Extracellular vesicle-mediated drug delivery in breast cancer theranostics.

Breast cancer (BC) continues to be a significant global challenge due to drug resistance and severe side effects. The increasing prevalence is alarming, requiring new therapeutic approaches to address these challenges. At this point, Extracellular vesicles (EVs), specifically small endosome-released nanometer-sized EVs (SEVs) or exosomes, have been explored by literature as potential theranostics. Therefore, this review aims to highlight the therapeutic potential of exosomes in BC, focusing on their advantages in drug delivery and their ability to mitigate metastasis. Following the review, we identified exosomes' potential in combination therapies, serving as miRNA carriers and contributing to improved anti-tumor effects. This is evident in clinical trials investigating exosomes in BC, which have shown their ability to boost chemotherapy efficacy by delivering drugs like paclitaxel (PTX) and doxorubicin (DOX). However, the translation of EVs into BC therapy is hindered by various challenges. These challenges include the heterogeneity of EVs, the selection of the appropriate parent cell, the loading procedures, and determining the optimal administration routes. Despite the promising therapeutic potential of EVs, these obstacles must be addressed to realize their benefits in BC treatment.

Association between Statin Use and Chemotherapy-Induced Cardiotoxicity: A Meta-Analysis.

Background: Chemotherapy-induced cardiac dysfunction (CIC) is a significant and concerning complication observed among cancer patients. Despite the demonstrated cardioprotective benefits of statins in various cardiovascular diseases, their effectiveness in mitigating CIC remains uncertain. Objective: This meta-analysis aims to comprehensively evaluate the potential cardioprotective role of statins in patients with CIC. Methods: A systematic literature search was conducted using PubMed, Embase, and Scopus databases to identify relevant articles published from inception until 10th May 2023. The outcomes were assessed using pooled odds ratio (OR) for categorical data and mean difference (MD) for continuous data, with corresponding 95% confidence intervals (95% CIs). Results: This meta-analysis comprised nine studies involving a total of 5532 patients, with 1904 in the statin group and 3628 in the non-statin group. The pooled analysis of primary outcome shows that patients who did not receive statin suffer a greater decline in the LVEF after chemotherapy compared to those who receive statin (MD, 3.55 (95% CI: 1.04-6.05), p = 0.01). Likewise, we observed a significantly higher final mean LVEF among chemotherapy patients with statin compared to the non-statin group of patients (MD, 2.08 (95% CI: 0.86-3.30), p > 0.001). Additionally, there was a lower risk of incident heart failure in the statin group compared to the non-statin group of patients (OR, 0.41 (95% CI: 0.27-0.62), p < 0.001). Lastly, the change in the mean difference for LVEDV was not statistically significant between the statin and non-statin groups (MD, 1.55 (95% CI: -5.22-8.33), p = 0.65). Conclusion: Among patients of CIC, statin use has shown cardioprotective benefits by improving left ventricular function and reducing the risk of heart failure.

Association between rheumatoid arthritis and atrial fibrillation: A systematic review and meta-analysis.

Rheumatoid arthritis (RA) is an autoimmune disorder with a varying range of organs involved leading to adverse outcomes. However, very little is known, with conflicting results about the association between RA and atrial fibrillation (AF). We aim to evaluate the association between RA and AF, and other clinical outcomes. We performed a systematic literature search using PubMed, Embase, and Scopus for relevant articles from inception until September 10, 2023. Primary clinical outcomes were AF. Secondary outcomes were acute coronary syndrome (ACS), stroke, and all-cause mortality (ACM). A total of 4 679 930 patients were included in the analysis, with 81 677 patients in the RA group and 4 493 993 patients in the nonrheumatoid arthritis (NRA) group. The mean age of the patients was 57.2 years. Pooled analysis of primary outcomes shows that RA groups of patients had a significantly higher risk of AF (odds ratios [OR], 1.53; 95% confidence interval [CI]: [1.16-2.03], p < .001) compared with NRA groups. Secondary Outcomes show that the RA group of patients had significantly higher odds of ACS (OR, 1.39; 95% CI: [1.26-1.52], p < .001), and ACM (OR, 1.19; 95% CI: [1.03-1.37], p = .02) compared with the NRA groups. However, the likelihood of stroke (OR, 1.02; 95% CI: [0.94-1.11], p = .61) was comparable between both groups of patients. Our study shows that RA groups of patients are at increased risk of having AF, ACS, and ACM.

Prevalence of latent tuberculosis infection in Asian nations: A systematic review and meta-analysis.

BACKGROUND: Tuberculosis (TB) is a serious public health concern around the world including Asia. TB burden is high in Asian countries and significant population harbor latent tuberculosis infection(LTBI). AIM: This systematic review and meta-analysis aims to evaluate the prevalence of LTBI in Asian countries. METHOD: We performed a systematic literature search on PubMed, Embase, and ScienceDirect to identify relevant articles published between January 1, 2005, and January 1, 2023 investigating the overall prevalence of latent TB among people of Asia. Subgroup analysis was done for Asian subregions during the study period of 2011 to 2016 and 2017 to 2023, for tuberculin skin test (TST) and interferon gamma release assay (IGRA), respectively, as well as for QuantiFERON-TB (QFT) and TSPOT TB tests. Der Simonian and Laird's random-effects model was used to pool the prevalence of LTBI found using TST and IGRA. RESULT: A total of 15 studies were included after a systematic search from standard electronic databases. The analysis showed that the prevalence of latent TB in Asia was 21% (95% confidence interval [CI]: 19%-23%) and 36% (95% CI: 12%-59%) according to IGRAs and TSTs (cut off 10 mm) results, respectively. Based on IGRA, the prevalence of latent TB was 20% (95% CI: 13%-25%) in 2011 to 2016 and 21% (95% CI: 18%-24%) in 2017 to 2023. Using QFT, the prevalence was 19% (95% CI: 17%-22%) and using TSPOT, the prevalence was 26% (95% CI: 21%-31%). According to the United Nations division of Asia, the prevalence was higher for the Southern region and least for the Western region using TST and higher in the South-Eastern region and least in the Western region using the IGRA test. CONCLUSION: Almost a quarter of the Asian population has LTBI. Its diagnosis often poses a diagnostic challenge due to the unavailability of standard test in certain areas. Given this prevalence, a mass screening program is suggested with the available standard test and public awareness along with anti-TB regimen should be considered for individuals who test positive. However, for it to be implemented effectively, we need to take the affordability, availability, and cost-effectiveness of such interventions into account.

The paradoxical role of cytokines and chemokines at the tumor microenvironment: a comprehensive review.

Tumor progression and eradication have long piqued the scientific community's interest. Recent discoveries about the role of chemokines and cytokines in these processes have fueled renewed interest in related research. These roles are frequently viewed as contentious due to their ability to both suppress and promote cancer progression. As a result, this review critically appraised existing literature to discuss the unique roles of cytokines and chemokines in the tumor microenvironment, as well as the existing challenges and future opportunities for exploiting these roles to develop novel and targeted treatments. While these modulatory molecules play an important role in tumor suppression via enhanced cancer-cell identification by cytotoxic effector cells and directly recruiting immunological effector cells and stromal cells in the TME, we observed that they also promote tumor proliferation. Many cytokines, including GM-CSF, IL-7, IL-12, IL-15, IL-18, and IL-21, have entered clinical trials for people with advanced cancer, while the FDA has approved interferon-alpha and IL-2. Nonetheless, low efficacy and dose-limiting toxicity limit these agents' full potential. Conversely, Chemokines have tremendous potential for increasing cancer immune-cell penetration of the tumor microenvironment and promoting beneficial immunological interactions. When chemokines are combined with cytokines, they activate lymphocytes, producing IL-2, CD80, and IL-12, all of which have a strong anticancer effect. This phenomenon opens the door to the development of effective anticancer combination therapies, such as therapies that can reverse cancer escape, and chemotaxis of immunosuppressive cells like Tregs, MDSCs, and TAMs.

RNA in cardiovascular disease: A new frontier of personalized medicine.

Personalized medicine has witnessed remarkable progress with the emergence of RNA therapy, offering new possibilities for the treatment of various diseases, and in particular in the context of cardiovascular disease (CVD). The ability to target the human genome through RNA manipulation offers great potential not only in the treatment of cardiac pathologies but also in their diagnosis and prevention, notably in cases of hyperlipidemia and myocardial infarctions. While only a few RNA-based treatments have entered clinical trials or obtained approval from the US Food and Drug Administration, the growing body of research on this subject is promising. However, the development of RNA therapies faces several challenges that must be overcome. These include the efficient delivery of drugs into cells, the potential for immunogenic responses, and safety. Resolving these obstacles is crucial to advance the development of RNA therapies. This review explores the newest developments in medical studies, treatment plans, and results related to RNA therapies for heart disease. Furthermore, it discusses the exciting possibilities and difficulties in this innovative area of research.

Navigating the path of TOF- A Literature review unveiling maternal-fetal dynamics, treatment strategies and psychological dimensions.

Tetralogy of Fallot (TOF) is a complex congenital heart defect that poses unique challenges for both mothers and their unborn children. This comprehensive review, aims to provide a holistic exploration of the maternal-fetal dynamics, treatment strategies, and psychological dimensions involved in navigating the path of TOF during pregnancy. It delves into the physiological changes that occur during pregnancy in TOF patients, including pulmonary regurgitation, right ventricular hypertrophy, and the overriding aorta. By understanding these dynamics, healthcare professionals can tailor treatment strategies to optimize maternal and fetal outcomes. The review further investigates the treatment strategies employed in managing TOF during pregnancy, encompassing medical interventions, cardiac monitoring, and multidisciplinary care. It explores the role of advanced imaging techniques, such as echocardiography and cardiac magnetic resonance imaging, in assessing TOF severity and guiding treatment decisions. The psychological factors influencing maternal adaptation, coping strategies, and the long-term implications on the child's psychological development are also examined. The integration of multidisciplinary approaches, including cardiac care, psychosocial support, and mental health interventions, can orchestrate a harmonious symphony of maternal-fetal well-being in the challenging journey of TOF pregnancies. Future research endeavours should continue to explore these dimensions, further refining treatment strategies and enhancing the understanding of TOF pregnancies for improved outcomes.

The impact of air quality on cardiovascular health: A state of the art review.

Air pollution is a global health challenge, increasing the risk of cardiovascular diseases such as heart disease, stroke, and arrhythmias. Particulate matter (PM), particularly PM2.5 and ultrafine particles (UFP), is a key contributor to the adverse effects of air pollution on cardiovascular health. PM exposure can lead to oxidative stress, inflammation, atherosclerosis, vascular dysfunction, cardiac arrhythmias, and myocardial injury. Reactive oxygen species (ROS) play a key role in mediating these effects. PM exposure can also lead to hypertension, a significant risk factor for cardiovascular disease. The COVID-19 pandemic resulted in a significant reduction of air pollutants, leading to a decline in the incidence of heart attacks and premature deaths caused by cardiovascular diseases. This review highlights the relationship between environmental air quality and cardiovascular health, elucidating the pathways through which air pollutants affect the cardiovascular system. It also emphasizes the need for increased awareness, collective efforts to mitigate the adverse effects of air pollution, and strategic policies for long-term air quality improvement to prevent the devastating effects of air pollution on global cardiovascular health.

Association Between Catheter Ablation and Dementia Among Patients With Atrial Fibrillation: A Systematic Review and Meta-analysis.

Atrial fibrillation (AF) is associated with an increased risk of Dementia. However, the association between catheter ablation (CA) in patients with atrial fibrillation and the risk of dementia is not well established, with conflicting results to date. We aimed to evaluate the association between CA patients and the risk of Dementia. We performed a systematic literature search using the PubMed, Embase, Scopus, and Cochrane libraries for relevant articles from inception until 10th May 2023. Hazard ratios (HR) were pooled using a random-effect model, and a P-value of < 0.05 was considered statistically significant. A total of 5 studies with 125,649 patients (30,192 in the CA group and 95,457 in the non-CA group) were included. The mean age of patients among CA and non-CA groups was comparable (58.7 vs 58.18). The most common comorbidity among CA and non-CA groups was hypertension (18.49% vs 81.51%), respectively. Pooled analysis of primary outcome showed that CA was associated with a significant reduction in the risk of Dementia (HR, 0.63 [95% CI: 0.52-0.77], P < 0.001). Similarly, pooled analysis of secondary outcomes showed that the patients with CA had a lower risk of Alzheimer's disease (HR, 0.78 [95% CI: 0.66-0.92], P < 0.001) compared with the non-CA group. However, there was no statistically significant difference in the risk of vascular dementia (HR, 0.63 [95% CI: 0.38-1.06], P = 0.08) between both groups of patients. Our study suggested that catheter ablation reduced the risk of dementia and Alzheimer's disease compared to the nonablation group of patients.

Neurological Manifestations of Coronavirus Disease 2019 and Mpox in Pediatric Patients and Their Management: A State-of-the-Art Systematic Review.

BACKGROUND: There is an increasing number of cases being reported of neurological manifestations of Coronavirus disease 2019 (COVID-19) infection and Monkeypox (Mpox), both during the course of the infection and as a presenting symptom. We aim to review the neurological manifestations of COVID-19 and monkeypox in pediatric patients and their management. METHODS: We conducted a systematic review that included cohort studies and case series or reports involving a pediatric population of patients with a confirmed COVID-19 or Mpox infection and their neurological manifestations. We searched the following electronic databases: PubMed, EMBASE, and Scopus. RESULTS: From 1136 articles identified, 127 studies were included. Headache, stroke, Guillain-Barré syndrome, seizure, nerve palsies, and multisystem inflammatory syndrome in children were the most common neurological symptoms caused by COVID-19, whereas encephalitis was commonly seen in patients with Mpox. Rare neurological manifestations of COVID-19 included cerebral venous sinus thrombosis, plexopathies, demyelinating disorders, encephalitis, etc., and rare neurological manifestations of Mpox included headache. CONCLUSIONS: Our review highlights the importance of investigating possible neurological manifestations and closely monitoring these patients to develop a better understanding of the treatment strategies that can be adopted.

Efficacy of lenvatinib versus sorafenib in the primary treatment of advanced hepatocellular carcinoma: A meta-analysis.

Background and Aim: Molecular-targeted agents such as lenvatinib and sorafenib have been approved to treat hepatocellular carcinoma (HCC). However, the choice between these two agents in the primary treatment for advanced HCC is still under debate with conflicting results. We sought to evaluate the efficacy of lenvatinib and sorafenib in patients with HCC. Methods: We performed a systematic literature search using PubMed, Embase, and Scopus for relevant articles from inception until February 10, 2023. The primary outcome of this meta-analysis was overall survival (OS). The secondary outcomes were progression-free survival (PFS), time to progression, objective response rate (ORR), and disease control rate (DCR). Results: A total of 13 studies with 3705 patients (1635 on lenvatinib and 2070 on sorafenib) were included in our analysis. The mean age of the patients in both groups was comparable (66.81 vs 65.9 years). Pooled analysis of primary outcomes showed that, compared with sorafenib, lenvatinib was associated with significantly better OS in patients treated with these drugs (HR 0.82, 95% CI: 0.69-0.97, P = 0.02). Pooled analysis also showed that PFS (HR 0.67, 95% CI: 0.57-0.78, P < 0.00001) and time to progression (HR 0.49, 95% CI: 0.31-0.79; P = 0.004) were significantly better in the lenvatinib group compared to the sorafenib group. It also showed that the lenvatinib group had significantly better ORR (odds ratio [OR] 5.43, 95% CI: 3.71-7.97; P < 0.00001) and DCR (OR 2.35, 95% CI: 1.75-3.16; P < 00001) than the sorafenib group. Conclusion: Our study shows that lenvatinib is superior to sorafenib regarding OS and PFS in patients with advanced HCC.

Sorption and recovery of phenolic compounds from aqueous phase of sewage sludge hydrothermal liquefaction using bio-char.

Bio-char, a by-product of thermochemical conversion processes, has a great potential in phenolic compounds sorption from the waste aqueous phase produced from the hydrothermal liquefaction (HTL) process while being a low-cost sorbent. This study investigated the effect of temperature, pH, bio-char concentration, and mixing speed on two types of bio-char sorption of phenolic compounds using Taguchi's design of experiment and response surface method. Isothermal kinetics and thermodynamic properties were also evaluated to explain the sorption mechanism. The experimental results were well described by the pseudo-second-order kinetic model for both types of bio-char. The Langmuir isotherm model was found to be more suitable at high sorption temperatures, while the Freundlich isotherm model was better at low temperatures. Finally, the alkaline desorption and regeneration experiments were examined, and the eluents with phenolic compounds were characterized using a liquid chromatography-mass spectrometer.

Internet addiction, depression, anxiety and stress among first year medical students after COVID-19 lockdown: A cross sectional study in West Bengal, India.

Objectives: 1. To assess the impact of COVID-19 lockdown on Internet addiction on first year medical students. 2. To evaluate the associations, if any, between internet addiction, anxiety, depression and stress. Methods: Internet addiction, depression, anxiety and stress among medical students across West Bengal have been studied using Young's Internet Addiction Test (IAT) scale and the Depression, Anxiety and Stress Scale (DASS-21). A web-based questionnaire was made and circulated via different social media platforms. All interested candidates who gave consent were included in the study. All statistical analyses were done using SPSS version 25.0. Results: The study population consisted of 37.2% of males and 63.8% of females. 80.23% of the participants showed moderate levels of internet addiction. Strong positive correlation was found between anxiety and stress (r = 0.83, P < 0.05), depression and anxiety (r = 0.92, P < 0.05) and between depression and stress (r = 0.86, P < 0.05). Conclusion: The unprecedented ramifications of lockdown are incessant, with internet addiction, magnification in depression, anxiety and stress to name a few. Internet addiction coupled with psychological disorders still remains a matter of concern for medical students.