Methylene blue reduces monoamine oxidase expression and oxidative stress in human cardiovascular adipose tissue.

Cardiovascular diseases represent the major cause of morbidity mainly due to chronic heart failure. Epicardial (EAT) and perivascular adipose tissues (PVAT) are considered major contributors to the pathogenesis of cardiometabolic pathologies. Monoamine oxidases (MAOs) are mitochondrial enzymes recognized as sources of reactive oxygen species (ROS) in cardiometabolic pathologies. Methylene blue (MB) is one of the oldest protective agents, yet no data are available about its effects on adipose tissue. The present pilot study was aimed at assessing the effects of MB: (i) on MAO expression and (ii) oxidative stress in EAT and PVAT harvested from patients with heart failure subjected to cardiac surgery (n = 25). Adipose tissue samples were incubated with MB (0.1 µM/24 h) and used for the assessment of MAO gene and protein expression (qPCS and immune fluorescence) and ROS production (confocal microscopy and spectrophotometry). The human cardiovascular adipose tissues contain both MAO isoforms, predominantly MAO-A. Incubation with MB reduced MAOs expression and oxidative stress; co-incubation with serotonin, the MAO-A substrate, further augmented ROS generation, an effect partially reversed by MB. In conclusion, MAO-A is the major isoform expressed in EAT and PVAT and contribute to local oxidative stress; both effects can be mitigated by methylene blue.

Liver and Pancreatic Toxicity of Endocrine-Disruptive Chemicals: Focus on Mitochondrial Dysfunction and Oxidative Stress.

In recent years, the worldwide epidemic of metabolic diseases, namely obesity, metabolic syndrome, diabetes and metabolic-associated fatty liver disease (MAFLD) has been strongly associated with constant exposure to endocrine-disruptive chemicals (EDCs), in particular, the ones able to disrupt various metabolic pathways. EDCs have a negative impact on several human tissues/systems, including metabolically active organs, such as the liver and pancreas. Among their deleterious effects, EDCs induce mitochondrial dysfunction and oxidative stress, which are also the major pathophysiological mechanisms underlying metabolic diseases. In this narrative review, we delve into the current literature on EDC toxicity effects on the liver and pancreatic tissues in terms of impaired mitochondrial function and redox homeostasis.

Metformin and empagliflozin modulate monoamine oxidase-related oxidative stress and improve vascular function in human mammary arteries.

Monoamine oxidases (MAOs), mitochondrial enzymes with two isoforms, A and B, have been recently recognized as significant contributors to oxidative stress in the cardiovascular system. The present study was purported to assess the effect of metformin and empagliflozin on MAO expression, oxidative stress and vascular reactivity in internal mammary arteries harvested from overweight patients with coronary heart disease subjected to bypass grafting. Vascular rings were prepared and acutely incubated (12 h) with high glucose (GLUC, 400 mg/dL) or angiotensin II (AII, 100 nM) and metformin (10 µM) and/or empagliflozin (10 µM) and used for the assessment of MAO expression (qRT-PCR and immune histochemistry), reactive oxygen species (ROS, confocal microscopy and spectrophotometry), and vasomotor function (myograph). Ex vivo stimulation with GLUC or AII increased both MAOs expression, ROS production and impaired relaxation to acetylcholine (ACh) of the vascular rings. All effects were alleviated by incubation with each antidiabetic drug; no cumulative effect was obtained when the drugs were applied together. In conclusion, MAO-A and B are upregulated in mammary arteries after acute stimulation with GLUC and AII. Endothelial dysfunction and oxidative stress were alleviated by either metformin or empagliflozin in both stimulated and non-stimulated vascular samples harvested from overweight cardiac patients.

Monoamine oxidase is a source of cardiac oxidative stress in obese rats: the beneficial role of metformin.

Diet-induced metabolic diseases, such as obesity, metabolic syndrome, and type 2 diabetes (T2DM) are the global threatening epidemics that share cardiovascular oxidative stress as common denominator. Monoamine oxidase (MAO) has recently emerged as a constant source of reactive oxygen species (ROS) in DM. Metformin, the first-line drug in T2DM, elicits cardiovascular protection via pleiotropic effects. The present study was aimed to assess the contribution of MAO to the early cardiac oxidative stress in a rat model of high-calorie junk food (HCJF) diet-induced obesity and prediabetes and whether metformin can alleviate it. After 6 months of HCJF, rats developed obesity and hyperglycemia. Hearts were isolated and used for the evaluation of MAO expression and ROS production. Experiments were performed in the presence vs absence of metformin (10 µM) and MAO-A and B inhibitors (clorgyline and selegiline, 10 µM), respectively. Both MAO isoforms were overexpressed and led to increased ROS generation in cardiac samples harvested from the obese animals. Acute treatment with metformin and MAO inhibitors was able to mitigate oxidative stress. More important, metformin downregulated MAO expression in the diseased samples. In conclusion, MAO contributes to oxidative stress in experimental obesity and can be targeted with metformin.

Placental oxidative stress and monoamine oxidase expression are increased in severe preeclampsia: a pilot study.

Preeclampsia (PE) is the most severe complication of pregnancy with substantial burden of morbidity and mortality for mother and neonate. The increased placental oxidative stress (OS) has been involved as central pathomechanism, yet the sources of reactive oxygen species (ROS) are partially elucidated. Monoamine oxidase (MAO) with 2 isoforms, A and B, at the outer mitochondrial membrane has emerged as a constant source of ROS in cardiometabolic pathologies. The present pilot study was purported to assess as follows: (i) the magnitude of placental OS in relation to the site of sampling and (ii) the expression of placental MAO in the setting of PE. To this aim, central and placental samples were harvested during cesarean section from mild and severe PE versus healthy pregnancies. ROS generation (dihydroethidium staining) and MAO expression were assessed (confocal microscopy). MAO gene transcript was evaluated by RT-PCR. The main findings are as follows: (i) a significant increase in placental OS was found in severe (but not in mild) PE with no regional differences between central and peripheral areas and (ii) placental MAO-A and B (gene and protein) were significantly increased in severe preeclampsia. The signal transduction of the latter finding, particularly in relation with mitochondrial dysfunction, is worth further studying.

Impairment of mitochondrial respiration in platelets and placentas: a pilot study in preeclamptic pregnancies.

Preeclampsia (PE) is a major complication of pregnancy with partially elucidated pathophysiology. Placental mitochondrial dysfunction has been increasingly studied as major pathomechanism in both early- and late-onset PE. Impairment of mitochondrial respiration in platelets has recently emerged as a peripheral biomarker that may mirror organ mitochondrial dysfunction in several acute and chronic pathologies. The present study was purported to assess mitochondrial respiratory dys/function in both platelets and placental mitochondria in PE pregnancies. To this aim, a high-resolution respirometry SUIT (Substrate-Uncoupler-Inhibitor-Titration) protocol was adapted to assess complex I (glutamate + malate)- and complex II (succinate)-supported respiration. A decrease in all respiratory parameters (basal, coupled, and maximal uncoupled respiration) in peripheral platelets was found in preeclamptic as compared to healthy pregnancies. At variance, placental mitochondria showed a dichotomous behavior in preeclampsia in relation to the fetal birth weight. PE pregnancies with fetal growth restriction were associated with decreased in coupled respiration (oxidative phosphorylation/OXPHOS capacity) and maximal uncoupled respiration (electron transfer/ET capacity). At variance, these respiratory parameters were increased for both complex I- and II-supported respiration in PE pregnancies with normal weight fetuses. Large randomized controlled clinical studies are needed in order to advance our understanding of mitochondrial adaptive vs. pathological changes in preeclampsia.

COVID-19 and the Human Eye: Conjunctivitis, a Lone COVID-19 Finding - A Case-Control Study.

OBJECTIVES: COVID-19 has varied clinical manifestations, from asymptomatic to severe cases, and conjunctivitis is one of them, but sometimes a lone initial symptom is found to be present. The aim of this study was to identify the prevalence of conjunctivitis as the first symptom in COVID-19 patients in a primary healthcare unit. METHODOLOGY: A retrospective study was conducted, analyzing the presenting complains/symptoms and results of COVID-19-confirmatory tests. RESULTS: Out of the 672 cases that were sent for RT-PCR testing, only 121 (18%) were found to be positive. Among these, 2.67% patients had both conjunctivitis and COVID-19, 77.77% patients had unilateral eye affected, while 22.22% had bilateral conjunctivitis of varying degrees. Fifteen patients diagnosed to have both acute conjunctivitis and COVID-19 presented other symptoms associated with COVID-19 infection. Three patients had only acute conjunctivitis during their entire course of COVID-19. CONCLUSIONS: Conjunctivitis is a symptom of COVID-19 and may be the first sign of the infection, until the onset of the classical manifestations; such patients may continue to be a viral reservoir. Physicians should not miss unilateral conjunctivitis as it can be the only presenting complaint of COVID-19 during the initial phase, which might worsen if undetected and can aid in the spread of the contagion.

Methotrexate and Cetuximab-Biological Impact on Non-Tumorigenic Models: In Vitro and In Ovo Assessments.

Background Objectives: The neoplastic process remains a major health problem facing humanity. Although there are currently different therapeutic options, they raise a multitude of shortcomings related to the toxic effects associated with their administration. Methotrexate (Met) and Cetuximab (Cet) are two basic chemotherapeutics used in cancer practice, but notwithstanding despite many years of use, the mechanisms by which the multitude of side-effects occur are not yet fully understood. Thus, the present study focused on the in vitro and in ovo evaluation of the associated toxic mechanisms on keratinocytes, keys cells in the wound healing process. Materials and Methods: The two chemotherapeutics were tested in eight different concentrations to evaluate keratinocytes viability, the anti-migratory effect, and the influence on the expression of markers involved in the production of cell apoptosis. In addition, the potential irritating effect on the vascular plexus were highlighted by applying the in ovo method, chick chorioallantoic membrane (HET-CAM). Results: The results revealed that Met induced decreased cell viability as well as increased expression of pro-apoptotic genes. In the vascular plexus of the chorioallantoic membrane, Met caused vascular irritation accompanied by capillary hemorrhage and vascular stasis. Conclusions: Summarizing, Cet presents a safer toxicological profile, compared to Met, based on the results obtained from both in vitro (cell viability, wound healing, RT-PCR assays), and in ovo (HET-CAM assay) techniques.

Are Inherited Combined Thrombophilia Mutations a Causative or an Additive Factor in Recurrent Venous Thrombotic Accidents?

BACKGROUND: Inherited thrombophilia represents a prothrombotic disorder that predisposes to thrombosis. METHODS: We present a case of a 67-year-old female with a personal and family history of iterative thrombotic events. She was admitted in the Surgical Clinic at the age of 59, presenting the classical symptoms and signs for left lower limb deep vein thrombosis, confirmed by a venous Duplex Ultrasonography. This was the third episode of a venous thrombosis. Under anticoagulant treatment the evolution was good. The patient was advised to test for inherited thrombophilia mutations. RESULTS: Four years later, she experienced another episode of thrombosis. The patient tested positive for five of the most frequent mutations found in inherited thrombophilia. CONCLUSIONS: Patients with recurrent venous thrombosis and positive family history for thrombotic events must be checked for thrombophilic conditions, inherited or acquired.

Biologics in Systemic Lupus Erythematosus: Recent Evolutions and Benefits.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by significant autoantibodies, particularly targeting nuclear antigens. SLE pathogenesis involves genetic, environmental, and hormonal factors. The disease course includes flares and remission and involves various organs. Recent therapeutic progresses, including biologics, have improved management and prognosis, though the long-term impact of novel therapies remains to be determined. Biologics in SLE: Rituximab, the earliest B-cell-oriented biologic, binds CD20 and depletes CD20+ B cells, leading to remission in some SLE patients. Belimumab is a B-cell-activating factor (BAFF) inhibitor with a recent additional indication for lupus nephritis. The CALIBRATE and BLISS-BELIEVE studies investigated combinations of these drugs with conventional therapies, showing varied efficacy. Ocrelizumab and obinutuzumab, newer CD20-oriented SLE therapies, together with ofatumumab and veltuzumab, are also promising. The latest trials highlight their efficacy and safety. Anifrolumab, targeting type-I interferon receptors, was evaluated in the TULIP 1/2 trials. The ongoing TULIP LTE trial supports the long-term safety and efficacy of anifrolumab. Additionally, the IRIS Phase III trial is exploring anifrolumab for lupus nephritis, showing favorable renal responses. Tocilizumab and secukinumab are being assessed for SLE, with mixed outcomes. Several biologics targeting the C5 complement protein, together with immunomodulators and immunotherapeutics, are also under investigation for potential benefits in SLE. DISCUSSION: Biologics in SLE target specific immune components, aiming to improve disease control and reduce the side effects of conventional therapy. However, trial outcomes vary due to factors like inclusion criteria and trial design. CONCLUSIONS: Biotechnology progress enables targeted biologic therapies for SLE, reducing disease activity and improving patients' quality of life.

Importance of Prenatal Diagnosis of Ileal Atresia in Gestational Diabetes Cases.

BACKGROUND Maldevelopment of the fetal bowel can result in the rare condition of intestinal atresia, which results in congenital bowel obstruction. This report describes a case of prenatal diagnosis of fetal ileal atresia at 22 weeks' gestation. CASE REPORT Here, we present a 24-year old woman who was 22 weeks into her first pregnancy when she underwent routine fetal ultrasound. She was diagnosed with gestational diabetes mellitus. Her body mass index was normal and she had normal weight gain. The ultrasonographic examination performed revealed a hyperechoic bowel and a small dilatation of the bowel. The couple was counselled for possible intestinal atresia and its postnatal implications. At 33 weeks of gestation, polyhydramnios appeared, and the intestinal distension was much more pronounced, with hyperechoic debris in the intestinal lumen (succus-entericus). After birth, surgery was performed and we concluded the patient had type II atresia, which was surgically treated. CONCLUSIONS This report has highlighted the importance of antenatal ultrasound in detecting fetal abnormalities, and has shown that rare conditions such as intestinal atresia can be accurately diagnosed and successfully managed. Surgical correction, if implemented promptly after stabilizing the general condition, can have a relatively good prognosis. Coexisting fetal ileal atresia and gestational diabetes mellitus are rare occurrences, which can make each condition even more difficult to treat.

Particularities of a Cardiac Amorphous Left Ventricular Tumor in a Patient with Coronary Artery Disease-Diagnostic and Therapeutic Challenges: A Case Report and Literature Review.

Background: Cardiac calcified amorphous tumors (CATs) are rare non-neoplastic formations containing amorphous fibrinous material and calcifications. In our research, we present the case of a 42-year-old male patient who developed, during his 6-months monitoring for coronary artery disease, a left ventricular (LV) CAT raising diagnostic challenges. Methods: To gather additional information on CATs, we researched the international medical literature for scientific articles published with the full text in English, on PubMed, ResearchGate, Clarivate, and Google Scholar between 2020 and 2024. Results: Compared to most described cases, our patient was a young male, without mitral annular calcification or chronic renal disease, but he was suffering from chronic peripheral and coronary artery disease, and genetic testing revealed a higher risk for thromboembolic events. During 6 months, he developed a LV CAT of 4.5/3.5/3 cm. Although we found in the medical literature 16 case reports of patients with CAT, only six authors could specify a precise postoperative evolution of the CAT, most of them sustaining that if completely removed, it would not relapse, an aspect observed also in our patient during 3 years of follow-up. Conclusions: CATs are rare heart tumors with slow growth, but with a high embolization risk that raises diagnostic and therapeutic challenges.

Time-to-Treatment Delays and Their Prognostic Implications in Pharyngeal Cancer-An Exploratory Analysis in Western Romania.

BACKGROUND: Diagnosis and treatment for pharyngeal cancer are decisive in determining prognosis. Diagnosis delays are frequent, representing a significant cause of avoidable mortality, and an important factor in subpar survival across the continuous HNC care delivery. METHODS: The present study represents a retrospective analysis of medical records from Western Romania, which included 180 patients, to evaluate the impact of time-to-treatment delay on patients diagnosed with pharyngeal cancer. The data analyses were performed using the Kaplan-Meier method R (version 3.6.3) packages, including tidyverse, final-fit, mcgv, survival, stringdist, janitor, and Hmisc. RESULTS: The mean days from diagnosis until the end of treatment were higher for the nasopharynx group. Cox regression analysis regarding diagnosis to treatment duration categories showed an increased risk mortality by 3.11 times (95%CI: 1.51-6.41, p = 0.0021) with a Harrell's C-index of 0.638 (95%CI: 0.552-0.723). The hypopharynx and oropharynx locations increased risk mortality by 4.59 (95%CI: 1.55-13.55) and 5.49 times (95%CI: 1.79-16.81) compared to the nasopharynx location. CONCLUSIONS: The findings of this study led to the conclusion that it seems there is a trend of mortality risk for oropharynx and hypopharynx cancers due to delays in the time to treatment over 70 days, standing as a basis for further research as there is an imperative need for prospective multicenter studies.

Challenges of Pharyngeal Cancer Screening in Lower-Income Countries during Economic and Social Transitions: A Population-Based Analysis.

Background and Objectives: The rate of head and neck cancer (HNC) is expected to increase by 30% by 2030. However, there are many similarities between the symptomatology of a benign and a malign diagnosis; thus, a protocol for conducting a full head and neck examination is of high importance since the absence of adenopathy does not exclude a malignant diagnosis and also a favorable prognosis. Material and methods: The current study presents a retrospective study on 515 adult patients who underwent a biopsy for possible head and neck tumor pathology. Results: The patients identified with cancer were older than the rest of the group, with a higher developing trend in men than in women. However, the top 10 symptomatology patterns were identical in the malign and benign groups, meaning that new HNC may be missed due to the common symptomatology between benign and malign outcomes. Conclusions: The importance of a full ear, nose, and throat (ENT) examination may be of significant relevance for a proper diagnosis that can improve the overall prognosis of a patient with cancer. The absence of routine screening tests and screening guidelines for oral and pharyngeal cancers represents a significant barrier to secondary HNC prevention.

Rhythm Disturbances in Post-Acute COVID-19 Syndrome in Young Men without Pre-Existing Known Cardiovascular Disease-A Case Series.

Current data indicate the existence of post-acute COVID-19 syndrome frequently expressing as cardiovascular and respiratory health issues. The long-term evolution of these complications is not yet fully known or predictable. Among the most common clinical manifestations of post-acute COVID-19 syndrome are dyspnea, palpitations, and fatigue, in most cases being transient and without underlying any morphological or functional changes. A single-center retrospective observational study was performed on cases that had presented with new-onset cardiac symptoms post-COVID-19 infection. Records of three male patients without pre-existing chronic cardiovascular pathology who had presented for dyspnea, fatigue, and palpitations around four weeks post-COVID-19 acute phase were studied in detail. The three post-COVID-19 cases exhibited arrhythmic complications after completely healing from the acute phase of the infection. Palpitations, along with chest pain, and possible aggravation or appearance of dyspnea, with syncopal episodes, were found to be present. All the three cases were non-vaccinated against COVID-19 infection. Isolated case reports showing arrhythmic complications such as atrial fibrillation and ventricular tachycardia on a small number of patients with these complications indicate the need for arrhythmic evaluation of large groups of patients in the post-acute stage of the COVID-19 syndrome for a better understanding of the phenomenon and implicitly better care of these patients. It would also be useful to evaluate large groups of patients divided into vaccinated/non-vaccinated against COVID-19 categories to determine whether vaccination per se can provide protection in the occurrence of these types of complications.

Prevalence of Gestational Diabetes in preCOVID-19 and COVID-19 Years and Its Impact on Pregnancy: A 5-Year Retrospective Study.

Gestational diabetes mellitus (GDM) affects a total of 3% to 9% of all pregnancies. It has a high impact on both mother and baby, increases the perinatal risks, and predicts the presence of long-term chronic metabolic complications. The aim of our study is to determine the incidence of GDM in tertiary hospitals in the west part of Romania to lay out the risk factors associated with GDM and to observe the evolution of pregnancy among patients with this pathology by emphasizing the state of birth of the fetus, the birth weight, and the way of birth. We also want to compare the prevalence of GDM in preCOVID-19 (Coronavirus disease) versus COVID-19 years. The study took place between January 2017 and December 2021 at the Municipal Emergency Hospital of Timisoara, Romania. The proportion of births with GDM was significantly increased during the COVID-19 period compared to the preCOVID-19 period (chi2 Fisher exact test, p < 0.001). The period 2020−2021 represents a significant risk factor for GDM births (OR = 1.87, with 95% CI = [1.30, 2.67]). COVID years represent a risk period for developing gestational diabetes, which can be explained by reduced physical activity, anxiety, or modified dietary habits, even if the follow-up period was not impacted.

Evaluation of Non-Pharmacological Measures Implemented in the Management of the COVID-19 Pandemic in Romania.

The management of the COVID-19 pandemic in Romania has included the involvement of not only the medical system, but also that of the administrative and social services. All these organizations are working together to lower the impact on the health of the general population, to increase the health system's response capabilities and even to diminish the negative effects upon the economy due to the epidemic's length. Therefore, non-pharmacological measures (NPMs) imposed through restrictive measures (administrative, economic and individual) have influenced the evolution of morbidity and mortality. Even from the first months of the pandemic's progression, researchers have shown the impact of the NPMs' existence, as there were many studies on all NPMs in conjunction, as well as those targeting specific measures such as school closures. Our study started by establishing a temporal relationship between the non-pharmacological measures found in most countries (wearing a mask, washing hands and physical distancing, limiting economic activities, closing schools, limiting internal and international movement, banning public and private events in closed spaces) and the evolution of the pandemic in Romania. The degree of novelty brought by this study consists of extending the analysis to the pre-existing state of the health system and to the measures meant to increase the resilience of the population, as well as to the measures aimed at reducing the type of risk, and factors that can equally influence the evolution of the number of cases. The results of the statistical analysis show the important effects of certain NPMs (mask mandates, online schooling, decisions regarding imposing or lifting local restrictions) as well as the reduced impact of other measures (hand disinfection, social distancing or the restriction of public and private events). Hence, it can be concluded that during such pandemics, implementing quick, simple measures can prevent the spread of the disease and help fight the contagion in a better manner.

Assessment of Platelet Mitochondrial Respiration in a Pediatric Population: A Pilot Study in Healthy Children and Children with Acute Lymphoblastic Leukemia.

Characterization of mitochondrial respiration in peripheral blood cells has recently emerged as a potential biomarker for the assessment of the severity of hematological malignancies (HM) in adults. Whether changes in platelet respiratory function occur in children with or without HM it is unknown. The present pilot study was double-aimed: (i) to investigate whether platelet respiration is age-dependent in non-HM children and (ii) to assess the platelet mitochondrial respiration in children with newly diagnosed acute lymphoblastic leukemia (ALL). Blood samples obtained from age-grouped children (10-11, 13-14 and 16-17 years) with non-HM and children with ALL (10-11 years) were used to isolate platelets via differential centrifugation. High-resolution respirometry studies of isolated platelets were performed according to a protocol adapted to evaluate complex I and II-supported respiration. An age-related decrease in respiration was observed in the non-HM pediatric population and had comparable values for the 13-14 and 16-17 years. groups. In children with ALL, a significant increase in C I-supported active respiration and decrease in maximal noncoupled respiration were found at the disease onset. In conclusion, in a pediatric population, platelet mitochondrial respiration is age-dependent. Platelet respiratory dysfunction occurs in children with newly-diagnosed ALL, an observation that warrants further investigation of this change as a disease biomarker.

Identification of Heavy Tobacco Smoking Predictors-Influence of Marijuana Consuming Peers and Truancy among College Students.

BACKGROUND: Poorly informed college students tend to adopt the habit of cigarette smoking. This habit often continues into their adulthoods, adversely affecting the population's health and increasing the burden on healthcare systems. AIM: We aimed at exploring the predictors of the avoidable habit of smoking. We performed an analysis of the correlation between the potential predictors (marijuana use among peers and truancy) and the tobacco smoking statuses of the students. MATERIAL AND METHOD: Our study sample included 2976 students from colleges in Timis County, Romania, during the 2018-2019 period. The gender distribution of the participants was 62.5% girls and 37.5% boys, between the ages 18 and 25 years. A logistic regression test was performed to determine the impact of some personal and environmental factors, which are responsible for heavy smoking in this population. RESULTS: Our findings suggest that the degree of marijuana smoking among friends and the frequency of college truancy are meaningful predictors of heavy smoking among young adults. The students with higher cigarette smoking rates had significantly more marijuana-smoking friends when compared to the students with average smoking rates. The truancy was higher among the students with higher cigarette smoking rates, compared to the students with average smoking rates.

Benefits of prescribing low-dose digoxin in atrial fibrillation.

INTRODUCTION: The role of digoxin (cardiac glycoside) in controlling the heart rate (HR) for the treatment of atrial fibrillation (AF) patients has not been explored in depth. METHODS: To contribute to the limited data, our team conducted retrospective analysis of the clinical records of 1444 AF patients. We divided the AF patients into two groups, wherein group 1 patients were treated with beta-blockers (BB), low-dose digoxin, and an anticoagulant (vitamin K antagonist/factor-IIa inhibitor/factor-Xa inhibitor), and group 2 patients were treated with just BB and an anticoagulant. Our objectives were to compare the impact of combination therapy of BB and digoxin on the resting HR in patients with permanent AF and the patients' quality of life (QOL) at periodic intervals. RESULTS: The findings of our study showed a better control of the resting HR rate (<110bpm) and an improved QOL among the group 1 patients when compared with group 2 patients. CONCLUSION: Our findings are indicative of the favorable clinical outcomes that resulted from the addition of a low-dose of digoxin to the AF treatment regimen. However, larger studies/trials elucidating the outcomes of AF patients treated with the dual rate control therapy are required, to clarify the role of digoxin, guide the choice of agents, and standardize the AF treatment protocol.