Folds In Patients Research Articles

The value of 1.5T MRI in the evaluation of vocal fold mobility in patients with goiter

The laryngoscopic examination remains the gold standard in the perioperative evaluation of the mobility of the vocal folds in patients with goiter. During the COVID-19 pandemic, many medical procedures, including laryngoscopy are optimized in terms of epidemiological safety. Therefore, it seems deeply justified to implement methods like i.e. ultrasound or MRI which can provide the diagnostic information usually obtained via laryngoscopic examination. Aim of the studyTo determine the value of dynamic MRI examination in the 1.5 T field in the assessment of the mobility of vocal folds in patients with goiter compared to healthy people and in relation to ultrasound examinations and routine laryngoscopy. Materials and methods35 healthy volunteers and 44 patients with goiter were subjected to videolaryngoscopy, dynamic examinations of the vocal folds during respiration and phonation using ultrasound and the MRI sequences: generic gradient echo (GRE) and true fast imaging with steady-state precession (TRUFI). The qualitative and quantitative data were analyzed, i.e. the angles of deviation from the midline of the vocal folds and the area of the right and left rima glottidis compartments. ResultsNo statistically significant differences were found between the groups of healthy volunteers and patients with goiter in the values of the angles of deviation of the vocal folds with the use of ultrasound and two MRI dynamic sequences - GRE and TRUFI. There were also no statistically significant differences in the areas of the rima glottidis compartments between these two groups with the use of two MRI dynamic sequences - GRE and TRUFI. Among the analyzed parameters, the maximum size of each rima glottidis compartment was the only one to show features of sexual dimorphism and was significantly higher in men (GRE p < 0.001 and TRUFI p = 0.001). There was no correlation between the size of the minimum and maximum rima glottidis compartment and the total volume of the thyroid lobes in patients with goiter for the GRE and TRUFI sequences. ConclusionsMRI is a promising tool for the objective assessment of the mobility of the vocal folds in patients with goiter, as well as for the qualification for treatment and monitoring its effects. It is particularly important during an epidemiological emergency due to its safety compared to laryngoscopy. The presence of the goiter and its volume do not limit the possibility of performing dynamic imaging studies of the vocal folds and do not affect the surface area of the glottis.

A multifield computational model explains the underlying mechanisms of cortical malformations in the developing brain

AbstractThe convoluted macroscopic shape of the mammalian brain plays an important role for brain function. To date, the link between the cellular processes during brain development and normal or abnormal cortical folding remains insufficiently understood. In the early stages of development, progenitor cells divide symmetrically and asymmetrically in the inner layers of our brain. The newly generated neurons then migrate from the inner layers towards the outer surface to form the cortex. After about 20 weeks of gestation, the neuronal cells in the cortex start to interconnect, which causes a significant expansion of the outer brain layers. As this expansion is constrained by slower growing inner layers, compressive stresses emerge, which eventually induce mechanical instabilities and cortical folding. Disruption of cellular division, migration, or connectivity may lead to malformations of cortical development associated with neurological disorders like schizophrenia, autism, or epilepsy. Here we present a computational model describing cellular division and migration on the cellular scale, as well as growth and cortical folding on the tissue or organ scale, in a continuous way by a coupled finite growth and advection‐diffusion model. We introduce the cell density as independent field controlling the volumetric growth. This allow us to study the influence of the migration velocity, the cell diffusivity, the local stiffness, and the local connectivity of cells on the cortical folding process during normal and abnormal brain development numerically. We show how disrupted cell migration leads to a thickened cortex and the absence of normal folds in patients with the malformation lissencephaly. When calibrated using clinical data, the presented model can help to understand and diagnose neurological disorders arising from abnormal cellular development and cortical malformations.

Bilateral chorioretinal folds in patients with central serous chorioretinopathy

Abstract Introduction: Chorioretinal folds accompanied by central serous chorioretinopathy (CSC) are relatively uncommon. Here, we report CARE-compliant 2 patients with bilateral CSC chorioretinal folds and CSC that was followed-up for 2 years. Patient concerns: Case 1 was a 68-year-old female who complained of central visual field disturbance in her left eye. At the initial visit, her visual acuity (VA) was 20/20 in her right eye and 20/40 in her left. She had a history of systemic hypertension and an optic neuropathy in her left eye 20 years previously. Case 2 was a 63-year-old female with CSC in her right eye. Her VA at her first visit was 20/200 in her right eye and 20/20 in her left. Diagnosis: In case 1, an examination revealed serous retinal detachment (SRD) in the macula and optic disc atrophy in her left eye and both fundi showed chorioretinal folds. Fluorescein angiography showed a fluorescein leakage area in her left eye. In case 2, examination of fundus showed marked SRD in her right macula and both fundi had chorioretinal folds. fluorescein angiography showed a fluorescein leakage area and indocyanine green angiography showed vascular hyperpermeability, but no choroidal neovascularization. Interventions and outcomes: In case 1, the patient rejected the photocoagulation treatment. Her SRD resolved spontaneously and the VA improved to 20/20 in her left eye nine months after the first visit. But the chorioretinal folds in both eyes remain till date. In case 2, photodynamic therapy was planned; however, her SRD disappeared spontaneously. Photocoagulation therapy was performed at the leak point and her VA improved to 20/20, but the bilateral chorioretinal folds remain till date. There has been no recurrence of CSC in both the patients in the 2 year follow-up. Conclusions: The exact mechanism of CSC remains uncertain. Choroidal vascular abnormalities, such as choroidal hyperpermeability and dilated choroidal vessels associated with congested vortex veins, have been previously reported even in the unaffected eye of CSC patients. We theorize that the bilateral chorioretinal folds in CSC patients were possibly induced by the outflow congestion of the vortex vein due to the marked CSC and choroidal dysregulation. As the choroid expanded due to CSC, the overlying Bruch membrane was forced into folds. Further investigation of the pathophysiology of CSC is needed.

Transcutaneous laryngeal ultrasonography: A promising tool for otolaryngologists during COVID-19.

PurposeWith the current COVID-19 outbreak, otolaryngologists are most exposed to the risk of infection due to the nature of the specialty.This is why they are required to find safer diagnostic alternatives minimizing aerosol-generating procedures. The aim of this study is to explore the accuracy of transcutaneous laryngeal ultrasonography (TLUSG) in order to assess vocal fold movement.Materials and methodsWe performed blindly both TLUSG and flexible fiberoptic laryngoscopy(FFL) on 38 patients, from March to June 2020. Patients were divided into two groups:the former with normally mobile vocal folds and the latter with unilateral vocal fold paralysis.ResultsOn FFL findings, 10/38 patients (26,31%) had unilateral vocal fold paralysis; on TLUSG results, 9/38 patients (23.68%) presented impaired vocal fold motion. In comparison to laryngoscopy, the sensitivity, specificity, positive predictive value and negative predictive value of TLUSG for assessment of vocal fold mobility was 80%, 96.42%, 88.88%, 93.10% respectively. A significant association between the two techniques was found on the Chi-square test: X2 = 19.7722 (p value <0.00001). Cohen's K value showed a substantial agreement: K = 0,79.ConclusionAlthough TLUSG could undoubtedly not replace laringoscopy, it represents a noninvasive and useful diagnostic tool for otolaryngologists especially during covid-19 pandemic.Data collected about its high sensitivity and specificity suggest that TLUSG could be a reliable method to screen vocal fold paralysis without performing aerosol-generating procedures, thus providing clear visualization of laryngeal real-time movements, even in non-compliant or high-risk infection patients. Our results allow us to consider TLUSG as part of the preoperative assessment of vocal folds in patients undergoing thyroidectomy.

Volumetric measures of the paralyzed vocal fold using computerized tomography; its clinical implication

Objective To report the volumetric measures of the paralyzed vocal fold in patients undergoing injection laryngoplasty. Material and method All the medical records of patients with unilateral vocal fold paralysis who had high resolution computerized tomography scan of the neck and chest prior to injection laryngoplasty between October 2015 and May 2018 were included. Volumetric evaluation of the vocal folds was performed by measuring the vocal fold height using coronal images and the vocal fold length and width using axial images. Results A total of 21 patients divided into 13 males and 8 females were identified. The mean age was 56.66 ± 20.94 years. The mean volume of the paralyzed vocal fold was significantly smaller than that of the non-paralyzed vocal fold (p < .05). Similarly, the mean length and height of the paralyzed vocal folds were smaller than those of the non-paralyzed vocal folds (p < .05). Conclusion Volumetric measurements of the paralyzed vocal fold in comparison to the normal vocal fold in a group of 21 patients with unilateral vocal fold paralysis shows the presence of significant difference between the normal and affected site, and the presence of large inter-subject variation. Information on the volume difference between the two vocal folds may be used to better estimate the amount that needs to be injected in medialization procedures.

Evaluation of Glycated Haemoglobin (HbA1c) Level in Type 2 Diabetic Chronic HCV Non-cirrhotic Treatment-Naïve Egyptian Patients Eradicated with Sofosbuvir Plus Daclatasvir

A prospective observational cross-sectional study, included 128 type 2 diabetic HCV patients with easy to treat criteria (non cirrhotic treatment-naïve patients with the following liver biochemical markers; total serum bilirubin ≤ 1.2 mg/dl, serum albumin ≥ 3.5 g/dl, INR≤ 1.2 and Platelet count≥ 150.000/mm3); according to the protocol of the Egyptian National Committee for Controlling HCV and the guidelines of the European Association for the Study of the Liver. HbA1c was done for all patients enrolled in the study before starting antiviral treatment, at the end of treatment and 3 months (12 weeks) after the end of treatment to patients who achieved sustained virological response (SVR) 12 only. According to their antidiabetic medications, patients were classified to Group I: 70 patients taking oral hypoglycemic drugs, Group II: 58 patients taking insulin therapy +/- oral hypoglycemic drugs. Regarding the glycemic profile, a statistically significant decrease of mean HbA1c % values was found in the studied patients (n=128), over the period of the study with p-value < 0.05. For better evaluation of improvement of glycemic control, we used a composite endpoint given by the reduction of HbA1c % (of a minimum of 0.5%). The endpoint was reached to 79% (101 patients) of all studied patients 3 months after the end of treatment. 75.7% (53 patients) reached the endpoint in group I, while 82.75 % (48 patients) of group II reached the endpoint 3 months after the end of treatment. This study supports the idea that HCV eradication leads to a reduction in HbA1c in patients with diabetes, which could delay the onset and progression of microvascular diabetes complications.

Compensatory Movement of Contralateral Vocal Folds in Patients With Unilateral Vocal Fold Paralysis

Previous studies of subjects with unilateral vocal fold paralysis (UVFP) as observed in a positron emission tomography-computed tomography (PET-CT) examination have demonstrated false positive results in the contralateral cricoarytenoid, in which the metabolism may be higher. This area may also be the site of contralateral compensatory movement in these patients. In this study, we compared the adduction speed of the contralateral vocal folds in patients with UVFP and in healthy subjects as measured by the stroboscopic laryngoscope frame rate. This study aimed to explore the contralateral compensatory movement of the vocal folds in subjects with UVFP. (1) We collected visual data from 14 patients with UVFP and 14 healthy subjects through a stroboscopic laryngoscope. These subjects were divided into a vocal fold paralysis group and a control group, and we analyzed the excessive adduction of the contralateral vocal folds in the vocal fold paralysis group by examining vocal fold movement speed (pixels/s) as featured in a stroboscopic laryngoscope video. (2) We analyzed the uptake of 18-FDG in the posterior vocal fold from positron emission tomography-computed tomography imaging from four subjects with UVFP and 12 healthy subjects. An independent sample t test and a χ2 test were used to compare data. Four subjects with UVFP had a higher metabolic rate in the contralateral cricoarytenoid joints, with a significant difference between the two groups, P < 0.05. Fifty percent of the cases of contralateral adduction of the vocal folds in the subjects with UVFP adducted past the midline, with a significant difference between the two groups, P < 0.05. The contralateral adduction of the vocal folds in subjects with UVFP had shorter video frames and higher adduction speed than the control group, and the difference was statistically significant, P < 0.05. There were fewer vocal fold abduction video frames and higher abduction speed of the healthy side of the vocal fold in subjects with UVFP than the control group, but there was no statistically significant difference, P > 0.05. Subjects with UVFP exhibited faster adduction compensation in the contralateral vocal folds, and the contralateral cricoarytenoid joint's metabolism in subjects with UVFP was higher. These data may help clarify the diagnostic criteria for laryngeal nerve damage.

Abstract 1719: Copper levels and the p53 protein: A delicate balance

Abstract The tumor suppressor p53 is mutated in 50% of all cancers and in about 90% of small lung cancers. Mutations lead to loss of p53 expression or the expression of mutant p53 proteins. These mutants often lose WT function, but they have also been shown to acquire invasive and metastatic functions. p53 requires a zinc molecule in its core domain to fold properly and to function as a transcription factor and tumor suppressor. Loss of this zinc through competition with copper causes p53 to unfold and to lose its transcription function. Copper is an essential heavy metal required for a large variety of biological processes as it is required for the function of many enzymes. In cancer patients, increased serum levels of copper have been found and people with a predisposition for copper accumulation in the liver (Wilson’s disease, mutations in ATP7B) are prone to develop liver cancers. Our preliminary results have indicated that an unfolded WT p53 molecule does not only lose its transcription function, but also gains mutant p53-like functions in promoting invasion. Copper-induced unfolded p53 interacted with the mutant p53 specific interacting proteins Dicer, Ago, p63 and p73 and impaired p63 function. These results raise the question as to why a WT molecule would lose its function and whether it perhaps could act as a redox sensor. Experiments are ongoing to explore p53 mediated transcription in response to copper exposure. In addition, we are setting up mouse models to investigate p53 folding in vivo in response to mild increases in copper serum levels and we are developing methods to better determine p53 folding in patients and in mice. These results will help us assess p53 status in relation to serum metal levels in vivo and determine whether p53 is important in the development of cancers and metastasis. Citation Format: Patricia Muller, Yannick von Grabowiecki, Callum Hall. Copper levels and the p53 protein: A delicate balance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1719.

Obstructive sleep apnoea as a late complication after tracheostomy

Obstructive sleep apnoea occurs consequent to partial or complete upper airway obstruction, caused mostly by the collapse of upper airway musculature. Drug-induced sleep endoscopy represents the 'gold standard' in identifying the obstruction site, from the palatal level to laryngeal entry. Breathing impairment in sleep caused by the collapse of cervical trachea after previous tracheostomy has not yet been described in the literature. This report presents two patients with severe obstructive sleep apnoea, in whom pre-operative drug-induced sleep endoscopy revealed upper airway and cervical trachea collapse at the level of previous tracheostomy. The female patient was successfully treated with resection of hypertrophic tissue of the tongue base via lateral pharyngectomy, and resection of the collapsed segment of the trachea with primary reconstruction of the trachea by end-to-end anastomosis. The male patient was recommended continuous positive airway pressure therapy because of serious co-morbidities and high operative risk. Drug-induced sleep endoscopy should always be used for visualisation of anatomical structures below the vocal folds in patients with a history of cervical trachea surgery. These two cases demonstrate the importance of drug-induced sleep endoscopy in planning conservative and surgical treatments, contributing significantly to operative success.

The use of direct laryngoscopy and ultrasound in the perioperative assessment of mobility of vocal folds in patients treated surgically due to goiter

Poland has about 25000–30000 thyroid glands operations per year. These kind of operations are in fourth place as to the frequency of scheduled operations. Most patients have total thyroidectomy. In addition to the classic method of accessing the collar cut at the neck, there are also alternative access, e.g. through the vestibule of the mouth or armpit. Surgery carries the risk of serious and even life-threatening consequences. One of the most serious complications of this surgery is failure of one or both laryngeal recurrents nerves. Laryngeal recurrents nerves are responsible for the proper functioning of vocal folds. Depending on the failure degree, results in disruption of phonation, difficulties in taking solid and liquid food, limitation of physical performance, impaired breathing to respiratory failure. The aim of this study is to assess the prevalence of early injury of the laryngeal nerves by evaluating the operation of vocal folds in direct laryngoscopy and ultrasonography. The study was carried out from 15/05/2018 to 17/01/2019 at the Department of General and Oncological Surgery. The patients were qualified for random examination from among the total number of patients qualified for goiter surgery in the Clinic. Direct laryngoscopy was performed in the Endoscopic Laboratory of the General and Oncological Surgery Clinic of the Medical University of Lodz. The ultrasound of the vocal folds was performed in the Department of Diagnostic Imaging. In the study period, 42 patients were qualified to participate in the study. In the study group, bilateral, early paresis of vocal folds was diagnosed in two patients (4.76%) and unilateral early paresis of vocal fold in seven patients (16.67%). Both operations, complicated by bilateral paresis of vocal folds, were performed without the use of intraoperative neuromonitoring (IONM - intraoperative neuromonitoring). One-sided paresis of vocal folds occurred in 3 patients (7.14%) operated without neuromonitoring, and 4 patients (9.52%) with intraoperative neuromonitoring. The study found that a severe complication in the form of early bilateral paresis of vocal folds occurred in operations without the use of neuromonitoring. A similar occurrence of one-sided damage to the vocal fold indicates a lack of connection with the additional support used in the form of intraoperative neuromonitoring.

Balcony genioplasty: a novel technique for better esthetic results in patients with deep mentolabial fold

BackgroundTo introduce a novel technique for advancement genioplasty helping surgeons to avoid soft tissue difficulties especially in short-faced patients with deep mentolabial fold and everted lower lip.Case presentationIn a trapezius-shaped, osteotomy was performed in the chin region. The mobilized segment was advanced, and the existing gap was grafted using interpositional allograft materials. Each side had been fixated by three-hole plates and two screws. The outcomes revealed no change in lower anterior teeth vitality. The patients did not report any changes of sensation in lower lip and chin either. The measurements indicated no increase in depth of mentolabial fold in patients undergoing this surgical technique. The postoperative evaluation showed a successful esthetic outcome for the patient and the surgeon concurrently.ConclusionBased on our experience, the authors concluded that the Balcony technique is a simple and reliable procedure for patients with a deep mentolabial fold.

Corrective Strategies for a Complex Deformity Caused by "European-Style Double Eyelid" Blepharoplasty in Asians.

"European-style double eyelid" blepharoplasty often leads to a complex deformity, which includes one or more of the following features: a high fold, upper eyelid depression, multiple folds, an obvious scar, blepharoptosis, and lower flap tumidness. However, there is still a lack of comprehensive research on evaluation and treatment strategies for this complex deformity. During a 6-year period, 65 patients (106 eyes) with a high fold and upper eyelid depression underwent corrective blepharoplasty. The authors classified this complex deformity as mild, moderate, or severe based on the extent of adhesion and tissue insufficiency, and we performed preaponeurotic fat flap transfer in 47 eyes (44.3%), free fat graft in 35 eyes (33%), and free dermis-fat graft in 24 eyes (22.6%), respectively. The outcomes in 87 eyelids were judged as excellent; and the grading was excellent in 41 eyes (87.2%) that underwent preaponeurotic fat flap transfer, 30 eyes (85.7%) that received a free fat graft, and 16 eyes (66.7%) that received a free dermis-fat graft. The outcomes in only 3 eyes (2.8%) were evaluated as unsatisfactory. The fundamental reasons behind this deformity were adhesion and tissue insufficiency above the supratarsal crease. The purpose of correction was to reconstruct the gliding system and restore the volume. The authors performed preaponeurotic fat flap transfer, free fat graft, and free dermis-fat graft and achieved satisfactory results. Great improvement in ptosis was achieved by releasing the adhesion and lowering the fold in patients with normal levator muscle function. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Hyaluronan in vocal folds and false vocal folds in patients with recurrent respiratory papillomatosis

Background: Hyaluronan (HA) is a glycosaminoglycan with viscoelastic properties necessary for vocal fold (VF) vibration and voice production. Changes in HAs molecular mass, possibly related to human papilloma virus, could affect formation/persistence of recurrent respiratory papillomatosis (RRP). Aims/Objective: Describing mass and localization of HA and localization of HA receptor CD44 in VF and false vocal folds (FVF) in RRP. Materials and Methods: Biopsies from VF and FVF from 24 RRP patients. Twelve were studied with histo-/immunohistochemistry for HA and CD44 in epithelium, stroma and RRP lesions. Twelve samples were analyzed for HA molecular mass distribution with gas-phase-electrophoretic-molecular-mobility-analyzer (GEMMA). Results: Three of 23 stains (VF and FVF combined) showed faint HA staining in the epithelium; there was more extensive staining in the stroma. CD44 was present throughout all areas in FVF and VF, it did not concur with HA. GEMMA analysis revealed very high mass HA (vHMHA) with more varying amounts in VF. Conclusions/Significance: HA was mainly distributed in the stroma. CD44 not binding to HA might explain the non-inflammatory response described in RRP. Possibly crosslinked vHMHA was seen in VF and FVF, with more variable amounts in VF samples. Counteracting HA crosslinking could become a treatment option in RRP.

Disorganized Gyrification Network Properties During the Transition to Psychosis

There is urgent need to improve the limited prognostic accuracy of clinical instruments to predict psychosis onset in individuals at clinical high risk (CHR) for psychosis. As yet, no reliable biological marker has been established to delineate CHR individuals who will develop psychosis from those who will not. To investigate abnormalities in a graph-based gyrification connectome in the early stages of psychosis and to test the accuracy of this systems-based approach to predict a transition to psychosis among CHR individuals. This investigation was a cross-sectional magnetic resonance imaging (MRI) study with follow-up assessment to determine the transition status of CHR individuals. Participants were recruited from a specialized clinic for the early detection of psychosis at the Department of Psychiatry (Universitäre Psychiatrische Kliniken [UPK]), University of Basel, Basel, Switzerland. Participants included individuals in the following 4 study groups: 44 healthy controls (HC group), 63 at-risk mental state (ARMS) individuals without later transition to psychosis (ARMS-NT group), 16 ARMS individuals with later transition to psychosis (ARMS-T group), and 38 antipsychotic-free patients with first-episode psychosis (FEP group). The study dates were November 2008 to November 2014. The dates of analysis were March to November 2017. Gyrification-based structural covariance networks (connectomes) were constructed to quantify global integration, segregation, and small-worldness. Group differences in network measures were assessed using functional data analysis across a range of network densities. The extremely randomized trees algorithm with repeated 5-fold cross-validation was used to delineate ARMS-T individuals from ARMS-NT individuals. Permutation tests were conducted to assess the significance of classification performance measures. The 4 study groups comprised 161 participants with mean (SD) ages ranging from 24.0 (4.7) to 25.9 (5.7) years. Small-worldness was reduced in the ARMS-T and FEP groups and was associated with decreased integration and increased segregation in both groups (Hedges g range, 0.666-1.050). Using the connectome properties as features, a good classification performance was obtained (accuracy, 90.49%; balanced accuracy, 81.34%; positive predictive value, 84.47%; negative predictive value, 92.18%; sensitivity, 66.11%; specificity, 96.58%; and area under the curve, 88.30%). These findings suggest that there is poor integration in the coordinated development of cortical folding in patients who develop psychosis. These results further suggest that gyrification-based connectomes might be a promising means to generate systems-based measures from anatomical data to improve individual prediction of a transition to psychosis in CHR individuals.

Role of Aldose Reductase in LPS‐inducible Intrahepatic Immune Infiltration and Inflammation

Aldose reductase (AR) is the rate‐limiting enzyme of the polyol pathway that converts glucose to sorbitol, which is further metabolized to fructose. AR has been widely investigated in pathogenesis of diabetic complications, cardiovascular disorders and cancer. Previous studies show that activation of AR is involved in glucose‐induced hepatitis in mice, hepatitis in rats and human autoimmune hepatitis. Recent findings demonstrate that AR is involved in inflammatory hepatic ischemia‐reperfusion injury. The gut‐liver axis is known to be involved in the development of both alcoholic and non‐alcoholic liver diseases. Gut permeability releases endotoxin (lipopolysaccharide, LPS) into circulation and then triggers inflammation. Inflammatory responses are among the most critical pathological processes associated with liver injury. This study investigated the role of AR in intrahepatic immune infiltration/activation and inflammation using mouse models and human specimens from patient with inflammatory liver disease.Wild type (WT, C57BL/6) and aldose reductase knockout mice (ARKO, AKR1B3−/−) were subjected to stimulation with or without LPS (2.0mg/kg) through intraperitoneal injection. Liver histology (H&amp;E staining), intrahepatic immune cell markers (F4/80, chloroacetate esterase stain) and apoptosis (TUNEL) were examined. Intrahepatic immune cells were isolated from mouse livers and analyzed by flow cytometry using immunofluorescence antibodies: anti‐CD11b, anti‐F4/80, anti‐ly6G and anti‐ly6C. The expression levels of AR in hepatitis patient livers were evaluated by real‐time PCR.Proinflammatory cytokines (TNFα, IL‐1β, IL‐6) and chemokines (CXCL2 and MCP‐1/CCL2) were significantly upregulated in WT mice exposed to LPS. The genetic deletion of AR greatly attenuated LPS‐induced cytokines/chemokines. LPS resulted in the infiltration of circulating neutrophils and monocytes into the liver and increased CD11b+Kuffer subsets in WT mice. The lack of AR in ARKO mice was associated with decreased populations of neutrophils, monocytes and CD11b+ Kuffer cells. Specifically, administration of LPS increased neutrophils (F4/80−/CD11b+/Ly6G+/SSCint) by 5 fold in WT mice and AR deficiency reduced this to 3 fold; LPS elevated intrahepatic inflammatory monocytes (F4/80−/CD11b+ /ly6Chi) by 2 fold in WT mice and AR deficiency reduced this to 1 fold. LPS increased the CD11b+Kupffer cell subset (F4/80+CD11b+) by 2 fold in WT mice and AR deficiency decreased this to 1 fold. Hepatic AR expression was significantly upregulated by 2 fold in patients with inflammatory liver disease. Taken together, our data show that AR is a key mediator of hepatic inflammation in response to endotoxin in mice. The upregulation of hepatic AR in patients with hepatitis emphasize the relevance of AR in human liver diseases associated with inflammation. The data also suggest that AR may be a novel therapeutic target for inflammatory hepatic injury.Support or Funding InformationNIH‐NIEHS, NIH‐NIAAA, DOD, VA, and UofL‐IPIBSThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

O10.1. DISORGANIZED GYRIFICATION NETWORK PROPERTIES DURING THE TRANSITION TO PSYCHOSIS

BackgroundThere is urgent need to improve the limited prognostic accuracy of psychopathology-based classifications to predict the onset of psychosis in clinical high-risk (CHR) subjects for psychosis. However, as yet no reliable biological marker has been established to differentiate CHR subjects who will develop psychosis from those who will not. This study investigated abnormalities in graph-based gyrification connectome in CHR subjects and patients with first-episode psychosis (FEP) and tested the accuracy of this systems-based approach to predict the transition to psychosis among CHR individuals.Methods44 healthy controls (HC), 63 at-risk mental state (ARMS) subjects without later transition to psychosis (ARMS-NT), 16 ARMS subjects with later transition (ARMS-T), and 38 antipsychotic-free patients with FEP were recruited from the specialized clinic for the early detection of psychosis at the Department of Psychiatry, University of Basel, Basel, Switzerland. Gyrification-based structural covariance networks (connectomes) were constructed to quantify global integration, segregation and small-worldness. Extremely randomized trees with repeated, nested cross-validation was performed to differentiate ARMS-T from ARMS-NT individuals. Permutation testing was used to assess the significance of classification performance measures.ResultsSmall-worldness is reduced in both ARMS-T and FEP patients, secondary to reduced integration and increased segregation in both groups. In addition, we also found that transitivity (segregation) was significantly higher in ARMS-T and FEP groups compared to both ARMS-NT and healthy controls. Using the connectome properties as features, we obtained a high classification accuracy of 90% (balanced accuracy: 81%, positive predictive value: 85%, negative predictive value: 92%.) All performance measures were highly significant as indicated by permutation tests (all p < 0.01).DiscussionOur findings suggest that there is poor integration in the coordinated development of cortical folding in patients who develop psychosis. This study further indicates that gyrification-based connectomes might be a promising means to generate systems-based measures from anatomical data that improves individual prediction of psychosis transition in CHR subjects.

Pharmacokinetics of oral tramadol in patients with liver cancer

There are no studies reported on pharmacokinetics of opioids in patients with hepatocellular carcinoma, the fifth most common cancer in the world. The authors have studied the pharmacokinetic profile of oral tramadol (50 mg) capsule in 20 patients with liver carcinoma (10 with primary carcinoma on top of chronic hepatitis C and 10 with secondary metastatic liver malignancy as a result of other primary) compared with 10 healthy controls. Plasma tramadol concentrations were measured in venous samples at intervals up to 12 hours by high-pressure liquid chromatography. Allpharmacokinetic variables were evaluated using one-compartment model. Tramadol bioavailability showed a substantial increase in patients with primary liver cancer and secondary metastatic than that of control (98 percent, 75 percent, and 68 percent, respectively). The area under the serum concentration-time curve increased significantly in patients with primary and metastatic cancer of liver than in control [1,933 microg/h/L (SD = 41), 1,327 microg/h/L (SD = 51), 1,138.5 microg/h/L (SD = 31), respectively]. Also, a significant difference in Cmax and Tmax was found between patients with malignant liver and control. Reduced clearance and impaired elimination was significantly observed in patients with liver carcinoma than control. Clearance was reduced to 50 percent of control, and elimination halflife increased up to three folds in patients with primary liver carcinoma than that of control. Satisfactory pain relief with minimal side effects was observed all over study period. It is recommended to lengthen the dose interval of oral tramadol, if it is to be used in patients with liver cancer for analgesic purposes, to 50 mg every 12 hours as it is proved to be effective and safe.

Endo-extralaryngeal Laterofixation of the Vocal Folds in Patients with Bilateral Vocal Fold Immobility.

Bilateral vocal fold paralysis can result in shortness of breath and severe dyspnea which can be life-threatening. Thirty-five patients with bilateral vocal fold paralysis who underwent endo-extralaryngeal laterofixation according to Lichtenberger were retrospectively analyzed regarding etiology, symptoms, treatment and complications. In 27 patients, laterofixation of the vocal cord alone was performed. Eight patients underwent laterofixation and additional posterior chordectomy of the opposite vocal cord according to Dennis and Kashima. The time of intervention ranged from 1 day to 38 years after the onset of bilateral vocal cord immobility. The intraoperative course was uneventful in all patients. None of the patients had postoperative aspiration. Postoperative voice function was acceptable in all patients. Complications of suture laterofixation were laryngeal edema, formation of fibrin, and malposition of the suture. Laterofixation of the vocal cords according to Lichtenberger is a safe and easy method that can be used as a first-stage treatment of vocal cord paralysis.

Videolaryngoscopy during Conscious Sedation in Patients Not Suitable for Phonosurgery by Microlaryngoscopy: A Pilot Study

Background: Microlaryngoscopy is the preferred and most widely used technique in phonosurgery for the treatment of benign and early malignant glottic lesions. However, the procedure may be technically difficult or impossible due to alterations of the cervical spine that may not allow hyperextension of the head or may present general anesthesia contraindications. The aim of this study is to evaluate the efficacy and safety of our surgical approach for lesions of the vocal folds in patients who are not suitable for phonosurgery by microlaryngoscopy. This approach applies videolaryngoscopy during conscious sedation, which combines local anesthesia with moderate analgosedation by using midazolam and fentanyl with premedication. Methods: A total of 235 patients affected by benign diseases or suspicious cancerous lesions of the vocal folds were retrospectively evaluated. Results: The method has shown a success rate of 95.5, 89, 52.3, and 86.7% in cases of polyps of the vocal folds, Reinke's edema, cysts of the vocal folds, and suspicious lesions of the larynx, respectively. Only 3 patients (1.27%) have been reported to experience adverse events. Conclusion: The results suggest that the method is an effective and safe procedure without relevant local and/or general complications.

Candida Albicans Versus Non Albicans Candiduria in the ICU Setting: Evaluation of Risk Factors

1.1.Background:The indiscriminate use of antibiotic is increasing the prevalence of candiduria worldwide, especially in the ICU setting. Limited studies describe the risk factors associated with candiduria depending on their species. 1.2.Objective: This study aims to speciate candida isolated from patients with candiduria admitted in the ICU and evaluate the risk factors associated with albicans vs non albicans candiduria. 1.3.Material and method: The risk factors were evaluated in 60 yeast isolates using Fisher’s exact test (two-tailed) and Odd’s ratio with 95% confidence interval. 1.4.Result:The non-albicancandidaspecies isolated were C. tropicalis (14), C. glabrata (11), C. krusie (5) and C. parapsilosis (10). Although there was no significant difference between risk factors associated with albicans vs non-albicanscandida spp., the risk of non-albicans candiduria increased by 3 folds with increasing age(>50yrs.) OR (95%CI) 3.3158 (1.045-10.8693) and by 6 folds in patients with history of antibiotic intake in ICU OR (95%CI) 6.3521 (0.3339-120.8452). Non-albicans candiduria was significantly associated with presence of more pus cells (11-30cells/hpf) P= 0.0002; while C. albicans candiduria was significantly present in patients with < 10 puscells/hpf, P= 0.0001. Pseudophyphae were significantly less in non-albicans candiduria (P= 0.0113). Use of carbapenems, tigecycline and fluoroquinolones were significantly associated with non-albicans candiduria (P= 0.034; 0.0057; 0.003 respectively). 1.5.Conclusion:The risk of acquiring non-albicanscandiduria is more than albicans despite having same risk factors. Non albicans candiduria has become more prevalent cause of nosocomial candiduria in the ICUs may be due to the frequent use of antibiotics like fluoroquinolones in the ICU patients. Further studies are required to assess risk factors associated with different candida spp. to manage candiduria in ICU patients.