples. The development of an analytical technique specific to the measurement of a medicinal chemical in a certain matrix requires careful consideration of the various equipment options and an understanding of their relative capabilities with regard to selectivity, sensitivity, usability, speed of investigation, etc. This article aimed to systematically analyze many popular quantitative analytical techniques for measuring some newly approved antidiabetic and antihypertensive drugs in pharmaceutical planning. Several chromatographic techniques have been employed for quantitative research into these pharmaceuticals. Rapid, accurate, cost-effective, and straightforward drug analysis methods are now essential for developing and using new technologies.

Hedgehog Pathway Inhibition by Novel Small Molecules Impairs Melanoma Cell Migration and Invasion under Hypoxia.

Melanoma is the principal cause of death in skin cancer due to its ability to invade and cause metastasis. Hypoxia, which characterises the tumour microenvironment (TME), plays an important role in melanoma development, as cancer cells can adapt and acquire a more aggressive phenotype. Carbonic anhydrases (CA) activity, involved in pH regulation, is related to melanoma cell migration and invasion. Furthermore, the Hedgehog (Hh) pathway, already known for its role in physiological processes, is a pivotal character in cancer cell growth and can represent a promising pharmacological target. In this study, we targeted Hh pathway components with cyclopamine, glabrescione B and C22 in order to observe their effect on carbonic anhydrase XII (CAXII) expression especially under hypoxia. We then performed a migration and invasion assay on two melanoma cell lines (SK-MEL-28 and A375) where Smoothened, the upstream protein involved in Hh regulation, and GLI1, the main transcription factor that determines Hh pathway activation, were chemically inhibited. Data suggest the existence of a relationship between CAXII, hypoxia and the Hedgehog pathway demonstrating that the chemical inhibition of the Hh pathway and CAXII reduction resulted in melanoma migration and invasion impairment especially under hypoxia. As in recent years drug resistance to small molecules has arisen, the development of new chemical compounds is crucial. The multitarget Hh inhibitor C22 proved to be effective without signs of cytotoxicity and, for this reason, it can represent a promising compound for future studies, with the aim to reach a better melanoma disease management.

Clinically approved carbon nanoparticles for enhanced photothermal-immunotherapy toward cancer metastasis

The development of new biomedical applications of approved drugs has several advantages in drug translation. In this study, carbon nanoparticle suspension injection (CNSI), clinically approved for lymph node tracer in China, is explored as a photothermal conversion agents for the treatment of metastatic cancer. Metastasis commonly through lymphatic circulation accounts for the principal cause of death in cancer patients. Up to now, immunotherapy has been already used clinically for metastatic cancer. However, the suppressive tumor immune microenvironment limits the effectiveness of immunotherapy. Herein, we use the photothermal effect of CNSI under near-infrared (NIR) irradiation to eliminate primary tumor and induce the immunogenic cell death (ICD). Further, CNSI under irradiation combined with aPD-1 spur immune response and inhibit the growth of distal tumors. Except for the primary tumor, phototherapy was used to treat metastatic lymph nodes synchronously, which can not only eradicate cancer cells, but also directly activate the immune response inside the lymph nodes. Combining with aPD-1 further enhance the anti-tumor effect to block lymphatic metastases and inhibit lung metastases. This study shows that the carbon nanoparticles have potential clinical application prospects for the treatment of tumor metastasis.

Microbiota in colorectal cancer related to liver metastasis.

The prevalence of colorectal cancer (CRC) is increasing annually and metastasis is the principal cause of death in patients with CRC, with the liver being the most frequently affected site. Many studies have shown a strong interplay between the gut flora, particularly Fusobacterium nucleatum (F. nucleatum), Escherichia coli, and Bacteroides fragilis, and the development of gut tumors. Some strains can induce gut inflammation and produce toxins that directly harm gut epithelial cells, ultimately accelerating the onset and progression of CRC. However, little clinical evidence exists on the specific interplay between the gut microflora and colorectal cancer liver metastasis (CRLM). Some research showed the existence of viable F. nucleatum in distant metastasis of CRC. Subsequently, gut microbiota products, such as lipopolysaccharides, sodium butyrate, and protein cathepsin K, were also found to affect the development of CRC. This article summarizes the mechanism and research status of the interplay between gut microflora and CRLM, discusses the importance of gut microflora in the treatment of CRLM, and proposes a new approach to understanding the mechanism of CRLM and potential treatments for the microbiome. It is anticipated that the gut microbiota will be a formidable therapeutic and prophylactic tool for treating and preventing CRLM.

Deep-Learning-Based Arrhythmia Detection Using ECG Signals: A Comparative Study and Performance Evaluation.

Heart diseases is the world's principal cause of death, and arrhythmia poses a serious risk to the health of the patient. Electrocardiogram (ECG) signals can be used to detect arrhythmia early and accurately, which is essential for immediate treatment and intervention. Deep learning approaches have played an important role in automatically identifying complicated patterns from ECG data, which can be further used to identify arrhythmia. In this paper, deep-learning-based methods for arrhythmia identification using ECG signals are thoroughly studied and their performances evaluated on the basis of accuracy, specificity, precision, and F1 score. We propose the development of a small CNN, and its performance is compared against pretrained models like GoogLeNet. The comparative study demonstrates the promising potential of deep-learning-based arrhythmia identification using ECG signals.

Even one dose of tocilizumab could hinder bad prognosis of cytokines storm in COVID-19 patients

Severe COVID-19 pneumonia is a principal cause of death due to cascade of hyper inflammatory condition that leading to lung damage. Therefore, an effective therapy to countercurrent the surge of uncontrolled inflammation is mandatory to propose. Anti-interlukin-6 receptor antagonist monoclonal therapy, tocilizumab (TCZ) showed potential results in COVID-19 patients. This study aimed to emphasize the factors associated with mortality in COVID-19 patients that treated with tocilizumab and may influence the level of serum IL-6. A retrospective cohort study included all patients with clinical parameters that pointed to presence of cytokines storm and treated with one or more doses of TCZ beside the regular protocol of COVID-19 pneumonia. The factors that influence the mortality in addition to the level of serum IL-6 were analyzed. A total of 377 patients were included, 69.5 % of them received only one dose of TCZ which started mainly at the third day of admission. The mortality rate was 29.44 %. Regardless the time of starting TCZ, just one dose was fair enough to prevent bad consequence; OR = 0.04, P = 0.001.However, in spite of protective action of TCZ, older age and female sex were significant risk factors for mortality, P = 0.001 and 0.01 respectively, as well heart disease. Moreover, increasing the level of neutrophil, AST and IL-6 were associated with bad prognosis. In the same line, treatment with ivermectin, chloroquine and remdesivir inversely affect the level of IL-6. Early treatments of COVID-19 pneumonia with at least one dose of tocilizumab minimized the fatality rate.

Pharmacotherapy in Cardiovascular Disease with Chronic Kidney Disease Medications: A Comprehensive Literature

A progressive decrease of renal function is a symptom of chronic kidney disease, commonly known as chronic kidney failure. The body may accumulate hazardous amounts of fluid, electrolytes, and wastes if the patient has advanced chronic kidney disease. There are several causative factors which lead to CKD which include high or low blood pressure, more accumulation of cholesterol, diabetes and many more. According to WHO global health statistics in 2012, 864,226 mortalities (or 15% of all deaths worldwide) were attributed to this illness. CKD was categorized 14th on the index of principal causes of death, having 122 mortalities per 100,000 persons. Most of the causes of deaths were due to sudden cardiac arrests in CKD patients. In this review, we made a list of 10 FDA approved medications which has proven to decrease CKD and fatalities caused by cardiac arrests. SGLT-2 inhibitors have shown promising results in manipulating kidney functions to improve the efficiency of heart.

Dynein-Powered Cell Locomotion Guides Metastasis of Breast Cancer.

The principal cause of death in cancer patients is metastasis, which remains an unresolved problem. Conventionally, metastatic dissemination is linked to actomyosin-driven cell locomotion. However, the locomotion of cancer cells often does not strictly line up with the measured actomyosin forces. Here, a complementary mechanism of metastatic locomotion powered by dynein-generated forces is identified. These forces arise within a non-stretchable microtubule network and drive persistent contact guidance of migrating cancer cells along the biomimetic collagen fibers. It is also shown that the dynein-powered locomotion becomes indispensable during invasive 3D migration within a tissue-like luminal network formed by spatially confining granular hydrogel scaffolds (GHS) made up of microscale hydrogel particles (microgels). These results indicate that the complementary motricity mediated by dynein is always necessary and, in certain instances, sufficient for disseminating metastatic breast cancer cells. These findings advance the fundamental understanding of cell locomotion mechanisms and expand the spectrum of clinical targets against metastasis.