Bilateral congenital coronary ostial obstruction: Exertional syncope in an otherwise healthy 8‐year‐old

Congenital stenosis/atresia of a coronary artery is an exquisitely rare anomaly (Congenit Heart Dis, 2, 2007, 347) with increased risk of sudden death. Bilateral coronary obstruction is even more unusual but has been reported in conjunction with aortic valve disease, syphilis, and Takayasu's arteritis. To the best of our knowledge, obstruction of both coronaries in a pediatric patient has only been reported once (Ann Thorac Surg, 55, 1993, 1564). We present a patient with an intramural, anomalous aortic origin of the right coronary artery from the contralateral sinus (AAORCA) with near atresia of the left main coronary ostium. The diagnosis was made by echocardiogram and confirmed by catheterization and magnetic resonance imaging.     

Neck Trauma: ENT Prospects

Neck trauma is a very important surgical emergency faced by ENT surgeons in day to day practice. They are potentially life threatening conditions due to the presence of many vital structures in this area. Timely presentation to the referral centre and proper multidisciplinary approach towards management plays a pivotal role in the healing pattern of the wound and prevention of serious complication like shock, sepsis, laryngeal stenosis or fistula formation. A retrospective study was done in ENT Department, NSCB Medical College, Jabalpur, Madhya Pradesh, India during the period of 2014–2016. 17 patients were included in the study. All the records regarding symptoms at presentation, type and mode of injury, level of injury were analyzed. Management plan undertaken were thoroughly studied and post operative complications like hoarseness, stenosis or fistula formation were noted carefully. 14 out of 17 patients were male, all 17 patients belonged to lower socioeconomic status. Most common age group presenting with neck trauma was between 22 and 40 years. 7 case were homicidal, 5 cases were suicidal and 4 were of accidental injury. Most cases reached hospital within 2–6 h of injury except 3 cases which took more than 8 h. Bleeding from wound site was most common symptom at presentation. Most injuries in 13 out of 17 cases were at thyroid cartilage level. Penetrating neck trauma was most common followed by blunt neck trauma. Most cases required emergency tracheostomy along with primary laryngotracheal repair. Most common post operative complication seen was wound dehiscence, subglottic stenosis and fistula formation. Neck trauma and cut throat injuries are potentially life threatening emergency that require multidisciplinary approach. Timely intervention can be crucial in preventing fatal complications and reducing morbidity period of the patient.     

Accelerating Regulated Bioanalysis for Biotherapeutics: Case Examples Using a Microfluidic Ligand Binding Assay Platform

The Gyrolab? xP is a microfluidic platform for conducting ligand binding assays (LBAs) and is recognized for its utility in discovery bioanalysis. However, few reports have focused on the technology for regulated bioanalysis. This technology has the advantage of low reagent consumption, low sample volume, and automated ligand binding methods. To improve bioanalysis testing timelines and increase the speed at which biotherapeutics are delivered to patients, we evaluated the technology for its potential to deliver high-quality data at reduced testing timelines for regulated bioanalysis. Six LBA methods were validated to support bioanalysis for GLP toxicokinetic or clinical pharmacokinetic studies. Validation, sample analysis, and method transfer are described. In total, approximately 4000 samples have been tested for regulated bioanalysis to support 6 GLP toxicology studies and approximately 1000 samples to support 2 clinical studies. Gyrolab? xP had high run pass rates (≥83%) and high incurred sample reanalysis (ISR) pass rates (>94%). The maximum total error observed across all QC levels for a given assay was <30% for all six LBAs. High instrument response precision (CV ≤5%) was observed across compact discs (CDs), and methods were validated to use a single standard curve across multiple CDs within a Gyrolab? xP run. Reduced bioanalysis timelines were achieved compared to standard manual plate-based methods, and methods were successfully transferred across testing labs, paving the way for this platform for use in late-stage clinical development.     

FTT0831c/FTL_0325 Contributes to Francisella tularensis Cell Division,Maintenance of Cell Shape,and Structural Integrity

The Francisella FTT0831c/FTL_0325 gene encodes amino acid motifs to suggest it is a lipoprotein and that it may interact with the bacterial cell wall as a member of the OmpA-like protein family. Previous studies have suggested that FTT0831c is surface exposed and required for virulence of Francisella tularensis by subverting the host innate immune response (M. Mahawar et al., J. Biol. Chem. 287:25216–25229, 2012). We also found that FTT0831c is required for murine pathogenesis and intramacrophage growth of Schu S4, but we propose a different model to account for the proinflammatory nature of the resultant mutants. First, inactivation of FTL_0325 from live vaccine strain (LVS) or FTT0831c from Schu S4 resulted in temperature-dependent defects in cell viability and morphology. Loss of FTT0831c was also associated with an unusual defect in lipopolysaccharide O-antigen synthesis, but loss of FTL_0325 was not. Full restoration of these properties was observed in complemented strains expressing FTT0831c in trans, but not in strains lacking the OmpA motif, suggesting that cell wall contact is required. Finally, growth of the LVS FTL_0325 mutant in Mueller-Hinton broth at 37°C resulted in the appearance of membrane blebs at the poles and midpoint, prior to the formation of enlarged round cells that showed evidence of compromised cellular membranes. Taken together, these data are more consistent with the known structural role of OmpA-like proteins in linking the OM to the cell wall and, as such, maintenance of structural integrity preventing altered surface exposure or release of Toll-like receptor 2 agonists during rapid growth of Francisella in vitro and in vivo.     

‘What ever I do it’s a lost cause.’ The emotional and behavioural experiences of individuals who are ulcer free living with the threat of developing further diabetic foot ulcers: a qualitative interview study

Objective Individuals who have had one diabetic foot ulcer (DFU) are at high risk for developing further DFUs. This study was designed to examine the emotional and behavioural consequences of living with this heightened risk of re‐ulceration. Participants and setting Fifteen women and men living in south‐west England were interviewed at home or at the university by an academic psychologist. Design Interviews were audiotaped and transcribed verbatim. Thematic analysis using the constant comparative method was employed for data analysis. Results Participants reported having little perceived control in preventing further DFUs. This lack of control was associated with a range of negative emotions including fears and worries about developing further foot ulcers, amputation and guilt for the past neglect. Tensions were present between participants’ beliefs and reported behaviours, that is, what they felt they ought to be doing and what they were actually doing to care for their feet; most engaged in ‘strategic adherence’, that is, conducting a trade‐off between living a normal life and following foot‐care advice. Conclusion A lack of perceived control appears central to the emotional and behavioural responses of individuals living with the threat of re‐ulceration. We propose that these responses may serve to increase individuals’ risk of re‐ulceration and that these ‘risk factors’ should be considered part of the management of this patient group.     

Recurrent progressive anterior segment fibrosis syndrome following a descemet-stripping endothelial keratoplasty in an infant with congenital aniridia

Progressive anterior segment fibrosis syndrome (ASFS), after intraocular surgery in older children (≥9 years) and adults with congenital aniridia, is described in the literature. In this report, we describe an unique case of ASFS in an infant with congenital aniridia following a combined trabeculotomy-ectomy and its recurrence after a descemet stripping endothelial keratoplasty. The ophthalmologists should be well aware of this entity and warn the parents about its possibilities. Use of immunomodulators or prolonged anti-inflammatory therapy may be considered to prevent its occurrence.     

An international pilot study of an internet‐based platform to facilitate clinical research in epilepsy: The EpiNet project

Purpose: We created an epilepsy patient database that can be accessed via the Internet by neurologists from anywhere in the world. The database was designed to enroll and follow large cohorts of patients with specific epilepsy syndromes, and to facilitate recruitment of patients for investigator‐initiated clinical trials. Methods: The EpiNet database records physician‐derived information regarding seizure type and frequency, epilepsy syndrome, etiology, drug history, and investigations. It can be accessed from any country by approved investigators via a secure, password‐protected Website. All data are encrypted. The database is for both research and clinical purposes. Investigators were invited to register any patient with epilepsy, but were particularly encouraged to register patients when uncertain of the optimal management. Participation required approval from investigators’ ethics committees and institutional review boards, and all patients or their caregiver provided written informed consent. Patients were not enrolled in clinical trials in this pilot study. Key Findings: The international pilot study recruited patients from September 2010 to November 2011. Sixty‐four investigators or research assistants from 25 centers in 13 countries registered 1,050 patients. Patients with a wide range of epilepsy syndromes and etiologies were registered. Patients’ ages ranged from 2 weeks to 90 years. Significance: The Website was successfully used by doctors working in different health systems. The pilot study confirmed that this low‐cost, collaborative approach to research has great potential. Large, multicenter cohort studies will commence in 2012, and randomized clinical trials are being planned. All epileptologists are invited to join this project.