TCF1-LEF1 co-expression identifies a multipotent progenitor cell (TH2-MPP) across human allergic diseases.

Repetitive exposure to antigen in chronic infection and cancer drives T cell exhaustion, limiting adaptive immunity. In contrast, aberrant, sustained T cell responses can persist over decades in human allergic disease. To understand these divergent outcomes, we employed bioinformatic, immunophenotyping and functional approaches with human diseased tissues, identifying an abundant population of type 2 helper T (TH2) cells with co-expression of TCF7 and LEF1, and features of chronic activation. These cells, which we termed TH2-multipotent progenitors (TH2-MPP) could self-renew and differentiate into cytokine-producing effector cells, regulatory T (Treg) cells and follicular helper T (TFH) cells. Single-cell T-cell-receptor lineage tracing confirmed lineage relationships between TH2-MPP, TH2 effectors, Treg cells and TFH cells. TH2-MPP persisted despite in vivo IL-4 receptor blockade, while thymic stromal lymphopoietin (TSLP) drove selective expansion of progenitor cells and rendered them insensitive to glucocorticoid-induced apoptosis in vitro. Together, our data identify TH2-MPP as an aberrant T cell population with the potential to sustain type 2 inflammation and support the paradigm that chronic T cell responses can be coordinated over time by progenitor cells.

Mapping the Ecological Terrain of Stroke Prehospital Delay: A Nationwide Registry Study.

BACKGROUND: Delays in hospital presentation limit access to acute stroke treatments. While prior research has focused on patient-level factors, broader ecological and social determinants have not been well studied. We aimed to create a geospatial map of prehospital delay and examine the role of community-level social vulnerability. METHODS: We studied patients with ischemic stroke who arrived by emergency medical services in 2015 to 2017 from the American Heart Association Get With The Guidelines-Stroke registry. The primary outcome was time to hospital arrival after stroke (in minutes), beginning at last known well in most cases. Using Geographic Information System mapping, we displayed the geography of delay. We then used Cox proportional hazard models to study the relationship between community-level factors and arrival time (adjusted hazard ratios [aHR] <1.0 indicate delay). The primary exposure was the social vulnerability index (SVI), a metric of social vulnerability for every ZIP Code Tabulation Area ranging from 0.0 to 1.0. RESULTS: Of 750 336 patients, 149 145 met inclusion criteria. The mean age was 73 years, and 51% were female. The median time to hospital arrival was 140 minutes (Q1: 60 minutes, Q3: 458 minutes). The geospatial map revealed that many zones of delay overlapped with socially vulnerable areas (https://harvard-cga.maps.arcgis.com/apps/webappviewer/index.html?id=08f6e885c71b457f83cefc71013bcaa7). Cox models (aHR, 95% CI) confirmed that higher SVI, including quartiles 3 (aHR, 0.96 [95% CI, 0.93-0.98]) and 4 (aHR, 0.93 [95% CI, 0.91-0.95]), was associated with delay. Patients from SVI quartile 4 neighborhoods arrived 15.6 minutes [15-16.2] slower than patients from SVI quartile 1. Specific SVI themes associated with delay were a community's socioeconomic status (aHR, 0.80 [95% CI, 0.74-0.85]) and housing type and transportation (aHR, 0.89 [95% CI, 0.84-0.94]). CONCLUSIONS: This map of acute stroke presentation times shows areas with a high incidence of delay. Increased social vulnerability characterizes these areas. Such places should be systematically targeted to improve population-level stroke presentation times.

Climate change and environmental sustainability in otolaryngology: A state-of-the-art review.

BACKGROUND: Climate change has been identified by the World Health Organization (WHO) as the greatest existing threat to human health. Given the direct exposure of the upper aerodigestive system to pollutants, patients in otolaryngology are at high risk for increased disease burden in the setting of climate change and worsening air quality. Given this and the environmental impact of surgical care, it is essential for surgeons to understand their role in addressing climate health through quality-driven clinical initiatives, education, advocacy, and research. METHODS: A state-of-the-art review was performed of the existing literature on the otolaryngologic health impacts of climate change and environmental sustainability efforts in surgery with specific attention to studies in otolaryngology - head and neck surgery. FINDINGS: Climate variables including heat and air pollution are associated with increased incidence of allergic rhinitis, chronic rhinosinusitis and head and neck cancer. A number of studies have shown that sustainability initiatives in otolaryngology are safe and provide direct cost benefit. CONCLUSION: Surgeons have the opportunity to lead on climate health and sustainability to address the public health burden of climate change.

Type 2 inflammation drives an airway basal stem cell program through insulin receptor substrate signaling.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a type 2 (T2) inflammatory disease associated with an increased number of airway basal cells (BCs). Recent studies have identified transcriptionally distinct BCs, but the molecular pathways that support or inhibit human BC proliferation and differentiation are largely unknown. OBJECTIVE: We sought to determine the role of T2 cytokines in regulating airway BCs. METHODS: Single-cell and bulk RNA sequencing of sinus and lung airway epithelial cells was analyzed. Human sinus BCs were stimulated with IL-4 and IL-13 in the presence and absence of inhibitors of IL-4R signaling. Confocal analysis of human sinus tissue and murine airway was performed. Murine BC subsets were sorted for RNA sequencing and functional assays. Fate labeling was performed in a murine model of tracheal injury and regeneration. RESULTS: Two subsets of BCs were found in human and murine respiratory mucosa distinguished by the expression of basal cell adhesion molecule (BCAM). BCAM expression identifies airway stem cells among P63+KRT5+NGFR+ BCs. In the sinonasal mucosa, BCAMhi BCs expressing TSLP, IL33, CCL26, and the canonical BC transcription factor TP63 are increased in patients with CRSwNP. In cultured BCs, IL-4/IL-13 increases the expression of BCAM and TP63 through an insulin receptor substrate-dependent signaling pathway that is increased in CRSwNP. CONCLUSIONS: These findings establish BCAM as a marker of airway stem cells among the BC pool and demonstrate that airway epithelial remodeling in T2 inflammation extends beyond goblet cell metaplasia to the support of a BC stem state poised to perpetuate inflammation.

Establishing the Essential Role of Household Extenders for Surgeon Wellbeing.

OBJECTIVE: The aim of this study was to investigate the association between a change in household support during the Covid-19 pandemic and surgeon stress. BACKGROUND: The hours and unpredictability of surgical practice often necessitate the employment of household extenders (eg, child caregivers) to maintain a safe home environment for surgeons and their families. The Covid-19 pandemic destabilized these relationships and provided an opportunity to reflect on the role that household extenders play in a surgical household. METHODS: A multi-institutional telephone survey of surgeons practicing at five geographically diverse academic institutions was conducted (May 15, 2020-June 5, 2020). Surgeons were classified by change in household extenders (HE) during the pandemic (decrease, increase, no change, or none). The primary outcome was self-reported surgeon stress level. Multivariable linear regression was used to examine the relationship between change in HE and surgeon stress, adjusting for training and relationship status, the presence of pets and children in the household, and study site. RESULTS: The majority (182, 54.3%) of surgeons employed HE before the pandemic; 121 (36.1%) reported a decrease in HE during the pandemic, 9 (2.7%) reported an increase, and 52 (15.5%) reported no change. Stress scores varied significantly by change in HE group ( P = 0.016). After controlling for potential confounders, having an increase in HE was associated with a higher stress score (+1.55 points) than having no decrease in HE (P = 0.033), and having a decrease in HE was associated with a higher stress score (+0.96 points) than having no decrease ( P = 0.004). CONCLUSIONS: Household extenders play a vital and complex role in enabling the healthcare workforce to care of the population. Surgeons who experienced a change in household extenders reported the highest stress levels. We suggest that health systems should proactively support surgeons by supporting the household extender workforce.

Association between Surgery, Anesthesia, and Obstetric Workforce and Emergent Surgical and Obstetric Mortality among United States Hospital Referral Regions.

OBJECTIVE: To determine the association between SAO workforce and mortality from emergent surgical and obstetric conditions within US HR Rs. BACKGROUND: SAO workforce per capita has been identified as a core metric of surgical capacity by the Lancet Commission on Global Surgery, but its utility has not been assessed at the subnational level for a high-income country. METHODS: The number of practicing surgeons, anesthesiologists, and obstetricians per capita was estimated for all HRRs using the US Health Resources & Services Administration Area Health Resource File Database. Deaths due to emergent general surgical and obstetric conditions were determined from the Center for Disease Control and Prevention WONDER database. We utilized B-spline quantile regression to model the relationship between SAO workforce and emergent surgical mortality at different quantiles of mortality and calculated the expected change in mortality associated with increases in SAO workforce. RESULTS: The median SAO workforce across all HRRs was 74.2 per 100,000 population (interquartile range 33.3-241.0). All HRRs met the Lancet Commission on Global Surgery lower target of 20 SAO per 100,000, and 97.7% met the upper target of 40 per 100,000. Nearly 2.8 million Americans lived in HRRs with fewer than 40 SAO per 100,000. Increases in SAO workforce were associated with decreases in surgical mortality in HRRs with high mortality, with minimal additional decreases in mortality above 60 to 80 SAO per 100,000. CONCLUSIONS: Increasing SAO workforce capacity may reduce emergent surgical and obstetric mortality in regions with high surgical mortality but diminishing returns may be seen above 60 to 80 SAO per 100,000. Trial Registration: N/A.

The Surgeon's Perceived Value of Patient-reported Outcome Measures (PROMs): An Exploratory Qualitative Study of 5 Different Surgical Subspecialties.

OBJECTIVE: To understand the surgeon's perceived value of PROMs in 5 different surgical subspecialties. SUMMARY OF BACKGROUND DATA: PROMs are validated questionnaires that assess the symptoms, function, and quality of life from the patient's perspective. Despite the increasing support for use of PROMs in the literature, there is limited uptake amongst surgeons. Furthermore, there is insufficient understanding of the surgeons' perceived value of PROMs. The aim of this study is to understand how surgeons perceive value in PROMs. METHODS: We conducted an exploratory qualitative study to understand the perceived value of PROMs from the perspective of surgeons in various subspecialties. Per convenience sampling, we conducted semi-structured interviews with 30 surgeons from 5 subspecialties across 3 academic medical centers. The surgical subspecialties included bariatric surgery, breast oncologic surgery, orthopedic surgery, plastic and reconstructive surgery, and rhinology. Interviews were transcribed, coded, and evaluated with thematic analysis. RESULTS: Surgeons endorsed that PROMs can be used to enhance clinical management, counsel patients in the preoperative and postoperative settings, and elicit sensitive information from patients that otherwise may go undetected. Obstacles to PROMs use include failure to generate actionable data, implementation obstacles, and inappropriate use of PROMs as a performance metric, with concerns regarding inadequate risk adjustment. CONCLUSIONS: Establishing an effective PROMs program requires an understanding of the surgeon's perspective of PROMs. Despite obstacles, different subspecialty surgeons find PROMs to be valuable in different settings, depending on the specialty and clinical context.

The Utility of a Novel Definition of Health Care Regions in the United States in the Era of COVID-19: A Validation of the Pittsburgh Atlas Using Pneumonia Admissions.

STUDY OBJECTIVE: The COVID-19 pandemic in the United States has underscored the need to understand health care in a regional context. However, there are multiple definitions of health care regions available for conducting geospatial analyses. In this study, we compare the novel Pittsburgh Atlas, which defined regions for emergency care, with the existing definitions of regions, counties, and the Dartmouth Atlas, with respect to nonemergent acute medical conditions using pneumonia admissions. METHODS: We identified patients hospitalized with a primary diagnosis of pneumonia or a primary admitting diagnosis of sepsis with a secondary diagnosis of pneumonia in the Agency for Healthcare Research and Quality's State Inpatient Databases. We calculated the percentage of region concordant care, the localization index, and market share for 3 definitions of health care regions (the Pittsburgh Atlas, Dartmouth Atlas, and counties). We used logistic regression identified predictors of region concordant care. RESULTS: We identified 1,582,287 patients who met the inclusion criteria. We found that the Pittsburgh Atlas and Dartmouth Atlas definitions of regions performed similarly with respect to both localization index (92.0 [interquartile range 87.9 to 95.7] versus 90.3 [interquartile range 81.4 to 94.5]) and market share (8.5 [interquartile range 5.1 to 13.6] versus 9.4 [interquartile range 6.7 to 14.1]). Both atlases outperformed the localization index (67.5 [interquartile range 49.9 to 83.9]) and market share (20.0% [interquartile range 11.4 to 31.4]) of the counties. Within a given referral region, the demographic factors, including age, sex, race/ethnicity, insurance status, and the level of severity, affected concordance rates between residential and hospital regions. CONCLUSION: Because the Pittsburgh Atlas also has the benefit of respecting state and county boundaries, the use of this definition may have improved policy applicability without sacrificing accuracy in defining health care regions for acute medical conditions.

The Affordable Care Act at 10 Years: Evaluating the Evidence and Navigating an Uncertain Future.

The year 2020 marks the 10th anniversary of the signing of the Affordable Care Act (ACA). Perhaps the greatest overhaul of the US health care system in the past 50 y, the ACA sought to expand access to care, improve quality, and reduce health care costs. Over the past decade, there have been a number of challenges and changes to the law, which remains in evolution. While the ACA's policies were not intended to specifically target surgical care, surgical patients, surgeons, and the health systems within which they function have all been greatly affected. This article aims to provide a brief overview of the impact of the ACA on surgical patients in reference to its tripartite aim of improving access, improving quality, and reducing costs.

Non-English Primary Language is Associated with Emergency Surgery for Diverticulitis.

BACKGROUND: Language barriers can limit access to care for patients with a non-English primary language (NEPL). The objective of this study was to define the association between primary language and emergency versus elective surgery among diverticulitis patients. MATERIALS AND METHODS: Retrospective cohort study of adult patients from the 2009-2014 New Jersey State Inpatient Database. Patients were included if they had primary language data and underwent a partial colon resection for diverticulitis. Primary language was dichotomized into NEPL versus English primary language (EPL). The primary outcome was surgical admission type - urgent/emergent (referred to as "emergency") versus elective. Descriptive and multivariable analyses were performed. RESULTS: A total of 9,453 patients underwent surgery for diverticulitis, of which 592 (6.3%) had NEPL. Among NEPL patients, 300 (51%) had Spanish as primary language and 292 (49%) had another non-Spanish primary language. Patients with NEPL and EPL were similar in age (median age 58 versus 59 years; P = 0.54) and sex (52% versus 53% female; P = 0.45). Patients with NEPL were less likely to have commercial insurance (45% versus 59%; P <0.001). On multivariable analysis, compared to patients with EPL, NEPL was associated with increased odds of emergency surgery for diverticulitis (OR 1.35; 95% Confidence Interval 1.13-1.62; P = 0.001) CONCLUSION: Patients with NEPL have higher odds of emergency versus elective surgery for diverticulitis compared to patients with EPL. Further research is needed to examine differences in referral pathways, patient-provider communication, and health literacy that may hinder access to elective surgery in patients with diverticulitis.

Impact of insurance on hospital course and readmission after resection of benign meningioma.

INTRODUCTION: Surgical outcomes and healthcare utilization have been shown to vary based on patient insurance status. We analyzed whether patients' insurance affects case urgency for and readmission after craniotomy for meningioma resection, using benign meningioma as a model system to minimize confounding from the disease-related characteristics of other neurosurgical pathologies. METHODS: We analyzed 90-day readmission for patients who underwent resection of a benign meningioma in the Nationwide Readmission Database from 2014-2015. RESULTS: A total of 9783 meningioma patients with private insurance (46%), Medicare (39%), Medicaid (10%), self-pay (2%), or another scheme (3%) were analyzed. 72% of all cases were elective; with 78% of cases in privately insured patients being elective compared to 71% of Medicare (p > 0.05), 59% of Medicaid patients (OR 2.3, p < 0.001), and 49% of self-pay patients (OR 3.4, p < 0.001). Medicare (OR 1.5, p = 0.002) and Medicaid (OR 1.4, p = 0.035) were both associated with higher likelihood of 90-day readmission compared to private insurance. In comparison, 30-day analyses did not unveil this discrepancy between Medicaid and privately insured, highlighting the merit for longer-term outcomes analyses in value-based care. Patients readmitted within 30 days versus those with later readmissions possessed different characteristics. CONCLUSIONS: Compared to patients with private insurance coverage, Medicaid and self-pay patients were significantly more likely to undergo non-elective resection of benign meningioma. Medicaid and Medicare insurance were associated with a higher likelihood of 90-day readmission; only Medicare was significant at 30 days. Both 30 and 90-day outcomes merit consideration given differences in readmitted populations.

Patient-Reported Morbidity Instruments: A Systematic Review.

OBJECTIVES: Although comorbidities play an essential role in risk adjustment and outcomes measurement, there is little consensus regarding the best source of this data. The aim of this study was to identify general patient-reported morbidity instruments and their measurement properties. METHODS: A systematic review was conducted using multiple electronic databases (Embase, Medline, Cochrane Central, and Web of Science) from inception to March 2018. Articles focusing primarily on the development or subsequent validation of a patient-reported morbidity instrument were included. After including relevant articles, the measurement properties of each morbidity instrument were extracted by 2 investigators for narrative synthesis. RESULTS: A total of 1005 articles were screened, of which 34 eligible articles were ultimately included. The most widely assessed instruments were the Self-Reported Charlson Comorbidity Index (n = 7), the Self-Administered Comorbidity Questionnaire (n = 3), and the Disease Burden Morbidity Assessment (n = 3). The most commonly included conditions were diabetes, hypertension, and myocardial infarction. Studies demonstrated substantial variability in item-level reliability versus the gold standard medical record review (κ range 0.66-0.86), meaning that the accuracy of the self-reported comorbidity data is dependent on the selected morbidity. CONCLUSIONS: The Self-Reported Charlson Comorbidity Index and the Self-Administered Comorbidity Questionnaire were the most frequently cited instruments. Significant variability was observed in reliability per comorbid condition of patient-reported morbidity questionnaires. Further research is needed to determine whether patient-reported morbidity data should be used to bolster medical records data or serve as a stand-alone entity when risk adjusting observational outcomes data.

Sex Differences in Faculty Rank Among Academic Surgeons in the United States in 2014.

OBJECTIVE: The aim of this study was to evaluate sex differences in full professorship among a comprehensive, contemporary cohort of US academic surgeons. SUMMARY OF BACKGROUND DATA: Previous work demonstrates that women are less likely than men to be full professors in academic medicine, and in certain surgical subspecialties. Whether sex differences in academic rank exist across all surgical fields, and after adjustment for confounders, is not known. METHODS: A comprehensive list of surgeons with faculty appointments at US medical schools in 2014 was obtained from Association of American Medical Colleges (AAMC) faculty roster and linked to a comprehensive physician database from Doximity, an online physician networking website, which contained the following data for all physicians: sex, age, years since residency, publication number (total and first/last author), clinical trials participation, National Institutes of Health grants, and surgical subspecialty. A 20% sample of 2013 Medicare payments for care was added to this dataset. Multivariable regression models were used to estimate sex differences in full professorship, adjusting for these variables and medical school-specific fixed effects. RESULTS: Among 11,549 surgeon faculty at US medical schools in 2014, 1692 (14.7%) were women. Women comprised 19.4% of assistant professors (1072/5538), 13.8% of associate professors (404/2931), and 7.0% of full professors (216/3080). After multivariable analysis, women were less likely to be full professors than men (adjusted odds ratio: 0.76, 95% confidence interval: 0.6-0.9). CONCLUSION: Among surgical faculty at US medical schools in 2014, women were less likely than men to be full professors after adjustment for multiple factors known to impact faculty rank.

Depression symptoms and lost productivity in chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is associated with significant losses of patient productivity that cost billions of dollars every year. The causative factors for decreases in productivity in patients with CRS have yet to be determined. OBJECTIVE: To determine which patterns of CRS symptoms drive lost productivity. METHODS: Prospective, cross-sectional cohort study of 107 patients with CRS. Sinonasal symptom severity was measured using the 22-item Sinonasal Outcomes Test, from which sleep, nasal, otologic or facial pain, and emotional function subdomain scores were calculated using principal component analysis. Depression risk was assessed with the 2-item Patient Health Questionnaire (PHQ-2), whereas nasal obstruction was assessed with the Nasal Obstruction Symptom Evaluation (NOSE) instrument. Lost productivity was assessed by asking participants how many days of work and/or school they missed in the last 3 months because of CRS. Associations were sought between lost productivity and CRS symptoms. RESULTS: A total of 107 patients were recruited. Patients missed a mean (SD) of 3.1 (12.9) days of work or school because of CRS. Lost productivity was most strongly associated with the emotional function subdomain (ß = 7.48; 95% confidence interval [CI], 5.71-9.25; P < .001). Reinforcing this finding, lost productivity was associated with PHQ-2 score (ß = 4.72; 95% CI, 2.62-6.83; P < .001). Lost productivity was less strongly associated with the nasal symptom subdomain score (ß = 2.65; 95% CI, 0.77-4.52; P = .007), and there was no association between lost productivity and NOSE score (ß = 0.01; 95% CI, -0.12 to 0.13; P = .91). CONCLUSION: Symptoms associated with depression are most strongly associated with missed days of work or school because of CRS. Further treatment focusing on depression-associated symptoms in patients with CRS may reduce losses in productivity.

Head and neck cancer in South Asia: macroeconomic consequences and the role of surgery.

BACKGROUND: Head and neck cancer, for which the diagnosis and treatment are often surgical, comprises a substantial proportion of the burden of disease in South Asia. Further, estimates of surgical volume suggest this region faces a critical shortage of surgical capacity. We aimed to estimate the total economic welfare losses due to the morbidity and mortality of head and neck cancer in India, Pakistan, and Bangladesh for 1 year (2010). METHODS: We used publicly available estimates from the Institute for Health Metrics and Evaluation regarding the morbidity and mortality of head and neck cancer in India, Pakistan, and Bangladesh, along with an economic concept termed the value of a statistical life, to estimate total economic welfare losses due to head and neck cancer in the aforementioned countries in the year 2010. The counterfactual scenario is absence of disease. Sensitivity analyses were done with regard to how the value of a statistical life changes with income. FINDINGS: In 2010, the most conservative estimate of economic welfare losses due to head and neck cancer in the three studied countries is US$16·9 billion (2010 USD, PPP), equivalent to 0·26% of their combined gross domestic product (GDP). The welfare losses experienced by the population younger than 70 years of age accounted for US$15·2 billion (90% of the total losses). When adjusted for the size of their respective economies, Bangladesh, the poorest of the three countries, incurred the greatest loss (US$930 million), equivalent to 0·29% of its GDP. India and Pakistan experienced welfare losses of US$14·1 billion and US$1·9 billion, respectively. These figures are equivalent to 0·26% of the GDP for both countries. Oropharyngeal and hypopharyngeal cancer made up the largest share of the total burden at 39% (US$6·6 billion), followed closely by oral cavity cancer at 34% (US$5·7 billion). INTERPRETATION: The burden of non-communicable diseases, to which cancer contributes greatly, is growing at a rapid pace in South Asia. Head and neck cancer is a leading cause of cancer-related mortality in this region, and this study suggests that the associated economic welfare losses, estimated to be US$16·9 billion in 2010 alone, are substantial. A number of strategies are available to address this burden. Surgery, as part of a multidisciplinary approach that includes radiation therapy and chemotherapy, plays a central part in the diagnosis and treatment of head and neck cancer, and building surgical capacity, which offers large economies of scope and scale, can not only address the burden of head and neck cancer, but also create a platform for beginning to confront the rising tide of non-communicable diseases. FUNDING: None.