Mapping Human Immunity and the Education of Waldeyer's Ring.

The development and deployment of single-cell genomic technologies have driven a resolution revolution in our understanding of the immune system, providing unprecedented insight into the diversity of immune cells present throughout the body and their function in health and disease. Waldeyer's ring is the collective name for the lymphoid tissue aggregations of the upper aerodigestive tract, comprising the palatine, pharyngeal (adenoids), lingual, and tubal tonsils. These tonsils are the first immune sentinels encountered by ingested and inhaled antigens and are responsible for mounting the first wave of adaptive immune response. An effective mucosal immune response is critical to neutralizing infection in the upper airway and preventing systemic spread, and dysfunctional immune responses can result in ear, nose, and throat pathologies. This review uses Waldeyer's ring to demonstrate how single-cell technologies are being applied to advance our understanding of the immune system and highlight directions for future research.

The utility of a symptom model to predict the risk of oesophageal cancer.

OBJECTIVE: To assess whether extra-oesophageal symptoms are predictive of oesophageal malignancy. METHODS: A prospective, single-centre cross-sectional questionnaire study at a tertiary referral unit for oesophageal cancer using the Comprehensive Reflux Symptoms Scale (CReSS) questionnaire tool. Respondents with oesophageal malignancy were compared with historical cohorts undergoing airway examination or upper gastrointestinal endoscopy and found to have benign diagnoses. We developed a model for predicting oesophageal cancer using linear discriminant analysis and logistic regression, assessed by Monte Carlo cross validation. RESULTS: Respondents with oesophageal malignancy (n = 146; mean age 70.5; male: female, 71:29) were compared with those undergoing airway examination (n = 177) and upper gastrointestinal endoscopy (n = 351), found to have benign diagnoses. No single questionnaire item, or group of co-varying items (factors), reliably discriminated oesophageal cancer from other diagnoses. Individual items which suggested higher risk of oesophageal malignancy included dysphagia (area under the curve (AUC) 0.68), low appetite (AUC 0.66), and early satiety (AUC 0.58). Conversely, throat pain (AUC 0.38), bloating (AUC 0.38) and heartburn (AUC 0.37) were inversely related to cancer risk. A forward stepwise regression analysis including a subset of 12 CReSS questionnaire items together with age and sex derived a model predictive of oesophageal malignancy in this cohort (AUC 0.89). CONCLUSION: We demonstrate a model comprised of 12 questionnaire items and 2 demographic parameters as a potential predictive tool for oesophageal malignancy diagnosis in this study population. Translating this model for predicting oesophageal malignancy in the general population is a valuable topic for future research.

No Evidence of Systemic Inflammation in Symptomatic Patients With Femoroacetabular Impingement.

Femoroacetabular impingement (FAI) is a common cause of hip pain and represents a major cause of early osteoarthritis. The role of systemic inflammation in pre-arthritic hip conditions remains largely unknown and uninvestigated. Serum-free light chains (sFLCs) are inflammatory markers produced by B cells. This study aimed to determine whether there was evidence of systemic inflammation in patients with FAI, defined by sFLCs, and whether this correlated with markers of disease severity. Participants for this study were recruited from a single center (Nuffield Orthopedic Center, Oxford) and were taking part in the Femoroacetabular Impingement Trial. The cohort comprised 115 individuals (38 male, 77 female, mean age 37 years): 57 individuals received surgical intervention and 58 received physiotherapy. All individuals provided patient-reported outcome measures and serum samples at baseline and follow-up 8 months post-randomization. sFLC concentrations were measured in serum samples by immunoturbidimetry. At baseline, for all individuals, mean polyclonal sFLC concentrations were 30.36 mg/l (standard deviation [SD] 9.23). At follow-up, the mean polyclonal sFLC concentrations were 31.68 mg/l (SD 9.61) in the surgical intervention cohort, and 29.48 mg/l (SD 7.85) in the physiotherapy intervention cohort. There was no significant correlation between sFLC concentrations and any of the patient reported outcome measures, or radiographic measures: average or maximum alpha angle, or center edge angle. In conclusion, in patients with symptomatic FAI there was no systemic inflammation, as defined by sFLC concentrations, and no correlation between sFLC concentrations and measures of disease severity. The lack of inflammation suggests FAI is a mechanical phenomenon. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2189-2196, 2019.