Management strategies in persons with inherited haemophilia requiring antithrombotic therapy: A scoping review.

BACKGROUND: Thromboembolic events are increasingly reported in the aging haemophilia population. The purpose of this study was to understand current practices and identify knowledge and research gaps in the management of persons with haemophilia requiring antithrombotic therapy for cardiovascular disorders (CVD) or venous thromboembolism (VTE). METHODS: We searched MEDLINE, EMBASE and Scopus for studies reporting on more than two patients with inherited haemophilia A or B, without inhibitors, requiring antithrombotic therapy for CVD or VTE. Data were extracted by two independent reviewers and analysed using descriptive statistics and narrative synthesis. RESULTS: We included 32 studies reporting on 432 persons with haemophilia. Three themes described the observed practice variation: (1) Difficulty weighing competing bleeding and thrombotic risks; (2) Tensions in providing standards of care and minimizing bleeding risk; (3) Advocacy for individualized strategies and multidisciplinary care. Different management strategies were used to treat persons with haemophilia in the setting of thromboembolic events, such as avoiding or choosing lower intensity antithrombotic therapy, or procedural alternatives to antithrombotic therapy. Initiation or alteration in haemostatic therapies along with antithrombotic therapy were common strategies and reported in 30 studies. However, data on target factor levels and bleeding and thrombotic events were largely missing. DISCUSSION: Our scoping review highlights unmet needs in the management of an aging population of persons with haemophilia with increasing prevalence of CVD and VTE. Management is inconsistent and divergent from those of non-haemophilic patients. Prospective data are needed to inform optimal and evidence-based management strategies of CVD and VTE in persons with haemophilia.

Somatic burden of attention-deficit/hyperactivity disorder across the lifecourse.

OBJECTIVE: A thorough and comprehensive knowledge base on the extent of comorbidity of attention-deficit/hyperactivity disorder (ADHD) and somatic conditions is needed. METHOD: We compared the prevalence of a wide range of somatic conditions in individuals with and without ADHD and described sex and lifecourse differences. Individuals with an ADHD diagnosis (N = 87,394) and age and sex-matched individuals without an ADHD diagnosis were identified from a large health claims dataset representative of the general German population, including both primary and specialized care (N = 4.874,754). Results were provided for the full sample as well as stratified for sex and age (<12 years, 13-17 years, 18-29 years, 30-59 years, ≥60 years). RESULTS: The results showed that ADHD is associated with a wide variety of somatic conditions across the entire lifecourse. Specifically neurological disorders such as Parkison's disease (odds ratio [OR]: 5.21) and dementia (OR: 2.23), sleep-related disorders (OR: 2.38) and autoimmune disorders affecting the musculoskeletal, digestive, and endocrine system (fibromyalgia OR: 3.33; lupus OR: 2.17) are strongly and significantly associated with ADHD. Additionally, ADHD is associated with higher occurrence of common acute diseases typically treated by the general practitioner, hinting at an overall general lower health status. Sex differences in somatic comorbidity were not prominent. Age differences, in contrast, stood out: in particular endocrine, cardiovascular, and neurological disorders had an early onset in individuals with compared to individuals without ADHD. CONCLUSION: This research underlines the high burden of disease due to somatic conditions among individuals with ADHD. The findings indicate the need for preventive measures to reduce comorbidity.

Enhanced IGF-IIRα Expression Exacerbates Lipopolysaccharide-Induced Cardiac Inflammation, Hypertrophy, and Apoptosis Through Calcineurin Activation.

Cardiovascular disease is one of the leading causes of death worldwide and has a high prevalence. Insulin-like growth factor-II receptor α (IGF-IIRα) acts as a stress-inducible negative regulator. This study focused on the substantial impact of heightened expression of IGF-IIRα in cardiac myoblasts and its association with the exacerbation of cardiac dysfunction. Using lipopolysaccharide (LPS)-induced H9c2 cardiac myoblasts as a model for sepsis, we aimed to elucidate the molecular interactions between IGF-IIRα and LPS in exacerbating cardiac injury. Our findings demonstrated a synergistic induction of cardiac inflammation and hypertrophy by LPS stimulation and IGF-IIRα overexpression, leading to decreased cell survival. Excessive calcineurin activity, triggered by this combined condition, was identified as a key factor exacerbating the negative effects on cell survival. Cellular changes such as cell enlargement, disrupted actin filaments, and upregulation of hypertrophy-related and inflammation-related proteins contributed to the overall hypertrophic and inflammatory responses. Overexpression of IGF-IIRα also exacerbated apoptosis induced by LPS in H9c2 cardiac myoblasts. Inhibiting calcineurin in LPS-treated H9c2 cardiac myoblasts with IGF-IIRα overexpression effectively reversed the detrimental effects, reducing cell damage and mitigating apoptosis-related cardiac mechanisms. Our study suggests that under sepsis-like conditions in the heart with IGF-IIRα overexpression, hyperactivation of calcineurin worsens cardiac damage. Suppressing IGF-IIRα and calcineurin expression could be a potential intervention to alleviate the impact of the illness and improve cardiac function.

Exposure to occupational air pollution and vascular endothelial dysfunction in workers of the steel industry in Iran.

Air pollution is recognized as a risk factor for cardiovascular diseases; however, the precise underlying mechanisms remain unclear. This study investigated the impact of occupational air pollution exposure on endothelial function in workers within the steel industry. Specifically, we examined male employees in the coke-making division of the Isfahan Steel Company in Iran, as well as those in administrative roles with no known history of cardiovascular risk. Data on age, body mass index, duration of employment, blood pressure, fasting blood sugar, and lipid profile were collected. To assess endothelial function, flow-mediated dilation (FMD) was measured. The baseline brachial artery diameter was greater (mean difference [95% CI] = 0.068 mm [0.008 to 0.128]), while the FMD was lower (mean difference [95% CI] = -0.908 % [-1.740 to -0.075]) in the coke-making group than in the control group. After controlling for potential confounding variables, it was observed that working in the coke-making sector of the industry was associated with lower FMD (F = 3.954, p = .049). These findings indicated that occupational air pollution exposure among workers in the steel industry is linked to impaired endothelium-dependent vasodilation.

Involvement of lysyl oxidase in the pathogenesis of arterial stiffness in chronic kidney disease.

Patients with chronic kidney disease (CKD) are at increased risk for adverse cardiovascular events. CKD is associated with increases in arterial stiffness, whereas improvements in arterial stiffness correlate with better survival. However, arterial stiffness is increased early in CKD, suggesting that there might be additional factors, unique to kidney disease, that increase arterial stiffness. Lysyl oxidase (LOX) is a key mediator of collagen cross linking and matrix remodeling. LOX is predominantly expressed in the cardiovascular system, and its upregulation has been associated with increased tissue stiffening and extracellular matrix remodeling. Thus, this study was designed to evaluate the role of increased LOX activity in inducing aortic stiffness in CKD and whether ß-aminopropionitrile (BAPN), a LOX inhibitor, could prevent aortic stiffness by reducing collagen cross linking. Eight-week-old male C57BL/6 mice were subjected to 5/6 nephrectomy (Nx) or sham surgery. Two weeks after surgery, mice were randomized to BAPN (300 mg/kg/day in water) or vehicle treatment for 4 wk. Aortic stiffness was assessed by pulse wave velocity (PWV) using Doppler ultrasound. Aortic levels of LOX were assessed by ELISA, and cross-linked total collagen levels were analyzed by mass spectrometry and Sircol assay. Nx mice showed increased PWV and aortic wall remodeling compared with control mice. Collagen cross linking was increased in parallel with the increases in total collagen in the aorta of Nx mice. In contrast, Nx mice that received BAPN treatment showed decreased cross-linked collagens and PWV compared with that received vehicle treatment. Our results indicated that LOX might be an early and key mediator of aortic stiffness in CKD.NEW & NOTEWORTHY Arterial stiffness in CKD is associated with adverse cardiovascular outcomes. However, the mechanisms underlying increased aortic stiffness in CKD are unclear. Herein, we demonstrated that 1) increased aortic stiffness in CKD is independent of hypertension and calcification and 2) LOX-mediated changes in extracellular matrix are at least in part responsible for increased aortic stiffness in CKD. Prevention of excess LOX may have therapeutic potential in alleviating increased aortic stiffness and improving cardiovascular disease in CKD.

Risk of myocardial infarction in Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Previous studies investigating cardiovascular disorders in patients with Parkinson's disease (PD) showed heterogeneous results regarding whether there is a higher or lower risk of myocardial infarction (MI) in these patients compared to the general population. Because of the inconsistency in findings, herein the aim was to perform a systematic review and meta-analysis to investigate the risk of MI in patients with PD. METHODS: A comprehensive literature search was performed using four databases, PubMed, Web of Science, Scopus and Embase, in June 2022. Peer-reviewed observational studies comprising case-controls, cohort, cross-sectional and longitudinal studies that reported MI in the PD population were included. RESULTS: After the screening, 20 studies with a total of 80,441 patients with PD and 802,857 controls were included in our qualitative and quantitative synthesis. The pooled estimated odds ratio for MI in PD patients compared to controls was 0.80 (95% confidence interval [CI] 0.56-1.05) which indicates that there is no association. The pooled prevalence of MI was 5% (95% CI 3%-7%) with a range of 1%-20% amongst patients with PD. The men (6%, 95% CI 1%-13%) and women (6%, 95% CI 1%-14%, Q = 29.27, I2 = 98.50%, p < 0.001) had similar MI prevalence. CONCLUSION: This comprehensive systematic review and meta-analysis provide compelling evidence that PD is associated with a reduced risk of MI. Whilst the exact mechanism underlying this association remains to be fully elucidated, it is clear that certain risk factors for cardiac events appear to be less present in PD patients, which may serve as a protective factor. However, given the reports of increased risk for cerebrovascular events in PD patients, it is possible that the major risk factors for MI and cardiovascular accidents in this population differ. These findings have important implications for clinical management and further research in this area is warranted.

Higher intakes of fiber, total vegetables, and fruits may attenuate the risk of all-cause and cause-specific mortality: findings from a large prospective cohort study.

BACKGROUND: Although studies have reported an inverse association between fruits, vegetables, and fiber consumption and all-cause and cause-specific mortality, the issue remains incompletely defined in the Middle Eastern population. AIMS: The current study aimed to investigate the association between dietary fiber, fruit, and vegetable intake and all-cause and cause-specific mortality. METHODS: A total of 48632 participants (mean age = 52years), 57.5% (n = 27974) women and 42.5% (n = 20658) men, were recruited from an ongoing large-scale prospective cohort study (the Golestan Cohort Study (GCS)), in the north of Iran. Using a validated semi-quantitative 116-item food questionnaire, dietary intakes were collected. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) of all-cause and cause-specific mortality were reported. RESULTS: After approximately 14 years of follow-up, 10,774 deaths were recorded. In the fully adjusted model, compared to those in the lowest quintile of intake, those in the second and third quintiles of dietary fiber intake had a 7%-10% reduction in risk of all-cause mortality, and a 15%-17% reduction in the risk of mortality from other causes. Increasing consumption of fruits was also associated with a decreased risk of mortality for all-cause mortality by 9%-11%, and all cancer by 15-20%. Further, those in the third and fourth quintiles of vegetables intake had 11%-12% lower risk for CVD mortality. DISCUSSION: The results from the GCS further support the current recommendations on following a healthy diet containing proper amounts of fiber, vegetables, and fruits, as health-protective dietary items. CONCLUSIONS: Higher intake of dietary fiber, fruits, and vegetables has the potential to reduce both overall and cause-specific mortality rates. However, additional cohort studies with larger sample size and long-term follow-up durations are required to establish these findings.

Patients' and GPs' duties and responsibilities in long-term care after myocardial infarction: a qualitative study of patients' perspectives.

BACKGROUND: Cardiovascular disease is one of the main causes of death in Europe and around the world. Effective and individualized long-term treatment of patients with chronic diseases such as cardiovascular disease and myocardial infarction reduces mortality and the risk of recurrence and prevents secondary disease. However, there is little data on patients' views. OBJECTIVE: To examine patients' perspectives on long-term care after myocardial infarction. METHODS: A qualitative interview study with patients after myocardial infarction in Berlin and Brandenburg, Germany. Fifteen episodic interviews were conducted, transcribed, coded, and analyzed using framework analysis. RESULTS: Participants consistently emphasized major functions fulfilled by general practitioners: monitoring, advice, diagnosis, referral, coordination. Furthermore, other functions such as empathy and feeling emotionally valued. Major patient roles emerged such as information sharing, lifestyle change, and coping. Responsibility toward doctors was expressed in terms of active participation in describing their symptoms, following the doctor's directions, and sharing in decision-making. Self-responsibility in participants showed 2 contrasting approaches. On the one hand, a passive attitude (acceptance, helplessness), and on the other, active resistance and taking action. CONCLUSION: The study underlines the importance of communication and awareness of the patient's perspective. General practitioners must address patients' aims and fears, encourage their initiative, and focus on empathy and education.

Peripheral artery disease (PAD) in primary care-educational experiences for PAD primary care in England-a mixed-method study.

BACKGROUND: Peripheral artery disease (PAD), the pathophysiologic narrowing of arterial blood vessels of the lower leg due to atherosclerosis, is a highly prevalent disease, with sharp increases in prevalence with age. Primary care is ideally located to identify and manage PAD. OBJECTIVES: This study aims to identify the educational experiences, opinions, and confidence of primary care clinicians (PCCs) regarding PAD. METHOD: This mixed-method study was conducted within primary care in England. An online survey was completed with follow-on semistructured interviews, between January and September 2021, with PCCs, namely GPs, practice nurses, and allied professionals (survey n = 874, interviews n = 50). RESULTS: PCCs report variation in PAD education received, where the content could not often be recalled. Patient-focussed experiential and self-directed learning, formed the largest method to gain PAD education. All PCCs recognized that they have an important role in recognizing PAD yet confidence in recognizing and diagnosing PAD was lacking. PCCs acknowledged that late or missed PAD diagnosis resulted in significant patient morbidity and mortality. Yet many did not recognize PAD as a common disease. CONCLUSION: As "specialist-generalists" with finite resources, education provided to primary care needs to be applicable for the multimorbid patient presentations often seen, utilizing resources available in primary care, with consideration to the time constraints endured.

Impact of healthy lifestyles on risk of hypertension in the Chinese population: finding from SHUN-CVD study.

INTRODUCTION: Lifestyle factors are known to play a role in the development of hypertension. We aimed to study the relationship between lifestyle and hypertension in a Chinese population. METHODS: This study involved 3,329 participants (1,463 men and 1,866 women) aged 18-96 years in the Shenzhen-Hong Kong United Network on Cardiovascular Disease. A healthy lifestyle score was derived from 5 factors: no smoking, no alcohol consumption, active physical activity, normal body mass index, and a healthy diet. Multiple logistic regression was used to investigate the relationship between lifestyle score and hypertension. The influence of each lifestyle component on hypertension was also assessed. RESULTS: In the overall population, 950 (28.5%) participants had hypertension. The risk of hypertension decreased with increasing healthy lifestyle scores. Compared with participants with the lowest score (score: 0), the multivariable odds ratios (ORs) and corresponding 95% confidence intervals for participants with scores 3, 4, and 5 were 0.65 (0.41-1.01), 0.62 (0.40-0.97), and 0.37 (0.22-0.61), respectively (P for trend <0.001). After adjusting for age, sex, and diabetes, the score was associated with hypertension risk (P for trend = 0.005). Compared with a lifestyle score of 0, the adjusted OR for hypertension for participants with a score of 5 was 0.46 (0.26-0.80). CONCLUSIONS: The risk of hypertension is inversely related to the healthy lifestyle score. This reinforces the need to address lifestyle to reduce the risk of hypertension.

Perceived barriers to effective use of telehealth in managing the care of patients with cardiovascular diseases: a qualitative study exploring healthcare professionals' views in Jordan.

BACKGROUND: The use of telehealth in the management of care and care delivery has been increasing significantly during the COVID-19 pandemic. Telehealth is an emerging technology used to manage care for patients with cardiovascular diseases (CVDs) in Jordan. However, implementing this approach in Jordan faces many challenges that need to be explored to identify practical solutions. PURPOSE: To explore the perceived challenges and barriers to using telehealth in managing acute and chronic CVDs among healthcare professionals. METHODS: A qualitative, exploratory study was conducted by interviewing 24 health professionals at two hospitals in different clinical areas in Jordan. RESULTS: Several barriers were reported by participants that affected the utilization of telehealth services. The barriers were categorized into the following four themes: Drawbacks related to patients, Health providers' concerns, Procedural faults, and telehealth To complement the service only. CONCLUSIONS: The study suggests that telehealth can be instrumental in supporting care management for patients with CVD. It means that understanding the advantages and barriers to implementing telehealth by the healthcare providers in Jordan can improve many aspects of the healthcare services for patients with CVD within the healthcare settings in Jordan.

Pharmacokinetics, pharmacodynamics, toxicity, and formulations of daidzein: An important isoflavone.

Daidzein, 7-hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one is a naturally occurring compound present in leguminous plants, especially in soybeans. Chemically it belongs to the isoflavone class and possesses high nutritive value. Daidzein acts on estrogen receptor and is non-steroidal in nature hence it can also be called as non-steroidal phytoestrogenic compound. Daidzein has been studied by many researchers for its pharmacological activities. Daidzein metabolites were also studied in detail for their health benefits. Researchers have developed novel formulations of daidzein in the past few years to improve its aqueous solubility and bioavailability. Self-emulsified daidzein, poly(lactic-co-glycolic) acid daidzein nanoparticles, nanoemulsion, nanoemulsion gel, and co-crystals are a few of them. The present review provides detailed information on the chemistry, drug development aspects, pharmacokinetics, and pharmacodynamics of daidzein. A literature search was performed using various datasets like PubMed, EBSCO, ProQuest Scopus, and selected websites including the National Institutes of Health and the World Health Organization. Daidzein has a wide range of pharmacodynamic properties in the treatment of cancer, neurodegenerative disorders, cardiac disorders, diabetes and its complication, osteoporosis, and skin disorders. The pharmacokinetic, pharmacodynamics, and drug development aspects of daidzein will help researchers to design further research work on daidzein in the future.

Small non-coding RNA therapeutics for cardiovascular disease.

Novel bio-therapeutic agents that harness the properties of small, non-coding nucleic acids hold great promise for clinical applications. These include antisense oligonucleotides that inhibit messenger RNAs, microRNAs (miRNAs), or long non-coding RNAs; positive effectors of the miRNA pathway (short interfering RNAs and miRNA mimics); or small RNAs that target proteins (i.e. aptamers). These new therapies also offer exciting opportunities for cardiovascular diseases and promise to move the field towards more precise approaches based on disease mechanisms. There have been substantial advances in developing chemical modifications to improve the in vivo pharmacological properties of antisense oligonucleotides and reduce their immunogenicity. Carrier methods (e.g. RNA conjugates, polymers, and lipoplexes) that enhance cellular uptake of RNA therapeutics and stability against degradation by intracellular nucleases are also transforming the field. A number of small non-coding RNA therapies for cardiovascular indications are now approved. Moreover, there is a large pipeline of therapies in clinical development and an even larger list of putative therapies emerging from pre-clinical studies. Progress in this area is reviewed herein along with the hurdles that need to be overcome to allow a broader clinical translation.

A nationwide case-control study on cardiovascular and respiratory-related disorders in patients with gambling disorder in Sweden.

OBJECTIVES: We aimed to examine potential relationships and gender differences between cardiovascular disease (CVD), diabetes, obesity, respiratory-related disorders, and gambling disorder (GD). We hypothesized that (1) GD patients would be more likely than controls to have CVD, diabetes, obesity, and respiratory-related diseases; and (2) females with GD would be more likely than men with GD to have CVD, diabetes, obesity, and respiratory-related diseases. STUDY DESIGN: National retrospective case-control study. METHODS: We used data from the Swedish National Board of Health and Welfare between 2005 and 2019. A total of 10,766 patients were included, and 3592 of them had GD. Every GD patient was matched with two age- and gender-matched controls. Patient data, including the history of medical diagnoses, were extracted. Descriptive statistics, Chi-squared and Fisher's exact tests were used to compare GD patients and controls. RESULTS: GD patients had a higher prevalence of CVD and respiratory-related disorders than controls. Diabetes rates were 5% for GD patients and 2% for controls; CVD (18% vs 12%); respiratory-related disease (7% vs 4%); and obesity (7% vs 3%). Women with a diagnosis of GD have a higher prevalence of obesity and somatic comorbidities other than diabetes compared to men. CONCLUSIONS: This is the largest case-control study conducted to date showing GD patients have a higher prevalence of CVD, diabetes, obesity, and respiratory-related disorders than controls. Women with GD appear to be more susceptible than men to CVD, obesity, and respiratory-related disorders; however, this may be partially explained by differences in help-seeking behavior. Thus, our findings highlight the importance of early identification of GD patients who may also have somatic conditions requiring treatment. This can be accomplished by implementing a screening program for GD, CVD, diabetes, obesity, and respiratory-related disorders, and by including healthy lifestyle management strategies.

Effects of risk factors on longitudinal changes in brain structure and function in the progression of AD.

INTRODUCTION: Past research on Alzheimer's disease (AD) has focused on biomarkers, cognition, and neuroimaging as primary predictors of its progression, albeit additional ones have recently gained attention. When turning to the prediction of the progression from one stage to another, one could benefit from the joint assessment of imaging-based biomarkers and risk/protective factors. METHODS: We included 86 studies that fulfilled our inclusion criteria. RESULTS: Our review summarizes and discusses the results of 30 years of longitudinal research on brain changes assessed with neuroimaging and the risk/protective factors and their effect on AD progression. We group results into four sections: genetic, demographic, cognitive and cardiovascular, and lifestyle factors. DISCUSSION: Given the complex nature of AD, including risk factors could prove invaluable for a better understanding of AD progression. Some of these risk factors are modifiable and could be targeted by potential future treatments.

Multiplatform-Integrated Identification of Melatonin Targets for a Triad of Psychosocial-Sleep/Circadian-Cardiometabolic Disorders.

Several psychosocial, sleep/circadian, and cardiometabolic disorders have intricately interconnected pathologies involving melatonin disruption. Therefore, we hypothesize that melatonin could be a therapeutic target for treating potential comorbid diseases associated with this triad of psychosocial-sleep/circadian-cardiometabolic disorders. We investigated melatonin's target prediction and tractability for this triad of disorders. The melatonin's target prediction for the proposed psychosocial-sleep/circadian-cardiometabolic disorder triad was investigated using databases from Europe PMC, ChEMBL, Open Targets Genetics, Phenodigm, and PheWAS. The association scores for melatonin receptors MT1 and MT2 with this disorder triad were explored for evidence of target-disease predictions. The potential of melatonin as a tractable target in managing the disorder triad was investigated using supervised machine learning to identify melatonin activities in cardiovascular, neuronal, and metabolic assays at the cell, tissue, and organism levels in a curated ChEMBL database. Target-disease visualization was done by graphs created using "igraph" library-based scripts and displayed using the Gephi ForceAtlas algorithm. The combined Europe PMC (data type: text mining), ChEMBL (data type: drugs), Open Targets Genetics Portal (data type: genetic associations), PhenoDigm (data type: animal models), and PheWAS (data type: genetic associations) databases yielded types and varying levels of evidence for melatonin-disease triad correlations. Of the investigated databases, 235 association scores of melatonin receptors with the targeted diseases were greater than 0.2; to classify the evidence per disease class: 37% listed psychosocial disorders, 9% sleep/circadian disorders, and 54% cardiometabolic disorders. Using supervised machine learning, 546 cardiovascular, neuronal, or metabolic experimental assays with predicted or measured melatonin activity scores were identified in the ChEMBL curated database. Of 248 registered trials, 144 phase I to IV trials for melatonin or agonists have been completed, of which 33.3% were for psychosocial disorders, 59.7% were for sleep/circadian disorders, and 6.9% were for cardiometabolic disorders. Melatonin's druggability was evidenced by evaluating target prediction and tractability for the triad of psychosocial-sleep/circadian-cardiometabolic disorders. While melatonin research and development in sleep/circadian and psychosocial disorders is more advanced, as evidenced by melatonin association scores, substantial evidence on melatonin discovery in cardiovascular and metabolic disorders supports continued R&D in cardiometabolic disorders, as evidenced by melatonin activity scores. A multiplatform analysis provided an integrative assessment of the target-disease investigations that may justify further translational research.

Free Light Chains κ and λ as New Biomarkers of Selected Diseases.

Diagnostic and prognostic markers are necessary to help in patient diagnosis and the prediction of future clinical events or disease progression. As promising biomarkers of selected diseases, the free light chains (FLCs) κ and λ were considered. Measurements of FLCs are currently used in routine diagnostics of, for example, multiple myeloma, and the usefulness of FLCs as biomarkers of monoclonal gammopathies is well understood. Therefore, this review focuses on the studies concerning FLCs as new potential biomarkers of other disorders in which an inflammatory background has been observed. We performed a bibliometric review of studies indexed in MEDLINE to assess the clinical significance of FLCs. Altered levels of FLCs were observed both in diseases strongly connected with inflammation such as viral infections, tick-borne diseases or rheumatic disorders, and disorders that are moderately associated with immune system reactions, e.g., multiple sclerosis, diabetes, cardiovascular disorders and cancers. Increased concentrations of FLCs appear to be a useful prognostic marker in patients with multiple sclerosis or tick-borne encephalitis. Intensive synthesis of FLCs may also reflect the production of specific antibodies against pathogens such as SARS-CoV-2. Moreover, abnormal FLC concentrations might predict the development of diabetic kidney disease in patients with type 2 diabetes. Markedly elevated levels are also associated with increased risk of hospitalization and death in patients with cardiovascular disorders. Additionally, FLCs have been found to be increased in rheumatic diseases and have been related to disease activity. Furthermore, it has been suggested that inhibition of FLCs would reduce the progression of tumorigenesis in breast cancer or colitis-associated colon carcinogenesis. In conclusion, abnormal levels of κ and λ FLCs, as well as the ratio of κ:λ, are usually the result of disturbances in the synthesis of immunoglobulins as an effect of overactive inflammatory reactions. Therefore, it seems that κ and λ FLCs may be significant diagnostic and prognostic biomarkers of selected diseases. Moreover, the inhibition of FLCs appears to be a promising therapeutical target for the treatment of various disorders where inflammation plays an important role in the development or progression of the disease.

Challenge of post-COVID era: management of cardiovascular complications in asymptomatic carriers of SARS-CoV-2.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), a highly pathogenic member of family coronaviridae, has caused an exponentially growing global pandemic termed as the coronavirus disease 2019 (COVID-19) with more than 12 million cases worldwide till date. This deadly disease has average fatality rate of 6.5% and even higher among elderly patients and patients with comorbidities. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE-2) as the entry receptor into host cell. ACE-2, a type-I transmembrane metallocarboxypeptidase, is a critical regulator of the renin-angiotensin system. The entry of SARS-CoV-2 within host cells results in a reduced availability of ACE-2 on the host cell surface followed by significant downregulation of ACE-2 gene expression. As ACE-2 is a well-known cardio-protective molecule, its downregulation could result in severe cardiac disorders. This review deals with a challenging aspect of SARS-CoV-2 infected patients who are asymptomatic or have mild syndromes similar to influenza infections. These patients are proving to be the Achilles' heel to combat COVID-19 mainly in developing countries of South Asia, where the average number of tests conducted per million individuals is considerably low. Consequently, there is high possibility that individuals with negligible respiratory trouble will not be tested for SARS-CoV-2. Hence, a huge percentage of the population have the risk of developing cardiovascular disorders as a bystander effect of viral infection apart from being potential reservoir of disease transmission. Based on available demographic as well as molecular data, this review predicts a huge spike in cardiovascular disorders among this undetected reservoir in post COVID-19 era.

Cardiovascular disturbances in COVID-19: an updated review of the pathophysiology and clinical evidence of cardiovascular damage induced by SARS-CoV-2.

Severe acute respiratory coronavirus-2 (SARS-Co-2) is the causative agent of coronavirus disease-2019 (COVID-19). COVID-19 is a disease with highly variable phenotypes, being asymptomatic in most patients. In symptomatic patients, disease manifestation is variable, ranging from mild disease to severe and critical illness requiring treatment in the intensive care unit. The presence of underlying cardiovascular morbidities was identified early in the evolution of the disease to be a critical determinant of the severe disease phenotype. SARS-CoV-2, though a primarily respiratory virus, also causes severe damage to the cardiovascular system, contributing significantly to morbidity and mortality seen in COVID-19. Evidence on the impact of cardiovascular disorders in disease manifestation and outcome of treatment is rapidly emerging. The cardiovascular system expresses the angiotensin-converting enzyme-2, the receptor used by SARS-CoV-2 for binding, making it vulnerable to infection by the virus. Systemic perturbations including the so-called cytokine storm also impact on the normal functioning of the cardiovascular system. Imaging plays a prominent role not only in the detection of cardiovascular damage induced by SARS-CoV-2 infection but in the follow-up of patients' clinical progress while on treatment and in identifying long-term sequelae of the disease.

The association of general practitioners' awareness of depression and anxiety with change in quality of life in heart failure patients: results of the prospective observational RECODE-HF cohort study.

BACKGROUND: Depression and anxiety are more prevalent in patients with heart failure (HF) than in the general population and reduce quality of life (QoL); therefore, clinical guidelines recommend screening HF patients for depression/anxiety. OBJECTIVE: We investigated, whether the general practitioners' (GPs) awareness of patients' symptoms of depression and/or anxiety (psychosocial distress) was associated with a change in QoL. METHODS: In this prospective observational study, we recruited 3,129 primary care HF patients in Germany. Patients completed baseline and 12-month follow-up questionnaires. Their GPs were interviewed. We identified 666 patients with psychosocial distress and compared 2 groups by analysis of covariance: 235 patients with psychosocial distress whose GP was aware of the psychosocial distress and 431 patients with psychosocial distress whose GP was unaware of such distress. Primary outcome was the change in QoL, assessed by the EQ-5D visual analogue scale. RESULTS: Patients with psychosocial distress showed lower baseline QoL than those without (45.9 vs 64.1; P < 0.001). Within the patients with psychosocial distress, the GPs' awareness of psychosocial distress was not associated with improvement of QoL (F = 1.285; P = 0.258) or remission of psychosocial distress (odds ratio = 0.887; P = 0.608). CONCLUSION: We found no association between the GPs' awareness of psychosocial distress and change in QoL. Although data for effective treatments of depression in HF are currently insufficient, psychosocial distress strongly impairs the QoL in HF patients. These findings might influence the development of clinical practice guidelines in HF.