Design of Degradable Polyphosphoester Networks with Tailor-Made Stiffness and Hydrophilicity as Scaffolds for Tissue Engineering.

In the recent decades, biodegradable and biocompatible polyphosphoesters (PPEs) have gained wide attention in the biomedical field as relevant substitutes for conventional aliphatic polyesters. These amorphous materials of low glass transition temperature offer promise for the design of soft scaffolds for tissue engineering. Advantageously, the easy variation of the nature of the lateral pendant groups of PPEs allows the insertion of pendent unsaturations valuable for their further cross-linking. In addition, varying the length of the pendent alkyl chains allows tuning their hydrophilicity. The present work aims at synthesizing PPE networks of well-defined hydrophilicity and mechanical properties. More precisely, we aimed at preparing degradable materials exhibiting identical hydrophilicity but different mechanical properties and vice versa. For that purpose, PPE copolymers were synthesized by ring-opening copolymerization of cyclic phosphate monomers bearing different pendent groups (e.g., methyl, butenyl, and butyl). After UV irradiation, a stable and well-defined cross-linked material is obtained with the mechanical property of the corresponding polymer films controlled by the composition of the starting PPE copolymer. The results demonstrate that cross-linking density could be correlated with the mechanical properties, swelling behavior, and degradation rate of the polymers network. The polymers were compatible to human skin fibroblast cells and did not exhibit significant cytotoxicity up to 0.5 mg mL-1. In addition, degradation products appeared nontoxic to skin fibroblast cells and showed their potential as promising scaffolds for tissue engineering.

Prevalence and Assessment of Factors Associated With Malnutrition in Children Residing in Slums of Mumbai: A Cross-Sectional Study.

Background Malnutrition in children continues to be a serious public health problem in India. Therefore, this study aims to evaluate the prevalence of malnutrition and assess factors contributing to it in children of the marginalized slum population of India, masked in the metropolitan cities.  Methods A retrospective data analysis with a cross-sectional model was conducted by medical volunteers affiliated with the Rotaract Club of Medicrew who had organized a free pediatric health check-up camp in the Dharavi village of Mumbai, India for children under five. Children under five years of age group of either sex residing in the slums of Dharavi and whose parents consented are included in the study. Neonates, children older than five years of age, and children whose parents did not consent for them to be included in the study were excluded. A pretested, pre-validated questionnaire was administered, and statistical analysis was done with p-values <0.05 considered to be statistically significant. Results  A total of 126 children were included. Out of these children, 109 of them (86.50%) had a mid-arm circumference of more than 12.5 cm (normal), 11 (8.73%) were between 11.5 cm and 12.5 cm (moderate acute malnutrition), and five (4.77%) were less than 11.5 cm (severe acute malnutrition). Among the 126 kids, 86 kids were above the age of two and their BMI was assessed, 36 (44.19%) were found to be underweight (<5th percentile) while 14 (16.3%) were obese (>95th percentile), and four (4.65%) were overweight (85th-95th percentile). For 106 (84.13%) of these children, the caregivers were mothers while others were fathers (n=4; 3.18%), grandmothers (n=5; 3.97%), sisters (n=5; 3.97%), and aunts (n=6; 4.76%). Out of those who had commenced receiving formal education, only 39 (55.71%) were in an appropriate grade for their age. The mean expenditure on food as a proportion of the total household income was 36.40% (standard deviation (SD) 15.0%). On the single-item sleep quality scale, the sleep of only 36 kids (28.58%) was reported by their caregivers as excellent. A high proportion of other medical problems were reported in the children. Conclusion Our study reports a substantial burden of malnutrition among children residing in the slums of Dharavi. Rigorous strengthening and conceptualization of on-ground nutritional programs targeted toward slum children should be done by Indian healthcare policymakers.

Interplay Between Diabetes Mellitus and the Occurrence of Osteoarthritis and Associated Conditions in Women of Menopausal Age.

Osteoarthritis (OA) and diabetes mellitus (DM) have long-term deleterious chronic effects and are among the most prevalent chronic disorders. DM and its associated factors, such as hyperglycemia, have a significant contribution to the pathophysiology of OA, particularly in post-menopausal women. Women who have uncontrolled diabetes (DM) are more prone to develop osteoarthritis (OA), which may be exacerbated by poor glycemic control. Furthermore, this category of female patients with DM has an increased risk of developing fractures, even in those with initially normal bone density scores, further illustrating the correlation between DM and bone health. Additionally, multiple risk factors, including obesity, metabolic syndrome, hypertension, estrogen-based hormone therapy, and hyperuricemia, in menopausal women can lead to the development and exacerbation of OA. It is discovered that these variables have a direct or indirect impact, frequently causing inflammation and hormonal changes, which contribute to the intricate interaction between DM and OA. The management of OA and DM in women thus calls for a multi-faceted management plan including glycemic control, weight control, exercise, and specialized pain management methods catering to the specific requirements of the patients. Regularly screening for OA should be implemented for menopausal women with DM and utmost care should be provided by healthcare professionals. Regular monitoring of joint health and early management, encouraging interdisciplinary cooperation, putting preventative measures into place, and creating individualized treatment programs are essential. A thorough understanding of the link between DM and OA will ultimately lead to improved health outcomes and a better future for these individuals.

Efficacy, Safety and Immunogenicity of Sun's Ranibizumab Biosimilar in Neovascular Age-Related Macular Degeneration: A Phase 3, Double-Blind Comparative Study.

INTRODUCTION: The study aimed to evaluate comparability in terms of efficacy, safety and immunogenicity of Sun's ranibizumab biosimilar with reference ranibizumab in patients with neovascular age-related macular degeneration (nAMD). METHODS: This prospective, randomised, double-blind, two-group, parallel-arm, multicentre, phase 3 comparative study included patients with nAMD ≥ 50 years, randomised (in a 2:1 ratio) in a double-blind manner to receive 0.5 mg (0.05 mL) intravitreal injection of either Sun's ranibizumab or reference ranibizumab in the study eye every 4 weeks until week 16 (total of four doses). RESULTS: Primary endpoint results demonstrated equivalence in the proportion of patients who lost fewer than 15 letters from baseline best-corrected visual acuity (BCVA) to the end of week 16 (99% of patients in Sun's ranibizumab and 100% in reference ranibizumab; p > 0.9999), with the proportional difference (90% confidence interval) at -1% (-2.51, +0.61) lying within a pre-specified equivalence margin. Visual acuity improved by 15 or more letters in 43% of Sun's ranibizumab group and 37% of the reference ranibizumab group (p = 0.4267). The mean increase in BCVA was 15.7 letters in Sun's ranibizumab group and 14.6 letters in the reference ranibizumab group (p < 0.001 within both groups and p = 0.5275 between groups). The mean change in central macular thickness was comparable between groups (p = 0.7946). Anti-ranibizumab antibodies were found in one patient of the reference ranibizumab group, while neutralising antibodies were not found in any patients. Both products were well tolerated. CONCLUSION: Sun's ranibizumab biosimilar is found to be therapeutically equivalent to reference ranibizumab in patients with nAMD. There were no additional safety or immunogenicity concerns. TRIAL REGISTRATION: CTRI/2020/09/027629, registered on 07 September 2020.

Impact of COVID-19 on heart failure hospitalization and outcome in India - A cardiological society of India study (CSI-HF in COVID 19 times study - "The COVID C-HF study").

OBJECTIVES: The presentation and outcomes of acute decompensated heart failure (ADHF) during COVID times (June 2020 to Dec 2020) were compared with the historical control during the same period in 2019. METHODS: Data of 4806 consecutive patients of acute HF admitted in 22 centres in the country were collected during this period. The admission patterns, aetiology, outcomes, prescription of guideline-directed medical therapy (GDMT) and interventions were analysed in this retrospective study. RESULTS: Admissions for acute heart failure during the pandemic period in 2020 decreased by 20% compared to the corresponding six-month period in 2019, with numbers dropping from 2675 to 2131. However, no difference in the epidemiology was seen. The mean age of presentation in 2019 was 61.75 (±13.7) years, and 59.97 (±14.6) years in 2020. There was a significant decrease in the mean age of presentation (p = 0.001). Also. the proportion of male patients decreased significantly from 68.67% to 65.84% (p = 0.037). The in-hospital mortality for acute heart failure did not differ significantly between 2019 and 2020 (4.19% and 4.,97%) respectively (p = 0.19). The proportion of patients with HFrEF did not change in 2020 compared to 2019 (76.82% vs 75.74%, respectively). The average duration of hospital stay was 6.5 days. CONCLUSION: The outcomes of ADHF patients admitted during the Covid pandemic did not differ significantly. The length of hospital stay remained the same. The study highlighted the sub-optimal use of GDMT, though slightly improving over the last few years.

Prospective ARNI vs. ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI): design and baseline characteristics.

AIMS: Patients surviving an acute myocardial infarction (AMI) are at risk of developing symptomatic heart failure (HF) or premature death. We hypothesized that sacubitril/valsartan, effective in the treatment of chronic HF, prevents development of HF and reduces cardiovascular death following high-risk AMI compared to a proven angiotensin-converting enzyme (ACE) inhibitor. This paper describes the study design and baseline characteristics of patients enrolled in the Prospective ARNI vs. ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI) trial. METHODS AND RESULTS: PARADISE-MI, a multinational (41 countries), double-blind, active-controlled trial, randomized patients within 0.5-7 days of presentation with index AMI to sacubitril/valsartan or ramipril. Transient pulmonary congestion and/or left ventricular ejection fraction (LVEF) ≤40% and at least one additional factor augmenting risk of HF or death (age ≥70 years, estimated glomerular filtration rate <60 mL/min/1.73 m2 , diabetes, prior myocardial infarction, atrial fibrillation, LVEF <30%, Killip class ≥III, ST-elevation myocardial infarction without reperfusion) were required for inclusion. PARADISE-MI was event-driven targeting 708 primary endpoints (cardiovascular death, HF hospitalization or outpatient development of HF). Randomization of 5669 patients occurred 4.3 ± 1.8 days from presentation with index AMI. The mean age was 64 ± 12 years, 24% were women. The majority (76%) qualified with ST-segment elevation myocardial infarction; acute percutaneous coronary intervention was performed in 88% and thrombolysis in 6%. LVEF was 37 ± 9% and 58% were in Killip class ≥II. CONCLUSIONS: Baseline therapies in PARADISE-MI reflect advances in contemporary evidence-based care. With enrollment complete PARADISE-MI is poised to determine whether sacubitril/valsartan is more effective than a proven ACE inhibitor in preventing development of HF and cardiovascular death following AMI.

Selection of hardware and cathlab preparation for transradial approach.

The percutaneous transradial approach for cardiac catheterization has been shown to be a safe alternative to femoral artery approach, owing to the favorable anatomical relation of the radial artery to surrounding structures and the dual blood supply to the hand. Selection of guide catheter is elementary but an issue of extreme importance in performance of percutaneous coronary interventions (PCI) and depends on the size of aorta, location of ostia on the aorta, the kind of back-up required and whether the artery arises from a normal origin or anomalously. Currently a variety of guiding catheters are available, each with a unique design and construction, which has vastly improved the technique of transradial PCI. However, much of the cause for procedural failure of the radial approach is associated with the need for higher technical skills and the difficulty in using femoral catheters in the smaller radial artery. There is a learning curve, and many interventionists are uncomfortable attempting a more technically challenging procedure. Nevertheless, it is a procedure that can be taught, and with the innovation of new catheters and devices made specifically for radial approach, it may become easier to adopt for interventionists with a sound knowledge of the anatomical considerations and skill on guiding catheters and hardwares. The current article provides a vivid insight on the various aspects of the learning curve for Transradial approach including proper patient selection, radial access assessment, troubleshooting arm vessel anomalies, guide catheter selection and engagement, augmentation of guide support, and adjunctive device selection.

Efficacy of PercuSurge in acute myocardial infarction patients undergoing revascularization with a special emphasis on procedural time.

AIM: To evaluate the efficacy of the PercuSurge Guardwire(R) Plus Temporary Occlusion and Aspiration System, the actual procedural time involved and long-term follow-up in acute MI patients undergoing primary/rescue percutaneous coronary intervention (PCI). METHODS & RESULTS: It was a single centred, prospective study in 67 prospective AMI patients undergoing PCI. They were divided randomly into two groups depending on whether PercuSurge was used (n=30) or not used (control n=37) during PCI. Final TIMI flow, TMP grade and the time involved in or necessary for various steps of the PCI were recorded. PercuSurge showed significantly greater achievement of TIMI III flow and TMP III grade (p<0.01). Its use was associated with less total procedural time (p<0.05). The time required from guidewire crossing to stent placement; from guidewire crossing to TIMI III flow and from predilatation/stent placement to optimal TIMI flow was significantly reduced with its use (p<0.05 for all). Slow/no-reflow was significantly reduced (p<0.001), thus reducing intracoronary vasodilators and GP IIb/IIIa antagonists requirements. A 2 years' follow-up revealed four deaths in control and one death in PercuSurge group. CONCLUSION: PercuSurge reduced the total procedural time with better and faster optimal TIMI flow and TMP grade in primary/rescue PCI and was associated with less long term events.

Beneficial effects of the addition of fenofibrate to statin therapy in patients with acute coronary syndrome after percutaneous coronary interventions.

OBJECTIVE: To find out whether the addition of fenofibrate to statin monotherapy produced any synergistic or additive beneficial effects in reducing risk factors, especially plasma fibrinogen, in patients with acute coronary syndrome (ACS) requiring percutaneous coronary interventions. METHODS: A randomized, non-blinded, prospective study with parallel group design. One hundred two ACS patients who underwent angioplasty were randomly assigned to atorvastatin (20 mg/day, n=25), simvastatin (40 mg/day, n=27), atorvastatin-fenofibrate (10 mg/day-200 mg/day) combination (n=25) or simvastatin-fenofibrate (20 mg/day-200 mg/day) combination (n=25). The serum lipid profile and plasma fibrinogen were recorded before initiation of therapy and after three months of the respective treatments. RESULTS: All patients already had desirable lipid levels as per the National Cholesterol Education Program - Adult Treatment Panel III guidelines. The addition of fenofibrate to statin monotherapy produced further benefits to the reduction in triglyceride and very low-density lipoprotein levels, and caused an increase in high-density lipoprotein levels. All the treatment groups showed a significant decrease in the plasma fibrinogen levels. Plasma fibrinogen did not correlate with study parameters such as age, body weight, hemo-dynamic characteristics and lipoprotein levels. Statin monotherapy as well as its combination with fenofibrate produced a significant decrease in the fibrinogen levels. CONCLUSIONS: The addition of fenofibrate to statins seems to be beneficial in patients with ACS. Statins decreased plasma fibrinogen significantly, contrary to results from various reports, and the addition of fenofibrate further enhanced this reduction of the novel risk factor fibrinogen.

Microscope-integrated optical coherence tomography: A new surgical tool in vitreoretinal surgery.

Optical coherence tomography (OCT) has revolutionized imaging of ocular structures and various disease conditions. Though it has been used in the clinic for some decades, the OCT has only recently found its way into the operating theater. Early attempts at intraoperative OCT, hand-held and microscope mounted, have already improved our understanding of the surgical pathology and the role it might play in surgical decision-making. The microscope-integrated OCT now allows seamless, high-resolution, real-time imaging of surgical maneuvers from the incision to wound closure. Visualization of instruments and intraoperative tissue manipulation are possible with this in vivo modality and, therefore, help improve the outcome of surgery. In this article, we describe the advantages it offers during various vitreoretinal procedures.

Effect of pioglitazone and its combination with statins in coronary artery disease patients with hyperinsulinemia.

The objective of the study was to demonstrate the effect of pioglitazone and pioglitazone in combination with statin on East Indian patients with hyperinsulinemia and hyperlipidemia. It was a randomized, placebo-controlled, double-blind study with a parallel-group design comprising 83 patients. Patients of either sex with cardiac complications, including hyperlipidemia and (or) diabetes mellitus with or without hyperinsulinemia, were enrolled. Patients over 70 years of age, with renal or hepatic failure, or with severe diabetes mellitus (total glucose >400 mg/dL) were excluded from the study. Enrolled patients were randomly assigned to 4 groups that received placebo, pioglitazone, atorvastatin, or both. Blood samples were collected before and after treatment for analysis of serum glucose, insulin, lipid profile, apolipoprotein (apo) A1, apo B, and fibrinogen. Data were compared with that of patients with normal insulin or hyperinsulinemia. The patients with hyperinsulinemia receiving only pioglitazone showed a significant decrease in insulin levels compared with those with normal insulin levels. These patients also showed a significant increase in HDL levels. However, no significant change was observed in patients treated with both atorvastatin and pioglitazone. Pioglitazone was also found to increase significantly the apo A1 levels in patients with hyperinsulinemia, but there was no significant increase in patients given both atorvastatin and pioglitazone. Our data suggests that pioglitazone should be given preferably to the patients with hyperinsulinemia and statin should not be coadministered.

Intracoronary boluses of adenosine and sodium nitroprusside in combination reverses slow/no-reflow during angioplasty: a clinical scenario of ischemic preconditioning.

No or slow reflow following percutaneous coronary intervention (PCI), despite the presence of a patent epicardial vessel, is a serious complication resulting in increased morbidity and mortality. In the present study, we have evaluated the combination therapy of adenosine and sodium nitroprusside administered as sequential intracoronary (IC) boluses on no-reflow during PCI. Seventy-five high risk acute coronary syndrome patients who underwent PCI with evidence of initial less than TIMI (thrombolysis in myocardial infarction) III flow or developed deterioration in TIMI flow during the procedure were randomized to prophylactic administration of multiple boluses of IC saline solution, adenosine (12 microg/bolus) or the combination of adenosine (12 microg/bolus) and sodium nitroprusside (50 microg/bolus), sequentially. Assessment of TIMI and the TMP (tissue myocardial perfusion) grade was done and major adverse cardiac events (MACE) were assessed at the end of 6 months. Slow or no-reflow was persistent in 70% patients receiving saline solution, 31% patients receiving adenosine, and 4% patient receiving the combination. IC injection with saline solution did not produce improvement in TIMI flow or TMP grade. IC injection with combination resulted in greater improvement of TIMI flow and TMP grade. The crossover of patients with no-reflow in saline solution group or adenosine with combination treatment was associated with reestablishment of TIMI II in 4 and TIMI III in 20 patients. Our data suggest that combination therapy of adenosine and nitroprusside is safe and provides better improvement in coronary flow and MACE as compared with IC adenosine alone in cases of impaired flow during coronary interventions.