The Causes and Consequences of DNA Damage and Chromosomal Instability Induced by Human Papillomavirus.

High-risk human papillomaviruses (HPVs) are the main cause of cervical, oropharyngeal, and anogenital cancers, which are all treated with definitive chemoradiation therapy when locally advanced. HPV proteins are known to exploit the host DNA damage response to enable viral replication and the epithelial differentiation protocol. This has far-reaching consequences for the host genome, as the DNA damage response is critical for the maintenance of genomic stability. HPV+ cells therefore have increased DNA damage, leading to widespread genomic instability, a hallmark of cancer, which can contribute to tumorigenesis. Following transformation, high-risk HPV oncoproteins induce chromosomal instability, or chromosome missegregation during mitosis, which is associated with a further increase in DNA damage, particularly due to micronuclei and double-strand break formation. Thus, HPV induces significant DNA damage and activation of the DNA damage response in multiple contexts, which likely affects radiation sensitivity and efficacy. Here, we review how HPV activates the DNA damage response, how it induces chromosome missegregation and micronuclei formation, and discuss how these factors may affect radiation response. Understanding how HPV affects the DNA damage response in the context of radiation therapy may help determine potential mechanisms to improve therapeutic response.

Trends in performance of hospital outpatient procedures and associated 30-day costs among Medicare beneficiaries from 2011 to 2018.

BACKGROUND: United States healthcare has increasingly transitioned to outpatient care delivery. The degree to which Academic Medical Centers (AMCs) have been able to shift surgical procedures from inpatient to outpatient settings despite higher patient complexity is unknown. METHODS: This observational study used a 20% sample of fee-for-service Medicare beneficiaries age 65 and older undergoing eight elective procedures from 2011 to 2018 to model trends in procedure site (hospital outpatient vs. inpatient) and 30-day standardized Medicare costs, overall and by hospital teaching status. RESULTS: Of the 1,222,845 procedures, 15.9% occurred at AMCs. There was a 2.42% per-year adjusted increase (95% CI 2.39%-2.45%; p < .001) in proportion of outpatient hospital procedures, from 68.9% in 2011 to 85.4% in 2018. Adjusted 30-day standardized costs declined from $18,122 to $14,353, (-$560/year, 95% CI -$573 to -$547; p < .001). Patients at AMCs had more chronic conditions and higher predicted annual mortality. AMCs had a lower proportion of outpatient procedures in all years compared to non-AMCs, a difference that was statistically significant but small in magnitude. AMCs had higher costs compared to non-AMCs and a lesser decline over time (p < .001 for the interaction). AMCs and non-AMCs saw a similar decline in 30-day mortality. CONCLUSIONS: There has been a substantial shift toward outpatient procedures among Medicare beneficiaries with a decrease in total 30-day Medicare spending as well as 30-day mortality. Despite a higher complexity population, AMCs shifted procedures to the outpatient hospital setting at a similar rate as non-AMCs. IMPLICATIONS: The trend toward outpatient procedural care and lower spending has been observed broadly across AMCs and non-AMCs, suggesting that Medicare beneficiaries have benefited from more efficient delivery of procedural care across academic and community hospitals.

Value of Ambulatory Modified Radical Mastectomy.

BACKGROUND: Modified radical mastectomy (MRM) still is largely performed in inpatient settings. This study sought to determine the value (expenditures and complications) of ambulatory MRM. METHODS: Health Care Utilization Project (HCUP) state databases from 2016 were queried for patients who underwent MRM. The study examined rates of 30-day readmission for surgical-site infection (SSI) or hematoma, charges by index care setting, and predictors of 30-day readmission. RESULTS: Overall, 8090 patients underwent MRM: 5113 (63 %) inpatient and 2977 (37 %) ambulatory patients. Compared with the patients who underwent inpatient MRM, those who underwent ambulatory MRM were older (61 vs. 59 years), more often white (66 % vs. 57 %), in the lowest income quartile (28 % vs. 21 %), insured by Medicare (43 % vs. 33 %) and residents in a small metro area (6 % vs. 4 %) (all p < 0.01). Of the 5113 patients treated as inpatients, 126 (2.5 %) were readmitted, whereas 50 (1.7 %) of the ambulatory patients were readmitted (p = 0.02). The adjusted charge for inpatient MRM without readmission was $113,878 (range, $107,355-120,402) compared with $94,463 (range, $86,021-102,907) for ambulatory MRM, and the charge for inpatient MRM requiring readmission was $159,355 (range, $147,142-171,568) compared with $139,940 (range, $125,808-154,073) for ambulatory MRM (all p < 0.01). This difference remained significant after adjustment for hospital length of stay. Adjusted logistic regression showed that the ambulatory setting was protective for readmission (odds ratio, 0.49; 95 % confidence interval, 0.35-0.70; p < 0.01). CONCLUSIONS: The analyses suggest that ambulatory MRM is both safe and less expensive. The findings advocate that MRM, a last holdout of inpatient care within breast surgical oncology, can be transitioned to the ambulatory setting for appropriate patients.

Supervised weight loss requirements disproportionately affect Black patients seeking weight loss surgery.

BACKGROUND: We use our high-volume institutional experience with a majority Black population to examine the role of supervised weight loss (SWL) requirements perpetuating disparities in bariatric surgery. OBJECTIVE: To determine if there are racial disparities in the required amount of supervised weight loss prior to approval for bariatric surgery. SETTING: University hospital. METHODS: A retrospective review was conducted of all patients seen at our institution's bariatric surgery clinic in 2018. Odds of undergoing surgery within 1 year and mean number of SWL requirements were determined using descriptive statistics for Black patients as compared with non-Hispanic White patients. Finally, a logistic model was constructed to examine likelihood of undergoing an operation within 1 year for patients of varying SWL requirements. RESULTS: A total of 335 patients were included (75% Black, 25% White). Within 1 year, 37% of Black patients compared with 53% of White patients had undergone an operation (relative risk .7, P = .01). Mean insurance-mandated SWL sessions were significantly higher for Black patients (3.6 ± 2.8) versus non-Hispanic White patients (2.2 ± 2.7) (P < .01). Mean program-mandated SWL sessions were also significantly higher for Black patients (2.5 ± 2.6) versus non-Hispanic White patients (.8 ± 1.8) (P < .01). Increasing SWL requirements significantly reduced the odds of undergoing surgery at 1 year within the entire cohort (odds ratio .86, P < .01). CONCLUSIONS: Black patients are disproportionally affected by SWL requirements, which strongly correlate with decreased likelihood of undergoing a bariatric operation as compared with their White counterparts. Even after overcoming barriers to see a bariatric surgery provider, Black patients still face disproportionally more barriers to surgery. Bariatric centers must be sensitive to the effect of SWL requirements, as it is negatively associated with the likelihood of a patient receiving a bariatric operation.

Longitudinal Trends in 30-Day Mortality Between Multi-Site and Single-Site Surgeons.

BACKGROUND: Quality leaders are concerned that creation of multi-hospital health systems may lead to surgeons traveling to and from distant hospitals and thus to more fragmented surgical care and worse outcomes for their patients. Despite this concern, little empirical data exist on outcomes of multi-site versus single-site surgeons. METHODS: Using national Medicare data, we assessed trends in the number of multi-site vs. single-site surgeons from 2011 to 2016. We performed a multivariable regression analysis to compare overall 30-day mortality differences, stratified by system and rural status, and examined trends over time. RESULTS: The number of multi-site surgeons and the percentage of multi-site surgeons per hospital decreased over time (24.2%-19.0%; 44.3%-41.8%). Overall, multi-site surgeons had lower 30-day mortality than single-site surgeons (2.24% vs 2.50%, P < 0.01). When stratified by system status, multi-site surgeons performed better in-system (2.47% vs 2.58%, P < 0.01); by rural status, multi-site surgeons had lower mortality in non-rural hospitals (2.42% vs 2.51%, P < 0.01). The statistically significant but small mortality advantage of multi-site versus single-site surgeons decreased over time, such that by 2016 there was no difference in outcomes between multi-site and single-site surgeons. CONCLUSION: For the majority of study years, multi-site surgeons had lower 30-day mortality than single-site surgeons, but this trend narrowed until outcomes were equivalent by 2016. Surgeons operating at multiple hospitals can provide surgical care to patients without any evidence of increased mortality.

How Should We Respond to Health Sector Emissions That Exacerbate Climate Change and Inequity?

A warming climate poses substantial risk to public health and worsens existing health inequity. As a contributor to greenhouse gas emissions and air pollution, the health sector has obligations and ample opportunities to protect health by decreasing waste and motivating more system-wide sustainable clinical practices. Such efforts will have important ethical implications for health equity.

Assessment of Oncologists' Perspectives on Omission of Sentinel Lymph Node Biopsy in Women 70 Years and Older With Early-Stage Hormone Receptor-Positive Breast Cancer.

Importance: Randomized clinical trial data have demonstrated that omission of surgical axillary evaluation does not affect overall survival in women 70 years and older with early-stage (clinical tumor category 1 [cT1] with node-negative [N0] disease) hormone receptor (HR)-positive and erb-B2 receptor tyrosine kinase 2 (ERBB2; formerly HER2)-negative breast cancer. Therefore, the Choosing Wisely initiative has recommended against routine use of sentinel lymph node biopsy (SLNB) in this population; however, retrospective data have revealed that more than 80% of patients eligible for SLNB omission still undergo the procedure. Multidisciplinary factors involved in these patterns remain unclear. Objective: To describe surgical, medical, and radiation oncologists' perspectives on omission of SLNB in women 70 years and older with cT1N0 HR-positive, ERBB2-negative breast cancer. Design, Setting, and Participants: This qualitative study used in-depth semi-structured interviews to explore the factors involved in oncologists' perspectives on providing care to older women who were eligible for SLNB omission. Purposive snowball sampling was used to recruit a sample of surgical, medical, and radiation oncologists representing a wide range of practice types and number of years in practice in the US and Canada. A total of 29 oncologists who finished training and were actively treating patients with breast cancer were interviewed. Interviews were conducted between March 1, 2020, and January 17, 2021. Main Outcomes and Measures: Recordings from semi-structured interviews were transcribed and deidentified. Thematic analysis was used to identify emergent themes. Results: Among 29 physicians (16 women [55.2%] and 13 men [44.8%]) who participated in interviews, 16 were surgical oncologists, 6 were medical oncologists, and 7 were radiation oncologists. Data on race and ethnicity were not collected. Participants had a range of experience (median [range] years in practice, 12.0 [0.5-30.0]) and practice types (14 academic [48.3%], 7 community [24.1%], and 8 hybrid [27.6%]). Interviews revealed that the decision to omit SLNB was based on nuanced patient- and disease-level factors. Wide variation was observed in oncologists' perspectives on SLNB omission recommendations and supporting data. In addition, participants' statements suggested that the multidisciplinary nature of cancer care may increase oncologists' anxiety regarding SLNB omission. Conclusions and Relevance: In this study, findings from interviews revealed that oncologists' perspectives may have implications for the largely unsuccessful deimplementation of SLNB in women 70 years and older with cT1N0 HR-positive, ERBB2-negative breast cancer. Interventions aimed at educating physicians, improving patient-physician communication, and facilitating preoperative multidisciplinary conversations may help to successfully decrease SLNB rates in this patient population.

Autologous Posterior Rectus Sheath as a Vascularized Onlay Flap: a Novel Approach to Hiatal Hernia Repair.

INTRODUCTION: Complex and recurrent paraesophageal hernia repairs are a challenge for surgeons due to their high recurrence rates despite the use of various prosthetic and suturing techniques. METHODS: Here we describe the use of vascularized fascia harvested from the posterior rectus sheath with peritoneum during robotic hiatal hernia repair in two patients with large complex diaphragmatic defects. RESULTS: Successful harvesting and onlay of the right posterior rectus sheath based on a falciform vascular pedicle was achieved robotically by rotating and securing the flap to the diaphragmatic hiatus as an onlay flap following cruroplasty of the hiatal defect. CONCLUSIONS: In patients with difficult to repair large paraesophageal hernias, we demonstrate a promising new technique to restore the dynamic hiatal complex with the tensile strength of autologous vascularized fascia and peritoneum.

Variation in Use of Surgical Care During the COVID-19 Pandemic by Surgical Urgency and Race and Ethnicity.

Importance: The extent of the disruption to surgical care during the COVID-19 pandemic has not been empirically characterized on a national level. Objective: To characterize the use of surgical care across cohorts of surgical urgency during the COVID-19 pandemic, and to assess for racial and ethnic disparities. Design Setting and Participants: This was a retrospective observational study using the geographically diverse, all payer data from 767 hospitals in the Premier Healthcare Database. Procedures were categorized into 4 cohorts of surgical urgency (elective, nonelective, emergency, and trauma). A generalized linear regression model with hospital-fixed effects assessed the relative monthly within-hospital reduction in surgical encounters in 2020 compared with 2019. Main Outcomes and Measures: Outcomes were the monthly relative reduction in overall surgical encounters and across surgical urgency cohorts and race and ethnicity. Results: The sample included 13 175 087 inpatient and outpatient surgical encounters. There was a 12.6% relative reduction in surgical use in 2020 compared to 2019. Across all surgical cohorts, the most prominent decreases in encounters occurred during Spring 2020 . For example, elective encounters began falling in March, reached a trough in April, and subsequently recovered but never to prepandemic levels (March: -26.8%; 95% CI, -29.6% to -23.9%; April: -74.6%; 95% CI, -75.5% to -73.5%; December: -13.3%; 95% CI, -16.6%, -9.8%). Across all operative surgical urgency cohorts, White patients had the largest relative reduction in encounters. Conclusions and Relevance: As shown by this cohort study, the COVID-19 pandemic resulted in large disruptions to surgical care across all categories of operative urgency, especially elective procedures. Racial and ethnic minority groups experienced less of a disruption to surgical care than White patients. Further research is needed to explore whether the decreased surgical use among White patients was owing to patient discretion and to document whether demand for surgical care will rebound to baseline levels.

Toward Autonomy and Conditional Independence: A Standardized Script Improves Patient Acceptance of Surgical Trainee Roles.

BACKGROUND: Progressive autonomy leading to conditional independence is necessary to achieve competence in surgical skills and decision making. Trust and transparency are ethical imperatives, but practices vary regarding the extent of disclosure of specific resident roles. We tested whether a standardized preoperative script would improve patient acceptance of resident involvement in perioperative care. METHODS: Patients admitted to a resident-run acute care general surgery service between October 2017 and October 2018 were enrolled in an IRB-approved study. During the first half of the rotation (control), operative consent was obtained according to individual practice without specified explanation of resident roles. During the second half (intervention), the senior resident read a short semistructured script specifically explaining team roles and responsibilities, including the degree of resident independence and supervision by attendings. On postoperative day 3, patients completed a survey assessing understanding of their surgical care. RESULTS: Sixty-two patients under the care of 10 rotating chief residents were enrolled; 46 patients completed the survey, 23 in each arm (74% response rate). Ten patients in the control arm (43%) compared to only 3 (13%) in the intervention arm indicated that residents should not be allowed to perform portions of operations (odds ratio 4.94, p = 0.047). Patients in the intervention arm felt that care team roles were more adequately explained to them before their operation (p = 0.002). There was no difference in the number of patients naming a resident as "their doctor." CONCLUSIONS: Use of a short script specifying resident roles improves patient acceptance of trainee participation in perioperative care.

Factors Influencing Adolescent and Young Adults' First Pelvic Examination Experiences: A Qualitative Study.

STUDY OBJECTIVE: To understand the factors that influence individuals' experiences during their first pelvic examination. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: We conducted semistructured interviews with adolescents and young adults, aged 18-24, who had received at least 1 pelvic examination. Interviews explored contextual factors of the first pelvic examination, including visit acuity and clinical setting and individuals' experiences with the pelvic examination itself and elicited recommendations on how to improve the examination experience. Interviews were transcribed and computer-assisted content analysis was performed; salient themes are presented. RESULTS: Thirty participants completed interviews. Nineteen participants described their first pelvic examination experience as positive; 11 described this examination as a negative or neutral experience. Factors influencing the experience include the examination indication and acuity, examination location and physical space, provider features, relational and interpersonal features, and procedural aspects. Recommendations included: (1) establish rapport and educate before the examination; (2) establish practices to orient patients; (3) make no assumptions about identity; and (4) elicit continuous feedback. CONCLUSION: Individuals' first pelvic examination experiences are influenced by a variety of factors. Although some factors are directly modifiable by providers, other factors that might not be modifiable are important to elicit to optimize the examination experience. These findings call for best practice guidelines and educational interventions to prepare providers to perform the first pelvic examination.

Robot-Assisted Endocrine Surgery: Indications and Drawbacks.

BACKGROUND: Over the last few decades, robotic surgery with the da Vinci system has become increasingly prevalent. Endocrine surgeons are witnessing a rapid growth in enthusiasm for robotic approaches for treating thyroid, parathyroid, and adrenal disease. For carefully selected patients, the robotic system may be the preferred technique, although its use remains controversial and indications are in evolution. The goal of this article is to review current robotic procedures for thyroidectomy, parathyroidectomy, and adrenalectomy, and scrutinize the existing literature for application of these approaches. METHODS: We systematically searched and reviewed relevant articles on PubMed and MEDLINE databases for robotic or robot-assisted thyroidectomy, parathyroidectomy, or adrenalectomy. RESULTS: The safety and feasibility for robotic thyroidectomy, parathyroidectomy, and adrenalectomy have been repeatedly demonstrated. Although robotic thyroid and parathyroid surgery offers better cosmetic results compared to the conventional open operation, remote-access techniques introduce new risks. Similar outcomes have been reported for laparoscopic and robotic adrenalectomy, but robot-assisted techniques may extend the capabilities of minimally invasive surgery, particularly performing subtotal adrenalectomy. CONCLUSIONS: While robotic procedures offer better ergonomics for the endocrine surgeon and improved cosmesis for the patient, the major drawback to the robot system almost universally is the higher cost. With new robotically assisted surgical devices on the way that could drive down costs and speed up innovation, the indications for robotic endocrine surgery may greatly expand.

Factors Influencing Young Women's Preparedness for Their First Pelvic Examination.

OBJECTIVE: To understand factors contributing to women's level of preparedness for their first pelvic examination. METHODS: We conducted semistructured interviews with young women, aged 18-24 years, who had undergone at least one pelvic examination. This analysis explored 1) gynecologic and health care experience before the first pelvic examination, 2) preprocedure expectations and concerns, and 3) preprocedure knowledge about the examination. Interviews were transcribed and computer-assisted content analysis was performed; salient themes are presented. RESULTS: Thirty women completed interviews. Thirteen women described feeling poorly prepared for their first pelvic examination and 17 women described feeling prepared for the examination. Factors influencing women's level of preparedness for their first pelvic examination included 1) age at first examination, 2) pre-examination knowledge of the examination, 3) medical trust or mistrust, 4) overall comfort with one's body, and 5) prior sexual experiences and trauma. CONCLUSION: Preparedness for the first pelvic examination emerges as a subjective concept shaped and determined by the interplay of many factors. Although some factors such as age and personal sexual and reproductive health history may not be modifiable by clinical practice, other factors, including information that young women receive before experiencing their first pelvic examination, may be modifiable by clinical practice.