Effect of SGLT2 inhibitors on kidney function of type 2 diabetes patients during Ramadan: A systematic review.

Background: SGLT2 inhibitors are known for their osmotic diuretic effect, and their use by Muslim patients with type 2 diabetes during the fasting month of Ramadan may pose an increased risk of volume depletion, potentially impacting renal function. Methods: We conducted a systematic review registered on PROSPERO (registration number CRD42020204582) of studies published between 2013 and January 2023, sourced from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. The study selection criteria included controlled studies that reported the use of SGLT2 inhibitors (SGLT2i) by fasting adult type 2 diabetes patients and provided data on creatinine or estimated glomerular filtration rate (eGFR) as outcomes. Results: Two prospective observational studies, encompassing a total of 359 participants, of which 197 utilized SGLT2 inhibitors, were identified. Our findings indicated that the use of SGLT2 inhibitors during Ramadan did not result in a significant alteration in eGFR. In one study by Hassanein et al., the mean changes in eGFR for the SGLT2i group, as compared to the non-SGLT2i group, were -1.2 ± 19.4 and 3.1 ± 14.8, respectively (p = 0.06). In a study by Shao et al., the least squares mean changes for eGFR in the SGLT2i group, compared to the non-SGLT2i group, were -6.0 ± 1.5 (95% CI, -8.9 to -3.1) and -4.2 ± 1.6 (95% CI, -7.3 to -1.1), respectively (p = 0.39). Conclusion: Despite the limited number of observational studies available, our analysis suggests that the use of SGLT2 inhibitors by type 2 diabetes patients during Ramadan does not appear to significantly impact kidney function.

Effect of SGLT2 inhibitors on kidney function of type 2 diabetes patients during Ramadan: A systematic review.

Background: SGLT2 inhibitors are known for their osmotic diuretic effect, and their use by Muslim patients with type 2 diabetes during the fasting month of Ramadan may pose an increased risk of volume depletion, potentially impacting renal function. Methods: We conducted a systematic review registered on PROSPERO (registration number CRD42020204582) of studies published between 2013 and January 2023, sourced from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. The study selection criteria included controlled studies that reported the use of SGLT2 inhibitors (SGLT2i) by fasting adult type 2 diabetes patients and provided data on creatinine or estimated glomerular filtration rate (eGFR) as outcomes. Results: Two prospective observational studies, encompassing a total of 359 participants, of which 197 utilized SGLT2 inhibitors, were identified. Our findings indicated that the use of SGLT2 inhibitors during Ramadan did not result in a significant alteration in eGFR. In one study by Hassanein et al., the mean changes in eGFR for the SGLT2i group, as compared to the non-SGLT2i group, were -1.2 ± 19.4 and 3.1 ± 14.8, respectively (p = 0.06). In a study by Shao et al., the least squares mean changes for eGFR in the SGLT2i group, compared to the non-SGLT2i group, were -6.0 ± 1.5 (95% CI, -8.9 to -3.1) and -4.2 ± 1.6 (95% CI, -7.3 to -1.1), respectively (p = 0.39). Conclusion: Despite the limited number of observational studies available, our analysis suggests that the use of SGLT2 inhibitors by type 2 diabetes patients during Ramadan does not appear to significantly impact kidney function.

Endolysosomal trapping of therapeutics and endosomal escape strategies.

Internalizing therapeutic molecules or genes into cells and safely delivering them to the target tissue where they can perform the intended tasks is one of the key characteristics of the smart gene/drug delivery vector. Despite much research in this field, endosomal escape continues to be a significant obstacle to the development of effective gene/drug delivery systems. In this review, we discuss in depth the several types of endocytic pathways involved in the endolysosomal trapping of therapeutic agents. In addition, we describe numerous mechanisms involved in nanoparticle endosomal escape. Furthermore, many other techniques are employed to increase endosomal escape to minimize entrapment of therapeutic compounds within endolysosomes, which have been reviewed at length in this study.

Exploiting transcription factors to target EMT and cancer stem cells for tumor modulation and therapy.

Transcription factors (TFs) are essential in controlling gene regulatory networks that determine cellular fate during embryogenesis and tumor development. TFs are the major players in promoting cancer stemness by regulating the function of cancer stem cells (CSCs). Understanding how TFs interact with their downstream targets for determining cell fate during embryogenesis and tumor development is a critical area of research. CSCs are increasingly recognized for their significance in tumorigenesis and patient prognosis, as they play a significant role in cancer initiation, progression, metastasis, and treatment resistance. However, traditional therapies have limited effectiveness in eliminating this subset of cells, allowing CSCs to persist and potentially form secondary tumors. Recent studies have revealed that cancer cells and tumors with CSC-like features also exhibit genes related to the epithelial-to-mesenchymal transition (EMT). EMT-associated transcription factors (EMT-TFs) like TWIST and Snail/Slug can upregulate EMT-related genes and reprogram cancer cells into a stem-like phenotype. Importantly, the regulation of EMT-TFs, particularly through post-translational modifications (PTMs), plays a significant role in cancer metastasis and the acquisition of stem cell-like features. PTMs, including phosphorylation, ubiquitination, and SUMOylation, can alter the stability, localization, and activity of EMT-TFs, thereby modulating their ability to drive EMT and stemness properties in cancer cells. Although targeting EMT-TFs holds potential in tackling CSCs, current pharmacological approaches to do so directly are unavailable. Therefore, this review aims to explore the role of EMT- and CSC-TFs, their connection and impact in cellular development and cancer, emphasizing the potential of TF networks as targets for therapeutic intervention.

Early coronary angioplasty fails to lower all-cause mortality in patients with out-of-hospital cardiac arrest without ST-segment elevation: A systematic review and meta-analysis.

Introduction: Out-of-hospital cardiac arrest (OHCA) is defined as the loss of functional mechanical activity of the heart in association with an absence of systemic circulation, occurring outside of a hospital. Immediate coronary angiography (CAG) with percutaneous coronary intervention is recommended for OHCA with ST-elevation. We aimed to evaluate the effect of early CAG on mortality and neurological outcomes in OHCA patients without ST-elevation. Methods: This meta-analysis and systemic review was conducted as per principles of Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) group. A protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO, Ref No. = CRD42022327833). A total of 674 studies were retrieved after scanning several databases (PubMed Central, EMBASE, Medline, and Cochrane Central Register of Controlled Trials). Results: A total of 18 studies were selected for the final analysis, including 6 randomized control trials and 12 observational studies. Statistically, there was no significant difference in primary outcome, i.e., mortality, between early and delayed CAG. In terms of the grade of neurological recovery as a secondary outcome, early and delayed CAG groups also showed no statistically significant difference. Conclusion: Early CAG has no survival benefits in patients with no ST elevations on ECG after OHCA.

Long COVID-19 Syndrome: Insights From a Major Tertiary Center in the UK on Who Is at Greater Risk.

INTRODUCTION: The COVID-19 pandemic triggered the unprecedented 'long COVID' crisis, with persistent symptoms beyond two months post-infection. This study explores the nexus between long COVID symptoms, patient demographics such as age, gender, and smoking, and clinical factors like vaccination, disease severity, and comorbidities. METHODS: A retrospective analysis of records was conducted between September 2021 and December 2022. The analysis covered adults with confirmed COVID-19 diagnoses. Data encompassed demographics, medical history, vaccination, disease severity, hospitalization, treatments, and post-COVID symptoms, analyzed using logistic regression. RESULTS: Among 289 participants, the average age was 51.51 years. Around 62.6% were females, and 93% received the COVID-19 vaccination, i.e., primarily the mRNA vaccine (48.4%) and the adenovirus vector-based vaccine (34.8%). Reinfections occurred in 11.76% of cases. Disease severity varied, with 75% having mild, 15% having moderate, and 10% having severe infections. Hospitalization rates were significant (25.6%), including 10.7% requiring intensive care. Thirteen distinct post-COVID symptoms were reported. Fatigue, shortness of breath upon exertion, and brain fog emerged as the most prevalent symptoms. Notably, females exhibited higher symptom prevalence. Significant correlations were established between higher BMI and smoking with augmented symptomatology. Conversely, a link between booster doses and symptom reduction was discerned. Using multinomial regression analysis, gender and smoking were identified as predictors of post-COVID-19 symptoms. CONCLUSION: The study underscores obesity, smoking, and the female gender's impact on long COVID symptoms; boosters show promise in alleviation. Respiratory pathology might underlie persistent symptoms in cases with radiological abnormalities and abnormal spirometry. Findings contribute to risk stratification, intervention strategies, and further research.