The Plastic Surgery Central Application versus ERAS: Which is Preferred?

Background: The Plastic Surgery Central Application (PSCA), designed to provide an equitable and streamlined application for both applicants and programs, was first designed in 2019, piloted in the 2020-21 application cycle, and is now in its fourth cycle in 2023-24. It has included preference signaling since the 2022-23 cycle, a feature in which applicants can send five "signals" to programs to express interest. We surveyed both program directors (PDs) and applicants following the 2023 match on their perceptions of PSCA versus Electronic Residency Application Service (ERAS). Methods: Surveys were deployed to applicants from three integrated plastic surgery programs during the 2022-23 cycle and all PDs. Respondents were asked basic demographic information, which application system they preferred: PSCA or ERAS, how well they were able to highlight/evaluate different areas of the application, and about their experiences specifically with preference signaling. Results: Forty-two (48%) PDs and 93 (29%) applicants responded. Most PDs (72%) and applicants (59%) preferred PSCA, with only 18% and 27% preferring ERAS. The remainder had no preference. Ninety-three percent of applicants reported that the cost savings of the PSCA were important. Most applicants (78%) and PDs (80%) were in favor or strongly in favor of the preference signaling program. Conclusions: Most applicants and PDs prefer PSCA over ERAS. These data, in conjunction with the cost savings, suggest that the PSCA may be a better alternative for the integrated plastic surgery match. Future analyses of these application systems will help provide the best application for prospective residents.

Looking Across the Drape: A Novel Quality Improvement Approach to Understanding Surgeon and Anesthesiologist Burnout.

OBJECTIVE: To identify well-being threats for surgeons and anesthesiologists and develop interventions using the Quality of Life Improvement (QOLI) approach. BACKGROUND: Developing feasible perioperative well-being interventions requires identifying shared and specialty-specific well-being needs. The QOLI framework integrates human-centered design, implementation science, and quality improvement to address well-being needs. METHODS: Anesthesia and surgery faculty in eight perioperative departments at an academic medical center completed cross-sectional surveys containing validated measures of well-being and workplace satisfaction, and open-ended questions about professional motivations, pain points, strategies for improvement, and well-being priorities. Using template analysis, we analyzed open-ended survey data and presented resulting themes at a joint-specialty town hall for live-voting to identify well-being priorities. RESULTS: 104 perioperative faculty completed the survey. Across specialties, higher MHC-SF scores (representative of individual global well-being) were associated with higher satisfaction with workplace control, values, decision latitude, and social support. Anesthesiologists reported lower satisfaction and control than surgeons across multiple domains. Template analysis yielded five areas for intervention: (1) Work culture, (2) Work environment/resources, (3) Sources of fulfillment, (4) Work/life harmony, (5) Financial compensation. Surgeons and anesthesiologists both prioritized high-quality patient care but differed in their other top priorities. The most frequently cited well-being threats for surgeons were OR inefficiencies/delays and excessive workload, while anesthesiologists cited understaffing and unpredictable work hours. CONCLUSIONS: Surgeons and anesthesiologists share many needs and priorities, with pain points that are often negatively synergistic. Applying the QOLI approach across specialties allows for well-being interventions that honor complexity and promote the development of feasible solutions.

Concurrent abdominal body contouring and hernia repair are safe choices: An analysis of the 2015-2020 ACS-NSQIP database.

BACKGROUND: Concurrent hernia repair (HR) with abdominal body contouring procedures (ABD), panniculectomy, and abdominoplasty, has been discussed as a strategy. The purpose of this study is to evaluate potential medical and surgical complications following concurrent ABD-HR, with a greater emphasis on cosmetic abdominoplasty. METHODS: The 2015-2020 ACS-NSQIP datasets were utilized to identify patients who underwent ABD or ABD-HR. Propensity score (PS) matching was used to reduce selection bias by equating groups (ABD vs. ABD-HR) based on covariates. Bivariate analyses of independent variables by our outcomes of interest were performed using the Pearson Chi-Square and Fisher's Exact tests for categorical variables and the Wilcoxon rank-sum test for continuous variables. RESULTS: Of the 14,115 patients identified in the ACS-NSQIP, 13,634 had ABD, while 481 had both ABD and HR. Following PS-matching of the cohorts, ABD (n = 481) and ABD-HR (n = 481), bivariate analysis of the combination of incisional, umbilical, and epigastric hernias indicated longer operative times (mean: 209.6 min) (P < 0.001) and a longer hospital length of stay (mean: 1.9 days) (P < 0.001). The incidence rate of postoperative complications such as wound dehiscence, deep venous thromboembolism, DVT, unplanned return to the OR within 30 days, and other medical complications revealed no significant differences between the two cohorts. A sub-group analysis of wound complications found no significant difference for any wound type. Analysis was also conducted for each type of hernia separately, yielding the same results. CONCLUSION: Our results show no increase in postoperative morbidity when combining ABD and HR compared to ABD alone, suggesting that these procedures can be safely performed concurrently and regardless of the type of hernia.

The Efficacy of Human Papillomavirus Vaccination as an Adjuvant Therapy in Recurrent Respiratory Papillomatosis.

OBJECTIVE: To characterize the efficacy of human papillomavirus (HPV) vaccination as an adjuvant therapy in recurrent respiratory papillomatosis (RRP). DATA SOURCES: PubMed, Embase, Cochrane, Google Scholar, ClinicalTrials.gov, and Web of Science databases were queried for articles published before April 2021. REVIEW METHODS: All retrieved studies (n = 870) were independently analyzed by two reviewers according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement using predefined inclusion and exclusion criteria. 13 studies met inclusion criteria. A random-effects meta-analysis was performed to study intersurgical interval (ISI) and number of surgical procedures per year before and after vaccination. RESULTS: The systematic review included 13 studies, comprising 243 patients. All studies utilized the Gardasil® quadrivalent vaccine, and one study (Yiu et al. 2019) utilized both the quadrivalent and Gardasil® 9-valent vaccines. Our meta-analysis included 62 patients with ISI data across 4 studies, and 111 patients with data on the number of surgical procedures per month across 7 studies. The mean number of surgical procedures decreased by 4.43 per year after vaccination (95% CI, -7.48 to -1.37). Mean ISI increased after vaccination, with a mean difference of 15.73 months (95% CI, 1.46-29.99). Two studies reported on HPV sero-conversion, with HPV seropositivity of 100% prior to vaccination and 25.93% after vaccination. CONCLUSION: The addition of HPV vaccination was associated with an increase in time between surgeries and reduction in the number of surgical procedures required. HPV vaccination may be a beneficial adjuvant treatment for RRP. LEVEL OF EVIDENCE: NA Laryngoscope, 133:2046-2054, 2023.

Androgen and oestrogen receptor co-expression determines the efficacy of hormone receptor-mediated radiosensitisation in breast cancer.

PURPOSE: Radiation therapy (RT) and hormone receptor (HR) inhibition are used for the treatment of HR-positive breast cancers; however, little is known about the interaction of the androgen receptor (AR) and estrogen receptor (ER) in response to RT in AR-positive, ER-positive (AR+/ER+) breast cancers. Here we assessed radiosensitisation of AR+/ER+ cell lines using pharmacologic or genetic inhibition/degradation of AR and/or ER. METHODS: Radiosensitisation was assessed with AR antagonists (enzalutamide, apalutamide, darolutamide, seviteronel, ARD-61), ER antagonists (tamoxifen, fulvestrant) or using knockout of AR. RESULTS: Treatment with AR antagonists or ER antagonists in combination with RT did not result in radiosensitisation changes (radiation enhancement ratios [rER]: 0.76-1.21). Fulvestrant treatment provided significant radiosensitisation of CAMA-1 and BT-474 cells (rER: 1.06-2.0) but not ZR-75-1 cells (rER: 0.9-1.11). Combining tamoxifen with enzalutamide did not alter radiosensitivity using a 1 h or 1-week pretreatment (rER: 0.95-1.14). Radiosensitivity was unchanged in AR knockout compared to Cas9 cells (rER: 1.07 ± 0.11), and no additional radiosensitisation was achieved with tamoxifen or fulvestrant compared to Cas9 cells (rER: 0.84-1.19). CONCLUSION: While radiosensitising in AR + TNBC, AR inhibition does not modulate radiation sensitivity in AR+/ER+ breast cancer. The efficacy of ER antagonists in combination with RT may also be dependent on AR expression.

Estrogen receptor inhibition mediates radiosensitization of ER-positive breast cancer models.

Endocrine therapy (ET) is an effective first-line therapy for women with estrogen receptor-positive (ER + ) breast cancers. While both ionizing radiation (RT) and ET are used for the treatment of women with ER+ breast cancer, the most effective sequencing of therapy and the effect of ET on tumor radiosensitization remains unclear. Here we sought to understand the effects of inhibiting estrogen receptor (ER) signaling in combination with RT in multiple preclinical ER+ breast cancer models. Clonogenic survival assays were performed using variable pre- and post-treatment conditions to assess radiosensitization with estradiol, estrogen deprivation, tamoxifen, fulvestrant, or AZD9496 in ER+ breast cancer cell lines. Estrogen stimulation was radioprotective (radiation enhancement ratios [rER]: 0.51-0.82). Conversely, when given one hour prior to RT, ER inhibition or estrogen depletion radiosensitized ER+ MCF-7 and T47D cells (tamoxifen rER: 1.50-1.60, fulvestrant rER: 1.76-2.81, AZD9496 rER: 1.33-1.48, estrogen depletion rER: 1.47-1.51). Combination treatment resulted in an increase in double-strand DNA (dsDNA) breaks as a result of inhibition of non-homologous end joining-mediated dsDNA break repair with no effect on homologous recombination. Treatment with tamoxifen or fulvestrant in combination with RT also increased the number of senescent cells but did not affect apoptosis or cell cycle distribution. Using an MCF-7 xenograft model, concurrent treatment with tamoxifen and RT was synergistic and resulted in a significant decrease in tumor volume and a delay in time to tumor doubling without significant toxicity. These findings provide preclinical evidence that concurrent treatment with ET and RT may be an effective radiosensitization strategy.

Harnessing the Chaplain's Capacity to Identify Unmet Palliative Needs of Vulnerable Older Adults in the Emergency Department.

Objective: To explore chaplains' ability to identify unmet palliative care (PC) needs in older emergency department (ED) patients. Methods: A palliative chaplain-fellow conducted a retrospective chart review evaluating 580 ED patients, age ≥80 using the Palliative Care and Rapid Emergency Screening (P-CaRES) tool. An emergency medicine physician and chaplain-fellow screened 10% of these charts to provide a clinical assessment. One year post-study, charts were re-examined to identify which patients received PC consultation (PCC) or died, providing an objective metric for comparing predicted needs with services received. Results: Within one year of ED presentation, 31% of the patient sub-sample received PCC; 17% died. Forty percent of deceased patients did not receive PCC. Of this 40%, chaplain screening for P-CaRES eligibility correctly identified 75% of the deceased as needing PCC. Conclusion: Establishing chaplain-led PC screenings as standard practice in the ED setting may improve end-of-life care for older patients.

The effect of a relationship-centered communication program on patient experience and provider wellness.

OBJECTIVES: Despite evidence of the central importance of communication to patient experience, health outcomes, and provider wellness, communication training for clinicians is not a standard part of clinical education. The study explores the impact of an 8-hour relationship-centered communication (RCC) training program on patient experience and provider wellness. METHODS: 636 healthcare providers participated in 48 workshops conducted January-August 2018. 481 (76%) agreed to participate in research. Participants completed a pre/post assessment that included a wellness survey, the Professional Fulfillment Index (PFI). We conducted chi-squared analyses comparing wellness data immediately prior to the course to 3 months following course participation. Patient experience, assessed using Press Ganey likelihood to recommend care provider (PG-LTR CP) scores, were examined prior to an individual's course participation and following participation up to September 2019. RESULTS: 104 participants completed the three-month PFI (22% response rate). Participants demonstrated marked improvements in professional wellness after 3 months. In bivariate analyses, PG-LTR CP significantly increased and persisted more than 7 months following program completion. CONCLUSIONS: The RCC training program, a low-cost communication intervention, led to significant, beneficial changes in provider wellness and patient experience. PRACTICE IMPLICATIONS: Implementing a RCC course for providers may improve patient experience and provider wellness.

What is empathy? Oncology patient perspectives on empathic clinician behaviors.

BACKGROUND: Oncology patients and physicians value empathy because of its association with improved health outcomes. Common measures of empathy lack consistency and were developed without direct input from patients. Because of their intense engagement with health care systems, oncology patients may have unique perspectives on what behaviors signal empathy in a clinical setting. METHODS: As part of a cross-sectional study of patient perspectives on clinician empathy at an academic cancer center in the northeastern United States, the authors solicited up to 10 free-text responses to an open-ended question about what clinician behaviors define empathy. RESULTS: The authors categorized open-ended responses from 89 oncology patients into 5 categories representing 14 themes. These categories were relationship sensitivity, focus on the whole person, communication, clinician attributes, and institutional resources and care processes. Frequently represented themes, including listening, understanding, and attention to emotions and what matters most, aligned with existing measures of empathy; behaviors that were not well represented among existing measures included qualities of information sharing and other communication elements. Patients also associated clinician demeanor, accessibility, and competence with empathy. CONCLUSIONS: Oncology patients' perspectives on empathy highlight clinician behaviors and attributes that may help to refine patient experience measures and may be adopted by clinicians and cancer centers to enhance patient care and outcomes. High-quality communication skills training can promote active listening and paying attention to the whole person. A system-level focus on delivering empathic care may improve patients' experiences and outcomes. LAY SUMMARY: Oncology patients' responses to an open-ended question about empathic clinician behavior have revealed insights into a variety of behaviors that are perceived as demonstrative of empathy. These include behaviors that imply sensitivity to the clinician-patient relationship, such as listening and understanding and attention to the whole person. Participants valued caring communication and demeanor and clinician accessibility. Perspective taking was not common among answers. Many existing measures of clinical care quality do not include the behaviors cited by patients as empathic. These results can inform efforts to refine quality measures of empathy-associated behaviors in clinical practice. Cancer centers can use skills training to improve elements of communication.

What is clinical empathy? Perspectives of community members, university students, cancer patients, and physicians.

OBJECTIVES: To explore what undergraduates, community members, oncology patients, and physicians consider empathic behavior in a physician. METHODS: 150 undergraduates, 152 community members, 95 physicians, and 89 oncology patients rated 49 hypothetical physician behaviors for how well they fit their personal definition of physician empathy. Dimensions of empathy were explored and compared across groups. RESULTS: Three dimensions of empathy were Conscientious and Reassuring, Relationship Oriented, and Emotionally Involved. Relationship Oriented was the most strongly endorsed, followed by Emotionally Involved, with Conscientious and Reassuring coming in last. There were no group differences for Conscientious and Reassuring, but the Relationship Oriented factor was more endorsed by the clinical groups (physicians and patients) than the non-clinical groups. The Emotionally Involved factor was endorsed by physicians notably more than by patients. CONCLUSION: What is considered clinical empathy is not the same across individuals and stakeholder groups. PRACTICE IMPLICATIONS: Physicians and patients differ in how much they include the physicians' emotionality and emotion-related actions in their definition of empathy. Communication training for physicians that emphasizes behaviors associated with empathy (listening, understanding a person's feelings and perspectives, and showing interest in and concern for the whole person) may enhance patients' perception of clinical empathy.

Epidermal Growth Factor Receptor, Excision-Repair Cross-Complementation Group 1 Protein, and Thymidylate Synthase Expression in Penile Cancer.

OBJECTIVE: To describe the expression of tissue epidermal growth factor receptor (EGFR), excision-repair cross-complementation group 1 protein (ERCC1), and thymidylate synthase (TS) in patients with penile cancer and explore their association with stage and outcome. METHODS: A total of 52 patients with penile squamous cell cancer who were treated at the University of Southern California from 1995 to 2010 were identified. Paraffin-embedded tissue underwent mRNA quantitation and immunohistochemistry for expression of EGFR, ERCC1, and TS. KRAS mutations were evaluated using polymerase chain reaction-based sequencing. RESULTS: EGFR overexpression was common by mRNA (median, 5.09; range, 1.92-104.5) and immunohistochemistry. EGFR expression > 7 was associated with advanced stage and poor differentiation (P = .01 and .034 respectively) but not with survival in multivariate analysis. ERCC1 mRNA expression was a median of 0.65 (range, 0.21-1.87). TS expression was a median of 1.88 (range, 0.54-6.47). ERCC1 and TS expression were not associated with grade, stage, or survival. There were no KRAS mutations identified. A total of 17 men received chemotherapy; 8 (47%) had an objective response, including 1 with a pathologic complete response. There was a trend for lower expression of EGFR corresponding to a higher likelihood of response (response rate [RR]) to chemotherapy: 67% RR in EGFR mRNA < 7 versus 33% RR in EGFR > 7 (P = .31). CONCLUSIONS: High expression of EGFR mRNA in squamous cell carcinoma of the penis is associated with advanced stage and poor differentiation, but not survival. In our small heterogeneous subset, molecular marker expression did not show a correlation with the likelihood of chemotherapy response. A prospective evaluation of the role of the EGFR pathway and its regulatory environment in penile cancer is warranted. Given the rarity of this cancer, collaborative prospective cohort evaluations and trials need to be encouraged.

Clinicopathologic characteristics and outcomes of penile cancer treated at tertiary care centers in the Western United States.

BACKGROUND: This article reports on the experience with penile squamous cell carcinoma (PSCC) in a unique multiethnic patient population from Los Angeles, California, with regard to treatments rendered and clinical outcomes. PATIENTS AND METHODS: Available clinical, pathologic, and treatment information for PSCC patients treated at 3 hospitals associated with the University of Southern California from 1991 to 2011 was retrospectively reviewed. Associations of patient variables with prognosis were assessed using univariable and multivariable analyses. RESULTS: Of the 95 PSCC patients identified, clinicopathologic and outcome information was available on 89 men (median age, 53 years; median follow-up, 23 months). National minorities comprised 76.4% of the cohort with 57.3% Hispanics accounting for all patients. Presence of poorly differentiated tumors was associated with higher tumor stage (P = .020), nodal metastasis (P = .016), distant metastasis (P = .004), and advanced AJCC disease stage (P = .001). Univariate analysis showed that tumor (P = .008), nodal (P = .033), and metastasis (P < .001) stage, and tumor differentiation (P = .010) were associated with survival. When categorized according to the AJCC classification, patients with ≥ stage III disease had worse outcomes (P = .006). Type of primary therapy delivered did not affect outcomes. AJCC disease stage was independently prognostic in multivariable analysis (P = .035). CONCLUSION: These results confirm associations of several clinicopathologic factors with PSCC outcomes, although the presented population differs from others previously described from the United States with a relatively higher proportion of Hispanic men. This highlights the need for studies on the effects of race, cultural, health, and behavioral patterns on PSCC outcomes in multiethnic populations.

Adeno-associated virus replication induces a DNA damage response coordinated by DNA-dependent protein kinase.

The parvovirus adeno-associated virus (AAV) contains a small single-stranded DNA genome with inverted terminal repeats that form hairpin structures. In order to propagate, AAV relies on the cellular replication machinery together with functions supplied by coinfecting helper viruses such as adenovirus (Ad). Here, we examined the host cell response to AAV replication in the context of Ad or Ad helper proteins. We show that AAV and Ad coinfection activates a DNA damage response (DDR) that is distinct from that seen during Ad or AAV infection alone. The DDR was also triggered when AAV replicated in the presence of minimal Ad helper proteins. We detected autophosphorylation of the kinases ataxia telangiectasia mutated (ATM) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and signaling to downstream targets SMC1, Chk1, Chk2, H2AX, and XRCC4 and multiple sites on RPA32. The Mre11 complex was not required for activation of the DDR to AAV infection. Additionally, we found that DNA-PKcs was the primary mediator of damage signaling in response to AAV replication. Immunofluorescence revealed that some activated damage proteins were found in a pan-nuclear pattern (phosphorylated ATM, SMC1, and H2AX), while others such as DNA-PK components (DNA-PKcs, Ku70, and Ku86) and RPA32 accumulated at AAV replication centers. Although expression of the large viral Rep proteins contributed to some damage signaling, we observed that the full response required replication of the AAV genome. Our results demonstrate that AAV replication in the presence of Ad helper functions elicits a unique damage response controlled by DNA-PK.

Targeted reduction of KLF6-SV1 restores chemotherapy sensitivity in resistant lung adenocarcinoma.

Kruppel-like factor 6 splice variant 1 (KLF6-SV1) is an oncogenic splice variant of the KLF6 tumor suppressor gene that is specifically overexpressed in a number of human cancers. Previously, we have demonstrated that increased expression of KLF6-SV1 is associated with decreased survival in lung adenocarcinoma patient samples and that targeted reduction of KLF6-SV1 using siRNA induced apoptosis both alone and in combination with the chemotherapeutic drug cisplatin. Here, we demonstrate that chemoresistant lung cancer cells express increased levels of KLF6-SV1. Furthermore, targeted reduction of KLF6-SV1 using RNA interference restores chemotherapy sensitivity to lung cancer cells both in culture and in vivo through induction of apoptosis. Conversely, overexpression of KLF6-SV1 resulted in a marked reduction in chemotherapy sensitivity in a tumor xenograft model. Combined, these findings highlight a functional role for the KLF6-SV1 splice variant in the regulation of chemotherapy response in lung cancer and could provide novel insight into lung cancer therapy.

Functional role of the KLF6 tumour suppressor gene in gastric cancer.

Gastric cancer is the second most common cancer and a leading cause of cancer-related death worldwide. The Kruppel-like factor 6 (KLF6) tumour suppressor gene had been previously shown to be inactivated in a number of human cancers through loss of heterozygosity (LOH), somatic mutation, decreased expression and increased alternative splicing into a dominant negative oncogenic splice variant, KLF6-SV1. In the present study, 37 gastric cancer samples were analysed for the presence of loss of heterozygosity (LOH) of the KLF6 locus and somatic mutation. In total, 18 of 34 (53%) of the gastric cancer samples analysed demonstrated KLF6 locus specific loss. Four missense mutations, such as T179I, R198G, R71Q and S180L, were detected. Interestingly, two of these mutations R71Q and S180L have been identified independently by several groups in various malignancies including prostate, colorectal and gastric cancers. In addition, decreased wild-type KLF6 (wtKLF6) expression was associated with loss of the KLF6 locus and was present in 48% of primary gastric tumour samples analysed. Functional studies confirmed that wtKLF6 suppressed proliferation of gastric cancer cells via transcriptional regulation of the cyclin-dependent kinase inhibitor p21 and the oncogene c-myc. Functional characterisation of the common tumour-derived mutants demonstrated that the mutant proteins fail to suppress proliferation and function as dominant negative regulators of wtKLF6 function. Furthermore, stable overexpression of the R71Q and S180L tumour-derived mutants in the gastric cancer cell line, Hs746T, resulted in an increased tumourigenicity in vivo. Combined, these findings suggest an important role for the KLF6 tumour suppressor gene in gastric cancer development and progression and identify several highly cancer-relevant signalling pathways regulated by the KLF6 tumour suppressor gene.

Distinct requirements of adenovirus E1b55K protein for degradation of cellular substrates.

The E1b55K and E4orf6 proteins of adenovirus type 5 (Ad5) assemble into a complex together with cellular proteins including cullin 5, elongins B and C, and Rbx1. This complex possesses E3 ubiquitin ligase activity and targets cellular proteins for proteasome-mediated degradation. The ligase activity has been suggested to be responsible for all functions of E1b55K/E4orf6, including promoting efficient viral DNA replication, preventing a cellular DNA damage response, and stimulating late viral mRNA nuclear export and late protein synthesis. The known cellular substrates for degradation by E1b55K/E4orf6 are the Mre11/Rad50/Nbs1 DNA repair complex, the tumor suppressor p53, and DNA ligase IV. Here we show that the degradation of individual targets can occur independently of other substrates. Furthermore, we identify separation-of-function mutant forms of E1b55K that can distinguish substrates for binding and degradation. Our results identify distinct regions of E1b55K that are involved in substrate recognition but also imply that there are additional requirements beyond protein association. These mutant proteins will facilitate the determination of the relevance of specific substrates to the functions of E1b55K in promoting infection and inactivating host defenses.