Impact of Method of Preparation of Amorphous Solid Dispersions on Mechanical Properties: Comparison of Coprecipitation and Spray Drying

Usage of the amorphous phase of compounds has become the method of choice to overcome oral bioavailability problems related to poor solubility. Due to the unstable nature of glasses, it is clear that the method of preparation of the amorphous glass will have an impact on physical/chemical stability and in turn in vivo performance. The method of preparation can also have a profound impact on the mechanical properties of the amorphous phase. We have explored the impact of preparation method on the mechanical properties of an amorphous solid dispersion using a development compound, GDC-0810. Three methods were used to generate amorphous solid dispersions (ASDs) of 50% GDC-0810 with hydroxypropyl methylcellulose acetate succinate: (1) spray drying, (2) coprecipitation using overhead mixing, and (3) coprecipitation using resonant acoustic mixing. All 3 methods were found to generate ASDs with good phase mixing and similar glass transition temperatures. Coprecipitated ASD powders (overhead mixing and resonant acoustic mixing) demonstrated superior tabletability and flow properties when compared to the spray drying powder. Careful choice of manufacturing process can be used to tune material properties of ASDs to make them more amenable for downstream operations like tableting. Acoustic mixing has been demonstrated as a scalable new method to make ASDs through coprecipitation.     

Gynaecomastia correction: A review of our experience

Introduction:

Gynaecomastia is a common problem in the male population with a reported prevalence of up to 36%. Various treatment techniques have been described but none have gained universal acceptance. We reviewed all gynaecomastia patients operated on by one consultant over a 7-year period to assess the morbidity and complication rates associated with the procedure.

Materials and Methods:

Clinical notes and outpatient records of all patients who underwent gynaecomastia correction at University Hospital North Staffordshire between 01/10/2001 to 01/10/2009 were retrospectively reviewed. A modified version of the Breast Evaluation Questionnaire was used to assess patients satisfaction with the procedure.

Results:

Twenty-nine patients and a total of 53 breasts were operated on during the study period. Patients underwent either liposuction alone (6 breasts - 11.3%), excision alone (37 breasts - 69.8%) or both excision and liposuction (10 breasts - 18.9%). Twelve operated breasts (22.6%) experienced some form of complication. Minor complications included seroma (2 patients), superficial wound dehiscence (2 patients) and minor bleeding not requiring theatre (3 patients). Two patients developed haematomas requiring evacuation in theatre. No cases of wound infection, major wound dehiscence or revision surgery were encountered. Twenty-six patients (89.7%) returned the patient satisfaction questionnaire. Patients scored an average 4.12 with regards comfort of their chest in different settings, 3.98 with regards chest appearance in different settings, and 4.22 with regards satisfaction levels for themselves and their partner/family. Overall complication rate was 22.6%. Grade III patients experienced the highest complication rate (35.7%), followed by grade II (22.7%) and grade I (17.6%). Overall complication rates among the excision only group was the highest (29.8%) followed by the liposuction only group (16.7%) and the liposuction and excision group (10.0%). There were high satisfaction rates amongst both patients and surgeon. Eleven patients (37.9%) had their outcome classified as ‘excellent’ by the operating surgeon, 16 patients (55.2%) as ‘good’, 1 (3.4%) as ‘satisfactory’ and 1(3.4%) as ‘poor’.

Conclusion:

Gynaecomastia is a complex condition which poses a significant challenge to the plastic surgeon. Despite the possible complications our case series demonstrates that outcomes of operative correction can be favourable and yield high levels of satisfaction from both patient and surgeon.KEY WORDS: Plastic Surgery, University Hospital North Staffordshire, Correction, gynaecomastia, surgery     

Validation of the Maryland Aggregate Pathology Index (MAPI), a pre‐implantation scoring system that predicts graft outcome

Predicting graft outcome after renal transplantation based on donor histological features has remained elusive and is subject to institutional variability. We have shown in a retrospective study that the Maryland Aggregate Pathology Index score reliably predicts graft outcome. We sought to validate the scoring system in our center and a second transplant center. We analyzed 140 deceased donor kidneys pre‐implantation biopsies from center 1 and 65 from center 2. The patients had a mean follow‐up of 695 ± 424 and 656 ± 305 d respectively. Although MAPI scores were similar, there were significant differences in donor and recipient parameters between both centers. Despite this, MAPI was predictive of graft outcome for both centers by Cox univariate, multivariate and time dependent ROC analysis. For center 1 and 2, three yr graft survival within each MAPI group was statistically equivalent. The three‐yr graft survival at center 1 for low, intermediate, and high MAPI groups were 84.3%, 56.5%, and 50.0%, respectively, p ≤ 0.0001, and at center 2 were 83.3%, 33.3%, and 33.3%, p = 0.006. MAPI, which is based on a pre‐implantation biopsy, demonstrated similar predictive and outcome results from both centers. As expanded criteria donors (ECD) criteria have redefined marginal kidneys, MAPI has the potential to further define ECD kidneys, increase utilization, and ultimately improve outcomes.     

Breast vibro-acoustography: initial experience in benign lesions

Background

Functional magnetic resonance imaging (fMRI) analysis is commonly done with cross-correlation analysis (CCA) and the General Linear Model (GLM). Both CCA and GLM techniques, however, typically perform calculations on a per-voxel basis and do not consider relationships neighboring voxels may have. Clustered voxel analyses have then been developed to improve fMRI signal detections by taking advantages of relationships of neighboring voxels. Mean-shift clustering (MSC) is another technique which takes into account properties of neighboring voxels and can be considered for enhancing fMRI activation detection.

Methods

This study examines the adoption of MSC to fMRI analysis. MSC was applied to a Statistical Parameter Image generated with the CCA technique on both simulated and real fMRI data. The MSC technique was then compared with CCA and CCA plus cluster analysis. A range of kernel sizes were used to examine how the technique behaves.

Results

Receiver Operating Characteristic curves shows an improvement over CCA and Cluster analysis. False positive rates are lower with the proposed technique. MSC allows the use of a low intensity threshold and also does not require the use of a cluster size threshold, which improves detection of weak activations and highly focused activations.

Conclusion

The proposed technique shows improved activation detection for both simulated and real Blood Oxygen Level Dependent fMRI data. More detailed studies are required to further develop the proposed technique.     

Total Alloplastic Temporomandibular Joint Reconstruction for Management of TMJ Ankylosis

Introduction

Temporomandibular joint (TMJ) ankylosis involves the fusion of the mandibular condyle to the glenoid fossa, the skull base. The dilemma with regards to treatment planning whether distraction is done before gap arthroplasty or as a simultaneous procedure or after gap arthroplasty is still a controversy. In an attempt to carry out both the procedures simultaneously there is loss of vector control of the distal segment and the risk of pseudoarthrosis at the osteotomy site. This combined problem could be overcome by the use of total alloplastic joint prosthesis which offers a firm posterior stop for the proximal segment and negates aggressive physiotherapy.

Material and methods

The reference literatures were retrieved from Pub Med and Science Direct database. Three case reports of bilateral recurrent TMJ ankylosis successfully treated with custom made total TMJ by the authors are illustrated.

Conclusion

The purpose of this article is to review the world literature on various alloplastic joints available for TMJ reconstruction and to introduce our indigenous total joint prosthesis in the management of recurrent ankylosis.     

T2R bitter taste receptors regulate apoptosis and may be associated with survival in head and neck squamous cell carcinoma

Better management of head and neck squamous cell carcinomas (HNSCCs) requires a clearer understanding of tumor biology and disease risk. Bitter taste receptors (T2Rs) have been studied in several cancers, including thyroid, salivary, and GI, but their role in HNSCC has not been explored. We found that HNSCC patient samples and cell lines expressed functional T2Rs on both the cell and nuclear membranes. Bitter compounds, including bacterial metabolites, activated T2R‐mediated nuclear Ca²⁺ responses leading to mitochondrial depolarization, caspase activation, and ultimately apoptosis. Buffering nuclear Ca²⁺ elevation blocked caspase activation. Furthermore, increased expression of T2Rs in HNSCCs from The Cancer Genome Atlas is associated with improved overall survival. This work suggests that T2Rs are potential biomarkers to predict outcomes and guide treatment selection, may be leveraged as therapeutic targets to stimulate tumor apoptosis, and may mediate tumor‐microbiome crosstalk in HNSCC.     

Detection of SARS-CoV-2 RNA in a conjunctival swab sample in real-time-polymerase chain reaction positive COVID-19 patients and its association with comorbidity and severity at a designated COVID-19 hospital in Central India

Purpose:To evaluate the presence of SARS-CoV-2 RNA in the conjunctival swab sample of positive confirmed COVID-19 patients and to find out its association with comorbidity and severity of COVID-19 disease.Methods:We conducted an observational cross-sectional study at a dedicated tertiary COVID-19 hospital in central India for a period of 8 weeks from February 2021to March 2021. We included patients who tested positive for SARS-CoV-2 RNA through nasopharyngeal swab and were above 18 years of age. Swab samples have been collected within 48 h of admission. Conjunctival swab was taken from the lower fornix of both eyes and sent to microbiology laboratory for real-time- polymerase chain reaction (RT-PCR).Results:Out of 150 patients, conjunctival swab RT-PCR was positive in five patients (3.33%). Two patients had conjunctival manifestations in the form of conjunctivitis but conjunctival swab RT-PCR was negative in those patients. Among the RT-PCR positive patients, two (40%) were from mild, one (20%) was from moderate, and two (40%) were from severe category. No association could be established between conjunctival swab RT-PCR positivity and severity of the disease or associated comorbidity.Conclusion:Our study provides evidence that SARS-CoV-2 RNA could be detected in conjunctival secretions, and though the risk is relatively low, the eye may act as source of transmission. Extra caution should be taken by healthcare workers, and use of proper precautions like face shields and goggles should be encouraged.     

Spontaneous rupture of a coronary artery fistula presenting with post-exertional syncope and haemopericardium

An 8-year-old with a known diagnosis of an asymptomatic coronary artery fistula (CAF) presented with exertional syncope and haemopericardium due to contained rupture of CAF. A transcatheter closure was attempted, but the fistula ruptured again prompting emergency surgical repair. Spontaneous rupture is a catastrophic complication of CAF and warrants a high index of suspicion, timely diagnosis and team management.     

Evaluation of an interactive virtual surgical rotation during the COVID‐19 pandemic

ObjectiveTo evaluate medical student and attending surgeon experiences with a novel interactive virtual Otolaryngology ‐ Head and Neck Surgery (OHNS) medical student elective during the COVID‐19 pandemic.Study DesignA virtual OHNS elective was created, with three components: (1) interactive virtual operating room (OR) experience using live‐stream video‐conferencing, (2) telehealth clinic, (3) virtual didactics.SettingOHNS Department at the University of Pennsylvania (May 2020 to June 2020).MethodsSix medical students from the University of Pennsylvania; five attending otolaryngologists. Two surveys were designed and distributed to participating medical students and attending surgeons. Surveys included 5‐point Likert scale items, with 1 indicating “not at all” and 5 indicating “very much so”.ResultsResponse rate was 100% for both surveys. Students on average rated the educational value of the telehealth experience as 4.2 ± 1.2, and the virtual OR experience as 4.0 ± 0.6. Most students (n = 5, 83%) indicated that they had enough exposure to faculty they met on this rotation to ask for a letter of recommendation (LOR) for residency if needed, while attending surgeons had an average response of 3.0 ± 1.0 when asked how comfortable they would feel writing a LOR for a student they met through the rotation. A majority of students (n = 4, 67%) felt they connected enough with faculty during the rotation to ask for mentorship. Half the students (n = 5, 50%) indicated that the rotation allowed them to evaluate the department''s culture either “extremely well” or “somewhat well”.ConclusionsOverall, participating students described this innovative virtual surgical rotation as an educationally and professionally valuable experience. With the continued suspension of visiting student rotations due to the COVID‐19 pandemic, this virtual model may have continued relevance to medical education.