Phase II/III trial of hyperimmune anti-COVID-19 intravenous immunoglobulin (C-IVIG) therapy in severe COVID-19 patients: study protocol for a randomized controlled trial.

BACKGROUND: COVID-19 poses a global health challenge with more than 325 million cumulative cases and above 5 million cumulative deaths reported till January 17, 2022, by the World Health Organization. Several potential treatments to treat COVID-19 are under clinical trials including antivirals, steroids, immunomodulators, non-specific IVIG, monoclonal antibodies, and passive immunization through convalescent plasma. The need to produce anti-COVID-19 IVIG therapy must be continued, alongside the current treatment modalities, considering the virus is still mutating into variants of concern. In this context, as the present study will exploit pooled diversified convalescent plasma collected from recovered COVID-19 patients, the proposed hyperimmune Anti-COVID-19 intravenous immunoglobulin (C-IVIG) therapy would be able to counter new infectious COVID-19 variants by neutralizing the virus particles. After the successful outcome of the phase I/II clinical trial of C-IVIG, the current study aims to further evaluate the safety and efficacy of single low dose C-IVIG in severe COVID-19 patients for its phase II/III clinical trial. METHODS: This is a phase II/III, adaptive, multi-center, single-blinded, randomized controlled superiority trial of SARS-CoV-2 specific polyclonal IVIG (C-IVIG). Patients fulfilling the eligibility criteria will be block-randomized using a sealed envelope system to receive either 0.15 g/Kg C-IVIG with standard of care (SOC) or standard of care alone in 2:1 ratio. The patients will be followed-up for 28 days to assess the primary and secondary outcomes. DISCUSSION: This is a phase II/III clinical trial evaluating safety and efficacy of hyperimmune anti-COVID-19 intravenous immunoglobulin (C-IVIG) in severe COVID-19 patients. This study will provide clinical evidence to use C-IVIG as one of the first-line therapeutic options for severe COVID-19 patients. TRIAL REGISTRATION: Registered at clinicaltrial.gov with NCT number NCT04891172 on May 18, 2021.

Immunohistochemical Expression of MMP-9 and E-Cadherin in subtypes of Ameloblastoma.

BACKGROUND & OBJECTIVE: Ameloblastomas have been analyzed histologically for diagnostics and its sub-classification; however, the analysis carried out so far does not provide any authentic evidence regarding prognosis of Ameloblastoma. Subject categorization is still a topic of debate. The purpose of this study was to determine the immuno-expression of markers such as MMP-9 and E-Cadherin in different sub-types of ameloblastoma and establish their correlation with histological variants. METHODS: Analytical study of 71 cases of ameloblastoma was conducted in AFIP Rawalpindi, between January to June, 2019. Samples were taken from different intraoral sites including the patients with tumor of ameloblast. The tumor was sub classified histologically on the basis of WHO classification. 'Chi Square' Test was applied to find the association of MMP-9 and E-Cadherin with histological variants of ameloblastoma. P-value ≤ 0.05 were found statistically significant. RESULTS: On histopathological sub-classification, 52.1% were diagnosed as follicular type, 23.9% were plexiform type, 14.1% were Acanthomatous type and 9.9% were of unicystic ameloblastoma. 80% of the total Acanthomatous type and 59% of the total plexiform had strong immuno-expression, which was significantly different from follicular type MMP-9 (p ≤ 0.05). All cases of unicystic ameloblastoma and 67.6% of follicular type showed strong immuno-expression significantly different from 20% of Acanthomatous type and 59% of plexiform type E-Cadherin (p ≥ 0.05). On the other hand, when statistical analysis was carried out, an inverse relation between MMP-9 and E-cadherin was observed. CONCLUSION: The effect of MMP-9 and E-cadherin in ameloblastoma is aggressive in nature and effectiveness was seen in subtypes of ameloblastoma.

Words are just Noise, let your Actions Speak: Impact of Nonverbal Communication on Undergraduate Medical Education.

OBJECTIVE: To explore student's perceptions regarding impact of kinesics (facial expressions, gestures, head movements and postures) on undergraduate medical education. METHODS: A qualitative exploratory online survey was conducted from July-Sept 2020 among purposively chosen final year BDS students (n=150) of three dental colleges of Islamabad during COVID-19 lockdown phase. Semi-structured survey questions were validated and piloted before execution. Thematic analysis was performed, and consensus was built among all authors regarding findings, hence ensuring analytical triangulation. RESULTS: Response rate was 46% (69/150). Twenty sub-themes emerged under three domains of kinesics. Participants told that 'neutral expressions' frequently used by teachers create 'boring learning environment' and 'hesitation among students to ask questions.' A smile of teacher imparts 'new degree of interest in the subject' and gives 'freedom of expression' to the students. On contrary, anger 'demotivate' students, instills 'fear among them', make them anxious therefore, they are 'unable to understand lectures' which ultimately leads to 'loss interest in the subject'. Use of gestures by teachers creates 'enjoyable teaching-learning process' but movements such as clearing throat or shaky legs produce 'constant split-second interruption'. Moreover, standing posture of teachers bring 'interest and alertness among students'. CONCLUSION: Nonverbal communication can have positive or negative impact on undergraduate medical education. Therefore, teachers may start lecture with a smile and anger should be avoided to produce friendly and healthy learning environment. Faculty training is required for the effective use of nonverbal communication strategies to create an optimal learning environment for the students.