Indian Consensus on the Role and Position of Angiotensin Receptor-neprilysin Inhibitors in the Management of Heart Failure.

The incidence of heart failure (HF) in India is estimated to be 0.5-1.7 cases per 1,000 people per year, and approximately 4,92,000-1.8 million new cases are detected every year. Despite the high rate of mortality associated with HF, most patients do not receive maximal guideline-directed medical therapy (GDMT). Current guidelines advocate early multidrug combination therapy with four classes of drugs, namely, beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), angiotensin receptor-neprilysin inhibitors (ARNIs), and sodium-glucose transport protein 2 inhibitors (SGLT-2is), particularly in patients with heart failure with reduced ejection fraction (HFrEF). ARNIs reduce cardiac morbidity and mortality in patients with HFrEF. However, recent data indicated that only 4.8% of patients with HFrEF receive ARNI in India. Hence, at a national consensus on HF meeting, cardiology experts from India formulated a national consensus on the use of ARNI in HF based on current evidence and guidelines. The consensus states that ARNI should be used early in HF, particularly in de novo patients with HFrEF, and those with acute decompensated heart failure (ADHF), irrespective of the presence of low systolic blood pressure (SBP) or diabetes. Moreover, those with HFrEF on renin-angiotensin-aldosterone system (RAAS) inhibitors should be switched to ARNI to reduce the risk of repeated hospitalization for HF, worsening HF, and cardiac death, and to improve the quality of life (QoL). Starting ARNI during the first hospitalization is preferable, and it is safe and effective across all doses. ARNIs can also be used for secondary benefits in patients with preserved ejection fraction [heart failure with preserved ejection fraction (HFpEF)] and HF with mildly reduced EF [heart failure with mildly reduced ejection fraction (HFmrEF)].

Consensus Statement from India on the Renal Benefits of ARNi, SGLT-2i, and Bisoprolol in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a major contributor to morbidity and mortality in India. CKD often coexists with heart failure (HF), diabetes, and hypertension. All these comorbidities are risk factors for renal impairment. HF and CKD are pathophysiologically intertwined, and the deterioration of one can worsen the prognosis of the other. There is a need for safe renal pharmacological therapies that target both CKD and HF and are also useful in hypertension and diabetes. Neurohormonal activation achieved through the activation of the sympathetic nervous system (SNS), the renin-angiotensin-aldosterone system (RAAS), and the natriuretic peptide system (NPS) is fundamental in the pathogenesis and progression of CKD and HF. Angiotensin receptor neprilysin inhibitor (ARNi), sodium-glucose cotransporter 2 inhibitors (SGLT-2i), and selective ß1-blocker (B1B) bisoprolol suppress this neurohormonal activation. They also have many other cardiorenal benefits across a wide range of CKD patients with or without concomitant HF, diabetes, or hypertension. This consensus statement from India explores the place of ARNi, SGLT-2i, and bisoprolol in the management of CKD patients with or without HF and other comorbidities.

Current Place of SGLT2i in the Management of Heart Failure: An Expert Opinion from India.

Heart failure (HF) is a global health concern that is prevalent in India as well. HF is reported at a younger age in Indian patients with comorbidity of type 2 diabetes (T2DM) in approximately 50% of patients. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), originally approved for T2DM, are new guideline-recommended and approved treatment strategies for HF. Extensive evidence highlights that SGLT2i exhibits profound cardiovascular (CV) benefits beyond glycemic control. SGLT2i, in conjunction with other guideline-directed medical therapies (GMDT), has additive effects in improving heart function and reducing adverse HF outcomes. The benefits of SGLT2i are across a spectrum of patients, with and without diabetes, suggesting their potential place in broader HF populations irrespective of ejection fraction (EF). This consensus builds on the updated evidence of the efficacy and safety of SGLT2i in HF and recommends its place in therapy with a focus on Indian patients with HF.

Impact of in-hospital statin use on mortality in COVID-19 patients from a majority African American population.

BACKGROUND: The COVID-19 pandemic has claimed over 6.4 million lives globally. Finding effective medications to reduce mortality in hospitalized COVID-19 patients remains critical. No previous study has been published on the effects of statin use in a majority African American COVID-19 patient population. OBJECTIVE: This study aims to assess the relationship between in-hospital statin use and mortality in this population. METHODS: A retrospective chart review of patients diagnosed with COVID-19 from March 2020 to June 2020 admitted to the Phoebe Putney Health System in Albany, Georgia, an early epicenter of the COVID-19 pandemic, was conducted. The outcomes of 735 hospitalized COVID-19 positive patients from over 40 counties in Georgia were analyzed. The primary outcome of interest was all-cause mortality, with secondary outcomes of interest of ICU care, length of ICU stay, need for mechanical ventilator, duration of intubation, and need for dialysis. Multivariate logistic regression and Cox proportional hazards analysis were conducted to examine the effect of in-hospital statin use and mortality. RESULTS: 186 of 735 total patients were prescribed statins in-hospital. 83.8% were African American. Multivariate logistic regression found in-hospital statin use was not significantly associated with the primary outcome - all-cause mortality (p=0.23). Similar findings were seen in need for ICU care, length of ICU stay, need for mechanical ventilator, duration of intubation, and need for dialysis (p>0.05). Additionally, results from a Cox proportional hazards model found in-hospital statin use was not associated with survival time. Sensitivity analysis conducted on only African American patients validated that in-hospital statin use was not associated with all-cause mortality in these patients. Of note, immunosuppression and severe disease presentation were associated with a six-fold increase in risk of mortality and the largest decreases in survival time. CONCLUSION: It is possible statins have no mortality benefit for this patient population, but further research beyond this association study would need to be conducted to determine this conclusively. From this study, the best clinical recommendation would be to continue statins for COVID-19 patients with pre-hospital statin use and to launch a randomized clinical trial to definitively determine the efficacy of statins in the treatment of hospitalized COVID-19 patients.

COVID19-associated new-onset movement disorders: a follow-up study.

BACKGROUND: Neurological symptoms are common manifestation in acute COVID-19. This includes hyper- and hypokinetic movement disorders. Data on their outcome, however, is limited. METHODS: Cases with new-onset COVID-19-associated movement disorders were identified by searching the literature. Authors were contacted for outcome data which were reviewed and analyzed. RESULTS: Movement disorders began 12.6 days on average after the initial onset of COVID-19. 92% of patients required hospital admission (mean duration 23 days). In a fraction of patients (6 of 27; 22%; 4 males/2 females, mean age 66.8 years) the movement disorder (ataxia, myoclonus, tremor, parkinsonism) was still present after a follow-up period of 7.5 ± 3 weeks. Severe COVID-19 in general and development of encephalopathy were risk factors, albeit not strong predictors, for the persistence. CONCLUSIONS: The prognosis of new-onset COVID-19-associated movement disorder appears to be generally good. The majority recovered without residual symptoms within several weeks or months. Permanent cases may be due to unmasking of a previous subclinical movement disorder or due to vascular/demyelinating damage. Given the relatively low response rate of one third only and the heterogeneity of mechanisms firm conclusions on the (long-term) outome cannot, however, be drawn.

Role of Bisoprolol in Heart Failure Management: A Consensus Statement from India.

In India, heart failure (HF) is an important health concern affecting younger age groups than the western population. A limited number of Indian patients receive guideline-directed medical therapy (GDMT). Selective ß-1 blockers (BB) are one of the GDMTs in HF and play an important role by decreasing the sympathetic overdrive. The BB reduces heart rate (HR) reverse the adverse cardiac (both ventricular and atrial), vascular, and renovascular remodeling seen in HF. Bisoprolol, a ß-1 blocker, has several advantages and can be used across a wide spectrum of HF presentations and in patients with HF and comorbid conditions such as coronary artery disease (CAD), atrial fibrillation (AF), post-myocardial infarction (MI), uncontrolled diabetes, uncontrolled hypertension, and renal impairment. Despite its advantages, bisoprolol is not optimally utilized for managing HF in India. This consensus builds on updated evidence on the efficacy and safety of bisoprolol in HF and recommends its place in therapy with a focus on Indian patients with HF.

Biotherapy using Sperm Cell-oriented Transportation of Therapeutics in Female Reproductive Tract Cancer.

Female reproductive tract cancers like ovarian, cervical, vaginal, etc. have led to a serious concern for reproductive health as well as an increase in physical and psychological stresses amongst women. Various conventional techniques like surgery, radiation and chemotherapy are employed but possess limitations such as organ toxicity, infection, nausea, vomiting, etc. Also, several nanotechnology-based synthetic vehicle delivery systems like liposomes, nanoparticles, etc. are used but they lack targeting efficiency that results in poor propulsion and control. Therefore, there is a need for naturally-driven drug carriers to overcome such limitations. Sperm-based drug delivery is the new area for targeted delivery that offers self-propulsion to tumor sites, higher biocompatibility, longer lifespan and increased tissue penetration with enhanced localization. Drug-loaded sperm cells are harnessed with micro/nanomotor that will guide them to the intended target site. The critical analysis of the sperm-based drug delivery system was executed and summarized along with the current challenges. This article deals with the art of delivering the anticancer drug to female reproductive cancer sites with proof-of-concept-based research data and critical discussion on challenges in formulating the sperm-based delivery with a future perspective.

Biomacromolecule-Functionalized Nanoparticle-Based Conjugates for Potentiation of Anticancer Therapy.

Cancer is a rapidly growing life-threatening disease that affected 18.1 million people worldwide in 2018. Various conventional techniques like surgery, radiation, and chemotherapy are considered as a mainstream treatment for patients but show some limitations like cytotoxicity due to off-targeted action, poor intra-tumor localization, development of multi-drug resistance by tumor cells, physical and psychological stresses, etc. Such limitations have motivated the scientists to work towards more patient-centric and precision therapy using advanced drug delivery systems like liposomes, nanoparticles, nanoconjugates, etc. However, these carriers also face limitations like poor biocompatibility, lesser payload capacity, leakage of encapsulated drug, and short-term stability. So, this review article explores the profound insights for the development of biomacromolecule- functionalized nanoconjugates to potentiate the anticancer activity of therapeutic agents for various cancers like lung, colorectal, ovarian, breast and liver cancer. Researchers have shown interest in biofunctionalized nanoconjugates because of advantages like biocompatibility, site-specificity with better localization, higher entrapment with long-term stability and lesser off-target toxicity. The progressive trend of biomacromolecule nanoconjugates will encourage further research for the development of effective transport of drugs, nutraceuticals and phytoconstituents for on-site effect at cancer microenvironment and tumor cells with higher safety profile.

Profound racial disparities in COVID-19 associated hospitalizations in rural Southwest Georgia.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is responsible for one of the largest public health crises the United States has seen to date. This study explores the outcomes of African American and non-African American COVID-19-positive patients hospitalized in rural Southwest Georgia to identify differences in morbidity and mortality between the groups. METHODS: We performed a retrospective cohort analysis among adults aged ≥18 years admitted with COVID-19 between March 2, 2020 and June 17, 2020 at Phoebe Putney Health System. Data on demographics, comorbidities, presenting symptoms, and hospital course were obtained. Patients were divided into two groups: African Americans and non-African Americans. We examined differences in patient characteristics between groups using chi-square tests for categorical variables, t-test for parametric continuous variables, and Wilcoxon rank-sum tests for non-parametric continuous variables. Statistical Analysis Software (SAS) version 9.4 was used for statistical analysis. RESULTS: Among 710 patients, median age was 63 years, 43.8% were males, and 83.3% were African Americans. African Americans had higher prevalence of obesity and hypertension, were more likely to present with fever, and present with longer duration of symptoms prior to presentation. In-hospital mortality was similar between the groups, as was need for mechanical ventilation, ICU care, and new dialysis. African Americans were more likely to be discharged home compared to non-African Americans. CONCLUSIONS: There was no difference in in-hospital mortality; however, African Americans had disproportionately higher hospitalizations, likely to significantly increase the morbidity burden in this population. Urgent measures are needed to address this profound racial disparity.

Altered mental status is an independent predictor of mortality in hospitalized COVID-19 patients.

BACKGROUND/AIMS: Limited data exists on the outcomes of COVID-19 patients presenting with altered mental status (AMS). Hence, we studied the characteristics and outcomes of hospitalized COVID-19 patients who presented with AMS at our hospital in rural southwest Georgia. METHODS: Data from electronic medical records of all hospitalized COVID-19 patients from March 2, 2020, to June 17, 2020, were analyzed. Patients were divided in 2 groups, those presenting with and without AMS. Primary outcome of interest was in-hospital mortality. Secondary outcomes were needed for mechanical ventilation, need for intensive care unit (ICU) care, need for dialysis, and length of stay. All analyses were performed using SAS 9.4 and R 3.6.0. RESULTS: Out of 710 patients, 73 (10.3%) presented with AMS. Majority of the population was African American (83.4%). Patients with AMS were older and more likely to have hypertension, chronic kidney disease (CKD), cerebrovascular disease, and dementia. Patients with AMS were less likely to present with typical COVID-19 symptoms, including dyspnea, cough, fever, and gastrointestinal symptoms. Predictors of AMS included age ≥ 70 years, CKD, cerebrovascular disease, and dementia. After multivariable adjustment, patients with AMS had higher rates of in-hospital mortality (30.1% vs 14.8%, odds ratio (OR) 2.139, p = 0.019), ICU admission (43.8% vs 40.2%, OR 2.59, p < 0.001), and need for mechanical ventilation (27.4% vs 18.5%, OR 2.06, p = 0.023). Patients presenting with AMS had increased length of stay. CONCLUSIONS: Patients with COVID-19 presenting with AMS are less likely to have typical COVID-19 symptoms, and AMS is an independent predictor of in-hospital mortality, need for ICU admission, and need for mechanical ventilation.

Study of modified technique of ileal neobladder-Frog neobladder.

PURPOSE: Orthotopic neobladder is a well-established technique for continent urinary diversion after radical cystectomy. In this study, we evaluated a new Frog ileal neobladder technique. Since the reconstructed neobladder appears like a frog, the name Frog Neobladder was given to it. We have used two isoperistaltic ileal segments and implanted ureters in the nondetubularized proximal end of the ileal segment. SUBJECTS AND METHODS: This was a prospective, single-center (tertiary care hospital) study conducted from February 2008 to January 2018. Study patients were aged 39-94 years with biopsy-proven muscle-invasive localized bladder carcinoma. One hundred and twenty patients were included in the study, who had undergone Radical Cystectomy and were offered "FROG BLADDER"- a type of neobladder. Evaluation of complications, renal function, urodynamic parameters, post-void residual urine (PVR), continence, and need for clean intermittent catheterization was done in all patients with neobladder. RESULTS: A total of 120 patients were included in the study, the average age of the patients was 62 years. The operative mean time was 280 ± 29.8 min. There was no perioperative death, and perioperative or early and late complication rates were 31.2% and 18.7%, respectively. Six patients had uretero-enteric anastomosis stricture, of which two were managed by retrograde ureteroscopic dilatation, another three strictures were treated with antegrade approach, and one patient underwent open surgery. All patients were able to void urine, except for three patients who required self-catheterization. The mean capacity was increased to average of 398 ± 220 ml at 12 months in all patients. The mean PVR at 1 year was 46 ± 54.4 ml. CONCLUSION: The Frog neobladder has similar outcome similar to other neobladder technique, with added advantage of ability to accommodate shorter ureteric length and the ease of accessing ureter by retrograde approach for intervention.

A Systematic Review of the Incidence and Outcomes of In-Hospital Cardiac Arrests in Patients With Coronavirus Disease 2019.

OBJECTIVES: To investigate the incidence, characteristics, and outcomes of in-hospital cardiac arrest in patients with coronavirus disease 2019 and to describe the characteristics and outcomes for patients with in-hospital cardiac arrest within the ICU, compared with non-ICU patients with in-hospital cardiac arrest. Finally, we evaluated outcomes stratified by age. DATA SOURCES: A systematic review of PubMed, EMBASE, and preprint websites was conducted between January 1, 2020, and December 10, 2020. Prospective Register of Systematic Reviews identification: CRD42020203369. STUDY SELECTION: Studies reporting on consecutive in-hospital cardiac arrest with a resuscitation attempt among patients with coronavirus disease 2019. DATA EXTRACTION: Two authors independently performed study selection and data extraction. Study quality was assessed with the Newcastle-Ottawa Scale. Data were synthesized according to the Preferred Reporting Items for Systematic Reviews guidelines. Discrepancies were resolved by consensus or through an independent third reviewer. DATA SYNTHESIS: Eight studies reporting on 847 in-hospital cardiac arrest were included. In-hospital cardiac arrest incidence varied between 1.5% and 5.8% among hospitalized patients and 8.0-11.4% among patients in ICU. In-hospital cardiac arrest occurred more commonly in older male patients. Most initial rhythms were nonshockable (83.9%, [asystole = 36.4% and pulseless electrical activity = 47.6%]). Return of spontaneous circulation occurred in 33.3%, with a 91.7% in-hospital mortality. In-hospital cardiac arrest events in ICU had higher incidence of return of spontaneous circulation (36.6% vs 18.7%; p < 0.001) and relatively lower mortality (88.7% vs 98.1%; p < 0.001) compared with in-hospital cardiac arrest in non-ICU locations. Patients greater than or equal to 60 years old had significantly higher in-hospital mortality than those less than 60 years (93.1% vs 87.9%; p = 0.019). CONCLUSIONS: Approximately, one in 20 patients hospitalized with coronavirus disease 2019 received resuscitation for an in-hospital cardiac arrest. Hospital survival after in-hospital cardiac arrest within the ICU was higher than non-ICU locations and seems comparable with prepandemic survival for nonshockable rhythms. Although the data provide guidance surrounding prognosis after in-hospital cardiac arrest, it should be interpreted cautiously given the paucity of information surrounding treatment limitations and resource constraints during the pandemic. Further research is into actual causative mechanisms is needed.

Carbohydrate-based magnetic nanocomposites for effective cancer treatment.

The treatment of cancer includes several conventional therapies like surgery, radiation, chemotherapy, etc. but mostly associated with limitations like off-targeted action, fatigue and organ toxicity. The emergence of nanotechnology-enabled drug delivery systems shows revolutionary development to overcome the limitations of such therapies. Magnetic nanocomposites are the new area of research that consists of nanoscale magnetic materials for triggering the release of active in response to an external magnetic field. For targeted drug delivery and enhancing the biocompatibility, effective functionalization of magnetic nanocomposites is required. Therefore, several biological molecules like carbohydrate polymers, proteins, nucleic acids, antibodies, etc. are used. This review article focuses on the insights of advances in the development of carbohydrate-based magnetic nanocomposites for safe and effective cancer treatment. Carbohydrate-based magnetic nanocomposites offer significant advantages like greater stability, higher biocompatibility and lower toxicity with better physicochemical properties such as higher magnetic moments and anisotropy, larger heating properties, etc. Magnetic nanocomposites explore in almost all the areas of cancer therapeutics for drug delivery carrier, as antineoplastic and MRI contrast agents and in photothermal, photodynamic and in combinational therapies for the development of safer nanocarriers. Such progressive trend of carbohydrate-based magnetic nanocomposites will encourage the researchers for better site-specific delivery with higher safety profile in cancer therapy.