Examination of Sex Differences in a Chronic Rhinosinusitis Surgical Cohort.

OBJECTIVE: Sex discrepancies have been reported in chronic rhinosinusitis (CRS), but limited data exist exploring sex-specific biological processes and sinonasal quality of life. STUDY DESIGN: Prospective cohort. SETTING: Academic medical center. METHODS: Demographics, clinical data, and sinonasal mucus were collected from patients with CRS presenting for surgical consideration over a 5-year period. A random forest model and linear regression were used to assess predictor variables for the 22-item Sino-Nasal Outcome Test (SNOT-22) and subdomains. Enzyme-linked immunosorbent assays were used to measure substance P and tryptase in a subset of mucus samples to explore biological differences by sex. RESULTS: In total, 520 patients were studied (mean age 48.3 years, 50.9% female). Males were older (50.1 vs 46.6 years, P = .008), had more polyp disease (48.2% vs 35.5%, P = .004), and had higher mean Lund-Mackay CT score (11.3 vs 9.5, P = .004). Females had a higher overall mean SNOT-22 (40.9 vs 46.9, P = .001) and higher scores in ear/facial, psychological, and sleep domains (P < .01). Age, objective disease measures, and sex were top predictors for total SNOT-22. Neither mucus substance P or tryptase, alone or paired with sex, correlated with total SNOT-22. Analysis of mucus biomarkers by sex revealed correlation between mucus tryptase in females with the extranasal subdomain (P = .01). CONCLUSION: Sex differences exist in CRS disease manifestations and presentation for surgical consideration. Detection of mucus (substance P and tryptase) was reliable, but in this exploratory study, we were not able to establish neurogenic or allergic inflammatory processes as a large source of differential disease features between sexes.

Patient Chief Complaint and Otolaryngology Referral Rationale: Discordance and Opportunities for Quality Improvement.

OBJECTIVE: As medical systems focus on patient satisfaction as an important care outcome, specialty clinics are tasked with continued improvement of patients' experience. When patient expectations for a consultation differ from that of the specialty provider, dissatisfaction with the experience can occur. One source of differing expectations is discordance between the patient's chief complaint and the clinical rationale for the consultation as requested by the referring provider. We sought to better understand when this discordance occurs, as well as factors contributing to this disorientation of patient and provider expectations in a safety net otolaryngology practice. METHODS: A retrospective observational study was performed and records were examined from new patient consultations. Patient questionnaires, including self-reported chief concerns, were compared with the electronic referral documentation. A difference between the patient's Chief Complaint (CC) and Referral Reason (RR) was defined as CC-RR Discordance. Medical records, pre-consultation patient communication, and scheduling data were also reviewed to evaluate contributing factors. RESULTS: Of the 1155 consultations examined, 952 were included in the analysis. A CC-RR Discordance was found in 175 (18.4%) of new-patient encounters, including 117 (12.3%) that were unable to articulate a CC (unsure of the reason for the appointment), and 58 (6.1%) that stated a CC that was different than the RR. The rate of CC-RR Discordance was higher in patients with female sex (P < .05), older age (P < .001), and longer time intervals between referral and appointment (P < .05). Lack of communication with the patient (instructions or referral notification) by the referring provider was not associated with CC-RR Discordance. CONCLUSIONS: Discordance between patient CC and the rationale for a consultation is common in this safety-net otolaryngology practice and may be an important source of patient dissatisfaction. Future opportunities for quality improvement include pre-consultation communication between the specialist and the patient and reducing time intervals between referral and appointment.

Pain Scores and Activity Tolerance in the Early Postoperative Period After Hip Arthroscopy.

BACKGROUND: Despite the rapid growth in the use of hip arthroscopy, standardized data on postoperative pain scores and activity level are lacking. PURPOSE: To quantify narcotic consumption and use of the stationary bicycle in the early postoperative period after hip arthroscopy. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: In this prospective case series, patients undergoing a primary hip arthroscopy procedure by a single surgeon were asked to fill out a daily survey for 9 days postoperatively. Patients were asked to report their pain level each day on a visual analog scale from 1 to 10, along with the amount of narcotic pain pills they used during those postoperative days (PODs). Narcotic usage was converted to a morphine-equivalent dosage (MED) for each patient. Patients were also instructed to cycle daily starting on the night of surgery for a minimum of 3 minutes twice per day and were asked to rate their pain as a percentage of their preoperative pain level and the number of minutes spent cycling on a stationary bicycle per day. RESULTS: A total of 212 patients were enrolled in this study. Pain levels (POD1, 5.5; POD4, 3.8; POD9, 2.9; P < .0001) and the percentage of preoperative pain (POD1, 51.6%; POD4, 31.8%; POD9, 29.5%; P < .01) significantly decreased over the study period. The amount of narcotics used per day (reported in MED) also significantly decreased (POD1, 27.3; POD4, 22.3; POD9, 8.5; P < .0001). By POD4, 41% of patients had discontinued all narcotics, and by POD9, 65% of patients were completely off narcotic medication. Patients were able to significantly increase the number of minutes spent cycling each day (POD1, 7.6 minutes; POD4, 13.8 minutes; POD9, 19.0 minutes; P < .0001). Patients who received a preoperative narcotic prescription for the affected hip were significantly more likely to require an additional postoperative narcotic prescription (P < .001). CONCLUSION: Patients can expect a rapid decrease in narcotic consumption along with a high degree of activity tolerance in the early postoperative period after hip arthroscopy.

Neonatal and infant immunity for tuberculosis vaccine development: importance of age-matched animal models.

Neonatal and infant immunity differs from that of adults in both the innate and adaptive arms, which are critical contributors to immune-mediated clearance of infection and memory responses elicited during vaccination. The tuberculosis (TB) research community has openly admitted to a vacuum of knowledge about neonatal and infant immune responses to Mycobacterium tuberculosis (Mtb) infection, especially in the functional and phenotypic attributes of memory T cell responses elicited by the only available vaccine for TB, the Bacillus Calmette-Guérin (BCG) vaccine. Although BCG vaccination has variable efficacy in preventing pulmonary TB during adolescence and adulthood, 80% of endemic TB countries still administer BCG at birth because it has a good safety profile and protects children from severe forms of TB. As such, new vaccines must work in conjunction with BCG at birth and, thus, it is essential to understand how BCG shapes the immune system during the first months of life. However, many aspects of the neonatal and infant immune response elicited by vaccination with BCG remain unknown, as only a handful of studies have followed BCG responses in infants. Furthermore, most animal models currently used to study TB vaccine candidates rely on adult-aged animals. This presents unique challenges when transitioning to human trials in neonates or infants. In this Review, we focus on vaccine development in the field of TB and compare the relative utility of animal models used thus far to study neonatal and infant immunity. We encourage the development of neonatal animal models for TB, especially the use of pigs.

Minipigs as a neonatal animal model for tuberculosis vaccine efficacy testing.

Many vaccines against childhood diseases are administered early after birth, but vaccine development studies frequently test efficacy in adult rather than in neonatal animal models. In countries with endemic tuberculosis (TB), Bacillus Calmette-Guerin (BCG) is administered as part of the neonatal vaccine regimen because it prevents against the disseminated form of TB in children, although it has variable efficacy against pulmonary TB. Several promising new vaccines against TB are currently being tested in adult animal models. Here we evaluated neonatal piglets as an animal model to test vaccine efficacy. For this purpose, minipigs were vaccinated or not with BCG 48 h after birth and their immune response followed longitudinally until adolescence. We characterized the memory and activation phenotype of T cells, cytokine profile, and monocyte activation in response to BCG stimulation from 4 weeks of age into adolescence- age of 24 weeks. Immunological responses in vaccinated and non-vaccinated animals were further monitored upon infection with a low dose exposure to Mycobacterium tuberculosis strain HN878 via the aerosol route. Comparing the immunological response elicited by BCG vaccination in minipigs vs similar studies in infants, suggest that minipigs have the potential to serve as an effective neonatal animal model for vaccine development.

The minipig as an animal model to study Mycobacterium tuberculosis infection and natural transmission.

In endemic countries more than 20% of tuberculosis (TB) cases are in infants and children. Current animal models study TB during adulthood but animal models for infant TB are scarce. Here we propose that minipigs can be used as an animal model to study adult, adolescent and infant TB including natural transmission. In these studies, two-month old minipigs (representing infant age in humans) and six-month old minipigs (representing adolescence in humans) were infected via the aerosol route with hyper-virulent clinical strain W-Beijing Mycobacterium tuberculosis (Mtb) HN878 and were monitored for 11 or 36 weeks post-challenge, respectively. In the same studies, infected and unchallenged animals were housed together. Viable bacteria were recovered from pulmonary and thoracic lymph nodes from both -infected and their initially unchallenged natural contacts. Bacillary load, gross lesions and histopathology revealed similarities to the spectrum of disease observed in human TB. The study did not reach terminal end point, thus it was not possible to annotate definitive clinical symptoms of active TB. The results demonstrated that minipigs are experimental hosts of Mtb HN878, and the pathology developed in their lungs resembles pathological findings described in human TB. Importantly, within communities of Mtb infected minipigs natural transmission occurs.

Characterization of conformation-dependent prion protein epitopes.

Whereas prion replication involves structural rearrangement of cellular prion protein (PrP(C)), the existence of conformational epitopes remains speculative and controversial, and PrP transformation is monitored by immunoblot detection of PrP(27-30), a protease-resistant counterpart of the pathogenic scrapie form (PrP(Sc)) of PrP. We now describe the involvement of specific amino acids in conformational determinants of novel monoclonal antibodies (mAbs) raised against randomly chimeric PrP. Epitope recognition of two mAbs depended on polymorphisms controlling disease susceptibility. Detection by one, referred to as PRC5, required alanine and asparagine at discontinuous mouse PrP residues 132 and 158, which acquire proximity when residues 126-218 form a structured globular domain. The discontinuous epitope of glycosylation-dependent mAb PRC7 also mapped within this domain at residues 154 and 185. In accordance with their conformational dependence, tertiary structure perturbations compromised recognition by PRC5, PRC7, as well as previously characterized mAbs whose epitopes also reside in the globular domain, whereas conformation-independent epitopes proximal or distal to this region were refractory to such destabilizing treatments. Our studies also address the paradox of how conformational epitopes remain functional following denaturing treatments and indicate that cellular PrP and PrP(27-30) both renature to a common structure that reconstitutes the globular domain.