Objective Neck masses are common in adults, but often the underlying etiology is not easily identifiable. While infections cause most of the neck masses in children, most persistent neck masses in adults are neoplasms. Malignant neoplasms far exceed any other etiology of adult neck mass. Importantly, an asymptomatic neck mass may be the initial or only clinically apparent manifestation of head and neck cancer, such as squamous cell carcinoma (HNSCC), lymphoma, thyroid, or salivary gland cancer. Evidence suggests that a neck mass in the adult patient should be considered malignant until proven otherwise. Timely diagnosis of a neck mass due to metastatic HNSCC is paramount because delayed diagnosis directly affects tumor stage and worsens prognosis. Unfortunately, despite substantial advances in testing modalities over the last few decades, diagnostic delays are common. Currently, there is only 1 evidence-based clinical practice guideline to assist clinicians in evaluating an adult with a neck mass. Additionally, much of the available information is fragmented, disorganized, or focused on specific etiologies. In addition, although there is literature related to the diagnostic accuracy of individual tests, there is little guidance about rational sequencing of tests in the course of clinical care. This guideline strives to bring a coherent, evidence-based, multidisciplinary perspective to the evaluation of the neck mass with the intention to facilitate prompt diagnosis and enhance patient outcomes. Purpose The primary purpose of this guideline is to promote the efficient, effective, and accurate diagnostic workup of neck masses to ensure that adults with potentially malignant disease receive prompt diagnosis and intervention to optimize outcomes. Specific goals include reducing delays in diagnosis of HNSCC; promoting appropriate testing, including imaging, pathologic evaluation, and empiric medical therapies; reducing inappropriate testing; and promoting appropriate physical examination when cancer is suspected. The target patient for this guideline is anyone ≥18 years old with a neck mass. The target clinician for this guideline is anyone who may be the first clinician whom a patient with a neck mass encounters. This includes clinicians in primary care, dentistry, and emergency medicine, as well as pathologists and radiologists who have a role in diagnosing neck masses. This guideline does not apply to children. This guideline addresses the initial broad differential diagnosis of a neck mass in an adult. However, the intention is only to assist the clinician with a basic understanding of the broad array of possible entities. The intention is not to direct management of a neck mass known to originate from thyroid, salivary gland, mandibular, or dental pathology as management recommendations for these etiologies already exist. This guideline also does not address the subsequent management of specific pathologic entities, as treatment recommendations for benign and malignant neck masses can be found elsewhere. Instead,...

Objective To evaluate the prevalence and characteristics of olfactory or gustatory dysfunction in coronavirus disease 2019 (COVID-19) patients. Study Design Multicenter case series. Setting Five tertiary care hospitals (3 in China, 1 in France, 1 in Germany). Subjects and Methods In total, 394 polymerase chain reaction (PCR)–confirmed COVID-19-positive patients were screened, and those with olfactory or gustatory dysfunction were included. Data including demographics, COVID-19 severity, patient outcome, and the incidence and degree of olfactory and/or gustatory dysfunction were collected and analyzed. The Questionnaire of Olfactory Disorders (QOD) and visual analog scale (VAS) were used to quantify olfactory and gustatory dysfunction, respectively. All subjects at 1 hospital (Shanghai) without subjective olfactory complaints underwent objective testing. Results Of 394 screened subjects, 161 (41%) reported olfactory and/or gustatory dysfunction and were included. Incidence of olfactory and/or gustatory disorders in Chinese (n = 239), German (n = 39), and French (n = 116) cohorts was 32%, 69%, and 49%, respectively. The median age of included subjects was 39 years, 92 of 161 (57%) were male, and 10 of 161 (6%) were children. Of included subjects, 10% had only olfactory or gustatory symptoms, and 19% had olfactory and/or gustatory complaints prior to any other COVID-19 symptom. Of subjects with objective olfactory testing, 10 of 90 demonstrated abnormal chemosensory function despite reporting normal subjective olfaction. Forty-three percent (44/102) of subjects with follow-up showed symptomatic improvement in olfaction or gustation. Conclusions Olfactory and/or gustatory disorders may represent early or isolated symptoms of severe acute respiratory syndrome coronavirus 2 infection. They may serve as a useful additional screening criterion, particularly for the identification of patients in the early stages of infection.

Numerous proteins targeted for the secretory pathway are increasingly implicated in functional or pathological roles at alternative cellular destinations. The parameters that allow secretory or membrane proteins to reside in intracellular locales outside the secretory pathway remain largely unexplored. In this study, we have used an extremely sensitive and quantitative assay to measure the in vivo efficiency of signal sequence-mediated protein segregation into the secretory pathway. Our findings reveal that segregation efficiency varies tremendously among signals, ranging from >95 to <60%. The nonsegregated fraction is generated by a combination of mechanisms that includes inefficient signal-mediated translocation into the endoplasmic reticulum and leaky ribosomal scanning. The segregation efficiency of some, but not other signal sequences, could be influenced in cis by residues in the mature domain or in trans by yet unidentified cellular factors. These findings imply that protein compartmentalization can be modulated in a substrate-specific manner to generate biologically significant quantities of cytosolically available secretory and membrane proteins. INTRODUCTIONIn mammalian cells, an estimated one-fifth to one-third of all proteins reside in or transit through the secretory pathway. The decisive step in segregating these proteins from the cytosol is their cotranslational targeting to and translocation across the endoplasmic reticulum (ER) membrane (reviewed by Walter and Johnson, 1994;Rapoport et al., 1996;Johnson and van Waes, 1999). Both targeting and initiation of translocation are dependent on a signal sequence, often at the N terminus, encoded in secretory and membrane proteins. Although the primary sequence of signals varies broadly (von Heijne, 1985), they contain shared features (such as hydrophobicity) that allow their common recognition by a ubiquitous machinery for ER translocation. Thus, proteins containing signal sequences are generally considered to have their intended functions at destinations accessed via the secretory pathway.Increasingly, however, many signal-containing proteins have been implicated in functional, pathological, or yet unknown roles at sites outside the secretory pathway. For example, the ER lumenal chaperone calreticulin (CRT) was identified completely independently as a cytosolic integrinbinding protein (Leung-Hagesteijn et al., 1994;Coppolino et al., 1995Coppolino et al., , 1997, a nuclear export factor (Holaska et al., 2001), a regulator of steroid hormone receptor activity (Burns et al., 1994;Dedhar et al., 1994), and an mRNA binding protein that regulates p21 translation (Iakova et al., 2004). In each of these instances, both functional and physical interactions with the respective cytosolic components have been demonstrated. Similarly, a different ER resident protein, the ␤ subunit of glucosidase II (Trombetta et al., 1996), was originally discovered (and given the name 80K-H) as a target of protein kinase C (Sakai et al., 1989;Hirai and Shimizu, 1990). More recentl...

interpretation of data, 102 writing, revising it critically. All of them agreement to be accountable for all aspects of 103 the work in ensuring that questions related to the accuracy or integrity of any part of 104 the work are appropriately investigated and resolved. 105 106 Abstract 123