-
Iranian Journal of Kidney Diseases Mar 2024We recently discovered that microvesicles (MVs) derived from mesenchymal stem cells (MSCs) overexpressing miRNA-34a can alleviate experimental kidney injury in mice....
We recently discovered that microvesicles (MVs) derived from mesenchymal stem cells (MSCs) overexpressing miRNA-34a can alleviate experimental kidney injury in mice. In this study, we further explored the effects of miR34a-MV on renal fibrosis in the unilateral ureteral obstruction (UUO) models. Methods. Bone marrow MSCs were modified by lentiviruses overexpressing miR-34a, and MVs were collected from the supernatants of MSCs. C57BL6/J mice were divided into control, unilateral ureteral obstruction (UUO), UUO + MV, UUO + miR-34aMV and UUO + miR-34a-inhibitor-MV groups. MVs were injected to mice after surgery. The mice were then euthanized on day 7 and 14 of modeling, and renal tissues were collected for further analyses by Hematoxylin and eosin, Masson's trichrome, and Immunohistochemical (IHC) staining. Results. The UUO + MV group exhibited a significantly reduced degree of renal interstitial fibrosis with inflammatory cell infiltration, tubular epithelial cell atrophy, and vacuole degeneration compared with the UUO group. Surprisingly, overexpressing miR-34a enhanced these effects of MSC-MV on the UUO mice. Conclusion. Our study demonstrates that miR34a further enhances the effects of MSC-MV on renal fibrosis in mice through the regulation of epithelial-to-mesenchymal transition (EMT) and Notch pathway. miR-34a may be a candidate molecular therapeutic target for the treatment of renal fibrosis. DOI: 10.52547/ijkd.7673.
Topics: Animals; Male; Mice; Cell-Derived Microparticles; Disease Models, Animal; Epithelial-Mesenchymal Transition; Fibrosis; Kidney; Kidney Diseases; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice, Inbred C57BL; MicroRNAs; Signal Transduction; Ureteral Obstruction
PubMed: 38660698
DOI: 10.5254/s9bdqs74 -
BMC Public Health Apr 2024Multimorbidity is prevalent among older adults and is associated with adverse health outcomes, including high emergency department (ED) utilization. Social determinants...
BACKGROUND
Multimorbidity is prevalent among older adults and is associated with adverse health outcomes, including high emergency department (ED) utilization. Social determinants of health (SDoH) are associated with many health outcomes, but the association between SDoH and ED visits among older adults with multimorbidity has received limited attention. This study aimed to examine the association between SDoH and ED visits among older adults with multimorbidity.
METHODS
A cross-sectional analysis was conducted among 28,917 adults aged 50 years and older from the 2010 to 2018 National Health Interview Survey. Multimorbidity was defined as the presence of two or more self-reported diseases among 10 common chronic conditions, including diabetes, hypertension, asthma, stroke, cancer, arthritis, chronic obstructive pulmonary disease, and heart, kidney, and liver diseases. The SDoH assessed included race/ethnicity, education level, poverty income ratio, marital status, employment status, insurance status, region of residence, and having a usual place for medical care. Logistic regression models were used to examine the association between SDoH and one or more ED visits.
RESULTS
Participants' mean (± SD) age was 68.04 (± 10.66) years, and 56.82% were female. After adjusting for age, sex, and the number of chronic conditions in the logistic regression model, high school or less education (adjusted odds ratio [AOR]: 1.10, 95% confidence interval [CI]: 1.02-1.19), poverty income ratio below the federal poverty level (AOR: 1.44, 95% CI: 1.31-1.59), unmarried (AOR: 1.19, 95% CI: 1.11-1.28), unemployed status (AOR: 1.33, 95% CI: 1.23-1.44), and having a usual place for medical care (AOR: 1.46, 95% CI 1.18-1.80) was significantly associated with having one or more ED visits. Non-Hispanic Black individuals had higher odds (AOR: 1.28, 95% CI: 1.19-1.38), while non-Hispanic Asian individuals had lower odds (AOR: 0.71, 95% CI: 0.59-0.86) of one or more ED visits than non-Hispanic White individuals.
CONCLUSION
SDoH factors are associated with ED visits among older adults with multimorbidity. Systematic multidisciplinary team approaches are needed to address social disparities affecting not only multimorbidity prevalence but also health-seeking behaviors and emergent healthcare access.
Topics: Humans; Male; Female; Multimorbidity; Aged; Social Determinants of Health; Cross-Sectional Studies; Emergency Service, Hospital; Middle Aged; United States; Health Surveys; Aged, 80 and over; Chronic Disease; Emergency Room Visits
PubMed: 38658873
DOI: 10.1186/s12889-024-18613-8 -
JMIR Research Protocols Apr 2024Multiple myeloma (MM) is the second-most common cancer among hematological malignancies. Patients with active disease may experience several comorbidities, including...
Real-World Registry on the Pharmacotherapy of Multiple Myeloma and Associated Renal and Pulmonary Impairments in the Greater Gulf Region: Protocol for a Retrospective Real-World Data Study.
BACKGROUND
Multiple myeloma (MM) is the second-most common cancer among hematological malignancies. Patients with active disease may experience several comorbidities, including renal insufficiency and asthma, which may lead to treatment failure. The treatment of relapsed or refractory MM (RRMM) has been associated with multiple factors, causing a decline in progression-free survival as well as overall survival with subsequent lines of therapy. Data about the characteristics of this group of patients in the Greater Gulf region are lacking.
OBJECTIVE
The primary objective of this study is to describe the disease characteristics and various treatment approaches or regimens used in the management of patients with RRMM in the Greater Gulf region.
METHODS
We will conduct a regional, retrospective study collecting real-world and epidemiological data on patients with MM in countries of the Greater Gulf region. Medical records will be used to obtain the required data. Around 150 to 170 patients' records are planned to be retrospectively reviewed over 6 months without any cross-sectional or prospective intervention. Cases will be collected from Saudi Arabia, the United Arab Emirates, Kuwait, Oman, and Qatar. Descriptive as well as analytical statistics will be performed on the extracted data. The calculated sample size will allow us to estimate the percentages of RRMM cases with acceptable precision while complying with the challenges in light of data scarcity. We will obtain a comprehensive description of the demographic profile of patients with MM; treatment outcomes; the proportion of patients with MM with renal impairment and asthma, chronic obstructive pulmonary disease, or both at the time of diagnosis and any subsequent point; and data related to treatment lines, regimens, and MM-associated morbidities.
RESULTS
Patient medical records were reviewed between June 2022 and January 2023 for eligibility and data extraction. A total of 148 patients were eligible for study inclusion, of whom 64.2% (n=95) were male and 35.8% (n=53) were female. The study is currently in its final stages of data analysis. The final manuscript is expected to be published in 2024.
CONCLUSIONS
Although MM is a predominant hematological disease, data on its prevalence and patients' characteristics in the Greater Gulf region are scarce. Therefore, this study will give us real-world insights into disease characteristics and various management approaches of patients with MM in the Greater Gulf region.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
DERR1-10.2196/49861.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Middle East; Multiple Myeloma; Registries; Renal Insufficiency; Retrospective Studies; Research Design
PubMed: 38657230
DOI: 10.2196/49861 -
Frontiers in Medicine 2024Obesity is a multifactorial chronic disease characterized by an excess of adipose tissue, affecting people of all ages. In the last 40 years, the incidence of overweight... (Review)
Review
Obesity is a multifactorial chronic disease characterized by an excess of adipose tissue, affecting people of all ages. In the last 40 years, the incidence of overweight and obesity almost tripled worldwide. The accumulation of "visceral" adipose tissue increases with aging, leading to several cardio-metabolic consequences: from increased blood pressure to overt arterial hypertension, from insulin-resistance to overt type 2 diabetes mellitus (T2DM), dyslipidemia, chronic kidney disease (CKD), and obstructive sleep apnea. The increasing use of innovative drugs, namely glucagon-like peptide-1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2-i), is changing the management of obesity and its related cardiovascular complications significantly. These drugs, first considered only for T2DM treatment, are now used in overweight patients with visceral adiposity or obese patients, as obesity is no longer just a risk factor but a critical condition at the basis of common metabolic, cardiovascular, and renal diseases. An adipocentric vision and approach should become the cornerstone of visceral overweight and obesity integrated management and treatment, reducing and avoiding the onset of obesity-related multiple risk factors and their clinical complications. According to recent progress in basic and clinical research on adiposity, this narrative review aims to contribute to a novel clinical approach focusing on pathophysiological and therapeutic insights.
PubMed: 38654832
DOI: 10.3389/fmed.2024.1365183 -
MBio Jun 2024The airway milieu of individuals with muco-obstructive airway diseases (MADs) is defined by the accumulation of dehydrated mucus due to hyperabsorption of airway surface...
UNLABELLED
The airway milieu of individuals with muco-obstructive airway diseases (MADs) is defined by the accumulation of dehydrated mucus due to hyperabsorption of airway surface liquid and defective mucociliary clearance. Pathological mucus becomes progressively more viscous with age and disease severity due to the concentration and overproduction of mucin and accumulation of host-derived extracellular DNA (eDNA). Respiratory mucus of MADs provides a niche for recurrent and persistent colonization by respiratory pathogens, including , which is responsible for the majority of morbidity and mortality in MADs. Despite high concentration inhaled antibiotic therapies and the absence of antibiotic resistance, antipseudomonal treatment failure in MADs remains a significant clinical challenge. Understanding the drivers of antibiotic tolerance is essential for developing more effective treatments that eradicate persistent infections. The complex and dynamic environment of diseased airways makes it difficult to model antibiotic efficacy . We aimed to understand how mucin and eDNA concentrations, the two dominant polymers in respiratory mucus, alter the antibiotic tolerance of . Our results demonstrate that polymer concentration and molecular weight affect survival post antibiotic challenge. Polymer-driven antibiotic tolerance was not explicitly associated with reduced antibiotic diffusion. Lastly, we established a robust and standardized model for recapitulating the antibiotic tolerance of observed in expectorated sputum across age, underlying MAD etiology, and disease severity, which revealed the inherent variability in intrinsic antibiotic tolerance of host-evolved populations.
IMPORTANCE
Antibiotic treatment failure in chronic lung infections is associated with increased morbidity and mortality, illustrating the clinical challenge of bacterial infection control. Understanding the underlying infection environment, as well as the host and bacterial factors driving antibiotic tolerance and the ability to accurately recapitulate these factors , is crucial for improving antibiotic treatment outcomes. Here, we demonstrate that increasing concentration and molecular weight of mucin and host eDNA drive increased antibiotic tolerance to tobramycin. Through systematic testing and modeling, we identified a biologically relevant condition that recapitulates antibiotic tolerance observed in treated sputum. Ultimately, this study revealed a dominant effect of evolved bacterial populations in defining inter-subject antibiotic tolerance and establishes a robust and translatable model for therapeutic development.
Topics: Pseudomonas aeruginosa; Anti-Bacterial Agents; Pseudomonas Infections; Mucus; Humans; Mucins; Drug Resistance, Bacterial; Polymers; Persistent Infection; Lung; Respiratory Tract Infections; Adaptation, Physiological
PubMed: 38651896
DOI: 10.1128/mbio.03451-23 -
Advances in Kidney Disease and Health Mar 2024The concept of structural kidney damage and renal dysfunction as a result of jaundice attracted attention in the medical community in the early and mid-20th century. The... (Review)
Review
The concept of structural kidney damage and renal dysfunction as a result of jaundice attracted attention in the medical community in the early and mid-20th century. The postulated doctrine of the time was that the excretion of elevated concentrations of bile results in bile-stained casts occupying collecting and distal convoluted tubules, degeneration of tubular epithelium, and decreased renal function. Compared to the hepatorenal syndrome, the poster child of hepatology and nephrology collaboration, the notion of structural kidney damage and renal dysfunction as a result of cholemia lost its traction and has almost disappeared from modern textbooks. Today, cholemic nephropathy is experiencing a renaissance, with multiple case reports and case series of jaundiced patients with kidney dysfunction and evidence of bile acid casts upon histologic examination. Published cases include acute hepatitis, chronic liver injury, cirrhosis, and obstructive etiologies. Diagnosis of cholemic nephropathy is based on histological examination, typically showing intraluminal bile casts predominantly located in the distal tubules. In common bile duct-ligated mice, the histomorphological and functional alterations of cholemic nephropathy mimic those seen in humans. Some argue against the concept of cholemic nephropathy and postulate that bile casts are a secondary phenomenon. What we need are carefully designed trials to establish diagnostic criteria and subsequently translate this knowledge into evidence-based therapies.
Topics: Humans; Acute Kidney Injury; Cholestasis; Liver Cirrhosis; Animals; Bile Acids and Salts
PubMed: 38649215
DOI: 10.1053/j.akdh.2023.07.001 -
Journal of Craniovertebral Junction &... 2024With the increasing amount of elective spine fusion patients presenting with cardiac disease and congestive heart failure, it is becoming difficult to assess when it is...
BACKGROUND
With the increasing amount of elective spine fusion patients presenting with cardiac disease and congestive heart failure, it is becoming difficult to assess when it is safe to proceed with surgery. Assessing the severity of heart failure (HF) through ejection fraction may provide insight into patients' short- and long-term risks.
PURPOSE
The purpose of this study was to assess the severity of HF on perioperative outcomes of spine fusion surgery patients.
STUDY DESIGN/SETTING
This was a retrospective cohort study of the PearlDiver database.
PATIENT SAMPLE
We enrolled 670,526 patients undergoing spine fusion surgery.
OUTCOME MEASURES
Thirty-day and 90-day complication rates, discharge destination, length of stay (LOS), physician reimbursement, and hospital costs.
METHODS
Patients undergoing elective spine fusion surgery were isolated and stratified by preoperative HF with preserved ejection fraction (P-EF) or reduced ejection fraction (R-EF) (International Classification of Diseases-9: 428.32 [chronic diastolic HF] and 428.22 [chronic systolic HF]). Means comparison tests (Chi-squared and independent samples t-tests, as appropriate) compared differences in demographics, diagnoses, comorbidities, procedural characteristics, LOS, 30-day and 90-day complication outcomes, and total hospital charges between those diagnosed with P-EF and those not R-EF. Binary logistic regression assessed the odds of complication associated with HF, controlling for levels fused (odds ratio [OR] [95% confidence interval]). Statistical significance was set at < 0.05.
RESULTS
Totally 670,526 elective spine fusion patients were included. Four thousand and seventy-seven were diagnosed with P-EF and 2758 R-EF. Overall, P-EF patients presented with higher rates of morbid obesity, chronic kidney disease, chronic obstructive pulmonary disease, diabetes mellitus, and hypertension (all < 0.001). In relation to No-HF, P-EF patients had higher rates of 30-day major complications including pulmonary embolism, pneumonia, cerebrovascular accident (CVA), myocardial infarctions (MI), sepsis, and death (all < 0.001). Furthermore, P-EF was associated significantly with increased odds of pneumonia (OR: 2.07 [1.64-2.56], < 0.001) and sepsis (OR: 2.09 [1.62-2.66], < 0.001). Relative to No-HF, R-EF was associated with significantly higher odds of MI (OR: 3.66 [2.34-5.47]), CVA (OR: 2.70 [1.67-4.15]), and pneumonia (OR: 1.85 [1.40-2.40]) (all < 0.001) postoperative within 30 days. Adjusting for prior history of MI, CAD, and the presence of a pacemaker R-EF was a significant predictor of an MI 30 days postoperatively (OR: 2.2 [1.14-4.32], = 0.021). Further adjusting for history of CABG or stent placement, R-EF was associated with higher odds of CVA (OR: 2.11 [1.09-4.19], = 0.028) and MI (OR: 2.27 [1.20-4.43], = 0.013).
CONCLUSIONS
When evaluating the severity of HF before spine surgery, R-EF was associated with a higher risk of major complications, especially the occurrence of a myocardial infarction 30 days postoperatively. During preoperative risk assessment, congestive HF should be considered thoroughly when thinking of postoperative outcomes with emphasis on R-EF.
PubMed: 38644919
DOI: 10.4103/jcvjs.jcvjs_186_23 -
PLOS Global Public Health 2024Chronic kidney disease (CKD) is a significant contributor to the global burden of non-communicable disease. Early intervention may facilitate slowing down of progression...
Chronic kidney disease (CKD) is a significant contributor to the global burden of non-communicable disease. Early intervention may facilitate slowing down of progression of CKD; recognition of at-risk patient groups may improve detection through screening. We retrospectively reviewed the clinical records of 960 patients attending a specialist nephrology outpatient clinic during the period 1 January 2011-31 December 2021. A significant proportion (47.8%) of patients were referred with established CKD stage G4 or G5. Non-national immigration status, previous diagnosis with diabetes, and advancing age were associated with late referral; antecedent diagnosis with HIV reduced the odds of late referral. Black African patients comprised most of the sample cohort and were younger at referral and more frequently female than other ethnicities; non-nationals were younger at referral than South Africans. Hypertension-associated kidney disease was the leading ascribed aetiological factor for CKD (40.7% of cases), followed by diabetic kidney disease (DKD) (19%), glomerular disease (12.5%), and HIV-associated kidney disease (11.8%). Hypertension-related (25.9%) and diabetic (10.7%) kidney diseases were not uncommon in people living with HIV. Advancing age and male sex increased the likelihood of diagnosis with hypertensive nephropathy, DKD and obstructive uropathy; males were additionally at increased risk of HIV-associated kidney disease and nephrotoxin exposure, as were patients of Black African ethnicity. In summary, this data shows that hypertension, diabetes, and HIV remain important aetiological factors in CKD in the South African context. Despite the well-described risk of CKD in these disorders, referral to nephrology services occurs late. Interventions and policy actions targeting at-risk populations are required to improve referral practices.
PubMed: 38635562
DOI: 10.1371/journal.pgph.0003119 -
IJID Regions Jun 2024COVID-19 affects the quality of life (QoL) in a reverse way after recovery, which might be multiplied by the comorbid non-communicable diseases. This study explored the...
OBJECTIVES
COVID-19 affects the quality of life (QoL) in a reverse way after recovery, which might be multiplied by the comorbid non-communicable diseases. This study explored the relationship between comorbidities and the QoL of people who recovered from COVID-19 in Bangladesh.
METHODS
The cross-sectional study was conducted among 3244 participants between June 2020 and November 2020 using a pre-tested questionnaire through over-the-phone interviews. The WHOQOL-BREF was used to explore the QoL among the study participants. A multivariable linear regression model was conducted to identify the effects of the number of comorbidities on QoL scores of all four domains.
RESULTS
Of 3244 patients who recovered from COVID-19, over one-third (39.4%) had one or more chronic diseases, such as hypertension, diabetes mellitus, ischemic heart disease, bronchial asthma/chronic obstructive pulmonary disease, chronic kidney disease, and cancer. Around 46.85% of the participants aged above 40 years presented with one to two chronic diseases, and 16.33% had three or more chronic diseases. Among all comorbidities, the participants with cancer and chronic kidney disease were found to have relatively lower scores in all four domains than other comorbidities. The lowest QoL scores were observed in the psychological domain. Those with three or more simultaneous chronic comorbidities had the lowest QoL score in all four domains: physical, psychological, social relationship, and environmental.
CONCLUSIONS
Persons who recovered from COVID-19 with comorbidities undergo a lower QoL. Therefore, special attention is required to these vulnerable groups to ensure their smooth recuperation.
PubMed: 38634072
DOI: 10.1016/j.ijregi.2024.03.006 -
Learning Health Systems Apr 2024Clinical decision support (CDS) systems (CDSSs) that integrate clinical guidelines need to reflect real-world co-morbidity. In patient-specific clinical contexts,...
INTRODUCTION
Clinical decision support (CDS) systems (CDSSs) that integrate clinical guidelines need to reflect real-world co-morbidity. In patient-specific clinical contexts, transparent recommendations that allow for contraindications and other conflicts arising from co-morbidity are a requirement. In this work, we develop and evaluate a non-proprietary, standards-based approach to the deployment of computable guidelines with explainable argumentation, integrated with a commercial electronic health record (EHR) system in Serbia, a middle-income country in West Balkans.
METHODS
We used an ontological framework, the Transition-based Medical Recommendation (TMR) model, to represent, and reason about, guideline concepts, and chose the 2017 International global initiative for chronic obstructive lung disease (GOLD) guideline and a Serbian hospital as the deployment and evaluation site, respectively. To mitigate potential guideline conflicts, we used a TMR-based implementation of the Assumptions-Based Argumentation framework extended with preferences and Goals (ABA+G). Remote EHR integration of computable guidelines was via a microservice architecture based on HL7 FHIR and CDS Hooks. A prototype integration was developed to manage chronic obstructive pulmonary disease (COPD) with comorbid cardiovascular or chronic kidney diseases, and a mixed-methods evaluation was conducted with 20 simulated cases and five pulmonologists.
RESULTS
Pulmonologists agreed 97% of the time with the GOLD-based COPD symptom severity assessment assigned to each patient by the CDSS, and 98% of the time with one of the proposed COPD care plans. Comments were favourable on the principles of explainable argumentation; inclusion of additional co-morbidities was suggested in the future along with customisation of the level of explanation with expertise.
CONCLUSION
An ontological model provided a flexible means of providing argumentation and explainable artificial intelligence for a long-term condition. Extension to other guidelines and multiple co-morbidities is needed to test the approach further.
PubMed: 38633019
DOI: 10.1002/lrh2.10391