Neighborhood child opportunity is associated with hospital length of stay following pediatric burn injury.

INTRODUCTION: Pediatric burns are associated with socioeconomic disadvantage and lead to significant morbidity. The Child Opportunity Index (COI) is a well-validated measure of neighborhood characteristics associated with healthy child development. We sought to evaluate the relationship between COI and outcomes of burn injuries in children. METHODS: We performed a single-institution retrospective review of pediatric (<16 years) burn admissions between 2015 and 2019. Based on United States residential zip codes, patients were stratified into national COI quintiles. We performed a multivariate Poisson regression analysis to determine the association between COI and increased length of stay. RESULTS: 2095 pediatric burn admissions occurred over the study period. Most children admitted were from very low (n = 644, 33.2 %) and low (n = 566, 29.2 %) COI neighborhoods. The proportion of non-Hispanic Black patients was significantly higher in neighborhoods with very low (44.5 %) compared to others (low:28.8 % vs. moderate:11.9 % vs. high:10.5 % vs. very high:4.3 %) (p < 0.01). Hospital length of stay was significantly longer in patients from very low COI neighborhoods (3.6 ± 4.1 vs. 3.2 ± 4.9 vs. 3.3 ± 4.8 vs. 2.8 ± 3.5 vs. 3.2 ± 8.1) (p = 0.02). On multivariate regression analysis, living in very high COI neighborhoods was associated with significantly decreased hospital length of stay (IRR: 0.51; 95 % CI: 0.45-0.56). CONCLUSION: Children from neighborhoods with significant socioeconomic disadvantage, as measured by the Child Opportunity Index, had a significantly higher incidence of burn injuries resulting in hospital admissions and longer hospital length of stay. Public health interventions focused on neighborhood-level drivers of childhood development are needed to decrease the incidence and reduce hospital costs in pediatric burns. TYPE OF STUDY: Retrospective study LEVEL OF EVIDENCE: Level III.

Omission of Axillary Dissection in Node Positive Breast Cancer After Neoadjuvant Systemic Therapy.

INTRODUCTION: Guidelines recommend axillary lymph node dissection (ALND) for ypN + positive patients as patients receiving neoadjuvant systemic therapy (NST) were excluded from trials omitting ALND in pN + patients. We sought to characterize trends in omission of ALND in patients with ypN + disease. METHODS: Adult women with invasive breast carcinoma in the National Cancer Database between 2012 and 2019 who received NST (chemotherapy or endocrine) and had ypN + disease were included. Patients were excluded if they did not have definitive surgery within eight months of diagnosis. The primary study outcome was completion of ALND versus omission. Differences in demographics, tumor characteristics, and treatment were identified using bivariate and multivariate logistic regression models. RESULTS: In total, 103,121 women were included. Most had cT1 (26%) or cT2 (45%) tumors, cN + disease (71%), and ductal histology (83%). 69% of patients received neoadjuvant chemotherapy and 31% neoadjuvant endocrine without chemotherapy (30% both). ALND was performed in 77% of patients. Omission of ALND became more prevalent each year from 2012 (14%) to 2019 (34%). On multivariate modeling, year of diagnosis, black race, cN status, higher grade, estrogen receptor+/HER2-receptor subtype, and mastectomy were associated with increased prevalence of ALND. Age, Charlson/Deyo comorbidity index score, endocrine versus chemotherapy, and adjuvant radiation were not associated with receipt of ALND. CONCLUSIONS: Despite guidelines recommending ALND, omission is common in patients with ypN + breast cancer after NST. Omission of ALND increased significantly over time and is associated with clinical and demographic factors. Future study is needed to determine the oncologic safety of this approach.

Lymph node metastases in young patients with gastrointestinal stromal tumor: A nationwide analysis.

BACKGROUND: Children, adolescents, and young adults (CAYA) (age ≤39 years) with GIST have high rates of LNM, but their clinical relevance is undefined. This study analyzed the impact of LNM on overall survival (OS) for CAYA with GIST. METHODS: The National Cancer Database was queried for patients with resected GIST and pathologic nodal staging data from 2004-2019. Factors associated with LNM were identified. Survival was assessed stratified by presence of LNM. RESULTS: Of 4420 patients with GIST, 238 were CAYA (5.4%). When compared to older adults, CAYA more often had small intestine primaries (51.8% vs. 36.6%, p < 0.0001), T4 tumors (30.7% vs. 24.5%, p = 0.0275) and pN1 disease (11.3% vs. 4.7%, p < 0.0001). Within a multivariable Cox proportional hazards regression model adjusting for age, comorbid disease, mitotic rate, tumor size, and primary site, LNM were associated with increased hazard of death for older adults (hazard ratio [HR]: 1.83; confidence interval [CI]: 1.35-2.42; p < 0.0001), but not CAYA (HR: 3.38; CI: 0.50-14.08; p = 0.13). For CAYA, only high mitotic rate predicted mortality (HR: 4.68; CI: 1.41-18.37: p = 0.02). CONCLUSIONS: LNM are more commonly identified among CAYA with resected GIST who undergo lymph node evaluations, but do not appear to impact OS as observed in older adults. High mitotic rate remains a predictor of poor outcomes for CAYA with GIST.

The Role of Diversion During Ileal Pouch Anal Anastomosis (IPAA) Creation in Pediatric Ulcerative Colitis.

INTRODUCTION: In pediatric ulcerative colitis (UC), surgery is often postponed until disease is life-threatening or refractory to immune suppression. In these settings, diverting ileostomy (DI) is theorized to have a protective effect on the new anastomosis. However, analyses have been performed only in single-institution series and the true impact of performing DI at the time of IPAA on postoperative outcomes is unclear. METHODS: We performed a retrospective cohort study using claims data from the International Business Machines (IBM) MarketScan® database. Patients were sorted to the DI group if they carried a CPT code for ostomy closure within 6 months of index procedure. We examined demographics, preoperative risk factors, and performed regression analysis to compare 30-day postoperative outcomes between groups. RESULTS: We identified 317 patients ≤18yo that underwent IPAA procedure and met inclusion criteria from 2000 to 2019. Of these, 238 patients were assigned to the IPAA + DI cohort and 79 patients were assigned to the IPAA cohort. Adverse outcomes were comparable between cohorts. Surgical site infection (SSI) rates between IPAA and IPAA + DI were 10.1 vs. 11.3% (p = 0.67). Rates of intra-abdominal drainage procedures were 3.8 vs. 2.1% (p = 0.39). The rates of 30-day readmissions were 16.5 vs. 19.3% (p = 0.39). Creation of a DI was not associated with higher odds of 30-day readmission (OR = 1.4, p = 0.31). CONCLUSION: Creating a DI necessitates an additional surgery for closure and is not associated with decreased adverse outcomes. There is still a role for multicenter studies to define which patient populations may benefit from diversion. LEVEL OF EVIDENCE: Retrospective comparative study. TYPE OF STUDY: Level III.

Difference in Postoperative Outcomes and Perioperative Resource Utilization Between General Surgeons and Pediatric Surgeons: A Systematic Review.

Background: Both general surgeons (GS) and pediatric surgeons (PS) perform a high volume of appendectomies in pediatric patients, but there is a paucity of data on these outcomes based on surgeon training. We performed a systematic review and meta-analysis to compare postoperative outcomes and perioperative resource utilization for pediatric appendectomies.Methods: We searched PubMed to identify articles examining the association between surgeon specialization and outcomes for pediatric patients undergoing appendectomies. Study selection, data extraction, risk of bias assessment, and quality assessment were performed by one reviewer, with another reviewer to resolve discrepancies.Results: We identified 4799 articles, with 98.4% (4724/2799) concordance after initial review. Following resolution of discrepancies, 16 studies met inclusion criteria. Of the studies that reported each outcome, GS and PS demonstrated similar rates of readmission within 30 days (pooled RR 1.61 95% CI 0.66, 2.55) wound infections (pooled RR 1.07, 95% CI .55, 1.60), use of laparoscopic surgery (pooled RR 1.87, 95% CI .21, 3.53), postoperative complications (pooled RR 1.40, 95% CI .83, 1.97), use of preoperative imaging (pooled RR .98,95% CI .90, 1.05), and intra-abdominal abscesses (pooled RR .80, 95% CI .03, 1.58). Patients treated by GS did have a significantly higher risk of negative appendectomies (pooled RR 1.47, 95% CI 1.10, 1.84) when compared to PS.Discussion: This is the first meta-analysis to compare outcomes for pediatric appendectomies performed by GS compared to PS. Patient outcomes and resource utilization were similar among PS and GS, except for negative appendectomies were significantly more likely with GS.

The Effect of an Enhanced Recovery Protocol on Pediatric Colorectal Surgical Patient Outcomes at a Single Institution.

INTRODUCTION: Enhanced recovery protocols (ERP) have been associated with fewer postoperative complications in adult colorectal surgery patients, but there is a paucity of data on pediatric patients. Our aim is to describe the effect of an ERP, compared to conventional care, on pediatric colorectal surgical complications. MATERIALS AND METHODS: We performed a single institution, retrospective cohort study (2014-2020) on pediatric (≤18 years old) colorectal surgery patients pre- and post-implementation of an ERP. Bivariate analysis and logistic regression were used to assess the effect of an ERP on return visits to the emergency room, reoperation, and readmission within 30-days. RESULTS: There were 194 patients included in this study, with 54 in the control cohort and 140 in the ERP cohort. There was no significant difference in the age, BMI, primary diagnosis, or use of laparoscopic technique between the cohorts. The ERP cohort had a significantly shorter foley duration, postoperative stay, and had nerve blocks performed. After controlling for pertinent covariates, the ERP cohort experienced higher odds of reoperation within 30 days (OR 5.83, P = .04). There was no significant difference in the other outcomes analyzed. CONCLUSION: In this study, there was no difference in the odds of overall complications, readmission or return to the ER within 30-days of surgery. However, although infrequent, there were higher odds of returns to the OR within 30 days. Future studies are needed to analyze how adherence to individual components may influence patient outcomes to ensure patient safety during ERP implementation.

Medical Students' Reflections on Their Experiences in a Trauma Chaplain Shadowing Program.

The importance of spirituality in patient care is well recognized and efforts to develop educational opportunities to improve medical students' competency in spirituality and health are ongoing. In this regard, shadowing of healthcare chaplains has emerged as an experiential approach for providing exposure to and instruction in issues of spirituality in the patient experience and in patient care. Recently published data suggest that a 6-8 hour experience of shadowing a trauma chaplain is effective at introducing first-year medical students to healthcare chaplaincy, difficult spiritual conversations with patients and families, and interprofessional collaboration. As a follow-up to these data, this study provides a qualitative analysis of student reflections written immediately after their shadowing experience with the goal of further characterizing the educational impact of trauma chaplain shadowing. Qualitative analysis of 90 anonymous, student reflections indicated that trauma chaplain shadowing was an experience that provided insights about nature of chaplaincy, enabled opportunities to closely observe the relational skills of chaplains, allowed students to bear witness to suffering, fostered growth toward a professional identity, and facilitated recognition of shortcomings in medical education and clinical medicine. These data therefore provide further evidence of the value of chaplain shadowing in not only enhancing students' understanding of various dimensions of spirituality and medicine but also in promoting their development of a strong physician identity.

Awareness of link between obesity and breast cancer risk is associated with willingness to participate in weight loss intervention.

PURPOSE: To assess knowledge of obesity-associated cancer risk, self-awareness of BMI status, and willingness to engage in weight loss intervention in breast cancer survivors with overweight and obesity as a companion study for a novel weight loss program using a telehealth platform (NCT04855552). METHODS: Breast cancer survivors with BMI ≥ 25 kg/m2 were surveyed to assess self-perception of BMI, knowledge of obesity-related cancer risk, and willingness to participate in weight loss programs. Multivariable logistic regression was used to assess factors associated with willingness to participate. RESULTS: Of the 122 participants, 73 (59.8%) had BMI 25.0-29.9 kg/m2 (overweight) and 49 (40.2%) had BMI ≥ 30 (obesity). Patients with obesity were more likely to underestimate their BMI than those with overweight, 40.8% vs. 23.3% (p = 0.03). The majority (82.0%) indicated awareness that obesity increases breast cancer risk and 57.4% expressed interest in a weight loss program. Patients with knowledge of obesity-related breast cancer risk (91.4% willing vs. 69.2% not willing, p < 0.01) were more willing to participate in a weight loss program on univariable and multivariable analyses (p < 0.01). CONCLUSION: Our results underscore the importance of raising patients' awareness of obesity-related health risks and individual BMI category. Future work in the development of better education and communication tools to improve awareness will likely improve the adoption rate of healthy lifestyles in at-risk patients.

Surgical Implications of LGBTQ+ Health Disparities: A Review.

Lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ+) patients face challenging health care disparities. However, due to restrictions in reporting and collection of sexual orientation and gender identity (SOGI) demographic data, comprehensive studies of surgical disparities in the LGBTQ+ population are limited. This review aims to summarize the existing literature describing surgical disparities in LGBTQ+ patients and to identify areas of surgical care in which further studies are warranted. This review addresses the literature in infectious diseases, substance use disorders, bariatrics, cardiovascular medicine, oncology, and laryngology as relevant to surgical practice. Understanding the current landscape of knowledge in LGBTQ+ surgical disparities and the areas where gaps in research exist will help the surgeon to create a framework of practice to provide more equitable care to LGBTQ+ patients.

Preoperative MRI and Its Impact on Surgical Outcomes in Patients with Triple Negative Breast Cancer Treated with Primary Surgery: Did New Margin Guidelines or Cavity Shave Margins Practice Diminish the Role of Preoperative MRI?

BACKGROUND: Results of an earlier retrospective study from our institution suggested that patients with triple negative breast cancer (TNBC) who had preoperative MRI may have had an improved local recurrence rate (LRR) after breast conserving surgery (BCS). We aimed to clarify the impact of preoperative MRI on surgical outcomes in an expanded TNBC cohort treated by BCS in a contemporary era. METHODS: Our study cohort comprised 648 patients with TNBC who underwent BCS between 2009 and 2018. Demographic and clinical characteristics were compared between those with (n = 292, 45.1%) and without (n = 356, 54.9%) preoperative MRI. Multivariable logistic regression was performed to assess the association of preoperative MRI with surgical outcomes. RESULTS: The crude LRR of 3.5% was lower than previously reported. Univariable analyses demonstrated that the LRR and re-excision rates in the MRI and no-MRI groups were 3.4 and 3.7%, 21.6% and 27.2%, p = 0.876 and p = 0.10, respectively. Multivariable logistic regression analyses demonstrated that preoperative MRI was not associated with a lower LRR: odds ratio (OR) = 1.42 (p = 0.5). During our study period, new margin guidelines and shave margins practice were adopted in 2014 and 2015. To account for their effects, the year of diagnosis/surgery and other clinical variables were adjusted in multivariable logistic regression and inverse probability weighting models to demonstrate that preoperative MRI remained associated with a lower re-excision risk, OR 0.56, p = 0.04l; and a lower re-excision rate, 23.15% versus 36.0%, p < 0.01, respectively. CONCLUSIONS: Our findings suggested that patients with TNBC anticipating BCS may benefit from preoperative MRI.

Immediate Breast Reconstruction for Inflammatory Breast Cancer: Trends in Use and Clinical Outcomes 2004-2016.

INTRODUCTION: National guidelines specify against immediate breast reconstruction (IBR) among inflammatory breast cancer (IBC) patients. However, limited data exist regarding this practice. We report practice patterns and oncologic outcomes among nonmetastatic IBC patients receiving trimodality therapy, with or without IBR. METHODS: Using the National Cancer Database, we identified nonmetastatic IBC patients treated with trimodality therapy from 2004 to 2016. Primary outcome was overall survival (OS), assessed on unadjusted analysis using Kaplan-Meier estimates and on adjusted analysis using multivariable Cox proportional hazards and inverse probability weighting (IPW) models. OS analysis was also conducted with propensity score matched (PSM) cohorts. Secondary outcomes included IBR utilization rates, time to postmastectomy radiotherapy (PMRT), and surgical outcomes. RESULTS: 6589 women were included, including 5954 (90.4%) non-reconstructed and 635 (9.6%) IBR. Among IBR recipients, 250 (39.4%) underwent autologous reconstruction, 171 (26.9%) underwent implant-based reconstruction, and 214 (33.7%) unspecified. IBR utilization increased from 6.3% to 10.1% from 2004 to 2016 at a 4% average annual growth rate (P < 0.001). Median follow-up was 43 and 45 months for IBR and non-reconstructed patients, respectively (P = 0.29). On Cox multivariable analysis, IBR was associated with improved OS (HR 0.63, 95% CI 0.44-0.90, P = 0.01), but this association was not significant on IPW analysis (P = 0.06). In PSM cohorts, this association remained significant (HR 0.60, 95% CI 0.40-0.92, P = 0.02). Margin status, time to PMRT, 30-day readmission, and 30-/90-day mortality did not differ between groups (all P > 0.05). CONCLUSION: Although not endorsed by national guidelines, IBR is increasing among IBC patients; however, more granular data are needed to determine oncologic safety.

Effectiveness of a Short Duration of Neoadjuvant Endocrine Therapy in Patients with HR+ Breast Cancer-An NCDB Analysis (2004-2016).

BACKGROUND: National medical/surgical organizations have recommended the use of neoadjuvant endocrine therapy (NET) to bridge surgery delay of weeks to months for patients with hormone receptor positive (HR+) breast cancer during the ongoing coronavirus disease 2019 (COVID-19) pandemic. The effects of NET of varying durations on pathologic response are unclear. Using the National Cancer Database (NCDB), we evaluated objective response to short (< 9 weeks), moderate (9-27 weeks), and long (> 27 weeks) duration of NET. PATIENTS AND METHODS: The study cohort included female patients diagnosed with nonmetastatic invasive HR+ breast cancer, stratifying by those who received NET versus no NET between 2004 and 2016. Pathologic response was grouped into four categories (complete, downstaged, stable, upstaged) by comparing clinical and pathologic staging data. Objective response to NET included complete, downstaged, and stable pathologic response. Clinical characteristics were compared using χ2 and analysis of variance (ANOVA) tests. Multivariable logistic regression was used to determine factors associated with NET use and objective response according to NET duration. RESULTS: A minority (1.2%) received NET in our cohort. Factors associated with NET use included older age, non-Black patients, more advanced clinical stage, higher comorbidity score, government insurance, and lobular histology. Objective response rate (ORR) was 56.7%, 52.1%, and 49.0% after short, moderate, and long NET duration, respectively. CONCLUSION: Short NET duration did not result in an inferior ORR. Future study to evaluate the interaction between surgery delay and NET use on clinical outcome will provide insights into the safety of NET to bridge potential surgery delay in patients with HR+ breast cancer.

Is there an association between body mass index and 21-gene recurrence score?

PURPOSE: The 21-gene recurrence score (RS) is an established predictor of recurrence for early stage, hormone receptor positive breast cancer. The association between RS and other risk factors such as obesity has not been fully explored. We hypothesized that patients with obesity may present with primary breast cancers with higher recurrence scores. METHODS: We identified 1546 patients who have body mass index (BMI) recorded around the time of RS assay. Obesity was classified as per CDC definitions of overweight (BMI 25-30 kg/m2) and obesity (BMI >30 kg/m2). RS was assessed as a continuous variable and according to pre- and post-TAILORx classifications. Kaplan Meier survival analysis was employed to assess the interaction between RS and BMI on overall survival (OS) and disease-free survival (DFS). RESULTS: In univariate analyses, the median RS in patients with overweight was 15, which was significantly lower than the median RS (16) of patients with normal weight (p = 0.03). The overall recurrence rate of patients with obesity was 4.1%, which was significantly worse than the overall recurrence rate of patients with normal and overweight of 2.6% and 1.5%, respectively (p = 0.05). In multivariate analyses using the inverse probability weighted regression adjustment (IPWRA) method to adjust for imbalances between subgroups, patients with overweight or obesity had significantly lower RS than patients with normal weight, correlating to an average decrease in RS value of 2.37 and 1.71, respectively (both p < 0.01). A similar relationship was seen between BMI categories and RS as a categorical variable stratified according to pre- or post-TAILORx categories. This inverse effect was predominantly seen in post-menopausal patients. Despite the generally lower RS in patients with obesity, a high RS in these patients is associated with diminished DFS (p = 0.04). CONCLUSION: Tumors in post-menopausal women with higher BMI generally have lower RS. DFS is significantly worse in women with obesity whose RS ≥ 30. The reasons for poor outcomes for postmenopausal patients with obesity despite lower presenting RS merits further study.

Treatment Patterns and Clinical Outcomes of Adenoid Cystic Breast Carcinoma: A Single-Institution Experience.

BACKGROUND: Adenoid cystic breast carcinoma (ACC) is a rare subtype of triple-negative breast cancer. We aim to characterize the treatment patterns and clinical outcomes of women diagnosed with ACC at a large medical center. METHODS: Female patients diagnosed with ACC at our institution between 2009 and 2019 were retrospectively identified. Patients with limited clinicopathologic data were excluded. RESULTS: In our final study cohort (n = 9), the majority of ACCs (6/9, 66.7%) were hormone receptor (-) (HR-) and HER-2/neu (-) (HER2-), while 3 ACCs were HR+ HER2-. Two patients received adjuvant chemotherapy, and 4 patients received adjuvant radiotherapy. The crude local and distant recurrence rate of our cohort was 22.2% and 11.1% (median follow-up of 36 months). CONCLUSIONS: The majority of ACCs were triple negative but some ACCs were HR+. The unadjusted local and distant recurrence rates were not negligible, suggesting that adjuvant chemotherapy and radiotherapy may be warranted in select cases.

Refining the indications for neoadjuvant chemotherapy for patients with HER2+ breast cancer: A single institution experience.

BACKGROUND: We aim to compare the clinical outcomes of patients with early-stage HER2+ breast cancer treated with adjuvant chemotherapy (AC) and neoadjuvant chemotherapy (NAC). METHODS: Patients with non-metastatic HER2+ breast cancer treated from 2009 to 2018 at our institution comprised our study cohort (n = 1254). Pathologic complete response (pCR) was defined as the absence of invasive disease in the breast and axilla after NAC. Log-rank, Kaplan-Meier, and inverse probability of treatment weighting were used to assess differences in disease-free and overall survival between groups stratified by AC vs. NAC and pCR vs. non-pCR. RESULTS: The majority received AC (n = 787 or 62.8%) while 467 (37.2%) patients received NAC. Median follow up for AC and NAC groups was 46 and 28 months, respectively. The crude disease-free survival and overall survival of our study cohort were 92.2% and 89.1% for AC, 89.1% and 82.2% for NAC pCR, and 68.1% and 60.0% for NAC non-pCR, respectively. For clinical stage ≥IIB patients, NAC conferred a positive but statistically nonsignificant treatment effect over AC in multivariate analysis. CONCLUSIONS: After adjusting for imbalances in our subgroups, we found that, regardless of the sequence of chemotherapy (AC vs. NAC), patients with early-stage HER2+ breast cancer had excellent outcomes.

Impact of 21-Gene Expression Assay on Clinical Outcomes in Node-Negative ≤ T1b Breast Cancer.

BACKGROUND: Prior to the advent of Oncotype DX 21-gene recurrence score (oDX) assay, the National Comprehensive Cancer Network (NCCN) guideline supported omission of adjuvant chemotherapy in patients with ≤ 1 cm (T1b) hormone receptor-positive (HR +), human epidermal growth factor receptor 2 (HER2-) node tumors. However, around 30% of these patients would have an oDX recurrence score that warrants consideration of adjuvant chemotherapy. To clarify the potential benefit of oDX in these patients, we performed a retrospective analysis comparing clinical outcomes of women with T1a or T1b, N0 HR + HER2- according to performance of oDX. PATIENTS AND METHODS: After receiving institutional review board (IRB) approval, an institutional database was queried to identify patients with HR + HER2- ≤ T1bN0 tumors (n = 2307) diagnosed between 2009 and 2018. Patients were further stratified by recurrence score (RS) defined as low (< 18), intermediate (18-30), or high (> 30). Log-rank, Kaplan-Meier, and inverse probability of treatment weighting (IPW) analyses were used to compare disease-free survival (DFS) and overall survival (OS) across groups. RESULTS: Performance of oDX (n = 1149, 49.8%) was associated with larger tumors, younger age, and White race. On univariate analysis, performance of oDX was associated with improved OS (P < 0.01). On multivariate IPW analysis, performance of oDX lengthened DFS by an average of 16.5 months, while OS was similar between groups (P < 0.01 and P = 0.73). The improved DFS was mainly driven by those with tumors ≥ T1b. CONCLUSIONS: Overall, outcomes were excellent regardless of oDX testing. Performance of oDX testing was associated with improved DFS in patients with tumors ≥ T1b. Our results support routine use of oDX testing in patients with tumors ≥ T1b.