Factors affecting response variables with emphasis on drug release and loading for optimization of liposomes.

Drug delivery through Liposomes has shown tremendous potential in terms of the therapeutic application of nanoparticles. There are several drug-loaded liposomal formulations approved for clinical use that help mitigate harmful effects of life-threatening diseases. Developments in the field of liposomal formulations and drug delivery have made it possible for clinicians and researchers to find therapeutic solutions for complicated medical conditions. A key aspect in the development of drug-loaded liposomes is a careful review of optimization techniques to improve the overall formulation stability and efficacy. Optimization studies help in improving/modulating the various properties of drug-loaded liposomes and are vital for the development of this class of delivery systems. A comprehensive overview of the various process variables and factors involved in the optimization of drug-loaded liposomes is presented in this review. The influence of different independent variables on drug release and loading properties with the application of a statistical experimental design is also explained in this article.

Periodically, liposomes have shown tremendous potential as drug carriers as they are multifunctional nanoparticles with a unique ability to deliver drugs and other therapeutic moieties to target sites in the body. The use of statistical experimental designs and optimization models to develop drug-loaded liposomes is considered the most effective step in formulation development. A careful consideration of various factors and variables in optimizing liposome formulations has been specifically described in this review article. Thorough understanding of different factors that affect drug loading and release in liposomes provides deeper insights in achieving a stable, efficacious drug formulation. There are several new aspects and concepts which need to be explored as part of formulation development and optimization of drug-loaded liposomes and this article hopes to shed light on some important aspects in this scientific journey.

Myocardial ischemia-reperfusion injury released cellular fibronectin containing domain A (CFN-EDA): A destructive positive loop amplifying arterial thrombosis formation and exacerbating myocardial reperfusion injury.

Previous research has identified intravascular platelet thrombi in regions affected by myocardial ischemia-reperfusion (MI/R) injury and neighbouring areas. However, the occurrence of arterial thrombosis in the context of MI/R injury remains unexplored. This study utilizes intravital microscopy to investigate carotid artery thrombosis during MI/R injury in rats, establishing a connection with the presence of prothrombotic cellular fibronectin containing extra domain A (CFN-EDA) protein. Additionally, the study examines samples from patients with coronary artery disease (CAD) both before and after coronary artery bypass grafting (CABG). Levels of CFN-EDA significantly increase following MI with further elevation observed following reperfusion of the ischemic myocardium. Thrombotic events, such as thrombus formation and growth, show a significant increase, while the time to complete cessation of blood flow in the carotid artery significantly decreases following MI/R injury induced by ferric chloride. The acute infusion of purified CFN-EDA protein accelerates in-vivo thrombotic events in healthy rats and significantly enhances in-vitro adenosine diphosphate and collagen-induced platelet aggregation. Treatment with anti-CFN-EDA antibodies protected the rat against MI/R injury and significantly improved cardiac function as evidenced by increased end-systolic pressure-volume relationship slope and preload recruitable stroke work compared to control. Similarly, in a human study, plasma CFN-EDA levels were notably elevated in CAD patients undergoing CABG. Post-surgery, these levels continued to rise over time, alongside cardiac injury biomarkers such as cardiac troponin and B-type natriuretic peptide. The study highlights that increased CFN-EDA due to CAD or MI initiates a destructive positive feedback loop by amplifying arterial thrombus formation, potentially exacerbating MI/R injury.

Bilateral Renal Cell Carcinoma in the Horseshoe Kidney With Metastasis in Gallbladder, Pancreas and Duodenum: A Report of a Rare Case and Literature Review.

Horseshoe kidney is the most common renal fusion anomaly and is associated with various complications, ranging from infections to neoplasms. While renal cell carcinoma (RCC) is the most frequent renal neoplasm in adults, its occurrence in a horseshoe kidney is rare, and bilateral involvement is rarer. Furthermore, RCC metastasizing to organs is known and rare sites of metastasis are also documented. The report presents a unique case of bilateral RCC in a horseshoe kidney with synchronous metastasis to the gallbladder, pancreas, and duodenum. This presentation, involving metastasis to these specific organs, is exceedingly uncommon, making it a rarest of rare possibilities. The current case report underscores the importance of vigilant monitoring and comprehensive evaluation in patients with horseshoe kidneys, as they may be predisposed to unusual complications like RCC and rare site metastasis.

Does high dose statin pretreatment affect global strains in patients undergoing valve replacement.

Purpose: To study the effect of rosuvastatin 40 mg (initiated 7 days prior to surgery) in patients undergoing valve replacement (VR) for rheumatic mitral valve disease on left ventricular (LV) strain and biomarker release kinetics. Methods: In this randomized study, cardiac biomarkers viz. troponin I (TnI), Creatine kinase MB (CK-MB), N-terminal pro B-type natriuretic peptide (NTPBNP) were measured before surgery; and 8, 24 and 48 h postoperatively. Global LV (circumferential, global circumferential strain (GCS); longitudinal, GLS; radial, global radial strain (GRS)) strains were measured preoperatively; and 48 h and 30 days postoperatively. Results: Following VR, Global Longitudinal Strain (GLS), Global Circumferential Strain (GCS) and Global Radial Strain (GRS) declined at 48 h in both statin loaded (SL) and non loaded (NL) groups. The %decline in strain was significantly lower in SL group (% change in GLS 35.8% vs 38.8%, GCS 34% vs 44.1%, GRS 45.7% vs 52.6%; p < 0.001).All strain values improved at 30 days with higher improvement in SL group (GLS -15.92 ± 2.00% vs -12.6 ± 1.66%, GCS -15.12 ± 2.93% vs -13.04 ± 2.44%; GRS 22.12 ± 6.85% vs 19.32 ± 6.48%). While TnI, CKMB, NTPBNP increased following surgery, values at 8, 24 and 48 h were lower in the SL vs. NL group. Mean change (baseline to peak biomarker value) was also significantly lower in SL group.The SL group had shorter hospital and Intensive Care Unit (ICU) stay. On Receiver Operating Characteristic Curve (ROC) analysis, baseline GCS ≤ 14% best predicted postoperative 30 day Left Ventricular Ejection Fraction (LVEF) ≤ 50%. Conclusion: Pre-operative high dose rosuvastatin was "cardioprotective" with favorable effect on LV global strain and release kinetics of biomarkers. These cut-offs (described for the first time for rheumatic VR) can be used as prognostic predictors.

Liposomes for drug delivery: review of vesicular composition, factors affecting drug release and drug loading in liposomes.

Liposomes are considered among the most versatile and advanced nanoparticle delivery systems used to target drugs to specific cells and tissues. Structurally, liposomes are sphere-like vesicles of phospholipid molecules that are surrounded by equal number of aqueous compartments. The spherical shell encapsulates an aqueous interior which contains substances such as peptides and proteins, hormones, enzymes, antibiotics, antifungal and anticancer agents. This structural property of liposomes makes it an important nano-carrier for drug delivery. Extrusion is one of the most frequently used technique for preparing monodisperse uni-lamellar liposomes as the technique is used to control vesicle size. The process involves passage of lipid suspension through polycarbonate membrane with a fixed pore size to produce vesicles with a diameter near the pore size of the membrane used in preparing them. An advantage of this technique is that there is no need to remove the organic solvent or detergent from the final preparation. This review focuses on composition of liposome formulation with special emphasis on factors affecting drug release and drug-loading.

Liposomes are among the most effective and multifunctional nanocarriers. However, they possess certain prevalent limitations such as lack of targeting strategies, production challenges and slow overall transition of approved therapies into clinic. Improving drug loading and release capabilities of liposomal drug formulations with efficient delivery optimisation can be the most effective path in designing this class of nanoparticle drugs. Considering the numerous applications of liposomes, the drug delivery research community must utilise these nanocarriers to their maximum potential in an attempt to introduce novel medications against life threatening diseases.

Flecainide for conversion and maintenance of sinus rhythm after mitral valve replacement in rheumatic atrial fibrillation.

BACKGROUND: Despite successful mitral valve replacement (MVR), many patients remain in AF. Flecainide can be useful in these patients but has not been used because of underlying structural heart disease. METHODS: We assessed oral flecainide for conversion and maintenance of SR in 25 patients of chronic rheumatic AF following MVR (age 34.4 yrs, mean AF duration: 3.6 yrs). Non-converters underwent DC cardioversion at 24 h and 4 weeks. Patients received flecainide and bb/diltiazem at discharge. RESULTS: Single oral dose of Flecainide achieved SR in 6/25 (24%) while 19/25 achieved SR after DCC; at24 h 21/25 (84%) were in SR. With mean flecainide dose (93.10 ± 9.40 mg), successful maintenance of SR at 6 months was seen in 16/23 (69.5%). No significant changes in PR interval, QRS duration or QTc were noted; flecainide was well tolerated. Patients in SR had significantly better functional status, QOL scores and higher LA strain at 6 months (25.25 vs 17.43%, p < .0001). Baseline LA diameter ≤ 61 mm predicted SR at 6 months (sensitivity/specificity 93.7% and 85.71%) while the values for AF duration ≤ 4 years and LA strain > 21% for predicting SR were 87.5/71.43% and 100/85.71% respectively. CONCLUSION: Oral flecainide was safe and effective in post MVR rheumatic AF patients; maintenance of SR was achieved in 76% of initial converters and 64% of overall population, with better LA strain values. More studies are needed to validate these results.

Primary Mesenchymal Chondrosarcoma of the Mediastinum with Adrenal Metastasis: A Rare Scenario.

Mesenchymal chondrosarcoma (MC) is a rare malignant tumor that represents <3% of all chondrosarcomas. Herein, we describe extraskeletal MC involving the mediastinum in a 24-year-old gentleman with a rare phenomenon of adrenal metastasis.

The lytic skeletal lesions: A rare presentation of carcinoma prostate on 18F-fluorodeoxyglucose positron emission tomography/computed tomography.

ABSTRACT: We describe the 18F-fluorodeoxyglucose positron emission tomography/contrast enhanced computed tomography (FDG PET/CECT) images of a 63-year-old male who complained of back pain and was suspected of multiple myeloma based on magnetic resonance imaging. PET/CECT suggested the FDG avid lesion involving prostate, accompanied by multiple lytic skeletal lesions with no evidence to suggest other possible primary site. A bone marrow biopsy suggested a metastatic adenocarcinoma of primary prostatic origin. Post anti-androgen therapy follow-up FDG PET/CT revealed reductions in the metabolic activities and soft tissue components of most of the metastatic skeletal lesions. These images highlight the possible indication of FDG PET/CT in evaluation of prostatic malignancy in era of 68Ga-PSMA.

Routine hematology parameters in COVID-19: A predictor of disease severity and mortality.

Background: Our understanding of the pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still evolving and is limited for prognostication. The study was performed to predict severity and mortality based on hematology parameters in coronavirus disease (COVID-19). Material and Methods: The study was a single-center retrospective analysis of 240 patients with COVID-19. The hematological parameters were compared between different grades of severity. The receiver operating characteristics (ROC) curve along with the Classification and Regression Trees (CART) methods were used for the analysis. Result: The total leukocyte count, absolute neutrophil count, neutrophil-lymphocyte ratio (NLR), and neutrophil-monocyte ratio (NMR) were increasing along with an increase in severity; while the absolute lymphocyte count and lymphocyte-monocyte ratio (LMR) were decreasing (P < 0.001). For prediction of severity and mortality on admission, the NLR, NMR, and LMR were significant (P < 0.001). The NLR, NMR, and LMR had an area under the receiver operating characteristics curve (AUROC) of 0.86 (95% CI of 0.80-0.91), 0.822 (95% CI of 0.76-0.88), and 0.69 (95% CI of 0.60-0.79), respectively, for severity. While the NLR, NMR, and LMR had an AUROC value of 0.85 (95% CI of 0.79-0.92), 0.83 (95% CI of 0.77-0.89), and 0.67 (95% CI of 0.57-0.78), respectively, for mortality. Conclusion: With the increase in severity there was an increase in the total leukocyte count and absolute neutrophil count while the absolute lymphocyte count decreased. On admission, the cut-off value of NLR >5.2, NMR >12.1, while LMR <2.4 may predict severity and mortality in COVID-19.

Bronchial Carcinoid Tumor in an Adolescent Female: Diagnosis and Management by a Multi-Disciplinary Team.

Bronchial carcinoid is the most common primary malignant lung tumor in children; however, it remains a very rare diagnosis due to the overall low incidence of childhood lung malignancies. We report a case of a 17-year-old girl with respiratory symptoms who was initially misdiagnosed as a case of COVID pneumonia. She was later detected to have a right mainstem bronchial carcinoid which was managed successfully by a multi-disciplinary team.

Long-term performance of untreated fresh autologous pericardium as a valve substitute in pulmonary position.

Background: Pulmonary regurgitation is imminent after transannular patch (TAP). We analyze the long-term performance of untreated autologous pericardium (UAP) as valve substitute at pulmonary position in patients requiring TAP. Material and Methods: This cross-sectional study include patients operated between 2007 and 2012 (n = 92). A sample of 19 patients was selected for this study which had a follow-up of more than 3 years. This includes patients with no TAP (n = 4) and with TAP and valve substitute, a monocusp (n = 11) or a tricuspid valve (n = 4) at neopulmonary annulus. Patients underwent echocardiography for assessment of right ventricle function and 18 fluoro-deoxyglucose PET CT scan for measurements of valve substitute at neopulmonary annulus. The target to blood ratio (TBR) of uptake of glucose by monocusp was measured at the cooptation edge of the neopulmonary valve. Results: The median age of the patients is 14 (9 - 37). RV function is preserved (TAPSE 18.9 (10.6 - 22.8)) at a mean follow-up of 4 years (3-9). The measurements of monocusp shows a shrinkage in height of the cusp by 35.5% (70% - 1.0%) and length by 7% (-44% - +104%). There was less shrinkage observed in patients below 15 years of age. The TBR of monocusp was 0.945 (0.17 - 3.35) with a strong correlation between the TBR values of aortic valve leaflet and monocusp leaflet of same patient. Conclusion: The UAP is functional and successful as a valve substitute at neo pulmonary annulus at long-term follow-up. It has resisted calcification and has shown uptake of glucose in physiological limits.

A novel epidemiological scoring system for the prediction of mortality in COVID-19 patients.

BACKGROUND: Most of the reported risk score models for coronavirus disease 2019 (COVID-19) mortality are based on the levels of inflammatory markers, comorbidities or various treatment modalities, and there is a paucity of risk score models based on clinical symptoms and comorbidities. METHODS: To address this need, age, clinical symptoms and comorbidities were used to develop a COVID-19 scoring system (CSS) for early prediction of mortality in severe COVID-19 patients. The CSS was developed with scores ranging from 0 to 9. A higher score indicates higher risk with good discrimination quality presented by Mann Whitney U test and area under receiver operating characteristic curve (AUROC). RESULTS: Patient age of ≥60 y, cough, breathlessness, diabetes and any other comorbidity (with or without diabetes) are significant and independent risk factors for non-survival among COVID-19 patients. The CSS showed good sensitivity and specificity (i.e. 74.1% and 78.5% at CSS≥5, respectively), with an overall diagnostic accuracy of 82.8%, which was close to the diagnostic accuracy detected in the validation cohort (81.9%). In the validation cohort, high (8-9), medium (5-7) and low (0-4) CSS groups had 54.80%, 28.60% and 6.5% observed mortality, respectively, which was very close to the predicted mortality (62.40%, 27.60% and 5.2%, respectively, by scoring cohort). CONCLUSIONS: The CSS shows a positive relationship between a higher score and proportion of mortality and, as its validation showed, it is useful for the prediction of risk of mortality in COVID-19 patients at an early stage, so that referral for triage and admission can be predetermined even before admission to hospital.

Postoperative atrial fibrillation in coronary artery bypass grafting herald poor outcome.

Introduction: Atrial fibrillation in postoperative period is common. Although the event of atrial fibrillation is associated with reduced cardiac output and its consequences and cerebrovascular events, its effect on outcome is not clearly documented. This study is done to evaluate the effect of atrial fibrillation on outcome of the operation. Materials and Methods: This is a retrospective case-control study. A total of 263 patients received coronary artery bypass grafting during this period. The data for demographics, comorbidities, preoperative medications, operative details, and echocardiographic parameters of left ventricular functions were acquired. A total of 24 patients had atrial fibrillation (Group I), while 239 remained in normal sinus rhythm (Group II). The outcome is measured as combined of death and postoperative myocardial infarction (MI). Results: The groups are comparable in demographic, preoperative medications, operative, and left ventricular parameters. Of the 24 (9.12%) patients who had postoperative atrial fibrillation, 11 were discharged on medical management. Nine patients reverted to sinus rhythm at discharge. Atrial fibrillation persisted in 8 patients 1 week after discharge and 3 patients after 1 month. The requirement of intraaortic balloon pump (IABP) was statistically significant in group I (5 in group I vs. 10 in group II, n = 0.001). There were 4 deaths in group 1 and 7 in group 2 (P = 0.002), however, the combined end point was achieved in 4 (16.6%) vs. 22 (9.2%), respectively, P = 0.1. Conclusion: The appearance of atrial fibrillation heralds increased requirement of IABP, MI, and death in patients undergoing coronary artery bypass grafting.

Partial atrioventricular septal defect associated with wolff-parkinson-white syndrome: Perioperative dysrhythmias during the intracardiac repair.

Wolff-Parkinson-White syndrome (WPW) is rarely seen in association with atrioventricular septal defect. Although paroxysm's of palpitation due to supraventricular tachycardia can occur in these patients, rare, fatal, ventricular dysrhythmias can also occur. Herein, we report the case of a 20-year-old male patient with partial atrioventricular septal defect and WPW syndrome for intracardiac repair, developing intraoperative Torsades de pointes and postoperative cardiac arrest, adding to the difficulty in overall patient management.

Early experience with surgical strategies aimed at preserving the pulmonary valve and annulus during repair of tetralogy of Fallot.

BACKGROUND: During repair of tetralogy of fallot (TOF) we modified surgical strategies to preserve the valve and annulus if the pulmonary valve leaflets are pliable and not significantly dysplastic. METHODS: Initially, the repair was done from the main pulmonary artery (Group-1, 215 patients) and later through an additional incision in the infundibulum of the right ventricle (Group-2, 73 patients). Recently, we changed the approach to commissurotomy of the fused leaflets by releasing the supra valvar tethering and delamination of the cuspal apparatus till the base to improve the mobility of the cusps and do a controlled commissurotomy (Group-3, 14 patients). With delamination, we could extend the limit of the repair to a z-score of -3.5. RESULTS: There was no hospital mortality; two patients died at home after discharge. A mean follow-up of 42.01 months ± 19.25 is available for 198 patients (92%) for group 1, 16.03 ± 7.45 for group 2, and 4.07 ± 2.09 for group 3. The re-intervention-free survival is 94.4% in group 1. The z value improved from -3 (-3--2) to -1.2 (-3 - 0), P = 0.001 in Group 1, from -2.8 (-3--2.4) to -1 (-1.1--0.7), P = 0.001 in Group 2 and from -3 (-4--3) to -1, P = 0.001 in Group 3. In all the groups, there was trivial or mild pulmonary regurgitation. CONCLUSIONS: During repair of TOF, adequate valve/annulus sparing is possible if the repair is done from both the main pulmonary artery and infundibular incisions using the delamination technique.

Intracardiac hydatid cyst located in right ventricular outflow tract: a rare site.

Intracardiac hydatid cyst is relatively uncommon and involvement of right ventricular outflow tract is extremely rare. We report a rare case of intracardiac hydatid cyst involving the right ventricular outflow tract and do a review of literature.

Mechanical prosthetic valve thrombosis in current era: 5-year follow-up.

INTRODUCTION: The incidence of prosthetic valve dysfunction (stuck valve) is variable and is dependent on various factors. There are studies from Indian groups that have emphasized the success of thrombolysis; however, none of them reported a follow-up. This study was designed to emphasize on the follow-up of these patients at midterm. MATERIAL AND METHODS: The patients of prosthetic valve thrombosis between period of January 2013 and December 2017 were included in this retrospective observational study. Sixty-six patients were admitted with stuck valve during this period. Thrombolysis was preferred modality of treatment. Survivors were followed up with serial echocardiography, which included estimation of left ventricular and valve functions. RESULTS: Of a total of 66 patients, 59 were of stuck mitral valve and 7 stuck aortic valve. The event happened at a mean of 48.86 ± 48.80 months after index operation of valve replacement using mechanical valve prosthesis. The median age was 40.27 ± 10.8 years with 39 males and 27 females. Thrombolysis was successful in 61 patients with a mortality of 5 (7.57%). During a mean follow-up of 22.7 ± 20.9 months, 42 patients were alive with 14 (22.95%) patients dead and 5 patients lost to follow-up. The average follow-up was 18.7 ± 22.7 months before death. CONCLUSION: Following good early results after thrombolysis, patients of prosthetic heart valve thrombosis experience high mortality within 2 years of follow-up. These patients require frequent follow-up to avoid early mortality.

Early Experience With Pulmonary Root Translocation in Transposition of the Great Arteries With Left Ventricular Outflow Tract Obstruction.

BACKGROUND: The optimal surgical management of patients with transposition of the great arteries (TGA), ventricular septal defect (VSD), and left ventricular outflow tract obstruction (LVOTO) is debatable. This is our initial experience with pulmonary root translocation (PRT), a technique that aims to preserve the pulmonary valve function. METHODS: From July 2012 to October 2019, 16 patients underwent anatomical repair for TGA, VSD, and LVOTO. The median age was 12 months (range: 7 months to 13 years), and the median weight was 7.75 kg (range: 5.6-29.5 kg). Thirteen patients had a diagnosis of d-TGA and three had congenitally corrected transposition of the great arteries (cc-TGA). The surgical technique involved PRT from the left ventricle (LV) to the right ventricle and routing the LV to the aorta. The left ventricular outflow tract orifice resulting from the pulmonary root extraction was closed with a pericardial patch. In patients with cc-TGA, an atrial switch operation was added. A bidirectional Glenn was necessary in four patients with a long LV to aorta tunnel. One patient required a transannular patch to reconstruct the right ventricular outflow tract (RVOT). RESULTS: The median follow-up was 27 months. There was one hospital death due to residual mitral regurgitation. One patient died at home four months after hospital discharge. The remaining patients are doing well with adequate RVOT function and no valve regurgitation. CONCLUSIONS: Complete correction of TGA, VSD, and LVOTO using PRT was achieved with acceptable risk in patients with pliable and nondysplastic pulmonary valve. The translocated pulmonary root performed well in this short follow-up.

18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Findings of Osteoblastoma Of Rib - A Rare Benign Tumor with Unusual Site and Uncommon Age.

Osteoblastoma accounts for approximately 1% of all primary bone tumors. We report F18-fluorodeoxyglucose positron emission tomography/computed tomography (F18-FDG PET/CT) findings of an osteoblastoma in the rib of a 20-month-old girl child, who had fever with pain in the right shoulder for 4 months. This lesion was initially judged as a malignant bone tumor but a biopsy revealed it to be an osteoblastoma. The age of patient and predominant site of disease involvement contributes to uniqueness of our case. In our case, F18-FDG PET/CT has facilitated biopsy planning and ruled out other sites of disease involvement.

Primary Rectal Lymphoma: A Case Report and Review of Literature.

Lymphomas represent common hematological malignancy, and depending on site, they are classified as nodal or extranodal lymphoma. The term extranodal disease refers to lymphomatous infiltration of anatomic sites other than the primary lymphatic sites; however, the diagnosis of primary versus secondary extranodal lymphoma remains challenging. Among the extranodal locations, gastrointestinal system is the most frequent site. The involvement of the stomach, small intestine, and colon is noted. Rectum as primary site for lymphoma is rare in adults and extremely rare in children. We describe a case of primary rectal lymphoma (high-grade B-cell non-Hodgkin's lymphoma) in 11-year-old child. We believe that reporting this case will add to the data about clinical presentation, radiological, nuclear medicine findings, and treatment approaches of primary rectal lymphoma.