Long-term oncological outcomes of follicular thyroid cancer in adolescents and young adults: A nationwide population-based study.

BACKGROUND: Follicular thyroid carcinoma (FTC) in adolescents and young adults (AYAs) is rare and data on long-term oncological outcomes are scarce. This study aimed to describe the long-term recurrence and survival rates of AYAs with FTC, and identify risk factors for recurrence. METHODS: This is a retrospective cohort study combining two national databases, including all patients aged 15-39 years, diagnosed with FTC in The Netherlands between 2000 and 2016. Age, sex, tumor size, focality, positive margins, angioinvasion, pT-stage, and pN-stage were included in a Cox proportional hazard model to identify risk factors for recurrence. RESULTS: We included 192 patients. Median age was 31.0 years (IQR 24.7-36.3) and the male to female ratio was 1:4.1. Most patients presented with a minimally invasive FTC (MI-FTC) (95%). Five patients presented with synchronous metastases (2.6%), including two with locoregional metastases (1%) and three with distant metastases (1.6%). During a median follow-up of 12.0 years, three patients developed a recurrence (1.6%), of which one patient developed a local recurrence (33%), and two patients a distant recurrence (67%). Five patients died during follow-up (2.6%). Cause of death was not captured. A Cox proportional hazard model could not be performed due to the low number of recurrences. CONCLUSIONS: FTC in AYAs is generally characterized as a low-risk tumor, as it exhibits a very low recurrence rate, a high overall survival, and it typically presents as MI-FTC without synchronous metastases. These findings underscore the favorable long-term oncological prognosis of FTC in AYAs.

[Automatic hearing screening for better monitoring of hearing health using the example of the German armed forces]. / Automatisiertes Hörscreening zur verbesserten Überwachung der Hörgesundheit am Beispiel der Bundeswehr.

In the present study, the concept of a systematic automated screening of temporary soldiers was evaluated based on the example of the ENT Department of the Bundeswehr Central Hospital Koblenz. From 2014 to 2017, anonymized data of 169 individuals were collected from the setting of the Bundeswehr Central Hospital. Included in the data are results from measurements with automated pure-tone audiometry (APTA; e.g., [3]), from measurements with the digit triple test for determination of the speech discrimination threshold in noise (e.g., [20]), and from interviews with questionnaires (Hearing-Dependent Daily Activities [HDDA], e.g., [14]; HearCom questionnaire, e.g., [15]). There was an initial publication from this project evaluating the questionnaires in terms of their suitability for detecting hearing loss [14]. In the following (from March 2015), only the HDDA, which was described as more sensitive, was used for measurements at the hearing screening measurement station. A complete run with the three procedures took approximately 22 min. Approximately 17% of the examined participants had abnormal findings in at least one of the procedures at the screening station. The results of the respective methods taken together detect more than any method alone and can be assumed to be complementary. Deviations between APTA with level monitor and manual tone audiometry were within the measurement accuracy. In the range between 1 and 4 kHz, hearing thresholds are somewhat underestimated with APTA. The threshold for the HDDA questionnaire with an HDDA sum ≥ 19 was confirmed. Automated hearing screening offers a good opportunity to check hearing ability on a regular basis in a standardized and reliable manner, while keeping personnel requirements low.

Modelling Alzheimer's disease using human brain organoids: current progress and challenges.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by gradual memory loss and declining cognitive and executive functions. AD is the most common cause of dementia, affecting more than 50 million people worldwide, and is a major health concern in society. Despite decades of research, the cause of AD is not well understood and there is no effective curative treatment so far. Therefore, there is an urgent need to increase understanding of AD pathophysiology in the hope of developing a much-needed cure. Dissecting the cellular and molecular mechanisms of AD pathogenesis has been challenging as the most commonly used model systems such as transgenic animals and two-dimensional neuronal culture do not fully recapitulate the pathological hallmarks of AD. The recent advent of three-dimensional human brain organoids confers unique opportunities to study AD in a humanised model system by encapsulating many aspects of AD pathology. In the present review, we summarise the studies of AD using human brain organoids that recapitulate the major pathological components of AD including amyloid-ß and tau aggregation, neuroinflammation, mitochondrial dysfunction, oxidative stress and synaptic and circuitry dysregulation. Additionally, the current challenges and future directions of the brain organoids modelling system are discussed.

Mental health impact on healthcare workers due to the COVID-19 pandemic: a U.S. cross-sectional survey study.

BACKGROUND: The COVID-19 pandemic has impacted the mental health and well-being of health care workers (HCWs). This study examined mental health outcomes and COVID-related stress impacts among a diverse sample of ambulatory HCWs, including clinicians and support staff, as well as the associations between mental health outcomes and work impairments in this population. Detailing these results can help in designing interventions to alleviate this burden. METHODS: "The Health Care Worker Stress Survey" was administered to ambulatory care providers and support staff at three multispecialty care delivery organizations as part of an online, cross-sectional study conducted between June 8, 2020, and July 13, 2020. RESULTS: The greatest stress impact reported by HCWs was the uncertainty regarding when the COVID-19 outbreak would be under control, while the least reported concern was about self-dying from COVID-19. Differences in COVID-19 stress impacts were observed by age, gender, and occupational risk factors. Approximately 50% of participants reported more than a minimal level of anxiety, including 22.5% who indicated moderate to severe levels of anxiety. Higher levels of anxiety were observed with younger ages and female gender, while occupational roles with increased exposure risk did not report higher levels of anxiety. Roughly two-thirds of the sample reported less than good sleep quality and one-third to one-half of the sample reported other sleep related problems that differed by age and gender. Role limitations due to emotional health correlated with COVID-19 related stress, anxiety and sleep problems. CONCLUSIONS: Using established, validated measures, we quantified mental health outcomes within a diverse sample of ambulatory care HCWs during the pandemic. Younger and female HCWs reported greater anxiety burden; HCWs with higher occupational risk of COVID exposure did not report higher levels of anxiety. Notable proportions of HCWs reported sleep and work impairments. Due to the cross-sectional nature of the study, it is difficult to attribute these patterns to the pandemic. These results underscore the depth and extent of mental health outcomes in HCWs in ambulatory settings and raise important questions on new interventions to relieve that burden. Further research is needed to study specific interventions to support the mental health and wellbeing of HCWs.

Long-Term Oncological Outcomes of Papillary Thyroid Cancer and Follicular Thyroid Cancer in Children: A Nationwide Population-Based Study.

Introduction: Pediatric thyroid carcinoma is a rare malignancy and data on long-term oncological outcomes are sparse. The aim of this study was to describe the long-term oncological outcomes of pediatric papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) in a national cohort, and to identify risk factors for recurrence. Methods: We conducted a nationwide, retrospective cohort study, in which we combined two national databases. Patients aged <18 years, diagnosed with PTC or FTC in the Netherlands between 2000 and 2016, were included. pT-stage, pN-stage, multifocality and angioinvasion were included in a Cox-regression analysis for the identification of risk factors for recurrence. Results: 133 patients were included: 110 with PTC and 23 with FTC. Patients with PTC most often presented with pT2 tumors (24%) and pN1b (45%). During a median follow-up of 11.3 years, 21 patients with PTC developed a recurrence (19%). Nineteen recurrences were regional (91%) and 2 were pulmonary (9%). No risk factors for recurrence could be determined. One patient who developed pulmonary recurrence died two years later. Cause of death was not captured. Patients with FTC most often presented with pT2 tumors (57%). One patient presented with pN1b (4%). In 70%, no lymph nodes were collected. None of the patients with FTC developed a recurrence or died. Conclusion: Pediatric PTC and FTC are two distinct diseases. Recurrence in pediatric PTC is common, but in FTC it is not. Survival for both pediatric PTC and FTC is very good.

A care coordinator screening strategy to address health harming legal needs.

BACKGROUND: Medical legal partnerships provide an opportunity to help address various social determinants of health; however, the traditional practice of screening patients during clinical encounters is limited by the capacity of busy clinicians. Our medical legal partnership utilized care coordinators trained by the legal service attorneys to screen patients outside of clinical encounters for health harming legal needs. The goal of our study was to demonstrate that our novel model could successfully identify and refer patients of a safety-net healthcare system to appropriate legal services. METHODS: We conducted a mixed methods evaluation of the program. Data was collected during the implementation period of the program from March 2017 to August 2018. Operational data collected included number of patients screened, number of referrals to the legal partner, source and reason for referrals. Return on investment was calculated by subtracting program costs from the total reimbursement to the health system from clients' insurance benefits secured through legal services. RESULTS: During the 18-month study, 29,268 patients were screened by care coordinators for health harming legal needs, with 492 patients (1.7%) referred for legal assistance. Of the 133 cases closed in 2017, all clients were invited to participate in a telephone interview; 63 pre-consented to contact, 33 were successfully contacted and 23 completed the interview. The majority (57%) reported a satisfactory resolution of their legal barrier to health. This was accompanied by an improvement in self-reported health with a decrease of patients reporting less than optimal health from 16 (89%) prior to intervention to 8 (44%) after intervention [risk ratio (95% confidence interval): 0.20 (0.04, 0.91)]. Patients also reported improvements in general well-being for themselves and their family. The healthcare system recorded a 263% return on investment. CONCLUSIONS: In our medical legal partnership, screening for health harming legal needs by care coordinators outside of a clinical encounter allowed for efficient screening in a high risk population. The legal services intervention was associated with improvements in self-reported health and family well-being when compared to previous models. The return on investment was substantial.

Bare Metal Stents on Resveratrol-Coated Balloons in Porcine Coronary and Peripheral Arteries.

Balloon angioplasty and stent implantation are standard techniques to reopen stenotic vessels. Often, balloons or stents coated with cytostatic drugs are used to prevent re-occlusion of the arteries. Resveratrol, which is known for its numerous beneficial effects on cardiovascular health, is used as an antioxidant additive on paclitaxel-coated balloon catheters. What is still unclear is whether resveratrol-only balloon coating in combination with a bare metal stent (BMS) also has positive effects on vascular healing. Here, we analyzed neointimal thickening, fibrin deposition, inflammation, vasa vasorum density, and reendothelialization after implantation of BMS via a resveratrol coated balloon approach in a porcine model. In general, resveratrol treatment did not result in significantly altered responses compared to the control group in peripheral arteries. In coronary arteries, an increase in vasa vasorum density became evident three days after resveratrol treatment compared to the control group and abolished up to day 7. Significant effects of the resveratrol treatment on the fibrin score or intima-media area were transient and restricted to either peripheral or coronary arteries. In conclusion, local single-dose resveratrol treatment via a resveratrol-only coated balloon and BMS approach did not lead to adverse systemic or local effects, but also no significant beneficial effects on vascular healing were detected in the current study.

Complications After Thyroidectomy in Children: Lymph Node Dissection Is a Risk Factor for Permanent Hypocalcemia.

Background: Thyroidectomy is a treatment option in some benign thyroid disorders and the definitive treatment option for thyroid cancer. As postoperative mortality is extremely rare data on postoperative complications and long-term health consequences are important. Objective: To evaluate the frequencies of short- and long-term complications, and their risk factors in pediatric patients (0-18 years) who underwent a thyroidectomy in a tertiary children's hospital. Methods: A retrospective single center study was performed including all pediatric patients who underwent a thyroidectomy between January 2013 and February 2020. Results: Forty-eight patients were included in this study (mean age 14.6 years). Twenty-nine total thyroidectomies and 19 hemithyroidectomies were conducted. Thyroid carcinoma was the indication to perform a thyroidectomy in 12 patients, 36 patients underwent a thyroidectomy because of a benign thyroid disorder. Postoperative hypocalcemia was evaluated in patients who underwent a total thyroidectomy. Rapidly resolved hypocalcemia was observed in three patients (10.3%), transient hypocalcemia in 10 patients (34.5%) and permanent hypocalcemia in six patients (20.7%). Permanent hypocalcemia was only seen in patients who underwent a thyroidectomy combined with additional lymph node dissection because of thyroid carcinoma [thyroid carcinoma: OR 43.73, 95% CI (2.11-904.95); lymph node dissection: OR 76.14, 95% CI (3.49-458.98)]. Transient and permanent recurrent laryngeal nerve injury was reported in four (8.3%) and one (2.1%) of all patients, respectively. Conclusion: Permanent postoperative complications after thyroidectomy are rare in pediatric patients undergoing a thyroidectomy without lymph node dissection. However, in this age group permanent hypocalcemia occurs more frequently after thyroidectomy with additional lymph node dissection because of thyroid cancer. With respect to quality of life, especially of pediatric thyroid cancer patients, reducing this complication is an important goal.

Maximum Tolerated Dose and Anti-Tumor Activity of Intraperitoneal Cantrixil (TRX-E-002-1) in Patients with Persistent or Recurrent Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer: Phase I Study Results.

Survival outcomes in ovarian cancer are poor. The aims of this Phase I progressive design study (NCT02903771) were to evaluate the maximum tolerated dose (MTD), tolerability, and antitumor activity of Cantrixil-a novel third-generation benzopyran molecule-in patients (n = 25) with advanced, recurrent/persistent epithelial ovarian, primary peritoneal, or fallopian tube cancer. All had completed ≥ 2 prior regimens; 3 (12%) had platinum-refractory disease, and 17 (68%) had platinum-resistant disease. Following intraperitoneal (IP) port placement, patients received weekly IP Cantrixil in 3-week cycles as monotherapy (Cycles 1-2), and then in combination with intravenous (IV) chemotherapy (Cycles 3-8). Part A (dose escalation) enrolled 11 patients in 6 dose-level cohorts. An MTD of 5 mg/kg was established with dose-limiting toxicity of ileus. Most treatment-related adverse events were gastrointestinal. Across Parts A and B (dose expansion), 16 (64%) patients received ≥ 1 3-week Cantrixil cycle, and had ≥ 1 post-baseline efficacy measurement available. The results show promising anti-tumor activity in monotherapy (stable disease rate of 56%) and in combination with IV chemotherapy (objective response rate of 19%, disease control rate of 56%, and median progression-free survival of 13.1 weeks). The molecular target and mechanism of action of Cantrixil are yet to be confirmed. Preliminary analysis of stem cell markers suggests that IP Cantrixil might induce ovarian cancer stem cell death and sensitize cells to standard chemotherapy, warranting further evaluation.

Magnetic resonance imaging (MRI) of pharmacological ascorbate-induced iron redox state as a biomarker in subjects undergoing radio-chemotherapy.

Pharmacological ascorbate (P-AscH-) combined with standard of care (SOC) radiation and temozolomide is being evaluated in a phase 2 clinical trial (NCT02344355) in the treatment of glioblastoma (GBM). Previously published data demonstrated that paramagnetic iron (Fe3+) catalyzes ascorbate's oxidation to form diamagnetic iron (Fe2+). Because paramagnetic Fe3+ may influence relaxation times observed in MR imaging, quantitative MR imaging of P-AscH--induced changes in redox-active Fe was assessed as a biomarker for therapy response. Gel phantoms containing either Fe3+ or Fe2+ were imaged with T2* and quantitative susceptibility mapping (QSM). Fifteen subjects receiving P-AscH- plus SOC underwent T2* and QSM imaging four weeks into treatment. Subjects were scanned: pre-P-AscH- infusion, post-P-AscH- infusion, and post-radiation (3-4 h between scans). Changes in T2* and QSM relaxation times in tumor and normal tissue were calculated and compared to changes in Fe3+ and Fe2+ gel phantoms. A GBM mouse model was used to study the relationship between the imaging findings and the labile iron pool. Phantoms containing Fe3+ demonstrated detectable changes in T2* and QSM relaxation times relative to Fe2+ phantoms. Compared to pre-P-AscH-, GBM T2* and QSM imaging were significantly changed post-P-AscH- infusion consistent with conversion of Fe3+ to Fe2+. No significant changes in T2* or QSM were observed in normal brain tissue. There was moderate concordance between T2* and QSM changes in both progression free survival and overall survival. The GBM mouse model showed similar results with P-AscH- inducing greater changes in tumor labile iron pools compared to the normal tissue. CONCLUSIONS: T2* and QSM MR-imaging responses are consistent with P-AscH- reducing Fe3+ to Fe2+, selectively in GBM tumor volumes and represent a potential biomarker of response. This study is the first application using MR imaging in humans to measure P-AscH--induced changes in redox-active iron.

Feasibility of patient-reported diagnostic errors following emergency department discharge: a pilot study.

OBJECTIVES: The National Academy of Medicine identified diagnostic error as a pressing public health concern and defined failure to effectively communicate the diagnosis to patients as a diagnostic error. Leveraging Patient's Experience to improve Diagnosis (LEAPED) is a new program for measuring patient-reported diagnostic error. As a first step, we sought to assess the feasibility of using LEAPED after emergency department (ED) discharge. METHODS: We deployed LEAPED using a cohort design at three EDs within one academic health system. We enrolled 59 patients after ED discharge and queried them about their health status and understanding of the explanation for their health problems at 2-weeks, 1-month, and 3-months. We measured response rates and demographic/clinical predictors of patient uptake of LEAPED. RESULTS: Of those enrolled (n=59), 90% (n=53) responded to the 2-week post-ED discharge questionnaire (1 and 3-month ongoing). Of the six non-responders, one died and three were hospitalized at two weeks. The average age was 50 years (SD 16) and 64% were female; 53% were white and 41% were black. Over a fifth (23%) reported they were not given an explanation of their health problem on leaving the ED, and of those, a fourth (25%) did not have an understanding of what next steps to take after leaving the ED. CONCLUSIONS: Patient uptake of LEAPED was high, suggesting that patient-report may be a feasible method of evaluating the effectiveness of diagnostic communication to patients though further testing in a broader patient population is essential. Future research should determine if LEAPED yields important insights into the quality and safety of diagnostic care.

Differential Timing and Coordination of Neurogenesis and Astrogenesis in Developing Mouse Hippocampal Subregions.

Neocortical development has been extensively studied and therefore is the basis of our understanding of mammalian brain development. One fundamental principle of neocortical development is that neurogenesis and gliogenesis are temporally segregated processes. However, it is unclear how neurogenesis and gliogenesis are coordinated in non-neocortical regions of the cerebral cortex, such as the hippocampus, also known as the archicortex. Here, we show that the timing of neurogenesis and astrogenesis in the Cornu Ammonis (CA) 1 and CA3 regions of mouse hippocampus mirrors that of the neocortex; neurogenesis occurs embryonically, followed by astrogenesis during early postnatal development. In contrast, we find that neurogenesis in the dentate gyrus begins embryonically but is a protracted process which peaks neonatally and continues at low levels postnatally. As a result, astrogenesis, which occurs during early postnatal development, overlaps with the process of neurogenesis in the dentate gyrus. During all stages, neurogenesis overwhelms astrogenesis in the dentate gyrus. In addition, we find that the timing of peak astrogenesis varies by hippocampal subregion. Together, our results show differential timing and coordination of neurogenesis and astrogenesis in developing mouse hippocampal subregions and suggest that neurogenesis and gliogenesis occur simultaneously during dentate gyrus development, challenging the conventional principle that neurogenesis and gliogenesis are temporally separated processes.

Safety and Efficacy of Stereotactic Body Radiation Therapy for Locoregional Recurrences After Prior Chemoradiation for Advanced Esophageal Carcinoma.

Purpose: This study aimed to investigate the feasibility of stereotactic body radiation therapy (SBRT) as salvage therapy for locally recurrent esophageal cancer. We hypothesized that SBRT would provide durable treated tumor control with minimal associated toxicity in patients with progressive disease after definitive radiation, chemotherapy, and surgical resection. Methods: This single-institution retrospective study assessed outcomes in patients who received SBRT for locoregional failure of esophageal cancer after initial curative-intent treatment. Only patients who had received neoadjuvant chemoradiation (≥41.4 Gy) for esophageal cancer were selected. Subsequent surgical resection was optional but institutional follow-up by an oncologist was required. The primary endpoints of this study were gastrointestinal and constitutional toxicity, scored with the Common Terminology Criteria for Adverse Events v5.0. A secondary outcome, treated-tumor control, was assessed with RECIST v1.1. Results: Nine patients (11 locoregional recurrences) treated with SBRT were reviewed, with a median follow-up time of 10.5 months. Most patients initially presented with T3 (88.9%), N1 (55.6%), moderately differentiated (66.7%) adenocarcinoma (88.9%), and had received a median 50.4 Gy delivered over 28 fractions with concurrent carboplatin/paclitaxel chemotherapy followed by surgical resection. Median time to recurrence was 16.3 months. Median total dose delivered by SBRT was 27.5 Gy (delivered in five fractions). Two patients experienced acute grade 1 fatigue and vomiting. No patient experienced grade 3 or higher toxicity. One patient experienced failure in the SBRT treatment field at 5.8 months after treatment and six patients developed distant failure. The median progression-free survival time for SBRT-treated tumors was 5.0 months, and median overall survival time was 12.9 months. Conclusions: This single-institution study demonstrated the feasibility of SBRT for locoregional recurrence of esophageal cancer with minimal treatment-related toxicity and high rates of treated tumor control. Prospective studies identifying ideal salvage SBRT candidates for locoregional failure as well as validating its safety are needed.

Initial skin cancer screening for solid organ transplant recipients in the United States: Delphi method development of expert consensus guidelines.

Skin cancer is the most common malignancy affecting solid organ transplant recipients (SOTR), and SOTR experience increased skin cancer-associated morbidity and mortality. There are no formal multidisciplinary guidelines for skin cancer screening after transplant, and current practices are widely variable. We conducted three rounds of Delphi method surveys with a panel of 84 U.S. dermatologists and transplant physicians to establish skin cancer screening recommendations for SOTR. The transplant team should risk stratify SOTR for screening, and dermatologists should perform skin cancer screening by full-body skin examination. SOTR with a history of skin cancer should continue regular follow-up with dermatology for skin cancer surveillance. High-risk transplant patients include thoracic organ recipients, SOTR age 50 and above, and male SOTR. High-risk Caucasian patients should be screened within 2 years after transplant, all Caucasian, Asian, Hispanic, and high-risk African American patients should be screened within 5 years after transplant. No consensus was reached regarding screening for low-risk African American SOTR. We propose a standardized approach to skin cancer screening in SOTR based on multidisciplinary expert consensus. These guidelines prioritize and emphasize the need for screening for SOTR at greatest risk for skin cancer.

Transcriptomic Signatures of Postnatal and Adult Intrinsically Photosensitive Ganglion Cells.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) are rare mammalian photoreceptors essential for non-image-forming vision functions, such as circadian photoentrainment and the pupillary light reflex. They comprise multiple subtypes distinguishable by morphology, physiology, projections, and levels of expression of melanopsin (Opn4), their photopigment. The molecular programs that distinguish ipRGCs from other ganglion cells and ipRGC subtypes from one another remain elusive. Here, we present comprehensive gene expression profiles of early postnatal and adult mouse ipRGCs purified from two lines of reporter mice that mark different sets of ipRGC subtypes. We find dozens of novel genes highly enriched in ipRGCs. We reveal that Rasgrp1 and Tbx20 are selectively expressed in subsets of ipRGCs, though these molecularly defined groups imperfectly match established ipRGC subtypes. We demonstrate that the ipRGCs regulating circadian photoentrainment are diverse at the molecular level. Our findings reveal unexpected complexity in gene expression patterns across mammalian ipRGC subtypes.

Timing of surgery following neoadjuvant chemoradiation in rectal cancer: a retrospective analysis from an academic medical center.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) has been shown to achieve decreased local recurrence (LR) with lower toxicity in rectal cancer patients, but data confirming the optimal timing of surgery following this therapy is less robust. METHODS: The University of Iowa Cancer Registry was queried to identify all patients with stages II-III rectal cancer who received nCRT and surgery from 2000 through 2012. Primary endpoints were time interval to surgery (TI), and overall survival (OS). Secondary endpoints included pathologic outcomes, perioperative morbidities and postoperative complications. Patient characteristics and treatment regimens were compared. Univariate Cox proportional hazard models were used to study the association between TI and OS. Associations of TI with secondary endpoints were tested using Chi-square tests of association. RESULTS: Eighty-seven patients presented with stages II-III rectal cancer. Mean TI was 9.92 weeks. There was no significant association between TI and OS when comparing <8 to ≥8 weeks (P=0.23) or when considering the interval as a continuous variable (P=0.85). Increased LOS [median 7.00 days, P=0.05, HR 1.03 (1.00-1.06)] did correlate with worse survival outcomes. Delaying surgery beyond 8 weeks was associated with increased risk for wound infection (P=0.05). CONCLUSIONS: OS was not influenced by longer intervals between nCRT and surgery. Delaying surgery beyond 8 weeks was associated with increased risk for wound infection.