EGFR Targeting of Liposomal Doxorubicin Improves Recognition and Suppression of Non-Small Cell Lung Cancer.

Introduction: Despite improvements in chemotherapy and molecularly targeted therapies, the life expectancy of patients with advanced non-small cell lung cancer (NSCLC) remains less than 1 year. There is thus a major global need to advance new treatment strategies that are more effective for NSCLC. Drug delivery using liposomal particles has shown success at improving the biodistribution and bioavailability of chemotherapy. Nevertheless, liposomal drugs lack selectivity for the cancer cells and have a limited ability to penetrate the tumor site, which severely limits their therapeutic potential. Epidermal growth factor receptor (EGFR) is overexpressed in NSCLC tumors in about 80% of patients, thus representing a promising NSCLC-specific target for redirecting liposome-embedded chemotherapy to the tumor site. Methods: Herein, we investigated the targeting of PEGylated liposomal doxorubicin (Caelyx), a powerful off-the-shelf antitumoral liposomal drug, to EGFR as a therapeutic strategy to improve the specific delivery and intratumoral accumulation of chemotherapy in NSCLC. EGFR-targeting of Caelyx was enabled through its complexing with a polyethylene glycol (PEG)/EGFR bispecific antibody fragment. Tumor targeting and therapeutic potency of our treatment approach were investigated in vitro using a panel of NSCLC cell lines and 3D tumoroid models, and in vivo in a cell line-derived tumor xenograft model. Results: Combining Caelyx with our bispecific antibody generated uniform EGFR-targeted particles with improved binding and cytotoxic efficacy toward NSCLC cells. Effects were exclusive to cancer cells expressing EGFR, and increments in efficacy positively correlated with EGFR density on the cancer cell surface. The approach demonstrated increased penetration within 3D spheroids and was effective at targeting and suppressing the growth of NSCLC tumors in vivo while reducing drug delivery to the heart. Conclusion: EGFR targeting represents a successful approach to enhance the selectivity and therapeutic potency of liposomal chemotherapy toward NSCLC.

Optimizing Outcomes in Lymphedema Reconstruction.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Describe current surgical techniques for treating primary and secondary lymphedema. 2. Optimize the surgical care of patients with lymphedema. SUMMARY: Over the past decade, significant advances have been made in the surgical treatment of lymphedema. The most notable changes have been the reintroduction and evolution of physiologic techniques, including lymphovenous bypass-sometimes referred to as lymphovenous anastomosis in the literature-and vascularized lymph node transplant. These surgical modalities are now often used as first-line surgical options or may be combined with nonphysiologic approaches, including direct excision and suction-assisted lipectomy. Surgeons continue to debate the most appropriate sequence and combination of surgical treatment, particularly for patients at both extremes of the severity spectrum. Furthermore, debate remains around the need to apply different treatment approaches for patients with upper versus lower extremity involvement and primary versus secondary cause. In this article, we provide a summary of the surgical techniques currently used for both primary and secondary lymphedema and provide our recommendations for optimizing the surgical care of patients with lymphedema.

Radiation and free flaps: what is the optimal timing?

The debate over when to perform flaps in patients undergoing radiation remains an ongoing dilemma without definitive resolution. Classically, reconstructive surgeons recommended avoiding exposure of autologous flaps to radiotherapy due to concerns over surgical complications and poor aesthetic outcomes. However, delayed reconstruction carries its own risk profile and aesthetic limitations, given the irreversible changes to the breast envelope. Immediate reconstruction not only confers psychosocial benefits but allows for preservation of the native breast skin and footprint. In recent years, a growing body of evidence suggests that with modern radiation techniques, long-term outcomes of immediate vs. delayed autologous reconstruction may be more similar than previously thought. This review examines the advantages and disadvantages of each treatment algorithm and critically evaluates the existing literature on autologous breast reconstruction in the setting of post-mastectomy radiotherapy. Importantly, radiation regimens have varied widely over time and between institutions, introducing significant heterogeneity in published outcomes of flap contracture or fat necrosis after immediate reconstruction. While delayed autologous reconstruction remains a reasonable pathway, the benefits of immediate reconstruction should not be dismissed. Our findings ultimately corroborate the view that immediate flap reconstruction is a sound treatment option that can be safely offered to patients. The decision regarding which pathway to pursue should ultimately be patient-centric and driven by multidisciplinary consensus, rather than by prior dogma.

Health Disparities in Patients Seeking Physiological Surgical Treatment for Lymphedema.

BACKGROUND: Previous studies have demonstrated racial disparities in breast cancer treatment and secondary lymphedema. However, no studies have yet examined the effects of race and socioeconomic status on physiological surgical treatment for lymphedema. The authors aimed to evaluate whether disparities exist within patients seeking physiological surgical lymphedema treatment. METHODS: A retrospective review was performed of patients presenting for physiological surgical treatment of lymphedema from 2013 to 2019. Data on demographics, medical history, socioeconomic factors, lymphedema, and treatments were collected. RESULTS: A total of 789 patients (712 women and 77 men) seeking physiological surgical treatment of lymphedema were selected. Their mean age was 54.4 ± 13.4 years. A total of 620 patients (78.5%) self-reported as White, 120 (15.2%) as Black, 17 (2.2%) as Asian, five (0.6%) as Hispanic, and eight (2.4%) as multiracial. A total of 566 patients (71.7%) met criteria for surgical candidacy. White race was associated with increased rates of surgical candidacy compared with Black race (46.6% versus 77.2%; P < 0.0001). Compared with White patients, Black patients presented with a longer symptom duration (11.07 versus 6.99 years; P < 0.001), had a higher body mass index (mean, 34.5 versus 28.1; P < 1 × 10 -10 ), had a higher International Society of Lymphology stage ( P < 0.05), and were less likely to have maximized medical treatment for lymphedema (30.8% versus 55.4%; P < 0.01). CONCLUSIONS: This study demonstrates racial disparities in patients seeking physiological surgical treatment for lymphedema. Black patients present later with more severe disease, receive less nonsurgical treatment before consultation, and are less likely to meet criteria for physiological surgery. Improved patient and provider education on lymphedema and appropriate diagnosis and nonsurgical treatment is of primary importance to address this disparity.

"Immediate versus delayed autologous breast reconstruction in patients undergoing post-mastectomy radiation therapy: A paradigm shift".

BACKGROUND: While negative impacts of radiation on breast reconstruction have been well accepted, timing of autologous breast reconstruction in the setting of postmastectomy radiation therapy (PMRT) is still evolving. This study aims to address the dilemma of breast reconstruction timing in patients receiving PMRT. METHODS: A retrospective chart review was performed evaluating patients who underwent PMRT and autologous breast reconstruction. Postoperative complication and revision rates were compared. RESULTS: Thirty-six immediate (immediate breast reconstruction [IBR]) and 89 delayed reconstructions (delayed breast reconstruction [DBR]) were included with comparable patient characteristics between groups. Overall complication rates were not significantly different, or when separately assessing for surgical site infections, wound dehiscence, fat necrosis, or substantial volume loss. No free flaps were lost in either group. Revision rates were significantly lower in the IBR group (p = 0.02). DBR resulted in appreciably larger volumes of fat grafting to the therapeutically reconstructed breast (p = 0.01) and more contralateral mastopexies (p = 0.02). No significant difference was observed in fat necrosis excision, breast reduction, or need for secondary flap reconstruction or prosthetic use for volume loss. CONCLUSIONS: IBR in the setting of PMRT does not result in higher rates of complications and requires fewer overall revisions, making it a compelling option for patients undergoing PMRT.

Outcomes of progressive tension donor-site closure in abdominal-based autologous breast reconstruction.

BACKGROUND: The use of progressive tension sutures (PTSs) for drain-free abdominoplasty closure has been well published in the esthetic literature and found to be effective at reducing abdominal drainage without a worse complication profile. This research aims to evaluate the outcomes of incorporating PTS into donor-site closures for abdominal-based breast reconstruction. METHODS: A retrospective chart review was performed evaluating patients at the University of Chicago Medicine, who underwent autologous breast reconstruction and either PTS closure or standard abdominal closure between 2018 and 2021. RESULTS: A total of 100 patients were included with 50 patients receiving PTS closure and 50 with traditional abdominal closures. Patient demographics, including age (p = 0.82), body mass index (BMI; p = 0.17), diabetes (p = 1.00), tobacco use (p = 0.15), and chemotherapy (p = 1.00) did not significantly differ. Total drain output over the first 72 h was significantly lower in the PTS group compared with the standard closure (SC) group (p = 0.00005). Mean duration of drain placement was shorter by 2 days in the PTS group, but this did not reach significance (p = 0.08). Overall complication rates were lower in the PTS group (p = 0.03), however, no difference was appreciated when separately assessing for seromas (p = 1.00), hematomas (p = 1.00), wound dehiscence (p = 0.58), or surgical-site infections (p = 1.00). More abdominal revisions were observed in the SC group, however, this did not reach significance (p = 0.15) CONCLUSION: The use of PTS with placement of a single drain is a safe option for donor-site closure, and is a compelling technique for patients undergoing abdominal-based breast reconstruction.

Physical and Functional Outcomes of Simultaneous Vascularized Lymph Node Transplant and Lymphovenous Bypass in the Treatment of Lymphedema.

BACKGROUND: The authors analyze the outcomes of simultaneous vascularized lymph node transplant and lymphovenous bypass for treatment of primary and secondary lymphedema. To the best of their knowledge, this is the largest study to date with long-term outcome data of this novel approach. METHODS: Three hundred twenty-eight patients who underwent physiologic surgical treatment over a 5.5-year period were evaluated using a prospective database and chart review. Preoperative characteristics, operative details, and postoperative outcomes (volume difference change, Lymphedema Life Impact Scale score) were assessed. Statistical analysis including multivariate regression was performed. RESULTS: Two hundred twenty patients (67.1 percent) underwent simultaneous vascularized lymph node transplant and lymphovenous bypass. Mean body mass index was 26.9 ± 4.7 kg/m 2 . Ninety-two patients (41.8 percent) had lymphedema of the lower extremity, 121 (55.0 percent) had upper extremity involvement, and seven had lymphedema of upper and lower extremities (3.2 percent). Average duration of lymphedema was 95.4 ± 103.6 months. Thirty patients (13.6 percent) had primary lymphedema and 190 patients (86.4 percent) had secondary lymphedema. The majority improved and experienced volume reduction of an average 21.4 percent at 1 year ( p < 0.0001), 36.2 percent at 2 years ( p < 0.0001), 25.5 percent at 3 years ( p = 0.1), and 19.6 percent at 4 years. Median Lymphedema Life Impact Scale scores were 7.0 points lower ( p < 0.0001) at 3 months and improved progressively over time to 27.5 points lower at 3 years postoperatively ( p < 0.005). CONCLUSIONS: Simultaneous vascularized lymph node transplant and lymphovenous bypass is an appropriate and effective approach for both early and advanced stages of primary and secondary lymphedema, with significant objective and subjective improvements. Volume reduction in the affected limb was observed at all time points postoperatively, with significant improvement in Lymphedema Life Impact Scale scores. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Soft-Tissue Considerations in Shoulder Surgery in the Patient With Lymphedema.

Lymphedema is a chronic, progressive, and often debilitating condition that results in swelling of the affected tissue. Secondary lymphedema is most commonly recognized by unilateral swelling of the ipsilateral extremity after the treatment of cancer. It is estimated that nearly 1.45 million women suffer from breast cancer-related lymphedema in the United States. The number of patients suffering from upper extremity lymphedema is expected to increase because multimodal treatment of breast cancer increases the long-term survival after diagnosis. Because this population ages, the likelihood of encountering a patient with concurrent lymphedema and shoulder pathology requiring orthopaedic intervention is likely to rise. A patient with an already edematous arm and/or impaired drainage of that arm is likely to have different and more complex intraoperative and postoperative courses than patients with normal lymphatic drainage. Although a lymphedematous arm should not preclude surgical intervention, there are considerations when approaching shoulder surgery in the setting of upper extremity lymphedema that may help mitigate complications and aid the patient in their orthopaedic recovery.

Plastic Surgery Away Rotations During the Coronavirus Disease Pandemic: A Virtual Experience.

BACKGROUND: Plastic surgery has traditionally been a specialty that places a strong emphasis on away rotations during the final year of medical school. These rotations allow the program and residency candidates to become better acquainted and are often crucial, as a large portion of applicants match at programs where they rotated. The coronavirus disease 2019 (COVID-19) pandemic forced many institutions to modify their educational curriculums when away rotations were canceled. We present our experience creating and implementing a virtual plastic surgery rotation. METHODS: Our virtual program was designed to mirror the in-person away rotations as much as possible. Prerotation and postrotation surveys from the students as well as feedback interviews with the students, residents, and faculty were used to gather information on the experience. RESULTS: We created a 2-week curriculum including approximately 20 hours of lecture time, 28 hours of operating room time, 2.5 hours of one-on-one mentorship, and 3 hours of social opportunities. Students reported that they learned more about plastic surgery and the residency program, but in contrast to this, some found it difficult to make an impression. CONCLUSIONS: We developed a novel 2-week virtual curriculum that provided visiting medical students from across the country an opportunity to learn more about plastic surgery and our residency program. Virtual learning is becoming a vital part of education, and our study provides pearls and pitfalls when structuring these experiences.

Outcomes for Physiologic Microsurgical Treatment of Secondary Lymphedema Involving the Extremity.

OBJECTIVE: The aim of this study was to examine the long-term impact of physiologic surgical options, including VLNT and LVB, on patients with secondary lymphedema of the upper or lower extremity (UEL/LEL). SUMMARY BACKGROUND DATA: VLNT and LVB have become increasingly popular in the treatment of lymphedema. However, there is a paucity of long-term data on patient outcomes after use of these techniques to treat lymphedema. METHODS: An analysis of prospectively collected data on all patients who underwent physiologic surgical treatment of secondary lymphedema over a 5.5-year period was performed. Patient demographics, surgical details, subjective reported improvements, LLIS scores, and postoperative limb volume calculations were analyzed. RESULTS: Two hundred seventy-four patients with secondary lymphedema (197 upper, 77 lower) were included in the study. More than 87% of UEL patients and 60% of LEL patients had reduction in excess limb volume postoperatively. At 3 months postoperatively, patients with UEL had a 31.1% reduction in volume difference between limbs, 33.9% at 6 months, 25.7% at 12 months, 47.4% at 24 months and 47.7% at 4 years. The reduction in limb volume difference followed a similar pattern but was overall lower for LEL patients. Greater than 86% of UEL and 75% of LEL patients also had improvement in LLIS scores postoperatively. Fifty-nine complications occurred (12.9%); flap survival was >99%. CONCLUSIONS: Patients with secondary UEL/LEL who undergo VLNT/LVB demonstrate improved functional status and reduced affected limb volumes postoperatively. Patients with UEL seem to have a more substantial reduction in limb volume differential compared to LEL patients.

Advances in surgical treatment of lymphedema.

An estimated 250 million people worldwide suffer from lymphedema. In the past, the firstline option for treatment was nonsurgical management, either in the form of compression garments or wrapping, or comprehensive decongestive therapy, with debulking surgery reserved for the more advanced cases. However, with improvements in microsurgical techniques and imaging modalities, surgical intervention is increasingly being utilized. This review highlights recent advancements in the surgical treatment of lymphedema, specifically focusing on improvements in imaging, surgical techniques, and prevention of lymphedema.

Surgical Treatment of Lymphedema: A Systematic Review and Meta-Analysis of Controlled Trials. Results of a Consensus Conference.

BACKGROUND: The goal of this consensus conference, sponsored by the American Association of Plastic Surgeons, was to perform a systematic review and meta-analysis of controlled trials to examine both the benefits and risks of surgical treatment and surgical prevention of upper and lower extremity lymphedema. METHODS: The panel met in Boston for a 3-day, face-to-face meeting in July of 2017. After an exhaustive review of the existing literature, the authors created consensus recommendations using the Grading of Recommendations, Assessment, Development and Evaluation criteria. Important directions for future research were also identified. RESULTS: There is evidence to support that lymphovenous anastomosis can be effective in reducing severity of lymphedema (grade 1C). There is evidence to support that vascular lymph node transplantation can be effective in reducing severity of lymphedema (grade 1B). Currently, there is no consensus on which procedure (lymphovenous bypass versus vascular lymph node transplantation) is more effective (grade 2C). A few studies show that prophylactic lymphovenous bypass in patients undergoing extremity lymphadenectomy may reduce the incidence of lymphedema (grade 1B). More studies with longer follow-up are required to confirm this benefit. Debulking procedures such as liposuction are effective in addressing a nonfluid component such as fat involving lymphedema (grade 1C). There is a role for liposuction combined with physiologic procedures although the timing of each procedure is currently unresolved (grade 1C). CONCLUSIONS: Many studies seem to support some efficacy of lymphovenous bypass and vascular lymph node transplantation. Many studies show the important role of lymphedema therapy and other procedures such as liposuction and debulking. The management of lymphedema is a challenging field with many promising advances. However, many questions remain unanswered.

Immune checkpoint-related serum proteins and genetic variants predict outcomes of localized prostate cancer, a cohort study.

BACKGROUND: The clinical predictors and biological mechanisms for localized prostate cancer (PCa) outcomes remain mostly unknown. We aim to evaluate the role of serum immune-checkpoint-related (ICK) proteins and genetic variations in predicting outcomes of localized PCa. METHODS: We profiled the serum levels of 14 ICK-related proteins (BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, Tim-3, CD28, CD80, 4-1BB, CD27, and CTLA-4) in 190 patients with localized PCa. The genotypes of 97 single nucleotide polymorphisms (SNPs) from 19 ICK-related genes were analyzed in an extended population (N = 1762). Meta-data from ArrayExpress and TCGA was employed to validate and to probe functional data. Patients were enrolled and tumor aggressiveness, biochemical recurrence (BCR), and progression information were obtained. Statistical analyses were performed analyzing associations between serum biomarkers, genotypes, mRNA and outcomes. RESULTS: We showed that serum (s)BTLA and sTIM3 levels were associated with PCa aggressiveness (P < 0.05). sCD28, sCD80, sCTLA4, sGITR, sHVEM and sIDO correlated with both BCR and progression risks (all P < 0.05). We further identified ICK variants were significantly associated with aggressiveness, BCR and progression. Among them, 4 SNPs located in CD80 (rs7628626, rs12695388, rs491407, rs6804441) were not only associated with BCR and progression risk, but also correlated with sCD80 level (P < 0.01). rs491407 was further validated in an independent cohort. The CD80 mRNA expression was associated with BCR (HR, 1.85, 95% CI 1.06-3.22, P = 0.03) in meta-analysis of validation cohorts. CONCLUSION: We highlight the prognostic value of serum ICK-related proteins for predicting aggressiveness, BCR and progression of PCa. The genetic variations and mRNA expression in CD80 could be predictors and potential targets of localized PCa.

Axillary dissection in sentinel lymph node positive breast cancer: Is the staging information worthwhile for patients?

AIMS: The Z0011 randomized trial demonstrated no significant difference in axillary recurrence rate or survival with or without axillary dissection in patients with a positive sentinel node biopsy. However, there is continuing controversy regarding the generalizability of its results, and axillary dissection provides additional pathologic staging information that may guide adjuvant therapy. Thus, axillary dissection after positive sentinel node biopsy is being further investigated in an actively recruiting randomized trial. We elicited patients' preferences for axillary dissection versus no axillary dissection after positive sentinel node biopsy for early breast cancer. METHODS: Patients who had undergone axillary dissection after positive sentinel node biopsy as part of breast conserving therapy were provided with a validated, self-rated questionnaire. The questionnaire comprised two trade-off questions to determine the maximum chance of developing arm side-effects from axillary dissection to justify the benefit of additional axillary staging information. Social, demographic, and clinical details were collected. RESULTS: Ninety-nine of the 126 eligible patients returned the questionnaire and 76 completed the trade-off assessment. The median age of participants was 62 years. The median numbers of sentinel and axillary nodes removed were 2 and 12, respectively. Forty-seven percent of participants had arm swelling or tenderness of any severity. Seventy-five percent of participants would have axillary dissection even if the chance of arm side-effects like they had experienced was 100%. CONCLUSION: Most patients with early breast cancer preferred axillary dissection after positive sentinel node biopsy for the additional staging information even though there was no survival benefit from axillary dissection.

Combined Approach to Surgical Treatment of Lymphedema.

Physiologic surgical interventions, including lymphovenous bypass (LVB) and vascularized lymph node transplant (VLNT), are increasingly being used to treat lymphedema. LVB has been shown to be effective in improving the severity of lymphedema, particularly for patients with still-functional superficial lymphatic vessels that can be identified for bypass. However, in many patients, there is a paucity of functional lymphatic vessels for bypass and, thus, they are not ideal candidates for LVB alone. Unlike LVB, VLNT does not depend on the presence of functioning lymphatic vessels, but the effects of VLNT are delayed, as the proposed mechanisms of action require more time for optimal function. The author has offered a combined approach to microsurgical treatment of lymphedema for both the upper and lower extremities. Simultaneous VLNT and LVB are safe and effective for patients with both early and advanced stages of primary and secondary lymphedema. Our experience shows that a majority of patients can expect some long-term improvement, in both overall limb volume and quality of life, after surgical intervention with LVB and/or VLNT.

Genetic associations of T cell cancer immune response-related genes with T cell phenotypes and clinical outcomes of early-stage lung cancer.

BACKGROUND: Recent advances in T cell-related immunotherapy have brought remarkable progress in the treatment of non-small cell lung cancer (NSCLC). However, whether and how genetic variations of T cell cancer immune response genes can influence clinical outcomes of NSCLC patients remain obscure. METHODS: In this multiphase study, we assessed 2450 single-nucleotide polymorphisms (SNPs) from 280 T cell cancer immune response-related genes in 941 early-stage NSCLC patients (discovery n=536; validation n=405) to analyze the variants' associations with outcomes and to observe the effects on T cell phenotypes. RESULTS: We found 14 SNPs in 10 genes were associated with NSCLC outcomes (p<0.05) in both phases. Among them, TRB:rs1964986 was the most significant variant associated with recurrence risk after meta-analysis (HR 1.84, 95% CI 1.35 to 2.52, p=1.15E-04), while IDO1:rs10108662 was the most significant SNP associated with death risk (HR 1.87, 95% CI 1.40 to 2.51, p=2.17E-05). Analysis of unfavorable genotypes indicated cumulative effects on death and recurrence risks. Seven treatment-specific variants were found to predict opposite outcomes in surgery-only and surgery-plus-chemotherapy subgroups. Expression quantitative trait loci analysis indicated that six SNPs significantly correlated with their corresponding gene expression. T cells from high-risk subjects displayed reduced degranulation (p=0.02) and decreased cytotoxicity against cancer cells (p<0.01). Gene expression profile indicated increased IDO1 expression and decreased IL2, PRF and GZMB expression in high-risk subjects. CONCLUSIONS: Genetic variations in T cell cancer immune response pathways can impact outcomes and may be served as predictors for treatment efficacy in early-stage NSCLC patients. The correlation between immune genotypes and T cell antitumor immunity suggests a biological link between host immune genetics and NSCLC prognosis.

Evaluating the Effects of COVID-19 on Plastic Surgery Emergencies: Protocols and Analysis From a Level I Trauma Center.

BACKGROUND: The COVID-19 crisis has brought many unique challenges to the health care system. Across the United States, social distancing measures have been put in place, including stay-at-home (SAH) orders, to combat the spread of this infection. This has impacted the type and volume of traumatic injuries sustained during this time. Meanwhile, steps have been taken in our health care system to assure that adequate resources are available to maintain a high standard of patient care while recognizing the importance of protecting health care providers. Using comparative data, we aim to describe the trends in traumatic injuries managed by our plastic surgery service and detail the changes in consultation policies made to minimize provider exposure. METHODS: A retrospective chart review was performed of all plastic surgery emergencies at our institution during the 3 weeks preceding the issuance of SAH orders in Chicago and the 3 weeks after. The electronic medical record was queried for patient age, type and mechanism of injury, location where injury was sustained, presence of domestic violence, length of inpatient hospital stays, and treatment rendered. The two 3-week periods were then comparatively analyzed to determine differences and trends in these variables and treatment rendered. The 2 periods were then comparatively analyzed to determine differences and trends in these variables. RESULTS: There was a significant decrease in trauma consults since the issuance of SAH (88 pre-SAH vs 62 post-SAH) with a marked decrease in trauma-related hand injuries. There was an increase in the percentage of assault-related injuries including those associated with domestic violence, whereas there was an overall decrease in motor vehicle collisions. There was no notable change in the location where injuries were sustained. Significantly fewer patients were seen by house staff in the emergency room, whereas those requiring surgical intervention were able to receive care without delay. CONCLUSIONS: Stay-at-home orders in Chicago have impacted traumatic injury patterns seen by the Section of Plastic and Reconstructive Surgery at a level I Trauma Center. Safe and timely care can continue to be provided with thorough communication, vigilance, and guidance from our colleagues.

Genetic variants in epithelial-mesenchymal transition genes as predictors of clinical outcomes in localized prostate cancer.

BACKGROUND: Epithelial-mesenchymal transition (EMT) plays a pivotal role in the progression of prostate cancer (PCa). However, little is known about genetic variants in the EMT pathway as predictors of aggressiveness, biochemical recurrence (BCR) and disease reclassification in localized PCa. PATIENTS AND METHODS: In this multistage study, we evaluated 5186 single nucleotide polymorphisms (SNPs) from 264 genes related to EMT pathway to identify SNPs associated with PCa aggressiveness and BCR in the MD Anderson PCa (MDA-PCa) patient cohort (N = 1762), followed by assessment of the identified SNPs with disease reclassification in the active surveillance (AS) cohort (N = 392). RESULTS: In the MDA-PCa cohort, 312 SNPs were associated with high D'Amico risk (P < 0.05), among which, 14 SNPs in 10 genes were linked to BCR risk. In the AS cohort, 2 of 14 identified SNPs (rs76779889 and rs7083961) in C-terminal Binding Proteins 2 gene were associated with reclassification risk. The associations of rs76779889 with different endpoints were: D'Amico high versus low, odds ratio [95% confidence interval (CI)] = 2.89 (1.32-6.34), P = 0.008; BCR, hazard ratio (HR) (95% CI) = 2.88 (1.42-5.85), P = 0.003; and reclassification, HR (95% CI) = 2.83 (1.40-5.74), P = 0.004. For rs7083961, the corresponding risk estimates were: D'Amico high versus low, odds ratio (95% CI) = 1.69 (1.12-2.57), P = 0.013; BCR, HR (95% CI) = 1.87 (1.15-3.02), P = 0.011 and reclassification, HR (95% CI) = 1.72 (1.09-2.72), P = 0.020. There were cumulative effects of these two SNPs on modulating these endpoints. CONCLUSION: Genetic variants in EMT pathway may influence the risks of localized PCa's aggressiveness, BCR and disease reclassification, suggesting their potential role in the assessment and management of localized PCa.