Drug carrier wonders: Synthetic strategies of zeolitic imidazolates frameworks (ZIFs) and their applications in drug delivery and anti-cancer activity.

With the rapid advancement of nanotechnology, stimuli-responsive nanomaterials have emerged as a feasible choice for the designing of controlled drug delivery systems. Zeolitic imidazolates frameworks are a subclass of Metal-organic frameworks (MOFs) that are recognized by their excellent porosity, structural tunability and chemical modifications make them promising materials for loading targeted molecules and therapeutics agents. The biomedical industry uses these porous materials extensively as nano-carriers in drug delivery systems. These MOFs not only possess excellent targeted imaging ability but also cause the death of tumor cells drawing considerable attention in the current framework of anticancer drug delivery systems. In this review, the outline of stability, porosity, mechanism of encapsulation and release of anticancer drug have been reported extensively. In the end, we also discuss a brief outline of current challenges and future perspectives of ZIFs in the biomedical world.

Representation of Chronic Kidney Disease in Randomized Controlled Trials Among Patients With Heart failure With Reduced Ejection Fraction: A Systematic Review.

Patients with advanced chronic kidney disease (CKD) have largely been excluded from randomized control trials (RCTs) in heart failure (HF). This creates a paucity of high quality evidence for guideline directed medical therapy (GDMT), particularly in patients with heart failure with reduced ejection fraction (HFrEF) and CKD. This is a systematic review looking at the patterns and rates of inclusion of CKD in RCTs among patients with HFrEF. The search included RCTs from January 2010 to December 2020. A heat map was constructed to reflect the stages of CKD stages. The percentage of studies that included advanced CKD (stages IV-V) was recorded and log transformed, and then fitted into a time regression model. A P value of <0.05 was considered statistically significant. Out of the 3052 screened, 706 studies were included in the analysis. Only 61% of the RCTs reported at least some information on kidney function. There was a trend of increase in percentage of studies that included CKD stages IV-V from years 2010 to 2020. This was confirmed with a statistically significant linear trend P = 0.02 while the percentage of studies that included dialysis and kidney transplant recipients remained consistently low. There is a paucity of high-quality evidence for GDMT in the HFrEF population with CKD, particularly in those with advanced non-dialytic CKD, those on maintenance dialysis and kidney transplant recipients. There is a pressing need for wider inclusion of patients with advanced CKD in RCTs of GDMT in HFrEF.

Subaortic Membrane Co-existing With Hypertrophic Cardiomyopathy: A Clinically Challenging Diagnosis.

Subaortic Membrane is the most common type of subaortic stenosis. That, coexisting with hypertrophic obstructive cardiomyopathy (HOCM) is an extremely rare combination and clinically underappreciated. In this report, we will discuss an 18-year-old male patient who presented with chest pain and dyspnea due to fixed (sub-aortic membrane), as well as dynamic (HOCM), left ventricular outflow tract obstruction (LVOT) obstruction.

Effects of Renin-Angiotensin-Aldosterone System Inhibition on Left Ventricular Hypertrophy, Diastolic Function, and Functional Status in Patients With Hypertrophic Cardiomyopathy: A Systematic Review.

The renin-angiotensin-aldosterone system (RAAS) plays a vital role in cardiovascular homeostasis by regulating blood pressure, salt, and water balance. The kidneys produce renin which converts angiotensinogen to angiotensin-1 (AT-I) and angiotensin-converting enzyme (ACE) to angiotensin-II (AT-II). AT-II binds to receptors in the adrenal cortex to release aldosterone. AT-II and aldosterone promote water and salt retention, vascular tone, and myocardial contractility. These physiological changes raise blood pressure and circulation. Reduced renal perfusion pressure sensed by baroreceptors and the sympathetic nervous system's ß-adrenergic receptors trigger renin release and RAAS activation. RAAS restores hemodynamic stability in pathological states associated with low perfusion. This adaptive response is important for restoring perfusion and hemodynamic stability, but prolonged RAAS activation has deleterious effects on the cardiovascular system. Long-term mineralocorticoid exposure has been linked to left ventricular hypertrophy (LVH) and remodeling. AT-II activates fibroblasts and cardiac myocytes to promote cardiac remodeling. Blocking RAAS can eliminate the long-term negative effects of RAAS activation. Direct renin inhibitors, ACE inhibitors, angiotensin receptor blockers, and aldosterone antagonists are RAAS blockers. RAAS blockade improves mortality and hospitalization in systolic heart failure and acute myocardial infarction. RAAS blockade has not demonstrated the same benefits in other cardiac populations, such as those with preserved ejection fraction. Hypertrophic cardiomyopathy (HCM) causes LVH and asymmetric septal hypertrophy. When the outflow tract gradient exceeds 30 mmHg and is associated with septal hypertrophy, it is known as obstructive HCM. Dyspnea on exertion, syncope, and exertional angina are symptoms of HCM. RAAS activation worsens LVH by increasing blood pressure and by directly affecting cardiac myocytes with AT-II and aldosterone. RAAS blockade reverses myocardial fibrosis and slows HCM progression in animal models. We performed a meta-analysis of randomized clinical trials to further investigate the potential benefit of RAAS blockade in HCM patients. Although our findings included significant results for some of the RAAS blockade agents, these findings were not consistent throughout all the studies. Mavacamten, one of the newest treatments, has shown promising outcomes.

Mitral valve chord rupture in a pregnant patient with uncontrolled hyperthyroidism.

Summary: Graves' disease can have multiple cardiac manifestations. A rare complication is that of severe mitral regurgitation secondary to mitral valve chordae rupture, due to both compromise of valve integrity by deposition of glycosaminoglycans and the hemodynamic stresses of thyrotoxicosis. Pregnancy, with its related hemodynamic changes, is another setting in which mitral valve chordae rupture has occasionally been documented. We present a unique case of a 36-year-old female with uncontrolled Graves' disease who presented during pregnancy at 13 weeks gestation with atrial flutter and features of congestive heart failure. Echocardiogram found severe mitral regurgitation secondary to a ruptured mitral chord. She was treated conservatively with diuresis and ultimately delivered her baby without complication at 28 weeks when she had preterm premature rupture of membranes. She is currently on methimazole and propranolol and pending definitive management of her Graves' disease. This represents not only a rare cardiac complication in a patient with Graves' disease but also is the first in the literature, to our knowledge, which describes this complication in a pregnant patient with Graves' disease. Learning points: Thyroid disease can have multiple effects on the heart through hemodynamic and structural changes and can result in heart failure, arrhythmias, valvular disease, and pulmonary hypertension. Graves' disease can cause glycosaminoglycan deposition in valvular tissue resulting in fragile leaflets that can rupture with little stress. Pregnancy and thyrotoxicosis have similar hemodynamic consequences with increased cardiac output and reduced systemic vascular resistance. Be vigilant in those with hyperthyroidism with a new murmur or features of acute heart failure, as a ruptured valve chord can result in increased morbidity and mortality if not recognized and addressed quickly.

Differences in ejection fraction as inclusion criterion in randomized controlled trials among patients with heart failure with reduced ejection fraction: a systematic review.

INTRODUCTION: Heart failure (HF) with reduced ejection fraction (HFrEF) has been defined by varying ejection fraction (EF) criteria in clinical trials, leading to differences in quantifying treatment effects. AREAS COVERED: The definitions of HFrEF in randomized controlled trials from 2010 until 2020 were collected. The EF ranges were clustered into very low (<30%), low (30-39%) and mildly reduced (40-49%) stratified by intervention. A time series regression analysis was performed. A total of 3052 articles were screened and 706 were included. Interventions included were pharmacologic (37%), device therapy (10%), and a combination of programs, procedural, and laboratory testing (53%). Regarding EF cutoffs, 41% of the studies utilized <40% while 26% used <35%. About 31% did not have a clearly defined EF. Between 2010 and 2020, studies with HFrEF ranges 30-39% have significantly decreased (p value < 0.001 for trend), but those which included very low EF (<30%) and mildly reduced EF (40-49%) have remained the same. EXPERT OPINION: EF definitions across clinical trials in HFrEF varied widely. Defining the specific target HF population phenotype when designing trials or in patient treatment is important as various beneficial effects of different heart failure treatment modalities can be modified or even attenuated across the spectrum of EF.

A Case of Seronegative ANA Hydralazine-Induced Lupus Presenting With Pericardial Effusion and Pleural Effusion.

Hydralazine induced lupus syndrome (HILS), a form of Drug-Induced Lupus (DIL), was first reported in 1953. Since then, studies have shown an increasing incidence of HILS. It presents with lupus-like symptoms such as arthralgia, fever, chest pain, anorexia, fatigue, petechiae, and rash. Though rare, HILS may initially present with pericardial effusion. Lab findings of HILS usually show positive anti-nuclear antibody (ANA) in >95% of cases, antihistone abs in >95% of cases, rheumatoid factor ab in 20%, and anti-double-strand DNA in <5%. Herein we present a case of HILS which initially presented with a seronegative ANA and pericardial effusion. An 82-year-old woman who presented with shortness of breath was found to have bilateral pleural effusion and pericardial effusion. Common etiologies of pericardial effusion have been ruled out, after careful review of her home medications, hydralazine was suspected to be the culprit of her pericardial effusion. Initial ANA testing was negative, however given high clinical suspicion autoimmune disease screening was done revealing positive anti-histone antibodies. Hydralazine was deemed to be the etiology of her pericardial effusion which led to the discontinuation of the drug. Serial echocardiography revealed no recurrence of the effusion.

A Case of Pneumomediastinum and Pneumoperitoneum with Concurrent Massive Subcutaneous Emphysema due to Repositioning of a Tracheostomy Tube.

Tracheostomy is a common procedure seen in critically ill patients that require long term ventilatory support. As with all airway access procedures, tracheotomy with prolonged tracheal tube placement comes with possible risks such as tracheal scarring, tracheal rupture, pneumothorax, tracheoesophageal fistula among others. Another possible complication, though rare, is escape of free air into the surrounding tissue, as well as pneumomediastinum (PM). This may occur due to various reasons, some of them being tracheal rupture, barotrauma or tracheal tube mispositioning. Pneumomediastinum may present with concurrent free air in other body cavities such as the peritoneum, thorax or subcutaneous tissue. Though often not life-threatening it may require treatment including high flow oxygen, ventilator management or occasionally, surgical intervention. Herein we describe a rare case of PM with communicating pneumoperitoneum and massive subcutaneous emphysema due to tracheal tube mispositioning along with a review of the literature.