Induction of Intestinal Graft-versus-host Disease and Its Mini-endoscopic Assessment in Live Mice.

Acute graft-versus-host disease (GvHD) represents the most severe complication that patients previously undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT) face and is frequently associated with a poor clinical outcome. While, for instance, GvHD manifestations of the skin are usually responsive to established immune-suppressive therapies and are, hence, not taking a fatal course, the presence and the intensity of intestinal GvHD, especially of the mid-to-lower parts of the gut, strongly influence the outcome and overall survival of patients with acute GvHD. Therapeutic options are essentially limited to the classic immune-suppressive agents yielding only moderate disease-mitigating effects. Hence, detailed knowledge about the tissue-resident immune cascade, changes in the intestinal microbiota, and the stromal response prior, upon, and after intestinal GvHD onset are urgently needed to understand the events and mechanisms underlying its pathogenesis and to develop innovative therapeutic options. Murine models of GvHD are frequently employed to identify and functionally assess molecules and pathways putatively driving intestinal GvHD. However, means to specifically monitor and evaluate intestinal inflammation over time are essentially lacking since established scores to assess and grade acute GvHD are routinely comprised of various parameters which rather reflect systemic GvHD manifestations. The detailed evaluation of intestinal GvHD has been restricted to studies using euthanized mice, thereby essentially excluding longitudinal (i.e., kinetic) analyses of the colonic compartment under a given experimental condition (e.g., antibody-mediated blockade of a proinflammatory cytokine) in live mice (i.e., in vivo). The mini-endoscopic in situ assessment of the distal colon of allo-HCT-treated mice described here allows a) a detailed macroscopic evaluation of different aspects of intestinal inflammation and b) the option to collect tissue samples for downstream analyses at various time points over the course of the observation period. Overall, the mini-endoscopic approach provides a major advance in preclinical noninvasive monitoring and assessment of intestinal GvHD.

Gene expression profile of endoscopically active and inactive ulcerative colitis: preliminary data.

AIM: Multiple cytokines and chemokines related to immune response, apoptosis and inflammation have been identified as molecules implicated in ulcerative colitis (UC) pathogenesis. The aim of this study was to identify the differences at gene expression level of a panel of candidate genes in mucosa from patients with active UC (UCA), patients in remission (UCR), and normal controls. PATIENTS, MATERIALS AND METHODS: Eleven individuals were enrolled in the study: eight UC patients (four with active lesions, four with mucosal healing) and three controls without inflammatory bowel disease (IBD) seen on endoscopy. All the individuals underwent mucosal biopsy during colonoscopy. Gene expression profile was evaluated by polymerase chain reaction (PCR) array, investigating 84 genes implicated in apoptosis, inflammation, immune response, cellular adhesion, tissue remodeling and mucous secretion. RESULTS: Seventeen and three genes out of 84 were found significantly differentially expressed in UCA and UCR compared to controls, respectively. In particular, REG1A and CHI3L1 genes reported an up-regulation in UCA with a fold difference above 200. In UCR patients, the levels of CASP1, LYZ and ISG15 were different compared to controls. However, since a significant up-regulation of both CASP1 and LYZ was observed also in the UCA group, only ISG15 levels remained associated to the remission state. CONCLUSIONS: ISG15, that plays a key role in the innate immune response, seemed to be specifically associated to the UC remission state. These preliminary data represent a starting point for defining the gene profile of UC in different stages in Romanian population. Identification of genes implicated in UC pathogenesis could be useful to select new therapeutic targets.

Medicolegal Issues in Endoscopic Sinus Surgery and Complications.

Complications occur during and after endoscopic sinus surgery. Complications leading to temporary or most commonly permanent injury often are involved in litigation for malpractice. This article concentrates on areas of importance that are considered during medicolegal deliberations.

Parental and youth understanding of the informed consent process for pediatric endoscopy.

OBJECTIVES: Informed consent (IC) is an essential communication between patient/representative and physician that acknowledges patient autonomy; assent is the equivalent process performed between youth and physician. For clinical procedures involving youth, only the IC process between guardian/parent and physician is required to be performed. Nevertheless, experts recommend that youth undergo assent whenever possible. In the present study, we explored both parental and youth understanding of required IC elements in IC discussions before pediatric endoscopy. METHODS: Following signing of IC documents on the day of endoscopy at a tertiary care academic medical center, youth and their parents underwent structured interviews to assess comprehension of key elements of the IC process. RESULTS: A total of 88 children and adolescents and their parents were evaluated. Two youth and 12 parents demonstrated comprehensive understanding of key IC elements for pediatric endoscopy. Suboptimal youth understanding was demonstrated for nature of the procedure (25% with adequate understanding) and related risks (17%), and alternatives (14%) to the procedure. Suboptimal parental understanding was demonstrated for procedure alternatives (24%). Youth overall understanding of IC varied by age, whereas parental global understanding of IC varied by physician. CONCLUSIONS: Understanding of IC performed for pediatric endoscopy could be improved in both parents and youth. Our findings suggest that interventions targeting parents, youth, and physicians may be helpful. Further study is needed to determine whether our findings are representative of IC understanding at other pediatric endoscopy centers.

[Comprehensive review on danger points, complications and medico-legal aspects in endoscopic sinus surgery]. / Fehler und Gefahren: Eingriffe an den Nasennebenhöhlen und der Frontobasis unter Berücksichtigung mediko-legaler Aspekte.

Endoscopic endonasal sinus surgery represents the overall accepted type of surgical treatment for chronic rhinosinusitis. Notwithstanding raised and still evolving quality standards, surgeons performing routine endoscopic interventions are faced with minor complications in 5% and major complications in 0.5-1%.A comprehensive review on all minor and major complications of endoscopic surgery of the paranasal sinuses and also on the anterior skull base is presented listing the actual scientific literature. The pathogenesis, signs and symptoms of each complication are reviewed and therapeutic regimens are discussed in detail relating to actual publication references. Potential medico-legal aspects are explicated and recent algorithms of avoidance are mentioned taking into account options in surgical training and education.

Physician accountability in iatrogenic cerebrospinal fluid leak litigation.

BACKGROUND: The potentially severe complications resulting from cerebrospinal fluid (CSF) leak makes iatrogenic injury a medicolegal area of concern for otolaryngologists and neurosurgeons. The objectives of this analysis were to study legal outcomes as well as medical and nonmedical elements affecting malpractice litigation. METHODS: Public court records available in the Westlaw legal database (Thomson Reuters, New York, NY) were searched for medical malpractice litigation related to iatrogenic CSF leak. Of the 18 jury verdicts and settlements included, outcomes and awards, patient demographic data, and other factors instrumental in determining legal responsibility were recorded for comparison. RESULTS: Ten (55.6%) cases were resolved in the defendant's favor, 2 (11.1%) resulted in damages awarded by a jury, and 6 (33.3%) were settled out of court before resolution of trial. Mean damages awarded were $1.1 million, while out of court settlements averaged $966,887. Malpractice stemming from patients who underwent endoscopic sinus surgery comprised 77.8% of cases analyzed. The most frequent alleged factors cited for litigation included having to undergo additional surgery (88.9%), developing meningitis (50.0%), and failing to recognize complications in a timely manner (44.4%). Perceived deficits in informed consent were alleged in one-third of cases. CONCLUSION: Although a slight majority of cases were resolved in the defendant's favor, payments made were considerable, averaging approximately $1 million. Strategies to decrease liability and allow patients to make more informed decisions should include clear communication with patients that explicitly states potential risks, such as meningitis, and possible need to undergo additional reparative surgery.

Medicolegal issues in endoscopic sinus surgery.

Endoscopic sinus surgery is one of the most litigated areas in otolaryngology. Physicians typically receive little education regarding medicolegal issues during training and may find themselves in an unfamiliar territory during litigation. This article reviews the scope of the problem and provides strategies to improve patient care and mitigate medicolegal risk in endoscopic sinus surgery.

Malpractice claims in nasal and sinus surgery: a review of 15 cases.

Otolaryngologists may encounter claims of medical malpractice during the course of their careers. A sample of 15 cases involving patient claims of medical malpractice relating to care delivered for problems of the nose and paranasal sinus is presented. A short summary of each case is provided, which may be useful to practicing otolaryngologists.

Sedation in endoscopy: when and how.

Sedation for endoscopy provides comfort for the patient and better examination conditions for the endoscopist. The high costs of providing anaesthesia by specialists and the relative lack of specialist personnel in many countries have led to the wider introduction of sedation delivered by non-anaesthesiologists. Such sedation should be targeted for moderate levels of sedation; however, personnel should be able to avoid - and rescue patients from - deeper sedation levels. Several conditions have to be fulfilled to provide proper and safe non-anaesthesiologist sedation for endoscopy, especially when propofol is to be used. These conditions include formal training, supervision by anaesthesiology staff, and definition of standard operating procedures on the national as well as local levels.

Exploraciones otorrinolaringológicas recomendables previas al inicio de actividades subacuáticas o aeronáuticas. Legislación vigente / Recommended otorhinolaryngological examination prior to diving or flying. Current legislation

Introducción, objetivos y métodos: El organismo humano está relativamente bien adaptado a los cambios de presión a los que se somete durante las actividades aeronáuticas e, incluso, las subacuáticas. Pequeñas alteraciones anatómicas o funcionales que no constituyen un problema a una presión atmosférica habitual, pueden originar complicaciones al someter al organismo a medios hipobáricoshiperbáricos. El objetivo de este capítulo es hacer una revisión de los criterios de aptitud en la legislación vigente, valorar las contraindicaciones para la práctica de buceo o actividades aeronáuticas y repasar las exploraciones necesarias en el área otorrinolaringológica (ORL) que permitan detectar procesos patológicos. Resultados: La valoración anatómica y funcional ORL nos permite descartar candidatos con distintas alteraciones que contraindican la práctica de estas actividades. No está tan claro cómo explorar las alteraciones funcionales y si hay relación entre los hallazgos y la posibilidad de aparición de complicaciones. La legislación vigente es poco clara en las actividades subacuáticas. Contraindica la actividad en personas con afectaciones que pruebas científicas recientes muestran que podrían ser aptas. La legislación en cuanto a pilotos y tripulantes de cabina de pasajeros de aeronaves comerciales estipula perfectamente las revisiones que se deben realizar, así como las contraindicaciones para la concesión de certificados de aptitud. Conclusiones: Es necesario realizar reconocimientos médicos en las personas que se someten a cambios de presión. En el área ORL, las exploraciones permiten hacer una buena valoración de los posibles problemas que pueden aparecer en los distintos candidatos (AU)

Introduction, objectives and methods. The human body is relatively well adapted to the pressure changes experienced during flying and even diving. Small anatomical or functional alterations that would not cause problems at a normal atmospheric pressure can cause complications when the body is subjected to hypobaric-hyperbaric environments. The present article aims to provide a review of the criteria for fitness to dive or fly according to current legislation, to evaluate the contraindications for the practice of diving or flying, and to describe the otorhinolaryngological (ORL) examinations that allow abnormalities to be detected. Results. Anatomical and functional ORL examination allows candidates with various alterations that contraindicate the practice of these activities to be excluded. Less clear are the methods for examining functional alterations and whether there is a relationship between these findings and the possible development of complications. Current legislation on diving is unclear. Subaquatic activities are contraindicated in persons with certain alterations, although recent scientific tests show that they may be fit to dive. Legislation on the pilots and cabin crews of commercial airplanes stipulate the examinations that should be performed as well as the contraindications for issuing certificates of fitness to fly. Conclusions. Medical examinations should be performed in persons undergoing changes in atmospheric pressure. ORL examinations allow the possible problems that may develop in distinct candidates to be thoroughly evaluated (AU)