The prognosis of heart failure (HF) patients is determined to a decisive extent by comorbidities. The present study investigates the association between a broad spectrum of diseases and the ...occurrence of HF in a large collective of outpatients. This retrospective case control study assessed the prevalence of 37 cardiac and extracardiac diseases in patients with an initial diagnosis of heart failure (ICD-10: I50) in 1,274 general practices in Germany between January 2005 and December 2019. The study is based on the Disease Analyzer database (IQVIA), which contains drug prescriptions, diagnoses, and basic medical and demographic data. Patients with and without heart failure were matched by sex, age, and index year. Hazard regression models were conducted to evaluate the association between different disease entities and heart failure. The present study included 162,246 patients with heart failure and 162,246 patients without heart failure. Mean age SD was 73.7 12.1 years; 52.6% were women. Out of 37 predefined diagnoses, 36 were more prevalent in HF patients. The highest prevalence was primary hypertension (63.4% in HF patients vs. 53.3% in controls, p < 0.001) followed by lipid metabolism disorders (34.6% in HF patients vs. 29.1% in HF patients p < 0.001) and diabetes mellitus type II (32.2% in HF patients vs. 25.2% in controls, p < 0.001). In the regression analysis, 19 diseases were significantly associated with heart failure. Non-cardiovascular diagnoses strongly associated with HF were obesity (HR = 1.46), chronic bronchitis and COPD (HR = 1.41), gout (HR: 1.41), and chronic kidney disease (HR = 1.27). In the present study, we identified a variety of cardiac and extracardiac diseases associated with heart failure. Our data underscore the immense importance of comorbidities, even as early as at the stage of initial diagnosis of heart failure.
Sepsis represents a major global health burden. Early diagnosis of sepsis as well as guiding early therapeutic decisions in septic patients still represent major clinical challenges. In this context, ...a whole plethora of different clinical and serum-based markers have been tested regarding their potential for early detection of sepsis and their ability to stratify patients according to their probability to survive critical illness and sepsis. Adipokines represent a fast-growing class of proteins that have gained an increasing interest with respect to their potential to modulate immune responses in inflammatory and infectious diseases. We review current knowledge on the role of different adipokines in diagnostic work-up and risk stratification of sepsis as well as critical illness. We discuss recent data from animal models as well as from clinical studies and finally highlight the limitations of these analyses that currently prevent the use of adipokines as biomarkers in daily practice.
Summary Background Tracheal tumours can be surgically resected but most are an inoperable size at the time of diagnosis; therefore, new therapeutic options are needed. We report the clinical ...transplantation of the tracheobronchial airway with a stem-cell-seeded bioartificial nanocomposite. Methods A 36-year-old male patient, previously treated with debulking surgery and radiation therapy, presented with recurrent primary cancer of the distal trachea and main bronchi. After complete tumour resection, the airway was replaced with a tailored bioartificial nanocomposite previously seeded with autologous bone-marrow mononuclear cells via a bioreactor for 36 h. Postoperative granulocyte colony-stimulating factor filgrastim (10 μg/kg) and epoetin beta (40 000 UI) were given over 14 days. We undertook flow cytometry, scanning electron microscopy, confocal microscopy epigenetics, multiplex, miRNA, and gene expression analyses. Findings We noted an extracellular matrix-like coating and proliferating cells including a CD105+ subpopulation in the scaffold after the reseeding and bioreactor process. There were no major complications, and the patient was asymptomatic and tumour free 5 months after transplantation. The bioartificial nanocomposite has patent anastomoses, lined with a vascularised neomucosa, and was partly covered by nearly healthy epithelium. Postoperatively, we detected a mobilisation of peripheral cells displaying increased mesenchymal stromal cell phenotype, and upregulation of epoetin receptors, antiapoptotic genes, and miR-34 and miR-449 biomarkers. These findings, together with increased levels of regenerative-associated plasma factors, strongly suggest stem-cell homing and cell-mediated wound repair, extracellular matrix remodelling, and neovascularisation of the graft. Interpretation Tailor-made bioartificial scaffolds can be used to replace complex airway defects. The bioreactor reseeding process and pharmacological-induced site-specific and graft-specific regeneration and tissue protection are key factors for successful clinical outcome. Funding European Commission, Knut and Alice Wallenberg Foundation, Swedish Research Council, StratRegen, Vinnova Foundation, Radiumhemmet, Clinigene EU Network of Excellence, Swedish Cancer Society, Centre for Biosciences (The Live Cell imaging Unit), and UCL Business.
Background
Diverticular disease represents a gastrointestinal disorder of high prevalence in developed countries that often leads to psychological distress. Here, we aimed at evaluating a potential ...association between diverticular disease and depression or anxiety disorders in outpatients in Germany.
Methods
Using the Disease Analyzer database featuring data of over 8 million patients treated in German general practices, we identified 61.556 patients with diverticular disease (ICD-10: K57) who were 1:1 matched by age, sex, index year, and the Charlson Comorbidity Index to 61.556 patients without diverticular disease. The association between diverticular disease and depression or anxiety disorders was evaluated in Cox regression models.
Results
Within 5 years after the initial diagnosis of diverticular disease, 14.0% of patients with and 10.6% of individuals without diverticular disease were diagnosed with depression (HR 1.34, 95%CI 1.29–1.39,
p
< 0.001). Similarly, the incidence of anxiety disorder was significantly higher in patients with diverticular disease (HR 1.55, 95%CI 1.46–1.64,
p
< 0.001). Finally, the prescription rate for antidepressant drugs was significantly higher in diverticular disease patients compared to individuals without diverticular disease (9.4% vs. 6.1%, HR 1.56, 95%CI 1.49–1.62,
p
< 0.001). These associations were confirmed for different age groups and both sexes.
Conclusion
Our data provide evidence that diverticular disease is associated with an increased incidence of depression and anxiety disorders. Despite that fact that confounding factors such as deprivation and patient personality have to be taken into account, we suggest that patients with diverticular disease are regularly screened for symptoms of depression and anxiety disorders.
As miRNAs are associated with normal cellular processes, deregulation of miRNAs is thought to play a causative role in many complex diseases. Nevertheless, the precise contribution of miRNAs in ...fibrotic lung diseases, especially the idiopathic form (IPF), remains poorly understood. Given the poor response rate of IPF patients to current therapy, new insights into the pathogenic mechanisms controlling lung fibroblasts activation, the key cell type driving the fibrogenic process, are essential to develop new therapeutic strategies for this devastating disease. To identify miRNAs with potential roles in lung fibrogenesis, we performed a genome-wide assessment of miRNA expression in lungs from two different mouse strains known for their distinct susceptibility to develop lung fibrosis after bleomycin exposure. This led to the identification of miR-199a-5p as the best miRNA candidate associated with bleomycin response. Importantly, miR-199a-5p pulmonary expression was also significantly increased in IPF patients (94 IPF versus 83 controls). In particular, levels of miR-199a-5p were selectively increased in myofibroblasts from injured mouse lungs and fibroblastic foci, a histologic feature associated with IPF. Therefore, miR-199a-5p profibrotic effects were further investigated in cultured lung fibroblasts: miR-199a-5p expression was induced upon TGFβ exposure, and ectopic expression of miR-199a-5p was sufficient to promote the pathogenic activation of pulmonary fibroblasts including proliferation, migration, invasion, and differentiation into myofibroblasts. In addition, we demonstrated that miR-199a-5p is a key effector of TGFβ signaling in lung fibroblasts by regulating CAV1, a critical mediator of pulmonary fibrosis. Remarkably, aberrant expression of miR-199a-5p was also found in unilateral ureteral obstruction mouse model of kidney fibrosis, as well as in both bile duct ligation and CCl4-induced mouse models of liver fibrosis, suggesting that dysregulation of miR-199a-5p represents a general mechanism contributing to the fibrotic process. MiR-199a-5p thus behaves as a major regulator of tissue fibrosis with therapeutic potency to treat fibroproliferative diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Individuals with Down syndrome are thought to have a unique tumor profile.
Using the IQVIA Disease Analyzer database, patients aged ≥18 years diagnosed with Down syndrome in German general practices ...between 2005 and 2021 were compared with patients without Down syndrome for cancer incidence, adjusting for age, sex, average annual visit frequency, and comorbidity. The 5-year cumulative incidence of cancer overall and specific cancers was analyzed using Kaplan-Meier curves and compared using the log-rank test. In addition, univariable Cox regression analysis was performed.
A total of 2438 patients with Down syndrome and 12,190 patients without Down syndrome were included; 3.9% of patients without Down syndrome and 3.1% of patients with Down syndrome were diagnosed with cancer (
= 0.143). Regression analysis showed no significant association between Down syndrome and subsequent cancer in the total population (HR: 0.79; 95% CI: 0.57-1.09), in women (HR: 0.89; 95% CI: 0.56-1.37), or in men (HR: 0.69; 95% CI: 0.43-1.11). Analyses by cancer type and sex showed a strong but not significant negative association between Down syndrome and breast cancer in women (HR: 0.33; 95% CI: 0.12-0.93).
Our results could form the basis for future studies to clarify whether and to what extent an adapted screening program needs to be modified for individuals with Down syndrome due to the particular cancer distribution pattern.
Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Most patients present with advanced or metastatic HCC at diagnosis and face a dismal prognosis. Tyrosine kinases are the gold ...standard treatment for this disease but yield limited survival benefits. Immune checkpoint inhibitors that augment adaptive immunity have been tested in HCC. Complex interactions between tumor cells, lymphocytes and the tumor environment determine the efficacy of such immunotherapies. Innate immune mechanisms – known drivers of liver disease progression in pre-HCC conditions such as fibrosis or cirrhosis – may either support or counteract tumor-related immune activation. In this review, we will highlight current concepts of the role of the innate immune system in hepatocarcinogenesis and discuss their relevance for translation into clinics.
Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in the western world. The excess mortality in NAFLD patients is strongly related to extrahepatic comorbidities. ...Recently, an association between NAFLD and chronic kidney disease (CKD) has been reported in various populations.
Based on the IQVIA Disease Analyzer database, this retrospective study examined two cohorts from Germany matched for sex, age, index year, annual visit frequency, hypertension, and diabetes, including 92,225 patients with and without NAFLD. The incidence of CKD was assessed as a function of NAFLD using Cox regression models.
A total of 92,225 NAFLD patients as well as 92,225 patients without NAFLD were included into analyses. CKD was diagnosed in 19.1% vs. 11.1% of patients with and without NAFLD within the 10 years observation period (p < 0.001). Cox regression confirmed a significant association between NAFLD and CKD with a hazard ratio (HR) of 1.80 (95%CI: 1.73-1.86, p < 0.001). Subgroup analyses revealed that this association was most pronounced in the age group of 18 to 50 years (HR: 2.13, 95%CI: 1.91-2.37, p < 0.001) and among female NAFLD patients (HR 1.85, 95%CI: 1.76-1.95, p < 0.001).
The results of this study confirm a significantly increased risk of developing CKD in a large, real-world cohort of adult NAFLD patients in Germany. Interdisciplinary care of NAFLD patients, which is currently gaining importance worldwide, should be considered to include systematic measures for prevention and/or early detection of CKD with the aim of minimizing long-term renal complications.
Background and Aims: While transarterial chemoembolization (TACE) represents a standard of therapy for intermediate-stage hepatocellular carcinoma (HCC) and is also routinely performed in patients ...with liver metastases, it is still debated which patients represent the ideal candidates for TACE therapy in terms of overall survival. Sarcopenia, the degenerative loss of skeletal muscle mass and strength, has been associated with an adverse outcome for various malignancies, but its role in the context of TACE has largely remained unknown. Here, we evaluated the role of sarcopenia on the outcome of patients undergoing TACE for primary and secondary liver cancer. Methods: The patients’ psoas muscle size was measured on axial computed tomography (CT) scans and normalized for the patients’ height squared. This value was referred to as the psoas muscle index (PMI). The PMI was correlated with clinical and laboratory markers. Results: While pre-interventional sarcopenia had no impact on the direct tumor response to TACE, sarcopenic patients with a pre-interventional PMI below our ideal cut-off value of 13.39 mm/m2 had a significantly impaired long-term outcome with a median overall survival of 491 days compared to 1291 days for patients with a high PMI. This finding was confirmed by uni- and multivariate Cox-regression analyses. Moreover, a progressive rapid decline in muscle mass after TACE was a predictor for an unfavorable prognosis. Conclusion: Our data suggest that sarcopenia represents a previously unrecognized prognostic factor for patients undergoing TACE therapy which might yield important information on the patients’ post-interventional outcome and should therefore be implemented into clinical stratification algorithms.
miR-192-5p has gained increasing relevance in various diseases, however, its function in acute liver injury is currently unknown. We analysed miR-192-5p serum levels and hepatic miR-192-5p expression ...in mice after hepatic ischaemia and reperfusion (I/R) as well as in toxic liver injury. On a functional level, miRNA levels were analysed in the different hepatic cell-compartments and in the context of tumour necrosis factor (TNF)-dependent liver cell death. We detected increased serum levels of miR-192-5p after hepatic I/R- and carbon tetrachloride (CCl4)-induced liver injury. miR-192-5p levels correlated with the degree of liver damage and the presence of hepatic cell death detected by TUNEL stainings (terminal deoxynucleotidyltransferase-mediated dUTP biotin nick-end labelling stainings). Moreover, expression of miR-192-5p was increased in a hypoxia/reoxygenation (H/R) model of in vitro hepatocyte injury, supporting that the passive release of miR-192-5p represents a surrogate for hepatocyte death in liver injury. In critically ill patients, miR-192-5p levels were elevated selectively in patients with liver injury and closely correlated with the presence of hepatic injury. In contrast with up-regulated miR-192-5p in the serum, we detected a down-regulation of miR-192-5p in both injured mouse and human livers. Deregulation of miR-192-5p in livers was dependent on stimulation with TNF. Functional experiments confirmed a protective effect of down-regulation of miR-192-5p in hepatocytes, suggesting a role of miR-192-5p in limiting liver injury. Finally, we identified Zeb2, an important regulator of cell death, as a potential target gene mediating the function of miR-192-5p Our data suggest that miR-192-5p is involved in the regulation of liver cell death during acute liver injury and might represent a potent marker of hepatic injury.
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