Clinical Outcomes With Once-Weekly Insulin Icodec Versus Once-Daily Insulin Glargine U100 in Insulin-Naïve and Previously Insulin-Treated Individuals With Type 2 Diabetes: A Meta-Analysis of Randomised Controlled Trials.

AIMS: The once-weekly insulin icodec, a new basal insulin analog, may positively support a reduction in injection frequency and improve adherence to therapy in type 2 diabetes (T2D). This study aimed to evaluate the safety and efficacy of insulin icodec compared with those of once-daily glargine U100. METHODS: A comprehensive literature search was conducted using PubMed/MEDLINE, Embase and the Cochrane Library from inception till September 2023. Data about clinical outcomes in both groups were extracted. Forest plots were generated using the random-effects model by pooling odds ratios (ORs) and mean differences (MDs). RESULTS: Five randomised controlled trials and 2019 individuals with T2DM were included. In the pooled analysis, time in range was significantly higher (MD = 4.35; 95% CI: 1.65 to 7.05; p = 0.002) in the icodec group than in the once-daily glargine group. The HbA1c levels were significantly reduced (MD = -0.13; 95% CI: -0.24 to -0.03; p = 0.02) in the weekly icodec group compared with those in the once-daily glargine group. The weight gain was significantly less in the glargine group than in the weekly icodec group (MD = 0.41; 95% CI: 0.04 to 0.78; p = 0.03); however, in the subgroup analysis, this change became statistically insignificant in both insulin-naïve and previously insulin-treated individuals. The results were comparable across two groups for fasting plasma glucose levels, hypoglycaemia alert (Level 1), clinically significant (Level 2) or severe hypoglycaemia (Level 3), and adverse events. CONCLUSION: Insulin icodec was associated with a reduction in glycated haemoglobin levels and higher time in range, with a similar safety profile as compared to insulin glargine U100. However, further evidence is still needed to reach a definitive conclusion.

Association Between Fluoroquinolones and Major Adverse Cardiovascular Events: A Systematic Review.

Fluoroquinolones (FQs) are routinely administered antibiotics that have demonstrated an increased propensity to cause major adverse cardiovascular events (MACE). We conducted a systematic review aimed to investigate the association between FQ usage and the risk of MACE. A comprehensive literature search was conducted using PubMed, Scopus, and the Cochrane Library from inception to September 2023 to retrieve studies comparing FQ administration with placebo and reporting the occurrence of MACE. Relevant studies that explored the occurrence of MACE, defined as "acute myocardial infarction, stroke, cardiovascular mortality, arrhythmia, or heart failure" with FQ usage were eligible for inclusion. Four studies with a total of 42,808 patients were included. Levofloxacin, moxifloxacin, and gatifloxacin were observed to have an increased propensity to cause MACE, particularly arrhythmias, whereas ciprofloxacin was associated with the lowest risk of causing MACE. Despite the methodological diversity in the included studies, this systematic review uncovered a consistent trend of heightened likelihood of MACE with FQ administration across studies, suggesting that elevated serum concentrations of some FQs may correlate with higher risks of MACE development. This systematic review emphasizes the need for cautious administration of FQs, particularly in patients with a preexisting cardiovascular condition. Routine cardiac monitoring using electrocardiograms is warranted for patients on high doses of FQs to preemptively detect the development of MACE, particularly arrhythmias.

Association between psoriasis and atrial fibrillation: A Systematic review and meta-analysis.

INTRODUCTION: Psoriasis is a prevalent inflammatory skin condition characterized by erythematous plaques with scaling. Recent research has demonstrated an increased risk of cardiovascular diseases in patients with psoriasis; however, current evidence on atrial fibrillation (AF) risk in psoriasis is limited. MATERIALS AND METHODS: A systematic literature search was performed on major bibliographic databases to retrieve studies that evaluated AF risk in patients with psoriasis. The DerSimonian and Laird random effects model was used to pool the hazard ratios (HR) with 95 % confidence intervals (CI). Subgroup analysis was conducted by dividing the patients into mild and severe psoriasis groups. Publication bias was assessed by visual inspection and Egger's regression test. Statistical significance was set at p < 0.05. RESULTS: Seven studies were included, with 10,974,668 participants (1,94,230 in the psoriasis group and 10,780,439 in the control group). Patients with psoriasis had a significantly higher risk of AF [Pooled HR: 1.28; 95 % CI: 1.20, 1.36; p < 0.00001]. In subgroup analysis, patients with severe psoriasis [HR: 1.32; 95 % CI: 1.23, 1.42; p < 0.00001] demonstrated a slightly higher risk of AF, although statistically insignificant (p = 0.17), than the mild psoriasis group [HR: 1.21; 95 % CI: 1.10, 1.33; p < 0.0001]. Egger's regression test showed no statistically significant publication bias (p = 0.24). CONCLUSION: Our analysis demonstrated that patients with psoriasis are at a significantly higher risk of AF and hence should be closely monitored for AF. Further large-scale and multicenter randomized trials are warranted to validate the robustness of our findings.

A clearer vision: insights into juvenile idiopathic arthritis-associated uveitis.

The aim of this narrative review is to synthesize existing evidence-based knowledge on juvenile idiopathic arthritis-associated uveitis (JIA-U). We highlight epidemiology, pathophysiology, causes and genetics, risk factors, clinical features, diagnosis and screening, laboratory biomarkers, treatment options, trials with recent advances, and research challenges pertaining to JIA-U. The prevalence of JIA-U varies with different JIA subtypes, most frequently associated with the oligoarticular subtype. The risk factors involved in the development of JIA-U include younger age, antinuclear antibody (ANA) positivity, and the oligoarticular subtype of JIA, along with some specific major histocompatibility complex genes. Certain laboratory biomarkers, such as ANA, rheumatoid factor, interferon-λ, erythrocyte sedimentation rate, and transthyretin, have been used in JIA-U diagnosis, progress monitoring, and prognostication. Clinical features of JIA-U can range from asymptomatic to ophthalmic symptoms like redness, blurred vision, decreased visual acuity, hypopyon, and posterior uveitis, which can lead to retinal detachment and macular edema. The management protocol involves topical and systemic steroids, cycloplegics, disease-modifying antirheumatic drugs, biologic drugs, and surgical options. Early detection combined with prompt treatment is crucial to preventing irreversible vision loss in JIA-U.

The role of renal denervation in cardiology and beyond: An updated comprehensive review and future directives.

Renal denervation (RDN) is a minimally invasive intervention performed by denervation of the nervous fibers in the renal plexus, which decreases sympathetic activity. These sympathetic nerves influence various physiological functions that regulate blood pressure (BP), including intravascular volume, electrolyte composition, and vascular tone. Although proven effective in some trials, controversial trials, such as the Controlled Trial of Renal Denervation for Resistant Hypertension (SYMPLICITY-HTN3), have demonstrated contradictory results for the effectiveness of RDN in resistant hypertension (HTN). In the treatment of HTN, individuals with primary HTN are expected to experience greater benefits compared to those with secondary HTN due to the diverse underlying causes of secondary HTN. Beyond its application for HTN, RDN has also found utility in addressing cardiac arrhythmias, such as atrial fibrillation, and managing cases of heart failure. Non-cardiogenic applications of RDN include reducing the intensity of obstructive sleep apnea (OSA), overcoming insulin resistance, and in chronic kidney disease (CKD) patients. This article aims to provide a comprehensive review of RDN and its uses in cardiology and beyond, along with providing future directions and perspectives.

The impact of chronic total occlusion in non-infarct related arteries on patient outcomes following percutaneous coronary intervention for STEMI superimposed with cardiogenic shock: A pilot systematic review and meta-analysis.

INTRODUCTION: Chronic total occlusion (CTO) is defined as a near-total blockage of a coronary artery and often occurs in arteries that are not directly responsible for the event, known as non-infarct-related arteries (NIRA). Cardiogenic shock (CS) is a complication of ST-elevated myocardial infarction (STEMI) that carries significant mortality. We performed a meta-analysis to find an association between mortality in patients undergoing PCI for STEMI that have superimposed CS, with the presence of CTO in the NIRA. MATERIALS AND METHODOLOGY: A comprehensive literature search was conducted using PubMed, EMBASE, Google Scholar and clinicaltrials.gov from inception till October 2023 to retrieve studies that compare the presence of CTO with the absence of CTO in NIRA in STEMI with CS patients undergoing PCI. The primary endpoint was 30-day mortality and the secondary endpoints were risk of all-cause mortality (ACM) and repeat myocardial infarction (MI). Forest plots were generated using the random effects model by pooling odds ratios (ORs) with a 95 % confidence interval. Statistical significance was set at p < 0.05. RESULTS: 5 observational studies with a total of 5186 patients (1031 with CTO in NIRA and 4155 with no CTO in NIRA) were included. The presence of CTO in NIRA was associated with higher odds of 30-day mortality [OR: 3.10; 95 % CI: 1.52, 6.32; p < 0.002], and ACM [OR: 2.37; 95 % CI: 1.83, 3.08; p < 0.00001]. The odds of repeat MI were comparable between the two groups [OR: 1.61, 95 % CI: 0.03, 74.36, p = 0.81]. CONCLUSIONS: The presence of CTO in the NIRA serves as an independent indicator of unfavorable clinical outcomes including increased risk of 30-day mortality and all-cause mortality. The risk of repeat MI was comparable between the two groups. Large-scale, multicenter trials are warranted to identify the most effective management approach for these patients.

Precision medicine in Myocardial Infarction With Non-obstructive Coronary Disease (MINOCA): A comprehensive review.

Cardiovascular diseases, particularly myocardial infarction (MI), are a significant cause of mortality globally. Traditional MIs are commonly linked to substantial coronary artery blockage. However, a distinct subset of patients experience MI with non-obstructive coronary arteries, known as MINOCA. Imaging techniques, such as invasive coronary angiograms, are employed to diagnose MI or assess predisposition to one. Coronary angiograms help visualize vessel blockages; however, these blockages are absent in MINOCA cases, posing a diagnostic challenge. Precision medicine aims to introduce new diagnostic tools to assist in early diagnosis and further management of MINOCA. As percutaneous coronary intervention (PCI) does not benefit MINOCA patients, medical management tailored to the specific pathophysiological mechanism of MINOCA is employed. For example, if MINOCA is attributed to plaque disruption with or without plaque thrombus formation, the fundamental treatments may include statins, agents that modulate the renin-angiotensin system (RAS), and antiplatelet therapies. On the other hand, if coronary artery spasm is identified as the primary cause, essential intervention involves the use of calcium channel blockers. This approach has been previously utilized in patients with vasospastic angina and could be utilized in MINOCA, although research specific to MINOCA is ongoing. Therefore, the handling of MINOCA underscores the necessity for a tailored therapeutic strategy that corresponds to the underlying physiological mechanism responsible for the patient's clinical symptoms. Ongoing research initiatives are directed at expanding the availability of these treatments, uncovering new biomarkers, creating advanced diagnostic instruments, and establishing a more individualized approach for managing MINOCA patients.

Exploring Transthyretin Amyloid Cardiomyopathy: A Comprehensive Review of the Disease and Upcoming Treatments.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a mutation-based genetic disorder due to the accumulation of unstable transthyretin protein and presents with symptoms of congestive heart failure (CHF) and numerous extracardiac symptoms like carpal tunnel syndrome and neuropathy. Two subtypes of ATTR-CM are hereditary and wild-type, both of which have different risk factors, gender prevalence and major clinical symptoms. Timely usage of imaging modalities like echocardiography, cardiac magnetic imaging resonance, and cardiac scintigraphy has made it possible to suspect ATTR-CM in patients presenting with CHF. Management of ATTR-CM includes appropriate treatment for heart failure for symptomatic relief, prevention of arrhythmias and heart transplantation for nonresponders. With the recent approval of tafamidis in the successful management of ATTR-CM, numerous potential therapeutic points have been identified to stop or delay the progression of ATTR-CM. This article aims to provide a comprehensive review of ATTR-CM and insights into its novel therapeutics and upcoming treatments.

Unveiling the relationship between gut microbiota and heart failure: Recent understandings and insights.

Gut microbiota, which comprises a broad range of bacteria inhabiting the human intestines, plays a crucial role in establishing a mutually beneficial relationship with the host body. Dysbiosis refers to the perturbations in the composition or functioning of the microbial community, which can result in a shift from a balanced microbiota to an impaired state. This alteration has the potential to contribute to the development of chronic systemic inflammation. Heart failure (HF) is a largely prevalent clinical condition that has been demonstrated to have variations in the gut microbiome, indicating a potential active involvement in the pathogenesis and advancement of the disease. The exploration of the complex interplay between the gut microbiome and HF presents a potential avenue for the discovery of innovative biomarkers, preventive measures, and therapeutic targets. This review aims to investigate the impact of gut bacteria on HF.

Assessment of the Relation Between Asthma Severity and Serum Vitamin D Levels: A Cross-Sectional Study.

Introduction Vitamin D3's importance for bone health in children and its potential role beyond musculocutaneous health is an ongoing area of research. This study assesses vitamin D3 deficiency prevalence in asthmatic children and its correlation with asthma cases and healthy controls.  Methods This cross-sectional study was conducted in a tertiary care hospital in Punjab, India among children between 5 and 15 years of age. Fifty children diagnosed with "bronchial asthma" who were under follow-up in the asthma clinic in outpatient and inpatient patients were enrolled as cases. Age-matched 50 healthy controls who presented for routine check-ups were enrolled in the control group. Demographic details were noted and clinical examination was done in all the cases. 25-(OH) vitamin D levels were estimated and compared in all cases and controls. The study also analyzed the relationship between 25-(OH) vitamin D levels with asthma control and severity. Results The study showed that serum vitamin D3 level was significantly decreased in asthmatic children (24.62 ± 14.95 ng/ml) as compared with the healthy control group (32.08 ± 12.22 ng/ml). Also, serum vitamin D3 level was significantly decreased in children with uncontrolled asthma (12.06 ± 4.68 ng/ml) as compared to children with well-controlled asthma (44.82 ± 10.48 ng/ml).  Conclusion The findings showed that low serum levels were observed more in asthmatic children as compared to healthy children. A correlation was also found between vitamin D3 levels and asthma severity, its control, and the number of acute exacerbations in the last year.

A Rare Sparkle: A Case of Calcified Kidneys in a Young Infant With Renal Failure.

Primary hyperoxaluria-1 (PH1) is an autosomal recessively inherited rare genetic condition due to the deficiency of the hepatic enzyme alanine:glyoxylate aminotransferase which leads to high systemic levels of oxalate and subsequently, early end-stage renal disease and death. Here, we present a case of a three-month-old male infant who presented with loose stools, reduced oral intake, and decreased activity for 12-13 days along with edema and a peeling rash on cheeks, lips, and genitalia. During the entire duration of the inpatient stay, the child was oligoanuric. Kidney ultrasound (USG) was suggestive of bilateral hyperechoic kidneys with increased cortical echogenicity and a computed tomography scan showed bilateral diffusely calcified renal cortices with well-preserved renal architecture. A diagnosis of "oxalate nephropathy" was made from renal biopsy and genetic testing confirmed it to be "primary hyperoxaluria-1". The child was initially managed conservatively, and then peritoneal dialysis was done, following which the child was shifted to intermittent hemodialysis.

Use of prostaglandin and cyclophosphamide for pediatric lupus with digital gangrene: Back to safety before hitting the axe!

Digital gangrene is a rare presenting feature of childhood lupus and only a reported incidence of 1.3%. We describe two cases of pediatric onset systemic lupus erythematosus (SLE), both 16 years old, presenting with digital gangrene and the successful salvage of the digits after using intravenous cyclophosphamide for immunosuppression and use of intravenous prostaglandin E1 infusions for limb reperfusion. Both of the patients responded exceptionally to the infusions with resolution of gangrene and near-total preservation of the functionality of toes.

Short-Term Efficacy and Adverse Effects of Sulfasalazine in the Management of Axial Spondyloarthropathy.

INTRODUCTION: Ankylosing spondylitis (AS) is an inflammatory spondyloarthropathy that involves the sacroiliac joints and the axial skeleton. Sulfasalazine's efficacy in treating the axial symptoms of AS has been a subject of controversy. METHODS: This prospective observational study recruited AS patients and categorized them into two groups: the first group had AS for less than or equal to four years and the second group had AS for more than four years. Erythrocytic sedimentation rate (ESR) and C-reactive protein (CRP) levels were recorded at baseline and at six-month follow-up. Disease severity was assessed using the ankylosing spondylitis disease activity score (ASDAS), Bath ankylosing spondylitis disease activity index (BASDAI) score, and Bath ankylosing spondylitis functional index (BASFI) score. RESULTS: A total of 33 patients diagnosed with AS were recruited in this study, mostly males (88%) and within 21-30 years of age. ESR and CRP values were measured at baseline and at six months post-treatment with sulfasalazine. Mean ESR and mean CRP values showed a statistically significant reduction of 43.5% (p=0.001) and 58.45% (p=0.0012) respectively, at the 6-month follow-up. Four patients (12.12%) reported gastrointestinal intolerance. The mean reduction in the ASDAS score was 24% (p=0.002), the BASDAI score was 40.08% (p=0.001), and the BASFI score was 39.54% (p=0.01). Additionally, the duration of symptoms did not appear to influence with efficacy of sulfasalazine. DISCUSSION: Sulfasalazine is a safe alternative therapy for patients with AS who cannot afford biologics, due to its reasonable short-term efficacy, good tolerability, cost-effective nature, and low incidence of adverse effects.