Sharps Injuries Among Medical Trainees and Attending Physicians.

PURPOSE: Sharps injuries are a particularly concerning occupational hazard faced by physicians and are largely preventable. This study compared the proportion and rate of sharps injuries among medical trainees with those among attending physicians by sharps injury characteristics. METHOD: The authors used data reported to the Massachusetts Sharps Injury Surveillance System from 2002-2018. Sharps injury characteristics examined were department where injury occurred, device, purpose or procedure for which device was used or intended, presence of sharps injury prevention feature, who was holding the device, and how and when the injury occurred. Global chi-square was used to assess differences in the percent distribution of sharps injury characteristics between physician groups. Joinpoint regression was used to evaluate trends in injury rates among trainees and attendings. RESULTS: From 2002-2018, 17,565 sharps injuries among physicians were reported to the surveillance system, 10,525 of which occurred among trainees. For attendings and trainees combined, sharps injuries occurred most in operating and procedure rooms and most often involved suture needles. Significant differences in sharps injuries were found between trainees and attendings with respect to department, device, and intended purpose or procedure. Sharps without engineered sharps injury protections accounted for approximately 4.4 times as many injuries (13,355, 76.0%) as those with protections (3,008, 17.1%). Among trainees, sharps injuries were highest in the first quarter of the academic year and decreased over time, while sharps injuries among attendings had a very slight, significant increase. CONCLUSIONS: Sharps injuries are an ongoing occupational hazard faced by physicians, particularly during clinical training. Further research is needed to elucidate the etiology of the observed injury patterns during the academic year. Medical training programs need to implement a multipronged approach to prevent sharps injuries, including increased use of devices with sharps injury prevention features and robust training on safe handling of sharps.

Diphyllobothriasis in a U.S. Military Aviator.

BACKGROUND: Diphyllobothriasis is estimated to afflict 10-20 million people worldwide; however, this is the first case reported in a United States military aviator. Among the largest parasites of humans, the "fish tapeworm" grows from 2-15 m in length, can live >20 yr in the intestines, and is contracted through consumption of uncooked, unfrozen freshwater or anadromous fish species. CASE REPORT: A 32-yr-old male F-22 pilot presented with mild stomach cramping, bloating, nausea, and intermittent loose stools. Symptoms were relieved with bismuth subsalicylate until several days later when the patient, during otherwise normal bowel movements, extracted multiple broken segments of tapeworm. Although physically asymptomatic, he was psychologically disturbed. Based on the large number of ova with characteristic shape, size, color, and operculum, coupled with the flattened body, yellowish coloration, and rectangular proglottids with centrally located "rosette" uteri, he was diagnosed with diphyllobothriasis (likely D. latum or D. nihonkaiense). Successful treatment with a single oral dose of praziquantel (>10 mg · kg-1) was confirmed by negative stool examination over 60 d posttreatment. He likely contracted the parasite from ingesting salmon sushi or sashimi while previously stationed in Japan. DISCUSSION: Despite only mild physical symptoms, the pilot's psychological distress and distraction from knowing about the meters-long tapeworm was significant. Prompt treatment was paramount to resumption of military operations. Aviators should be educated and encouraged to eat only well-cooked or previously frozen fish, especially when indulging in cultural cuisine.Kasteler SD. Diphyllobothriasis in a U.S. military aviator. Aerosp Med Hum Perform. 2018; 89(5):473-477.

Conditional overexpression of receptors for advanced glycation end-products in the adult murine lung causes airspace enlargement and induces inflammation.

Receptors for advanced glycation end-products (RAGE) are multiligand surface receptors detected abundantly in pulmonary tissue. Our previous work revealed increased RAGE expression in cells and lungs exposed to tobacco smoke and RAGE-mediated cytokine expression via proinflammatory mechanisms involving NF-κB. RAGE expression is elevated in various pathological states, including chronic obstructive pulmonary disease; however, precise contributions of RAGE to the progression of emphysema and pulmonary inflammation in the adult lung are unknown. In the current study, we generated a RAGE transgenic (RAGE TG) mouse and conditionally induced adult alveolar epithelium to overexpress RAGE. RAGE was induced after the period of alveologenesis, from weaning (20 d of age) until animals were killed at 50, 80, and 110 days (representing 30, 60, and 90 d of RAGE overexpression). Hematoxylin and eosin staining and mean chord length revealed incremental dilation of alveolar spaces as RAGE overexpression persisted. TUNEL staining and electron microscopy confirmed increased apoptosis and blebbing of alveolar epithelium in lungs from RAGE TG mice when compared with control mice. Immunohistochemistry for matrix metalloproteinase 9 revealed an overall increase in matrix metalloproteinase 9, which correlated with decreased elastin expression in RAGE TG mice. Furthermore, RAGE TG mice manifested significant inflammation measured by elevated bronchoalveolar lavage protein, leukocyte infiltration, and secreted cytokines. These data support the concept that innovative transgenic mice that overexpress RAGE may model pulmonary inflammation and alveolar destabilization independent of tobacco smoke and validate RAGE signaling as a target pathway in the prevention or attenuation of smoke-related inflammatory lung diseases.

Receptor for advanced glycation end-products signals through Ras during tobacco smoke-induced pulmonary inflammation.

We previously demonstrated up-regulation of the receptor for advanced glycation end-products (RAGE) and its ligands by cigarette smoke extract (CSE) in rat R3/1 cells, a type I-like alveolar epithelial cell line. However, RAGE-mediated intracellular signaling pathways that lead to pulmonary inflammation remained unclear. Using ELISAs, we demonstrate that alveolar epithelial cell lines exposed to 25% CSE for 2 hours induce the activation of Ras, a small GTPase that functions as a molecular switch in the control of several intracellular signaling networks. Conversely, cells treated with siRNA for RAGE (siRAGE) resulted in decreased Ras activation. Furthermore, Ras was significantly diminished in lungs from RAGE null mice exposed to chronic tobacco smoke when compared with smoke-exposed wild-type mice. The use of a luciferase reporter containing NF-κB binding sites also demonstrated elevated NF-κB activation in R3/1 cells after CSE stimulation and decreased NF-κB activation in cells transfected with siRAGE before CSE exposure. ELISA revealed an increase in the secretion of IL-1ß and CCL5 by R3/1 cells, two cytokines induced by NF-κB and associated with leukocyte chemotaxis. Furthermore, real-time RT-PCR and ELISAs revealed decreased cytokine secretion in RAGE null mouse lung exposed to tobacco smoke compared with lungs from smoke-exposed wild-type animals. These results support the conclusion that CSE-induced RAGE expression functions in pathways that involve Ras-mediated NF-κB activation and cytokine elaboration. This RAGE-Ras-NF-κB axis likely contributes to inflammation associated with several smoking-related inflammatory lung diseases.

Receptors for advanced glycation end-products targeting protect against hyperoxia-induced lung injury in mice.

Patients with acute lung injury almost always require supplemental oxygen during treatment; however, elevated oxygen itself is toxic. Receptors for advanced glycation end-products (RAGE) are multi-ligand cell surface receptors predominantly localized to alveolar type I cells that influence development and cigarette smoke-induced inflammation, but studies that address the role of RAGE in acute lung injury are insufficient. In the present investigation, we test the hypothesis that RAGE signaling functions in hyperoxia-induced inflammation. RAGE-null mice exposed to hyperoxia survived 3 days longer than age-matched wild-type mice. After 4 days in hyperoxia, RAGE-null mice had less total cell infiltration into the airway, decreased total protein leak, diminished alveolar damage in hematoxylin and eosin-stained lung sections, and a lower lung wet-to-dry weight ratio. An inflammatory cytokine antibody array revealed decreased secretion of several proinflammatory molecules in lavage fluid obtained from RAGE knockout mice when compared with wild-type control animals. Real-time RT-PCR and immunoblotting revealed that hyperoxia induced RAGE expression in primary alveolar epithelial cells, and immunohistochemistry identified increased RAGE expression in the lungs of mice after exposure to hyperoxia. These data reveal that RAGE targeting leads to a diminished hyperoxia-induced pulmonary inflammatory response. Further research into the role of RAGE signaling in the lung should identify novel targets likely to be important in the therapeutic alleviation of lung injury and associated persistent inflammation.

RAGE: developmental expression and positive feedback regulation by Egr-1 during cigarette smoke exposure in pulmonary epithelial cells.

The receptor for advanced glycation end-products (RAGE) is a member of the immunoglobin superfamily of multiligand receptors. Following ligand binding, mechanisms associated with host defense, tissue remodeling, and inflammation are activated. RAGE is highly expressed in pulmonary epithelium transitioning from alveolar type (AT) II to ATI cells and is upregulated in the presence of ligand; however, the regulation and function of RAGE during development are less clear. Herein, immunohistochemistry demonstrated a temporal-spatial pattern of RAGE expression in pulmonary epithelial cells from embryonic day 17.5 to postnatal day 10. Cotransfection experiments revealed that the mouse RAGE promoter was activated by early growth response gene 1 (Egr-1) and inhibited by thyroid transcription factor-1 (TTF-1) via interaction with specific regulatory elements. A rat ATI cell line (R3/1) with endogenous RAGE expression also differentially regulated RAGE when transfected with TTF-1 or Egr-1. Because Egr-1 is markedly induced in pulmonary epithelial cells exposed to cigarette smoke extract (CSE; Reynolds PR, Hoidal JR. Am J Respir Cell Mol Biol 35: 314-319, 2006.), we sought to investigate RAGE induction by CSE. Employing RT-PCR and Western blotting, RAGE and common ligands (amphoterin and S100A12) were upregulated in epithelial (R3/1 and A549) and macrophage (RAW) cell lines following exposure to CSE. Immunostaining for RAGE in cells similarly exposed and in lungs from mice exposed to cigarette smoke for 6 mo revealed elevated RAGE expression in pulmonary epithelium. After the addition of glyoxylated BSA, an advanced glycation end-product that binds RAGE, real-time RT-PCR detected a 200-fold increase in Egr-1. These results indicate that Egr-1 regulates RAGE expression during development and the likelihood of positive feedback involving Egr-1 and RAGE in cigarette smoke-related disease.