Phase III Pivotal comparative clinical trial of intranasal (iNCOVACC) and intramuscular COVID 19 vaccine (Covaxin®).

One of the most preferable characteristics for a COVID-19 vaccine candidate is the ability to reduce transmission and infection of SARS-CoV-2, in addition to disease prevention. Unlike intramuscular vaccines, intranasal COVID-19 vaccines may offer this by generating mucosal immunity. In this open-label, randomised, multicentre, phase 3 clinical trial (CTRI/2022/02/40065; ClinicalTrials.gov: NCT05522335), healthy adults were randomised to receive two doses, 28 days apart, of either intranasal adenoviral vectored SARS-CoV-2 vaccine (BBV154) or licensed intramuscular vaccine, Covaxin®. Between April 16 and June 4, 2022, we enrolled 3160 subjects of whom, 2971 received 2 doses of BBV154 and 161 received Covaxin. On Day 42, 14 days after the second dose, BBV154 induced significant serum neutralization antibody titers against the ancestral (Wuhan) virus, which met the pre-defined superiority criterion for BBV154 over Covaxin®. Further, both vaccines showed cross protection against Omicron BA.5 variant. Salivary IgA titers were found to be higher in BBV154. In addition, extensive evaluation of T cell immunity revealed comparable responses in both cohorts due to prior infection. However, BBV154 showed significantly more ancestral specific IgA-secreting plasmablasts, post vaccination, whereas Covaxin recipients showed significant Omicron specific IgA-secreting plasmablasts only at day 42. Both vaccines were well tolerated. Overall reported solicited reactions were 6.9% and 25.5% and unsolicited reactions were 1.2% and 3.1% in BBV154 and Covaxin® participants respectively.

Preclinical evaluation of safety and immunogenicity of a primary series intranasal COVID-19 vaccine candidate (BBV154) and humoral immunogenicity evaluation of a heterologous prime-boost strategy with COVAXIN (BBV152).

Most if not all vaccine candidates developed to combat COVID-19 due to SARS-CoV-2 infection are administered parenterally. As SARS-CoV-2 is transmitted through infectious respiratory fluids, vaccine-induced mucosal immunity could provide an important contribution to control this pandemic. ChAd-SARS-CoV-2-S (BBV154), a replication-defective chimpanzee adenovirus (ChAd)-vectored intranasal (IN) COVID-19 vaccine candidate, encodes a prefusion-stabilized version of the SARS-CoV-2 spike protein containing two proline substitutions in the S2 subunit. We performed preclinical evaluations of BBV154 in mice, rats, hamsters and rabbits. Repeated dose toxicity studies presented excellent safety profiles in terms of pathology and biochemical analysis. IN administration of BBV154 elicited robust mucosal and systemic humoral immune responses coupled with Th1 cell-mediated immune responses. BBV154 IN vaccination also elicited potent variant (omicron) cross neutralization antibodies. Assessment of anti-vector (ChAd36) neutralizing antibodies following repeated doses of BBV154 IN administration showed insignificant titers of ChAd36 neutralizing antibodies. However, the immune sera derived from the same animals displayed significantly higher levels of SARS-CoV-2 virus neutralization (p<0.003). We also evaluated the safety and immunogenicity of heterologous prime-boost vaccination with intramuscular (IM) COVAXIN-prime followed by BBV154 IN administration. COVAXIN priming followed by BBV154 IN-booster showed an acceptable reactogenicity profile comparable to the homologous COVAXIN/COVAXIN or BBV154/BBV154 vaccination model. Heterologous vaccination of COVAXIN-prime and BBV154 booster also elicited superior (p<0.005) and cross variant (omicron) protective immune responses (p<0.013) compared with the homologous COVAXIN/COVAXIN schedule. BBV154 has successfully completed both homologous and heterologous combination schedules of human phase 3 clinical trials and received the restricted emergency use approval (in those aged above 18 years) from the Drugs Controller General of India (DCGI).

Is cold blood cardioplegia absolutely superior to cold crystalloid cardioplegia in aortic valve surgery?

BACKGROUND: Experimental evidence suggests that blood cardioplegia (BCP) may be superior to cold crystalloid cardioplegia (CCP) for myocardial protection. However, robust clinical data are lacking. We compared postoperative outcome of patients undergoing aortic valve replacement (AVR) using cold anterograde-retrograde intermittent BCP versus anterograde (CCP). METHODS: Adult consecutive isolated AVR performed between April 2006 and February 2011 at the Royal Infirmary Hospital of Edinburgh were retrospectively analyzed. The use of anterograde CCP was compared with that of intermittent anterograde-retrograde cold BCP. End points were intra-operative mortality, 30-day hospital re-admission, need for RBC or platelet transfusion, mechanical ventilation time and renal failure. RESULTS: Of total 774 cases analyzed, 592 cases of BCP and 182 cases of CCP were identified. Demographics did not differ between groups (mean age: 67±12 years in CCP and 69±12 years in BCP). Groups (BCP vs. CCP) were indistinguishable (P>0.05, not significant) based on: average aortic cross clamp time 77.01±14.47 vs. 75.78±18.78 minutes, cardiopulmonary bypass time 104.07±43.70 vs. 100.34±25.90 minutes, surgery time 190.53±61.80 vs. 204.04±51.09 minutes and postoperative total blood consumption 1.38±2.11 vs. 1.61±2.4 units. The percentage of patients who required platelets' transfusion was similar: 12.8% BCP and 18.7% CCP (Fisher's exact test, P=0.053). Prevalence of respiratory failure was lower in BCP than in CCP: 2.6% vs. 6.3% (P=0.028). Admission time (days) at ICU was 3.63± 21.90 in BCP and 3.07±8.04 in CCP (not significant). Intra-hospital mortality, 30-day hospital re-admission, renal failure, sepsis, wound healing and stroke did not differ between groups. CONCLUSIONS: BCP was strictly not superior to CCP in every aspect. In particular it was definitely not superior in terms of postoperative ventricular function. Our results question the absolute superiority of BCP over CCP in terms of hard outcomes. Likelihood of serious complications should be considered to improve risk profile of patients before choosing a cardioplegic solution.

Clinical evaluation of Vatari guggulu, Maharasnadi kwatha and Narayan taila in the management of osteoarthritis knee.

BACKGROUND: In present era, pharmacological, bio-chemical and surgical interventions are not success remedy for Osteoarthritis (OA). Ayurveda and other complementary medicine have medication for OA. OBJECTIVES: The main aim of the study was to assess the efficacy and safety of therapeutic combination of Vatari guggulu along with Maharasnadi kwatha and Narayan taila with gentle massage for 15 min daily up to 12 weeks on affected knee joint pain assessed on Visual analogue scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). MATERIALS AND METHODS: It was an open label, multicentre, prospective, clinical study conducted on 142 patients of OA Knee. Vatari guggulu 500 mg thrice in a day along with Maharasnadi kwatha 20 ml with equal amount of water twice daily and Narayan taila 20 ml twice in a day for external application with gentle massage for 15 min up to 12 weeks were used to all the study participants. RESULTS: VAS, WOMAC score and clinical symptoms were reduced significantly from baseline to end of the treatment (P < 0.001). CONCLUSIONS: The study provides good evidence in support of the efficacy and safety of the Vatari guggulu along with Maharasnadi kwatha and Narayan taila in the management of Osteoarthritis knee.

End stage renal disease-induced hypercalcemia may promote aortic valve calcification via Annexin VI enrichment of valve interstitial cell derived-matrix vesicles.

Patients with end-stage renal disease (ESRD) have elevated circulating calcium (Ca) and phosphate (Pi), and exhibit accelerated progression of calcific aortic valve disease (CAVD). We hypothesized that matrix vesicles (MVs) initiate the calcification process in CAVD. Ca induced rat valve interstitial cells (VICs) calcification at 4.5 mM (16.4-fold; p < 0.05) whereas Pi treatment alone had no effect. Ca (2.7 mM) and Pi (2.5 mM) synergistically induced calcium deposition (10.8-fold; p < 0.001) in VICs. Ca treatment increased the mRNA of the osteogenic markers Msx2, Runx2, and Alpl (p < 0.01). MVs were harvested by ultracentrifugation from VICs cultured with control or calcification media (containing 2.7 mM Ca and 2.5 mM Pi) for 16 hr. Proteomics analysis revealed the marked enrichment of exosomal proteins, including CD9, CD63, LAMP-1, and LAMP-2 and a concomitant up-regulation of the Annexin family of calcium-binding proteins. Of particular note Annexin VI was shown to be enriched in calcifying VIC-derived MVs (51.9-fold; p < 0.05). Through bioinformatic analysis using Ingenuity Pathway Analysis (IPA), the up-regulation of canonical signaling pathways relevant to cardiovascular function were identified in calcifying VIC-derived MVs, including aldosterone, Rho kinase, and metal binding. Further studies using human calcified valve tissue revealed the co-localization of Annexin VI with areas of MVs in the extracellular matrix by transmission electron microscopy (TEM). Together these findings highlight a critical role for VIC-derived MVs in CAVD. Furthermore, we identify calcium as a key driver of aortic valve calcification, which may directly underpin the increased susceptibility of ESRD patients to accelerated development of CAVD.

Advanced mechanical circulatory support for post-cardiotomy cardiogenic shock: a 20-year outcome analysis in a non-transplant unit.

BACKGROUND: Post-cardiotomy cardiogenic shock (PCCS) has an incidence of 2-6 % after routine adult cardiac surgery. 0.5-1.5 % are refractory to inotropic and intra-aortic balloon pump (IABP) support. Advanced mechanical circulatory support (AMCS) can be used to salvage carefully selected number of such patients. High costs and major complication rates have lead to centralization and limited funding for such devices in the UK. We have looked the outcomes of such devices in a non-transplant, intermediate-size adult cardiothoracic surgery unit. METHODS: Inclusion criteria included any adult patient who had received salvage veno-arterial extra-corporeal membrane oxygenation (V-A ECMO) or a ventricular assist device (VAD) for PCCS refractory to IABP and inotropic support following cardiac surgery from April 1995-April 2015. RESULTS: Sixteen patients met the inclusion criteria. Age range was 34-83 years (median 71). There was a male predominance of 12 (75 %). Overall, 15 (94 %) had received ECMO of which, 10 (67 %) had received central ECMO and 5 (33 %) had received peripheral ECMO. One patient (6 %) had a VAD. The most common complication was haemorrhage. Stroke, femoral artery pseudo-aneurysm, sepsis and renal failure also occurred. Thirty-day survival was 37.5 %. Survival rate to hospital discharge was 31.2 %. All survivors had NYHA class I-II at 24 months follow-up. CONCLUSIONS: Our survival rate is similar to that reported in several previous studies. However, the use of AMCS for refractory PCCS is associated with serious complications. The survivors in our cohort appear to maintain an acceptable quality of life.

How to make an aortic root replacement simulator at home.

There is a paucity of low-fidelity and cost-efficient simulators for training cardiac surgeons in the aspects of aortic root/valve replacement. In this study we addressed this training challenge by creating a low-fidelity, low-cost but, at the same time, anatomically realistic aortic root replacement simulator for training purposes. We used readily available, low cost materials such as lint roller tubes, foam sheet, press-and-seal bags, glue, plywood sheet, heat-shrink sleeving tubes and condoms as the basic material to create a low-fidelity, aortic root, training simulator. We constructed a multi-purpose, anatomically realistic aortic root simulator using the above materials, both time- and cost-efficiently, using the minimum of surgical equipment. This simulator is easy to construct and enables self-training in major techniques of aortic root replacement as well as in stentless valve implantation for trainees in cardiac surgery.

Development and preclinical testing of HNVAC, a cell culture-based H1N1 pandemic influenza vaccine from India.

Several limitations of the use of embryonated eggs and the threat of pandemics have highlighted the need for other platforms for the production of influenza vaccines. We report the indigenous development and pre-clinical testing of an MDCK-based H1N1 pandemic influenza vaccine HNVAC from India. The cell bank and virus seed were characterized extensively. The cells were characterized by PCR, electron microscopy, and karyotyping, and found to be of female canine epithelial origin. The virus was confirmed by neutralization, haemagglutination inhibition, neuraminidase inhibition, and PCR and nucleotide sequencing. Adventitious agent testing was performed by both in vitro and in vivo studies. The in vitro studies included culturing, haemadsorption, haemagglutination, PCR and RT-PCR, whereas in vivo studies included passage in embryonated eggs and in laboratory animals. Both cell bank and virus seed were free of adventitious agents. MDCK cell lysates as well as cellular DNA did not produce tumours in newborn or adult laboratory animals. The bioprocess parameters were standardized to recover antigen with minimal levels of process-related impurities. The vaccine bulk was tested for the presence of specific antigen, and quantified by single radial immunodiffusion. Finally, non-adjuvanted and aluminium hydroxide adjuvanted vaccine formulations were found to be safe in preclinical toxicity studies in mice, rats, guinea pigs and rabbits, and immunogenic in mice and rabbits. This is the first and only cell culture-based influenza vaccine platform developed in any developing country.

Transcatheter aortic valve implantation: from fantasy to reality.

Increased life expectancy has led to the presentation of more complicated patients in old age for the replacement of the aortic valve. The emergence of Transcatheter Aortic Valve Implantation (TAVI) was considered as a significant breakthrough in the management of symptomatic, moribund patients suffering from aortic valve stenosis who had been rejected for surgical intervention. A novel technology often has a long journey from the point at which it is created to its every-day-use. It is now obvious that TAVI practice in multiple institutes around the world has gone beyond the evidence. Serious concerns have been raised questioning the current TAVI practice. Analysis of future TAVI use may assist clinicians and healthcare managers to understand and deploy this technology in accordance with the evidence.

Is it safe to cut pacing wires flush with the skin instead of removing them?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether it is safe to cut the temporary epicardial pacing wires (TEPWs) flush with the patient's skin surface prior to discharge. Altogether 105 relevant papers were identified of which 13 case reports represented the best evidence to answer the question. The author, journal, date, country of publication, complications, the culprit TEPW and relevant outcomes are tabulated. All case reports demonstrated a wide spectrum of complications. Complications from a retained TEPW mainly arise after a long dormant period. A recent case report has demonstrated the herniation of intra-abdominal contents through a diaphragmatic defect created by the abandoned epicardial pacing wires after a few decades. In multiple case reports, the migration of TEPW was the culprit of serious complications. In two case reports, the TEPWs attached to the right chambers of the heart had migrated to the pulmonary artery via the right atrium and then the right ventricle. In one case report, a similar migration of the right ventricular TEPW to the right ventricular outflow track was observed. The TEPW migration was not limited to the right side of the heart, as in one case report the right atrial TEPW had migrated to the right carotid artery via the ascending aorta. A distant extravascular migration of TEPWs to the skin surface and intraperitoneal and pelvic cavities has also been reported. Retained TEPWs have also been reported to inflict complications locally. One case report has shown a large right-sided para-cardiac mass caused by a right atrial TEPW. In two other case reports, the bronchocutaneous fistula, lobar consolidation and bronchiectasis were the manifestations of a retained TEPW. We conclude that the retention of TEPW after cardiac surgery is not necessarily safe and may cause severe complications. We recommend that TEPWs should be completely removed when possible. If TEPWs are retained, this should be appropriately documented and the surgeon should be mindful of this when the patient presents with complications postoperatively.

Prevalence of areca nut chewing in the middle school-going children of Indore, India.

OBJECTIVES: To assess areca nut chewing habit among middle school-aged children in Indore, India. Areca nut is chewed by itself, and in various scented preparations. It is associated with carcinogenesis, foreign body aspiration in children, and oral submucous fibrosis and may aggravate asthma. MATERIALS AND METHODS: A retrospective collection of data to evaluate the prevalence of areca nut chewing among 3896 children was done. A simple random sampling was done. Children of both sexes were included in this study. RESULTS: 27.06% of the school-going children (1054/3896) had areca nut chewing habit. More boys chewed areca nut than girls (2:1). 45.42% of school going children of rural area pander to areca nut chewing habit, whereas in urban area 20.09% children are indulged. Government school children are more involved in areca nut chewing habit. 81.02% of the children used sweetened and flavoured form of areca nut. The majority of the users were not aware of harmful effects that the use of areca nut might be harmful for health CONCLUSION: To diminish the use of areca nut, the Indian Government should consider limiting trade, advertising, and actively communicating its health risks to the public and should deem heavy taxes on it.

Free-floating giant left atrial ball thrombus with aortic valve disease--a rare entity and a near miss.

Large left atrial mural thrombi in the absence of mitral valve stenosis have been reported rarely in the literature. It is even rarer without history of atrial fibrillation (AF). These masses can cause systemic embolization and sudden circulatory collapse when they obstruct the mitral valve. We are presenting a case of giant, free floating ball thrombus, detected after aortic valve replacement for mixed aortic valve disease. It was found immediately before separation from cardiopulmonary bypass by transoesophageal echocardiography and was successfully removed. A ball thrombus without mitral valve disease and AF with aortic valve disease is not yet reported in the literature.

Pectoral hematoma mimicking a hemothorax in an octogenarian following aortic valve replacement--a near miss.

Open-heart surgery is associated with higher risk of complications in the octogenarians, specifically because of frailty of tissues and delayed healing secondary to various factors. Here, we present a near miss, where an 86-year-old lady underwent tissue aortic valve surgery complicated with formation of a large retro-pectoral hematoma, which on the initial chest X-ray mimicked a left hemothorax. This was successfully explored surgically and drained promptly within 8 h of the primary surgery. This is illustrated with chest radiographs. The case highlights one of the rare complications that we encountered in cardiac surgery of the elderly.

Mitral valve injury by cardiotomy suction during aortic valve replacement--a near miss.

Mitral valve injury due to cardiotomy suckers during aortic valve surgery has never been reported. We highlight the possibility of such injury experienced in our unit. We also discuss its preventive measures.

Genotype-phenotype correlations for SLC26A4-related deafness.

Pendred syndrome (PS) and non-syndromic enlarged vestibular aqueduct (EVA) are two recessive disorders characterized by the association of sensorineural hearing loss (SNHL) with inner ear malformations that range from isolated EVA to Mondini Dysplasia, a complex malformation that includes a cochlear dysplasia and EVA. Mutations in the SLC26A4 gene, coding for the protein pendrin, have been implicated in the pathophysiology of both disorders. In order to determine whether SLC26A4 genotypes can be correlated to the complexity and severity of the phenotypes, we ascertained 1,506 deaf patients. Inner ear abnormalities were present in 474 patients (32%). Mutation screening of SLC26A4 detected two mutations in 16% of patients, one mutation in 19% of patients and zero mutation in 65% of patients. When the distribution of SLC26A4 genotypes was compared across phenotypes, a statistically significant difference was found between PS patients and non-syndromic EVA-Mondini patients (P = 0.005), as well as between EVA patients and Mondini patients (P = 0.0003). There was a correlation between phenotypic complexity of inner ear malformations and genetic heterogeneity--PS patients have the most severe phenotype and the most homogeneous etiology while EVA patients have the least severe phenotype and the most heterogeneous etiology. For all patients, variability in the degree of hearing loss is seen across genotypes implicating other genetic and/or environmental factors in the pathogenesis of the PS-Mondini-EVA disease spectrum.

Laparoscopic-assisted transumbilical ovarian cystectomy in a neonate.

The occurrence of ovarian cysts in a neonate is common, but the management of the same is contentious. We present a case of a prenatally diagnosed complex ovarian cyst in a neonate, which was successfully treated by a novel laparoscopic technique. The literature was reviewed and the diagnosis, treatment options, and controversies in the management are discussed, highlighting the role of preservation of the ovary via the laparoscopic-assisted transumbilical ovarian cystectomy procedure.

Septic arthritis of the manubriosternal joint.

Pyarthrosis of the manubriosternal joint is exceedingly rare. Its rarity defies an early diagnosis, and other causes of chest pain would normally be ruled out first. We describe a patient with a short history of chest pain, pyrexia, and raised inflammatory markers. A destroyed manubriosternal joint with a large abscess was found during surgical exploration. This case illustrates an unusually rapid development of septic arthritis involving a fibrocartilaginous joint in an otherwise healthy young man. Nine other cases have been described in the literature and are reviewed. Early diagnosis followed by adequate surgical drainage and antibiotic therapy led to a good outcome.

Neonatal intestinal volvulus due to a persistent right vitelline artery.

We report a case of neonatal intestinal volvulus around a persistent right vitelline artery, presenting as an aberrant parieto-mesenteric band on exploratory laparotomy. To our knowledge, this is the first case report in the English literature of a persistent right vitelline artery causing axial intestinal volvulus in a neonate. A review of the literature and the embryopathogenesis is discussed, as well as the importance of emergent diagnoses of such lesions.

Massive CO2 embolism in cardiopulmonary bypass circuit - a near miss.

OBJECTIVES: We report a case of massive air embolism in the cardiopulmonary bypass (CPB) circuit to highlight the principle of its immediate management and its preventive measures. METHODS: The air embolism was caused by the accidental connection of carbon dioxide (CO(2)) supply to the monitoring arm of the retrograde cardioplegia delivery system. The CPB ceased, resulting in cardiac arrest requiring immediate internal cardiac massage. Cerebral protective measures were also instituted instantaneously and the air embolism was purged from the CPB circuit. The cause of air embolism was identified after high initial arterial CO(2) concentration was detected in the blood gas analysis. The CO(2) supply was disconnected, and CPB was restarted. Spontaneous cardiac activities resumed shortly after, and the operation was completed uneventfully. RESULTS: The patient had no immediate post-operative sequel and remained well at 6 weeks follow-up. CONCLUSION: Massive air embolism in cardiopulmonary bypass (CPB) circuit is a life-threatening emergency. Immediate cerebral protective manoeuvres and rectification of the cause of air embolism are vital for favourable outcome. However, high degree of vigilance and cooperation amongst all teams involved are paramount to prevent its occurrence in the first place.