Socioeconomic Status and Rurality Among Patients With Head and Neck Cancer.

OBJECTIVE: Describe the relationship among rurality, socioeconomic status (SES), and patient/tumor characteristics in patients presenting with head and neck cancer. STUDY DESIGN: Retrospective single-institution study. SETTING: Academic tertiary-level medical center. METHODS: Patients with head and neck cancer presenting between 2011 and 2015 were included. Stage at presentation, insurance status, and demographic characteristics were collected. Rurality was measured through Rural-Urban Continuum Codes. SES was measured by SES index scores of the Agency for Healthcare Research and Quality, which incorporate multiple components of SES. Associations among rurality, SES, and patient/tumor characteristics were assessed with univariate and multivariable statistics. All P values were calculated via 2-sided hypotheses. The threshold for statistical significance was set at P < .05. Statistical analyses were conducted with Stata/SE 14 (StataCorp). RESULTS: The study included 266 patients diagnosed with head and neck cancer between 2011 and 2015. Rural residence was associated with lower SES (P < .001). T and N stages were associated with rurality (P = .036 and .050, respectively). Higher educational status was associated with oropharyngeal cancer (P = .005). CONCLUSIONS: Rurality and SES have distinct impacts on patients with head and neck cancer. Specifically, rurality is associated with tumor stage among patients with head and neck cancer. Knowledge of disparities among patients with rural residency may help target interventions to facilitate earlier diagnosis.

Rapid telehealth implementation into an otolaryngology practice during the COVID-19 pandemic.

OBJECTIVE: Report outcomes of rapid implementation of telehealth across an academic otolaryngology-head and neck surgery department during the COVID-19 pandemic. METHODS: This is a retrospective, single-institution study of rapid deployment of telehealth during the COVID-19 pandemic. Characteristics of patients were compared between those who agreed and those who declined telehealth care. Reasons for declining telehealth visits were ascertained. Characteristics of telehealth visits were collected and patients were asked to complete a post-visit satisfaction survey. RESULTS: There was a 68% acceptance rate for telehealth visits. In multivariable analysis, patients were more likely to accept telehealth if they were being seen in the facial plastics subspecialty clinic (odds ratio [OR] 59.55, 95% confidence interval [CI] 2.21-1607.52; P = .015) compared to the general otolaryngology clinic. Patients with Medicare (compared to commercial insurance) as their primary insurance were less likely to accept telehealth visits (OR 0.10, 95% CI 0.01-0.77; P = .027). Two hundred and thirty one patients underwent telehealth visits; most visits (69%) were for established patients and residents were involved in 38% of visits. There was an 85% response rate to the post-visit survey. On a scale of one to ten, the median satisfaction score was 10 and 99% of patients gave a score of 8 or higher. Satisfaction scores were higher for new patient visits than established patient visits (P = .020). CONCLUSION: Rapid implementation of telehealth in an academic otolaryngology-head and neck surgery department is feasible. There was high acceptance of and satisfaction scores with telehealth. LEVEL OF EVIDENCE: 3.

Development and Assessment of an Otolaryngology-Specific Surgical Priority Scoring System.

OBJECTIVE: To develop and assess an otolaryngology-specific surgical priority scoring system that incorporates varying levels of mucosal involvement. STUDY DESIGN: Retrospective cohort. SETTING: Academic medical center. METHODS: A novel mucosal score was developed based on best available evidence. This mucosal score was incorporated into the Medically Necessary, Time-Sensitive (MeNTS) score to generate a MeNTS-Mucosal (MeNTS-M) score. A retrospective cohort of patients was identified to assess the surgical priority scoring systems. Inclusion criteria included all scheduled surgical procedures between March 23, 2020, and April 17, 2020. Decisions about whether to proceed or cancel were made based on best clinical judgment by surgeons, without use of any surgical priority scores. The predictive value of the surgical priority scoring systems was assessed in this retrospective cohort. RESULTS: The median MeNTS score was significantly lower in adult patients whose surgery proceeded compared to those for whom the surgery was cancelled (48 vs 56; P = .004). Mucosal and MeNTS-M scores were not statistically different based on whether surgery proceeded. Among adult patients, the highest area under the curve (AUC) was for the MeNTS scoring system (0.794); both the mucosal and MeNTS-M systems had lower AUC values (which were significantly lower than the AUC for the MeNTS scoring system). CONCLUSION: This study represents development and assessment of the first otolaryngology-specific surgical priority score and incorporates varying levels of mucosal disruption. The combined MeNTS-M scoring system could be a valuable tool in appropriately triaging otolaryngology-head and neck surgery procedures.

Evolving disparities in the epidemiology of oral cavity and oropharyngeal cancers.

Incidence rates of head and neck cancers (HNC) associated with human papillomavirus (HPVa) infection are increasing while non-HPV-associated (non-HPVa) HNC cancer rates are decreasing. As nearly all sexually active individuals will acquire an HPV infection, it is important to understand epidemiologic trends of HNCs associated with this sexually transmitted disease. We analyzed SEER 9 (1973-2012) and 18 data (2000-2012) for HPVa HNCs (oropharynx area; OP) and non-HPVa (oral cavity area; OC). Incidence rates were examined by gender, race, rurality, geographic location, and time. Joinpoint regression analyses assessed temporal variations. From 1973 to 2012, OC incidence decreased while OP increased, with changes largely driven by males (whose OP rate increased 106.2% vs female decrease of 10.3%). Males consistently had higher rates of both cancer groups across each registry except Alaska, OP rates among blacks changed from significantly above whites to below, and trend analysis indicated significant differences in rates over time by gender, race, and geography. Analysis of SEER 18 found that rates discordantly varied by group and gender across the 18 registries, as did the male/female rate ratio with overall means of 4.7 for OP versus 1.7 for OC (only Alaska and Georgia having overlapping ranges). Our findings indicate that much of the HPVa rate increases were driven by rate increases among males and that there were changing differences in risk between genders, race, and geographic location. The epidemiology of HNCs is complex, with locally relevant factors requiring further research for elucidation of demographic disparities in incidence.

Quantitative assessment of the longevity of poly-L-lactic acid as a volumizing filler using 3-dimensional photography.

OBJECTIVE: To demonstrate the efficacy and longevity of injectable poly-L-lactic acid as a volumizing injectable in the midface region quantitatively using 3-dimensional (3-D) imaging. DESIGN, SETTING, AND PARTICIPANTS: Prospective study assessing changes in midfacial volume in 15 women aged between 40 and 60 years using a 3-D imaging system at 12, 24, 36, and 48 weeks after 3 treatments with poly-L-lactic acid. Three-dimensional imaging was acquired using the 3-D camera and software. INTERVENTION: Patients were treated with poly-L-lactic acid. The first 2 treatments were 6 weeks apart. The third treatment was performed 12 weeks after the second treatment. MAIN OUTCOMES AND MEASURES: Changes in midfacial volume following 3 treatments of poly-L-lactic acid were measured quantitatively using the 3-D imaging system. A paired t test was used to analyze the difference between pretreatment and posttreatment values at each study time point. RESULTS: Of the 15 patients, 1 only received 2 treatments and was therefore excluded from the statistical analysis. There was a statistically significant increase in mean midfacial volume at all study time points, 12 weeks (mean [range], 7.2 [1.6-20.7] mL; P < .001), 24 weeks (mean [range], 7.2 [1.9-19.4] mL; P < .001), 36 weeks (mean [range], 4.6 [1.1-9.2] mL; P = .002), and 48 weeks (mean [range], 4.1 [0.8-6.4] mL; P < .001), compared with pretreatment volume. There was no significant change in volume between each of the follow-up time points. CONCLUSIONS AND RELEVANCE: Our prospective investigation quantitatively demonstrates the efficacy of poly-L-lactic acid as a long-acting volumizing agent, with an increase in midfacial volume from baseline sustained at least 1 year after treatment. LEVEL OF EVIDENCE: 2. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01307865.

Mechanisms of decreased intestinal epithelial proliferation and increased apoptosis in murine acute lung injury.

OBJECTIVES: The aim of this study was to determine the effects of acute lung injury on the gut epithelium and examine mechanisms underlying changes in crypt proliferation and apoptosis. The relationship between severity and timing of lung injury to intestinal pathology was also examined. DESIGN: Randomized, controlled study. SETTING: University research laboratory. SUBJECTS: Genetically inbred mice. INTERVENTIONS: Following induction of acute lung injury, gut epithelial proliferation and apoptosis were assessed in a) C3H/HeN wild-type and C3H/HeJ mice, which lack functional Toll-like receptor 4 (n = 17); b) C57Bl/6 mice that received monoclonal anti-tumor necrosis factor-alpha or control antibody (n = 22); and c) C57Bl/6 wild-type and transgenic mice that overexpress Bcl-2 in their gut epithelium (n = 21). Intestinal epithelial proliferation and death were also examined in animals with differing degrees of lung inflammation (n = 24) as well as in a time course analysis following a fixed injury (n = 18). MEASUREMENTS AND MAIN RESULTS: Acute lung injury caused decreased proliferation and increased apoptosis in crypt epithelial cells in all animals studied. C3H/HeJ mice had higher levels of proliferation than C3H/HeN animals without additional changes in apoptosis. Anti-tumor necrosis factor-alpha antibody had no effect on gut epithelial proliferation or death. Overexpression of Bcl-2 did not change proliferation despite decreasing gut apoptosis. Proliferation and apoptosis were not correlated to severity of lung injury, as gut alterations were lost in mice with more severe acute lung injury. Changes in both gut epithelial proliferation and death were apparent within 12 hrs, but proliferation was decreased 36 hrs following acute lung injury while apoptosis returned to normal. CONCLUSIONS: Acute lung injury causes disparate effects on crypt proliferation and apoptosis, which occur, at least in part, through differing mechanisms involving Toll-like receptor 4 and Bcl-2. Severity of lung injury does not correlate with perturbations in proliferation or death in the gut epithelium, and acute lung injury-induced changes in intestinal epithelial proliferation persist longer than those in apoptosis.

Iron dysregulation combined with aging prevents sepsis-induced apoptosis.

BACKGROUND: Sepsis, iron loading, and aging cause independent increases in gut epithelial and splenic apoptosis. It is unknown how their combination will affect apoptosis and systemic cytokine levels. MATERIALS AND METHODS: Hfe-/- mice (a murine homologue of hemochromatosis) abnormally accumulate iron in their tissues. Aged (24-26 months) or mature (16-18 months) Hfe-/- mice and wild type (WT) littermates were subjected to cecal ligation and puncture (CLP) or sham laparotomy. Intestine, spleen, and blood were harvested 24 h later and assessed for apoptosis and cytokine levels. RESULTS: Gut epithelial and splenic apoptosis were low in both aged septic and sham Hfe-/- mice, regardless of the amount of iron in their diet. Mature septic WT mice had increased apoptosis compared to age-matched sham WT mice. Mature septic Hfe-/- mice had similar levels of intestinal cell death to age-matched septic WT mice but higher levels of splenic apoptosis. Apoptosis was significantly lower in septic aged Hfe-/- mice than septic mature Hfe-/- animals. Interleukin-6 was elevated in septic aged Hfe-/- mice compared to sham mice. CONCLUSIONS: Although sepsis, chronic iron dysregulation, and aging each increase gut and splenic apoptosis, their combination yields cell death levels similar to sham animals despite the fact that aged Hfe-/- mice are able to mount an inflammatory response following CLP and mature Hfe-/- mice have elevated sepsis-induced apoptosis. Combining sepsis with two risk factors that ordinarily increase cell death and increase mortality in CLP yields an apoptotic response that could not have been predicted based upon each element in isolation.

Early antibiotic administration but not antibody therapy directed against IL-6 improves survival in septic mice predicted to die on basis of high IL-6 levels.

Elevated interleukin (IL)-6 levels correlate with increased mortality following sepsis. IL-6 levels >14,000 pg/ml drawn 6 h after cecal ligation and puncture (CLP) are associated with 100% mortality in ND4 mice, even if antibiotic therapy is initiated 12 h after septic insult. Our first aim was to see whether earlier institution of antibiotic therapy could improve overall survival in septic mice and rescue the subset of animals predicted to die on the basis of high IL-6 levels. Mice (n = 184) were subjected to CLP, had IL-6 levels drawn 6 h later, and then were randomized to receive imipenem, a broad spectrum antimicrobial agent, beginning 6 or 12 h postoperatively. Overall 1-wk survival improved from 25.5 to 35.9% with earlier administration of antibiotics (P < 0.05). In mice with IL-6 levels >14,000 pg/ml, 25% survived if imipenem was started at 6 h, whereas none survived if antibiotics were started later (P < 0.05). On the basis of these results, we examined whether targeted antibody therapy could improve survival in mice with elevated IL-6 levels. A different cohort of mice (n = 54) had blood drawn 6 h after CLP, and then they were randomized to receive either monoclonal anti-IL-6 IgG or irrelevant rat IgG. Anti-IL-6 antibody failed to improve either overall survival or outcome in mice with IL-6 levels >14,000 pg/ml. These results demonstrate that earlier systemic therapy can improve outcome in a subset of mice predicted to die in sepsis, but we are unable to demonstrate any benefit in similar animals using targeted therapy directed at IL-6.

Age disproportionately increases sepsis-induced apoptosis in the spleen and gut epithelium.

Both aging and sepsis independently increase splenic and gut epithelial apoptosis. Sepsis-induced apoptosis in either cell type is also associated with increased mortality in young mice. We sought to determine whether age alters sepsis-induced splenic and gut epithelial cell death. Young (2 months) and aged (22 months) male ND4 mice were subjected to either single-puncture cecal ligation and puncture (CLP) with a 23-gauge needle or sham laparotomy. Apoptosis was assessed 24 hours later in the spleen and gut epithelium by active caspase 3 and hematoxylin and eosin staining. Aged septic mice had increased splenic apoptosis compared with either young septic animals or aged sham animals (15 vs. 7 vs. 5 apoptotic cells/high-powered field, P < 0.05). Similarly, aged septic animals had an elevation in gut epithelial cell death compared with either young septic or aged sham mice (33 vs. 16 vs. 6 apoptotic cells/100 contiguous crypts, P < 0.05). Elevated intestinal cell death was not associated with changes in either gut proliferation or cell division. To verify that the increase in splenic apoptosis seen in septic aged animals was not strain specific, double-puncture CLP with a 25-gauge needle or sham laparotomy was performed on young (4 months) or aged (24 months) C57BL/6 male mice. Similar to results seen in outbred animals, aged septic animals in this inbred strain had increased splenic apoptosis compared with either young septic animals or aged sham animals (23 vs. 7 vs. 4 apoptotic cells/ high powered field, P < 0.05). These results indicate that although infection and aging each independently cause an increase in splenic and gut epithelial apoptosis, their combination leads to a disproportionate increase in cell death in these rapidly dividing cell populations,and potentially plays a role in the marked increase in mortality seen with aging in sepsis.

High-dose exogenous iron following cecal ligation and puncture increases mortality rate in mice and is associated with an increase in gut epithelial and splenic apoptosis.

OBJECTIVES: Despite having dysregulated iron metabolism, critically ill patients may receive exogenous iron for the treatment of anemia. Iron is associated with increased tissue apoptosis and may facilitate bacterial growth. We hypothesized that exogenous iron administration given after the onset of sepsis would lead to increased mortality rate. To discriminate between elevated cell death and bacterial overgrowth as potential mediators of mortality, we examined gut epithelial and lymphocyte apoptosis and systemic bacterial counts in animals given iron supplementation after the onset of sepsis. DESIGN: Prospective, randomized, controlled study. SETTING: Animal laboratory in a university medical center. SUBJECTS: Male C57BL/6 mice, 6-10 wks old. INTERVENTIONS: C57BL/6 mice were subjected to cecal ligation and puncture (CLP), a well-accepted model of intra-abdominal sepsis, followed by daily subcutaneous injections of either 1 mL of iron dextran (5 mg/mL) or 0.9% NaCl for a total of five doses. Animals (n = 78) were followed for survival for 8 days. Separate cohorts (n = 76) were killed 24 or 48 hrs after cecal ligation and puncture or sham laparotomy and were assayed for gut epithelial and splenic apoptosis as well as for quantitative blood cultures. MEASUREMENTS AND MAIN RESULTS: Eight-day survival was 7% in animals that received iron and 26% in mice that received 0.9% NaCl (p < .005). Iron supplementation after cecal ligation and puncture increased apoptosis by both active caspase 3 and hematoxylin and eosin staining in both the intestinal epithelium and spleen at 24 hrs (p < .05). Iron supplementation after sham laparotomy did not cause mortality or elevated apoptosis. Quantitative blood cultures revealed no detectable differences between septic animals that received iron and those that received 0.9% NaCl. CONCLUSIONS: High-dose iron supplementation with iron dextran after the onset of sepsis significantly increases mortality rate in this animal model. Iron-induced mortality may be mediated by an increase in gut epithelial and splenic apoptosis, whereas severity of bacteremia does not appear to play a causative role.

Antibiotics improve survival in sepsis independent of injury severity but do not change mortality in mice with markedly elevated interleukin 6 levels.

Genetically identical mice have a heterogeneous response to antibiotic therapy in sepsis, with only a subset deriving therapeutic benefit. We sought to determine whether the severity of a septic insult correlates with the survival benefit conferred by antibiotics. We also sought to determine whether antibiotics given 12 h after injury alter survival in animals predicted to die based upon high interleukin (IL)-6 levels drawn 6 h earlier. Adult male ND4 mice (n = 363) were subjected to double-puncture cecal ligation and puncture (CLP) with a 19-, 21-, or 23-gauge needle. Animals were randomized to receive imipenem or 0.9% NaCl every 12 h after CLP for 5 days. Ten-day survival was 16%, 26%, and 52%, respectively, for untreated animals. Antibiotics decreased the absolute risk of death 17% to 23% regardless of injury severity. In a separate cohort, mice (n = 37) were subjected to single or double-puncture CLP with a 21-gauge needle. IL-6 levels were assayed 6 h postoperatively and mice were followed for survival. Levels greater than 14,000 pg/mL were identified as predicting a 100% mortality (7/7 animals dead). A third set of mice (n = 94) then underwent double-puncture CLP with either 21-, 23-, or 25-gauge needle and had IL-6 levels measured in a similar fashion. Animals were randomized to receive imipenem or 0.9% NaCl beginning 12 h postoperatively (6 h after IL-6 levels were drawn) and continued for 5 days or until death. Although antibiotics decreased mortality overall, all animals with IL-6 levels greater than 14,000 pg/mL (n = 13) died, regardless of whether they received antibiotics or the gauge of needle used. These results indicate that antibiotics improve outcome in murine sepsis, regardless of injury severity. Furthermore, there is a threshold IL-6 level that can be identified 6 h after sepsis above which animals are destined to die, and antibiotic treatment does not alter their outcome.

Bcl-2 inhibits gut epithelial apoptosis induced by acute lung injury in mice but has no effect on survival.

Gut epithelial apoptosis is increased in human studies and animal models of noninfectious inflammation and sepsis. Elevated intestinal cell death appears to be physiologically significant in sepsis. Previous studies demonstrate that overexpression of the antiapoptotic protein Bcl-2 in the gut epithelium of transgenic mice is associated with improved survival from Pseudomonas aeruginosa pneumonia and cecal ligation and puncture. The functional significance of elevated gut apoptosis in noninfectious inflammation has not been examined. We hypothesized that intestinal apoptosis would be detrimental to survival in noninfectious critical illness. To address this issue, acute lung injury (ALI) was induced with intratracheal injection of lipopolysaccharide (LPS, 800 microg) in wild-type (WT) FVB/N mice and transgenic mice that overexpress Bcl-2 in their intestinal epithelium. Guts were harvested at 12, 24, 48, and 72 h and assessed for apoptosis by both hematoxylin and eosin and active caspase-3 staining in 100 contiguous crypts. ALI increased gut epithelial apoptosis 12 h after LPS instillation compared with shams (P < 0.01), whereas overexpression of Bcl-2 decreased intestinal apoptosis compared with WT animals with ALI when assayed by active caspase-3 (P < 0.05). Plasma levels of tumor necrosis factor alpha, interleukin (IL)-6, and IL-10 were similar between WT and transgenic animals with ALI, both of which had elevated IL-10 levels at 12 h and elevated IL-6 levels at 24 h compared with sham animals. In a separate experiment, transgenic and WT animals with ALI were followed for mortality to determine whether gut overexpression of Bcl-2 conferred a survival advantage. Survival at 10 days was 73% in WT animals (n = 33) and 65% in Bcl-2 animals (n = 23, P = ns). These results indicate that while gut epithelial apoptosis is elevated in multiple models of critical illness, prevention of intestinal cell death by overexpression of Bcl-2 is associated with a disparate survival effect between sepsis and noninfectious inflammation.