Fat Graft for Parotidectomy Defect Reconstruction in the Setting of Malignant Disease

Objectives: Currently, limited data examines the safety of utilizing fat transfers in the setting of malignant parotid disease. Here we evaluate the safety of fat graft reconstruction of parotidectomy defects in the setting of malignant disease. Study Design: Retrospective cohort study Methods: Electronic chart review of patients who underwent parotidectomy from 2012-2020 were reviewed. Results: Three hundred and sixty-one patients were identified at a single institution who underwent parotidectomy, and 113 (31.3%) were for malignancy. One hundred and thirty-two patients underwent fat graft reconstruction (49.2%, n=65 for umbilical, 50.8%, n=67 for dermal). One-third of patients had malignant pathology (34.8%, n=46). The most common malignant tumors were squamous cell carcinoma (n=15), acinic cell carcinoma (n=9), and mucoepidermoid carcinoma (n=6). Twenty patients (45.5%) received postoperative radiation therapy. Complications included: surgical site necrosis (13%), hematoma (4.3%), and infection (2.2%). Overall incidence of malignant recurrence was 4.4% with a mean time of follow-up of 10.3 (range 0 – 77.3) months. Incidence of malignant recurrence in the fat graft reconstruction subset was 0% with a mean follow-up of 9.8 (range 0.2 – 49.3) months. There was no association with use of fat graft and recurrence (p\u3e0.05). Conclusion: Parotidectomy defects for malignant neoplasms can be reconstructed with fat graft transfers with no impact on surveillance for disease recurrence.https://jdc.jefferson.edu/otoposters/1010/thumbnail.jp

Intraoperative Evaluation of Nasal Valve Repair Interventions: A Prospective Analysis

Objectives: To allow for early identification and treatment of inadequate nasal valve repair interventions in the intraoperative setting, based on degree of nasal valve collapse quantified by suction-assisted pressure readings. Patient outcomes were measured by comparison of pre- and post-operative Nasal Obstruction Symptom Evaluation (NOSE) surveys. Study Design: Prospective study. Methods: All enrolled patients undergo suction-assisted evaluation of nasal valve collapse before surgical intervention. Patients randomized into the experimental group underwent repeat assessment after various nasal valve interventions, compared to a control group where adequacy of interventions was assessed by palpation of the nasal ala. Results: 20 patients who underwent nasal valve repair were first randomized into control (10) or experimental (10) groups. Two patients in the control group did not receive nasal valve work due to pre-operative readings and were excluded from further analysis. Nasal valve interventions included alar rim grafts (5), spreader grafts (10), batten grafts (2), and nasal valve suture suspension (8). After nasal valve interventions, average suction reading at first sign of collapse increased by 92% (p \u3c 0.0001) and average suction reading at maximal collapse increased by 16% (p \u3c 0.0001). Pre-operative NOSE scores decreased by 55% (p \u3c 0.0001) at the first follow-up visit at 9.3±3.5 days. No patients in the experimental group required additional nasal valve interventions after repeat suction-assisted evaluations intraoperatively. Conclusion: Intraoperative suction-assisted evaluation of nasal valve collapse can help assess adequacy of nasal valve interventions and determine whether additional interventions are necessary to improve nasal valve integrity.https://jdc.jefferson.edu/otoposters/1011/thumbnail.jp

Avoidance of Maxillary Swing for Nasopharyngectomy via Combined Open Lateral and Endoscopic Approach

Objectives: Nasopharyngectomy performed via a solely endoscopic approach has limitations in access and feasibility, particularly regarding management of the carotid artery. To address these limitations, we report three cases with one cadaver dissection where nasopharyngectomy was performed via a combined open lateral an endoscopic approach. We highlight the benefits and technical considerations for this operative technique. Study Design: Case Series Methods: Patients diagnosed with recurrent nasopharyngeal carcinoma (NPC) that underwent combined open lateral and endoscopic nasopharyngectomy from 2016-2020 were analyzed. A cadaver dissection was also performed. Results: We present the details of the approach and follow-up in three patients with recurrent nasopharyngeal carcinoma. Briefly, a preauricular incision is extended down to the neck. The zygoma and mandibular ramus can be removed and replaced if required. V3, the pterygoid plates and the eustachian tube can be resected or mobilized. The carotid artery may be identified proximally in the neck and traced to the skull base, where the carotid canal may be drilled to the level of the foramen lacerum and protected with a pledget. Then, tumor mucosal cuts are made via an endoscopic endonasal approach and connected to the lateral exposure. No carotid artery injuries occurred. Conclusion: The combined open lateral approach and endoscopic nasopharyngectomy technique is a useful technique in salvage patients. It provides excellent control of major vessels, adequate access to the carotid canal, V3, and remainder of the skull base, and cervical protection.https://jdc.jefferson.edu/otoposters/1009/thumbnail.jp

Strengthening of short splices in RC beams using Post-Tensioned Metal Straps

This paper investigates the effectiveness of a novel and cost-effective strengthening technique using Post-Tensioned Metal Straps (PTMS) at enhancing the bond behaviour of short lap spliced steel bars in reinforced concrete (RC) beams. Twelve RC beams with a short lap splice length of 10d b (d b = bar diameter) at the midspan zone were tested in flexure to examine the bond splitting failure. The effect of confinement (no confinement, internal steel stirrups or external PTMS), bar diameter and concrete cover were examined. The results show that, whilst unconfined control beams failed prematurely due to cover splitting, the use of PTMS confinement enhanced the bond strength of the spliced bars by up to 58 % and resulted in a less brittle behaviour. Based on the test results, a new analytical model is proposed to predict the additional bond strength provided by PTMS confinement. The model should prove useful in the strengthening design of substandard lap spliced RC elements

Fas-Mediated Apoptosis Regulates the Composition of Peripheral αβ T Cell Repertoire by Constitutively Purging Out Double Negative T Cells

BACKGROUND: The Fas pathway is a major regulator of T cell homeostasis, however, the T cell population that is controlled by the Fas pathway in vivo is poorly defined. Although CD4 and CD8 single positive (SP) T cells are the two major T cell subsets in the periphery of wild type mice, the repertoire of mice bearing loss-of-function mutation in either Fas (lpr mice) or Fas ligand (gld mice) is predominated by CD4(-)CD8(-) double negative alphabeta T cells that also express B220 and generally referred to as B220+DN T cells. Despite extensive analysis, the basis of B220+DN T cell lymphoproliferation remains poorly understood. In this study we re-examined the issue of why T cell lymphoproliferation caused by gld mutation is predominated by B220+DN T cells. METHODOLOGY AND PRINCIPAL FINDINGS: We combined the following approaches to study this question: Gene transcript profiling, BrdU labeling, and apoptosis assays. Our results show that B220+DN T cells are proliferating and dying at exceptionally high rates than SP T cells in the steady state. The high proliferation rate is restricted to B220+DN T cells found in the gut epithelium whereas the high apoptosis rate occurred both in the gut epithelium and periphery. However, only in the periphery, apoptosis of B220+DN T cell is Fas-dependent. When the Fas pathway is genetically impaired, apoptosis of peripheral B220+DN T cells was reduced to a baseline level similar to that of SP T cells. Under these conditions of normalized apoptosis, B220+DN T cells progressively accumulate in the periphery, eventually resulting in B220+DN T cell lymphoproliferation. CONCLUSIONS/SIGNIFICANCE: The Fas pathway plays a critical role in regulating the tissue distribution of DN T cells through targeting and elimination of DN T cells from the periphery in the steady state. The results provide new insight into pathogenesis of DN T cell lymphoproliferation

The need for national medical licensing examination in Saudi Arabia

<p>Abstract</p> <p>Background</p> <p>Medical education in Saudi Arabia is facing multiple challenges, including the rapid increase in the number of medical schools over a short period of time, the influx of foreign medical graduates to work in Saudi Arabia, the award of scholarships to hundreds of students to study medicine in various countries, and the absence of published national guidelines for minimal acceptable competencies of a medical graduate.</p> <p>Discussion</p> <p>We are arguing for the need for a Saudi national medical licensing examination that consists of two parts: Part I (Written) which tests the basic science and clinical knowledge and Part II (Objective Structured Clinical Examination) which tests the clinical skills and attitudes. We propose this examination to be mandated as a licensure requirement for practicing medicine in Saudi Arabia.</p> <p>Conclusion</p> <p>The driving and hindering forces as well as the strengths and weaknesses of implementing the licensing examination are discussed in details in this debate.</p

An Efficient Targeted Drug Delivery through Apotransferrin Loaded Nanoparticles

BACKGROUND: Cancerous state is a highly stimulated environment of metabolically active cells. The cells under these conditions over express selective receptors for assimilation of factors essential for growth and transformation. Such receptors would serve as potential targets for the specific ligand mediated transport of pharmaceutically active molecules. The present study demonstrates the specificity and efficacy of protein nanoparticle of apotransferrin for targeted delivery of doxorubicin. METHODOLOGY/PRINCIPAL FINDINGS: Apotransferrin nanoparticles were developed by sol-oil chemistry. A comparative analysis of efficiency of drug delivery in conjugated and non-conjugated forms of doxorubicin to apotransferrin nanoparticle is presented. The spherical shaped apotransferrin nanoparticles (nano) have diameters of 25-50 etam, which increase to 60-80 etam upon direct loading of drug (direct-nano), and showed further increase in dimension (75-95 etam) in conjugated nanoparticles (conj-nano). The competitive experiments with the transferrin receptor specific antibody showed the entry of both conj-nano and direct-nano into the cells through transferrin receptor mediated endocytosis. Results of various studies conducted clearly establish the superiority of the direct-nano over conj-nano viz. (a) localization studies showed complete release of drug very early, even as early as 30 min after treatment, with the drug localizing in the target organelle (nucleus) (b) pharmacokinetic studies showed enhanced drug concentrations, in circulation with sustainable half-life (c) the studies also demonstrated efficient drug delivery, and an enhanced inhibition of proliferation in cancer cells. Tissue distribution analysis showed intravenous administration of direct nano lead to higher drug localization in liver, and blood as compared to relatively lesser localization in heart, kidney and spleen. Experiments using rat cancer model confirmed the efficacy of the formulation in regression of hepatocellular carcinoma with negligible toxicity to kidney and liver. CONCLUSIONS: The present study thus demonstrates that the direct-nano is highly efficacious in delivery of drug in a target specific manner with lower toxicity to heart, liver and kidney

Modified Needle-Tip PcrV Proteins Reveal Distinct Phenotypes Relevant to the Control of Type III Secretion and Intoxication by Pseudomonas aeruginosa

The type III secretion system (T3SS) is employed to deliver effector proteins to the cytosol of eukaryotic hosts by multiple species of Gram-negative bacteria, including Pseudomonas aeruginosa. Translocation of effectors is dependent on the proteins encoded by the pcrGVHpopBD operon. These proteins form a T3S translocator complex, composed of a needle-tip complex (PcrV), translocons (PopB and PopD), and chaperones (PcrG and PcrH). PcrV mediates the folding and insertion of PopB/PopD in host plasmic membranes, where assembled translocons form a translocation channel. Assembly of this complex and delivery of effectors through this machinery is tightly controlled by PcrV, yet the multifunctional aspects of this molecule have not been defined. In addition, PcrV is a protective antigen for P. aeruginosa infection as is the ortholog, LcrV, for Yersinia. We constructed PcrV derivatives containing in-frame linker insertions and site-specific mutations. The expression of these derivatives was regulated by a T3S-specific promoter in a pcrV-null mutant of PA103. Nine derivatives disrupted the regulation of effector secretion and constitutively released an effector protein into growth medium. Three of these regulatory mutants, in which the linker was inserted in the N-terminal globular domain, were competent for the translocation of a cytotoxin, ExoU, into eukaryotic host cells. We also isolated strains expressing a delayed-toxicity phenotype, which secrete translocators slowly despite the normal level of effector secretion. Most of the cytotoxic translocation-competent strains retained the protective epitope of PcrV derivatives, and Mab166 was able to protect erythrocytes during infection with these strains. The use of defined PcrV derivatives possessing distinct phenotypes may lead to a better understanding of the functional aspects of T3 needle-tip proteins and the development of therapeutic agents or vaccines targeting T3SS-mediated intoxication

The gut microbiome: scourge, sentinel or spectator?

The gut microbiota consists of trillions of prokaryotes that reside in the intestinal mucosa. This long-established commensalism indicates that these microbes are an integral part of the eukaryotic host. Recent research findings have implicated the dynamics of microbial function in setting thresholds for many physiological parameters. Conversely, it has been convincingly argued that dysbiosis, representing microbial imbalance, may be an important underlying factor that contributes to a variety of diseases, inside and outside the gut. This review discusses the latest findings, including enterotype classification, changes brought on by dysbiosis, gut inflammation, and metabolic mediators in an attempt to underscore the importance of the gut microbiota for human health. A cautiously optimistic idea is taking hold, invoking the gut microbiota as a medium to track, target and treat a plethora of diseases