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Samantha Sagaser,1 Richard Butterfield,2 Heidi Kosiorek,2 Yael Kusne,3 Juan Maldonado,4,5 Michael P Fautsch,6 Dharmendra Patel,3 Joanne F Shen3 1Mayo Clinic Alix School of Medicine, Scottsdale, AZ, USA; 2Research Biostatistics, Mayo Clinic, Scottsdale, AZ, USA; 3Ophthalmology, Mayo Clinic, Scottsdale, AZ, USA; 4Knowledge Enterprise, Genomics Core, Arizona State University, Tempe, AZ, USA; 5Center for Fundamental and Applied Microbiomics, The Biodesign Institute, Arizona State University, Tempe, AZ, USA; 6Ophthalmology, Mayo Clinic, Rochester, MN, USACorrespondence: Joanne F ShenMayo Clinic, 13400 East Shea Blvd, Scottsdale, AZ 85259, USAEmail Shen.Joanne@mayo.eduPurpose: To assess tear film transforming growth factor-beta (TGF-β) and ocular microbiome changes after intense pulsed light with meibomian gland expression (IPL-MGX) vs only MGX in treating ocular rosacea with dry eye symptoms.Methods: Twenty patients were randomly assigned to IPL-MGX or MGX. Patients were examined, treated, and administered the ocular surface disease index (OSDI) survey every 4– 6 weeks for four total treatments. Tear film and conjunctival samples were collected at first and last visits, and analyzed for TGF-β concentration and 16s rRNA amplicon sequencing of ocular microbiome. Wilcoxon Rank Sum and Sign-Rank were used to examine changes from baseline.Results: OSDI revealed significantly greater improvement in symptoms after IPL-MGX (p=0.030) compared to MGX. There was no significant difference in mean TGF-β 1, 2, or 3 concentration after IPL-MGX (p=0.385, 0.709, 0.948, respectively). Quantities of Clostridium, Klebsiella, Brevibacterium, Lactobacillus, Neisseria, Streptococcus, Corynebacterium, Butyricicoccus, and Actinomyces were significantly reduced from baseline in both groups but without a significant difference between the two treatment groups.Conclusion: IPL-MGX improved dry eye symptoms more than MGX alone. IPL treatment offered no additional benefit to MGX in decreasing virulent bacteria present on the ocular surface and did not influence TGF-β levels in tears. Prospective studies on IPL-MGX with larger sample sizes are needed to further investigate cytokines and IPL in patients suffering from ocular rosacea with dry eye symptoms.ClinicalTrials.gov Identifier: NCT03194698.Keywords: intense pulsed light, IPL, meibomian gland expression, dry eye disease, meibomian gland disorder, ocular rosacea, transforming growth factor-beta, TGF-β, tear cytokines, ocular microbiome, OSDI; ocular surface disease index

Purpose: There is a need to improve current risk stratification of stage II colorectal cancer to better inform risk of recurrence and guide adjuvant chemotherapy. We sought to examine whether integration of QuantCRC, a digital pathology biomarker utilizing hematoxylin and eosin-stained slides, provides improved risk stratification over current American Society of Clinical Oncology (ASCO) guidelines., Experimental Design: ASCO and QuantCRC-integrated schemes were applied to a cohort of 398 mismatch-repair proficient (MMRP) stage II colorectal cancers from three large academic medical centers. The ASCO stage II scheme was taken from recent guidelines. The QuantCRC-integrated scheme utilized pT3 versus pT4 and a QuantCRC-derived risk classification. Evaluation of recurrence-free survival (RFS) according to these risk schemes was compared using the log-rank test and HR., Results: Integration of QuantCRC provides improved risk stratification compared with the ASCO scheme for stage II MMRP colorectal cancers. The QuantCRC-integrated scheme placed more stage II tumors in the low-risk group compared with the ASCO scheme (62.5% vs. 42.2%) without compromising excellent 3-year RFS. The QuantCRC-integrated scheme provided larger HR for both intermediate-risk (2.27; 95% CI, 1.32-3.91; P = 0.003) and high-risk (3.27; 95% CI, 1.42-7.55; P = 0.006) groups compared with ASCO intermediate-risk (1.58; 95% CI, 0.87-2.87; P = 0.1) and high-risk (2.24; 95% CI, 1.09-4.62; P = 0.03) groups. The QuantCRC-integrated risk groups remained prognostic in the subgroup of patients that did not receive any adjuvant chemotherapy., Conclusions: Incorporation of QuantCRC into risk stratification provides a powerful predictor of RFS that has potential to guide subsequent treatment and surveillance for stage II MMRP colorectal cancers., (©2024 American Association for Cancer Research.)

Background: Postoperative urinary retention is a common complication after total hip and knee arthroplasty. Postvoid residual (PVR) scanning is a noninvasive method commonly used to evaluate this complication. Preoperatively increased PVR (PrePVR) has been suggested as a risk factor for postoperative catheterization. The aim of this study was to prospectively assess the importance of PrePVR and its relationship with urinary catheter placement, urology consult, and length of stay postoperatively., Methods: Data was prospectively and consecutively collected at a single institution. All patients were bladder scanned preoperatively to collect PrePVR and subsequently scanned on postoperative days zero and one to collect Postoperative PVR. Chart review was performed to determine the number of straight catheterizations, Foley placement, urology consult and length of stay as well as patient demographics., Results: Ninety-four consecutive patients were included in this study. There was a significantly increased postoperative PVR as compared to PrePVR (48.0 mL vs 21.0 mL; P < .0001). A PrePVR >50 mL was not associated with a significant difference in PVR between before and after surgery ( P  = .13); length of stay ( P  = .08); need for straight catheterization ( P  = .11); postoperative Foley placement ( P  = 1.0); or urology consult ( P  = 1.0). The only significant risk factor identified for postoperative Foley catheter placement was age (77.7 vs 64.2; P  = .02)., Conclusions: PrePVR >50 mL was not an accurate predictor of postoperative urinary retention after total joint arthroplasty. PVR significantly increased in all patients. Male sex and increasing age were associated with large increases in PVR postoperatively and an increased risk of catheterization., (© 2024 The Authors.)

Background: Although the number of women in medicine has increased, women remain underrepresented in leadership positions, specifically in medical societies. Specialty societies in medicine are influential in networking, career advancement, research and education opportunities, and providing awards and recognition. The goals of this study are to examine the representation of women in leadership positions in anesthesiology societies compared to women society members and women anesthesiologists and to analyze the trend in women society presidents over time., Methods: A list of anesthesiology societies was obtained from the American Society of Anesthesiology (ASA) website. Society leadership positions were obtained via the societies' websites. Gender was determined by images on the society website and images or pronouns on hospital websites and research databases. The percentage of women presidents, vice presidents/presidents-elect, secretaries/treasurers, board of directors/council members, and committee chairs was calculated. The percentage of women in society leadership positions was compared to the percentage of women society members when available, and the percentage of women anesthesiologists in the workforce (26%) using binomial difference of unpaired proportions tests. The trend of women presidents from 1980 to 2020 was analyzed using a Cochran-Armitage trend test., Results: A total of 13 societies were included in this study. Overall, women held 32.6% (189/580) of leadership positions. 38.5% (5/13) of presidents, 17.6% (3/17) of presidents-elect/vice presidents, and 45% (9/20) of secretaries/treasurers were women. In addition, 30.0% (91/303) of board of directors/council members and 34.2% (90/263) of committee chairs were women. The percentage of women holding society leadership positions was significantly greater than the percentage of women anesthesiologists in the workforce ( P < .001), as was the percentage of women as committee chairs ( P = .003). The percentage of women society members was available for 9 of 13 societies (69%), and the percentage of women leaders was similar to the percentage of women society members ( P = .10). There was a significant difference in the percentage of women leaders between society size categories. Small societies had 32.9% (49/149) women leaders, medium had 39.4% (74/188) women leaders, and the single large society had 27.2% (66/243) ( P = .03). There were also significantly more women leaders in the Society of Cardiovascular Anesthesiologists (SCA) than there are women members ( P = .02)., Conclusions: This study suggests that anesthesia societies may be more inclusive of women in leadership positions compared to other specialty societies. Although in anesthesiology, women remain underrepresented in academic leadership roles, there is a higher proportion of women in leadership roles in anesthesiology societies than proportion of women in the anesthesia workforce., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 International Anesthesia Research Society.)

Purpose: Myelofibrosis (MF) is a clonal myeloproliferative neoplasm characterized by systemic symptoms, cytopenias, organomegaly, and bone marrow fibrosis. JAK2 inhibitors afford symptom and spleen burden reduction but do not alter the disease course and frequently lead to thrombocytopenia. TGFβ, a pleiotropic cytokine elaborated by the MF clone, negatively regulates normal hematopoiesis, downregulates antitumor immunity, and promotes bone marrow fibrosis. Our group previously showed that AVID200, a potent and selective TGFβ 1/3 trap, reduced TGFβ1-induced proliferation of human mesenchymal stromal cells, phosphorylation of SMAD2, and collagen expression. Moreover, treatment of MF mononuclear cells with AVID200 led to increased numbers of progenitor cells (PC) with wild-type JAK2 rather than JAK2V617F., Patients and Methods: We conducted an investigator-initiated, multicenter, phase Ib trial of AVID200 monotherapy in 21 patients with advanced MF., Results: No dose-limiting toxicity was identified at the three dose levels tested, and grade 3/4 anemia and thrombocytopenia occurred in 28.6% and 19.0% of treated patients, respectively. After six cycles of therapy, two patients attained a clinical benefit by IWG-MRT criteria. Spleen and symptom benefits were observed across treatment cycles. Unlike other MF-directed therapies, increases in platelet counts were noted in 81% of treated patients with three patients achieving normalization. Treatment with AVID200 resulted in potent suppression of plasma TGFβ1 levels and pSMAD2 in MF cells., Conclusions: AVID200 is a well-tolerated, rational, therapeutic agent for the treatment of patients with MF and should be evaluated further in patients with thrombocytopenic MF in combination with agents that target aberrant MF intracellular signaling pathways., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background: Although the overall psychosocial benefits and body image gains of postmastectomy breast reconstruction are well-established, there is limited information on how postoperative complications affect patient quality of life (QOL)., Study Design: A single-institution cross-sectional survey analysis was performed on patients who underwent postmastectomy breast reconstruction between 2008 and 2020. QOL was assessed using the BREAST-Q and the Was It Worth It questionnaires. The results were compared among patients who had major complications, minor complications, and no complications. Responses were compared using 1-way ANOVA and chi-square tests as appropriate., Results: A total of 568 patients met inclusion criteria, and 244 patients responded (43% response rate). Most patients did not have any complications (n = 128; 52%), 41 had minor complications (17%), and 75 had major complications (31%). There were no differences in any of the BREAST-Q well-being metrics based on degree of complication. Across all 3 groups, patients reported that surgery was worthwhile (n = 212; 88%), they would choose reconstruction again (n = 203; 85%), and they would recommend it to a friend (n = 196; 82%). Overall, 77% reported that their overall experience either met or exceeded expectations, and 88% of patients had unchanged or improved overall QOL., Conclusions: Our study demonstrates that QOL and well-being are not negatively impacted by postoperative complications. Although patients who had no complications had an overall more positive experience, nearly two-thirds of all patients, no matter the degree of complication, stated that their overall experience either met or exceeded their expectations., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To identify cases of diabetes insipidus (DI) related to sedation in the ICU to determine which medications pose the greatest risk and understand patterns of presentation., Materials and Methods: We searched PubMed, Embase, Scopus, Google Scholar, and Web of Science. Search terms included "polyuria," "diabetes insipidus," "hypnotics and sedatives," "sedation," as well as individual medications. Case reports or series involving DI or polyuria related to sedation in the ICU were identified., Results: We identified 21 cases of diabetes insipidus or polyuria in the ICU attributed to a sedative. Dexmedetomidine was implicated in 42.9% of cases, followed by sevoflurane (33.3%) and ketamine (23.8%). Sevoflurane was implicated in all 7 cases in which it was used (100%; 95% CI 59.0%, 100.0%), dexmedetomidine in 9 of 11 cases (81.8%; 95% CI 48.2, 97.7), and ketamine in 5 of 9 cases (55.6%; 95% CI 21.2%, 86.3%)., Conclusions: Awareness of the potential for sedatives to cause DI may lead to greater identification with swifter medication discontinuation and subsequent resolution of DI., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Study Objective: To investigate the feasibility and predictive factors for same-day discharge (SDD) after robotic hysterectomy (RH) for benign indications to optimize patient selection by incorporating preoperative, intraoperative, and postoperative variables., Design: A single-center retrospective cohort study., Setting: Tertiary academic hospital., Patients: Patients undergoing RH for benign indications., Interventions: Patients were designated for SDD by implementing enhanced recovery after surgery protocol., Measurements and Main Results: The study included 890 patients who underwent RH for benign indications between the years 2016 and 2021. Of these, 618 (69.4%) were discharged the same day and 272 (30.5%) were admitted for overnight stay. Both groups had similar age (46.4 vs 46.2 years), body mass index (28.3 vs 28.9), and indications for surgery. In multivariable logistic regression, factors that were significant for overnight stay were American Society of Anesthesiologists score 3, Charlson comorbidity index, previous laparotomy, and operative time. Other factors such as surgery start time and preoperative hemoglobin levels were not statistically significant. Postoperative outcomes were comparable for both groups with similar readmission and reoperation rates., Conclusion: The likelihood of SDD after RH in this cohort after implementing enhanced recovery after surgery protocol was almost 70%, and most of the predictive factors for overnight stay were nonmodifiable. Importantly, both groups had similar outcomes after surgery., (Copyright © 2022 AAGL. Published by Elsevier Inc. All rights reserved.)

Background: We sought to evaluate the impact of mastectomy type, post-mastectomy reconstruction choice, and procedure bilaterality, on patient perceived postoperative quality of life (QoL)., Methods: Patients who underwent post-mastectomy reconstruction between 2008 and 2020 were identified in a prospective database. QoL was assessed with the BREAST-Q and the Was It Worth It (WIWI) questionnaires. The results were compared between reconstruction type, reconstruction laterality, and type of mastectomy. Responses were compared using one-way analysis of variance (ANOVA) and chi-square tests., Results: 568 patients met inclusion criteria, and 244 patients responded (43%). QoL did not significantly vary between different reconstructions selected, procedure laterality, or mastectomy type. Patients who underwent DIEP flap were significantly more satisfied with their reconstructed breasts than implant-based reconstruction. Overall, over 85% of patients experienced improved or unchanged QoL no matter what reconstruction choices were made., Conclusion: Most domains of QOL are not impacted by mastectomy type, post-mastectomy reconstruction, or laterality., Competing Interests: Declaration of competing interest All authors of “The Impact of Mastectomy and Reconstruction Technique on Patient Perceived Quality of Life” have no financial or commercial conflicts of interest to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Background: The COVID-19 pandemic led to wide adoption of telehealth in primary care. The impact of telehealth on subsequent follow-up visit volume is mixed. This study examines the association of newly expanded telehealth with short-interval follow-up visits during the COVID-19 pandemic in an academic primary care practice., Methods: Scheduling data were used to compare rates of 0 to 60-day follow-up visits after telehealth and in-person visits before and after onset of the COVID-19 pandemic., Results: Compared with in-person visits, telehealth visits were associated with significantly higher rates of total short-interval follow-ups and higher rates of first short-interval follow-ups occurring in 0 to 15 days., Discussion: Higher rates of short-interval follow-up may be due to inefficiencies created by rapid expansion of telehealth including suboptimal scheduling algorithms, pandemic-related safety considerations, and discomfort with the visit modality. Short-interval follow-ups have potential negative impacts on practice access, patient-centered outcomes, and sustainability of telehealth in primary care., Conclusion: Newly expanded telehealth visits conducted in the year after the onset of the COVID-19 pandemic resulted in higher rates and sooner first occurrence of short-interval follow-up visits. Future research should identify optimal scheduling processes for telehealth visits to minimize short-interval follow-ups., Competing Interests: Conflict of interest: All authors report no conflicting or competing interests., (© Copyright 2022 by the American Board of Family Medicine.)

Background: Although there has been a considerable increase in the representation of women in medicine, a gender gap still exists with regard to leadership positions. This gender discrepancy has been identified in the field of anesthesiology, in terms of first and senior authorship, as well as in general composition of editorial boards in Anesthesiology and Anesthesia & Analgesia. The goal of this study is to examine the current representation of women in editorial boards of anesthesia journals with respect to the hierarchy of different editorial positions and to assess whether there has been improvement toward equity in recent years., Methods: A comprehensive search was performed for anesthesiology journals indexed in the Scimago Journal and Country Rank in May 2020. The editorial boards of the top 20 journals by impact factor were analyzed. Editorial board members were categorized based on their title. Gender was assigned using images or pronouns on research databases or hospital-affiliated websites. The percentage of women within each category was calculated. When available, the year the editors obtained their medical degree was collected. A binomial proportion test was used to analyze the distribution of women overall and among editorial roles, compared to the proportion of women anesthesiologists (26%). A Wilcoxon rank-sum test was used to compare time since medical degree between genders. Additionally, women representation in anesthesiology editorial boards in 2020 was compared to 2010., Results: A total of 19 journals were included in this study, as 1 journal did not disclose editorial board membership. Overall, women occupied 18% of all editorial board positions. All editors-in-chief and assistant/associate/deputy editors-in-chief were men. Women consisted of 17.1% of executive/section/senior editors, 17.9% of editors, and 20.6% of associate/assistant editors. There were significantly fewer women editorial board members than the percentage of women anesthesiologists (18% vs 26%; P < .001). Editorial boards from 2010 were available for 14 journals, and of these journals, women comprised 12% of editorial board members in 2010 compared to 19% in 2020 (P = .001)., Conclusions: These findings suggest that in anesthesiology journals, women are underrepresented at all editorial levels, especially at higher levels. As editorial boards have a significant impact on which articles are published by a journal and thereby significant influence on the specialty as a whole, the lack of gender equity in editorial boards should be addressed., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 International Anesthesia Research Society.)

Background Biliary tract cancers (BTC) are rare, chemo resistant and are associated with a poor prognosis. Preclinical and early clinical work had demonstrated interesting anti-tumor activity from targeting fibroblast growth factor receptor (FGFR) pathway. We hypothesized that ponatinib, a multi-targeted tyrosine kinase inhibitor with activity against FGFR, would be active in BTC patients with FGFR alterations. Methods This was a multi-center, single institution pilot study of ponatinib in patients with advanced, refractory BTC with FGFR alterations. The primary end point was overall response rate, with secondary points of overall survival (OS), progression-free survival (PFS) and Health Related Quality of Life (HRQoL) assessment. Results Twelve patients were enrolled prior to early termination of the trial. Partial responses were observed in 1 from 12 patients. Median PFS was 2.4 months and median OS was 15.7 months. All observed toxicities were manageable and reversible. Toxicities were mild, with lymphopenia (75%), rash (63%) and fatigue (50%) being the most frequent. No significant detriment in global QoL was observed. Conclusions Ponatinib as a single agent in FGFR altered BTC is tolerable with limited clinical activity. This is the first report of prospective assessment of FGFR inhibition in BTC using ponatinib, and the first study to report its effect on HRQoL. Further development of ponatinib will involve correlative studies to better refine patient selection, focus on combinations with other molecular targeted agents, conventional cytotoxic chemotherapy, and studies to better understand mechanisms of treatment resistance., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Plasma-based circulating cell-free tumor DNA (ctDNA) genomic profiling by next-generation sequencing (NGS)is an emerging diagnostic tool for pancreatic cancer (PC). The impact of detected genomic alterations and variant allele fraction (VAF) in tumor response to systemic treatments and outcomes is under investigation., Methods: Patients with advanced PC who had ctDNA profiled at time of initial diagnosis were retrospectively evaluated. We considered the somatic alteration with the highest VAF as the dominant clone allele frequency (DCAF). ctDNA NGS results were related to clinical demographics, progression-free survival (PFS) and overall survival (OS)., Results: A total of 104 patients were evaluated. Somatic alterations were detected in 84.6% of the patients. Patients with ≥ 2 detectable genomic alterations had worse median PFS (p < 0.001) and worse median OS (p = 0.001). KRAS was associated with disease progression to systemic treatments (80.4% vs 19.6%, p = 0.006), worse median PFS (p < 0.001) and worse median OS (p = 0.002). TP53 was associated with worse median PFS (p = 0.02) and worse median OS (p = 0.001). The median DCAF was 0.45% (range 0-55%). DCAF >0.45% was associated with worse median PFS (p<0.0001) and median OS (p=0.0003). Patients that achieved clearance of KRAS had better PFS (p=0.047), while patients that achieved clearance of TP53 had better PFS (p=0.0056) and OS (p=0.037)., Conclusions: Initial detection of ctDNA in advanced PC can identify somatic alterations that may help predict clinical outcomes. The dynamics of ctDNA are prognostic of outcomes and should be evaluated in prospective studies., Competing Interests: Authors YF, LD and HD were employed by company Guardant Health, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Botrus, Uson Junior, Raman, Kaufman, Kosiorek, Yin, Fu, Majeed, Sonbol, Ahn, Chang, Drusbosky, Dada, Starr, Borad, Mody and Bekaii-Saab.)

Aim: This study examined the impact of diabetes mellitus (DM) on survival in squamous cell carcinoma (SCC) patients, and the impact of SCC on glycemic control., Materials & Methods: Patients with newly diagnosed SCC with and without DM were matched 1:1 (2007-2017). Overall survival and recurrence-free survival were estimated using the Kaplan-Meier method. Hemoglobin A 1c (HbA 1c ) and glucose level during the year following cancer diagnosis were compared using mixed models., Results: HbA 1c decreased over time in DM patients (p = 0.04). The 5-year overall survival was 61% in DM patients, compared with 78% in patients without DM (p = 0.004)., Conclusion: The presence of co-existing DM adversely impacted survival in patients with SCC. SCC did not affect glycemic control., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript., (© 2021 Mayo foundation for Medical Education and Research.)

Activation of the P53 pathway through inhibition of MDM2 using nutlins has shown clinical promise in the treatment of solid tumors and hematologic malignancies. There is concern, however, that nutlin therapy might stimulate the emergence or expansion of TP53-mutated subclones. We recently published the results of a phase 1 trial of idasanutlin in patients with polycythemia vera (PV) that revealed tolerability and clinical activity. Here, we present data indicating that idasanutlin therapy is associated with expansion of TP53 mutant subclones. End-of-study sequencing of patients found that 5 patients in this trial harbored 12 TP53 mutations; however, only 1 patient had been previously identified as having a TP53 mutation at baseline. To identify the origin of these mutations, further analysis of raw sequencing data of baseline samples was performed and revealed that a subset of these mutations was present at baseline and expanded during treatment with idasanutlin. Follow-up samples were obtained from 4 of 5 patients in this cohort, and we observed that after cessation of idasanutlin, the variant allele frequency (VAF) of 8 of 9 TP53 mutations decreased. Furthermore, disease progression to myelofibrosis or myeloproliferative neoplasm blast phase was not observed in any of these patients after 19- to 32-month observation. These data suggest that idasanutlin treatment may promote transient TP53 mutant clonal expansion. A larger study geared toward high-resolution detection of low VAF mutations is required to explore whether patients acquire de novo TP53 mutations after idasanutlin therapy., (© 2020 by The American Society of Hematology.)

Study Objective: To assess hormone replacement therapy (HRT) prescription pattern in patients undergoing premature surgical menopause on the basis of surgical indication., Design: Retrospective cohort study., Setting: Academic tertiary care center., Patients: Surgically menopausal patients aged ≤45 years who underwent a minimally invasive hysterectomy with salpingo-oophorectomy., Interventions: HRT prescription in the 6-week postoperative period., Measurements and Main Results: A total of 63 patients met inclusion criteria. Of these, 52% (n = 33) were prescribed HRT in the 6-week postoperative period. Indications for surgical menopause included pelvic pain or endometriosis (31.7%), gynecologic malignancy (20.6%), BRCA gene mutation (17.4%), breast cancer (9.5%), Lynch syndrome (4.8%), and other (15.8%). In total, 80% of patients with pelvic pain, 25% with gynecologic malignancies, 45% with BRCA gene mutations, 33.3% with breast cancer, and 66.6% with Lynch syndrome used HRT postoperatively. In patients who used HRT postoperatively, 76% were offered preoperative HRT counseling. This is in contrast with those patients who did not use HRT postoperatively, of whom only 33% were offered HRT counseling (p <.001). Perioperative complications were not predictive of HRT use postoperatively. In patients who did not use HRT postoperatively, 13.3% used alternative nonhormonal therapy., Conclusion: In patients who underwent premature surgical menopause, 52% used HRT postoperatively. Patients with pelvic pain and Lynch syndrome were more likely to use HRT, whereas those with gynecologic or breast malignancies and BRCA gene mutations were less likely to use HRT. Preoperative HRT counseling was associated with postoperative HRT use., (Copyright © 2020. Published by Elsevier Inc.)

Background: Nipple-sparing mastectomy (NSM) use is increasing. We investigated the relationships between body mass index (BMI), operative time (OT), and ischemic complications., Methods: A single center, retrospective review was performed of NSMs from 2006 to 2018. Analysis included descriptive statistics, Wilcoxon rank-sum test and logistic regression., Results: Among 294 patients, 510 breast reconstructions were performed (216 bilateral). Median OTs in the prosthetic-based (266 patients, 90.5%) and autologous tissue groups (28 patients, 9.5%) were 266 and 529 min, respectively. Median OTs ranged from 236 to 358 min for those with BMI <20 and ≥ 40, respectively. Increasing BMI correlated with OT (r = 0.33, p < 0.001) and was associated with slightly higher odds of major NAC ischemic complications (OR = 1.09, p = 0.02)., Conclusion: Higher BMI is associated with up to 50% longer OT, but is not a contraindication to NSM with reconstruction. Surgeons should recognize increased time and resource utilization., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Factors predicting allogeneic hematopoietic cell transplantation (HCT) outcomes in myelofibrosis in the early post-HCT period have not been defined thus far. We attempt to study such factors that can help identify patients at a higher risk of relapse or death. This retrospective study included 79 patients who underwent first HCT for myelofibrosis at three centers between 2005 and 2016. Univariate analysis showed that red blood cell (RBC) transfusion dependence (HR 9.02, 95% CI 4.0-20.35), platelet transfusion dependence (HR 8.17, 95%CI 3.83-17.37), 100% donor chimerism in CD33 + cells (HR 0.21, 95%CI 0.07-0.62), unfavorable molecular status (HR 4.41, 95%CI 1.87-10.39), normal spleen size (HR 0.42, 95%CI 0.19-0.94), grade ≥ 2 bone marrow fibrosis (vs. grade ≤ 1; HR 2.7, 95%CI 1.1-6.93) and poor graft function (HR 2.6, 95%CI 1.22-5.53) at day +100 were statistically significantly associated with relapse-free survival (RFS). RBC transfusion dependence and unfavorable molecular status were also statistically significant in the multivariate analysis. Patients in whom both of these factors were present had a significantly worse RFS when compared to those with one or none. While limited by a small sample size, we demonstrate the significance of transfusion dependence and molecular status at day +100 in predicting outcomes.

Introduction: The aim of this study was to investigate long-term breast reconstruction outcomes at a single institution in order to offer data-driven counseling for patients., Methods: A retrospective review was performed of 399 patients who underwent mastectomy with 1-stage implant-based breast reconstruction (IBBR), 2-stage IBBR, or autologous tissue reconstruction (ATR) for invasive breast cancer or ductal carcinoma in situ at our institution from 2010 to 2017. Complications were classified as major for any unplanned return to the operating room (OR)., Results: Overall complication rates were similar among 1-stage IBBR (59%), 2-stage IBBR (60%), and ATR (52%, p = 0.54). Factors independently associated with major complications were diabetes (OR = 25.4 95% CI: 3.2-202.4; p = 0.002), and 1-stage IBBR vs. ATR (1-stage: OR = 2.0 95% CI: 1.0-4.0; p = 0.04). Bilateral procedures were also at increased risk of major complications on univariate analysis (OR = 1.59 95% CI: 1.0-2.5; p = 0.04)., Conclusions: Long-term breast reconstruction complication rates are higher than previously anticipated. Patients should be counseled that IBBR is associated with higher rates of complications, including unplanned return to the OR, compared to ATR., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Prior studies have reported high response rates with recombinant interferon-α (rIFN-α) therapy in patients with essential thrombocythemia (ET) and polycythemia vera (PV). To further define the role of rIFN-α, we investigated the outcomes of pegylated-rIFN-α2a (PEG) therapy in ET and PV patients previously treated with hydroxyurea (HU). The Myeloproliferative Disorders Research Consortium (MPD-RC)-111 study was an investigator-initiated, international, multicenter, phase 2 trial evaluating the ability of PEG therapy to induce complete (CR) and partial (PR) hematologic responses in patients with high-risk ET or PV who were either refractory or intolerant to HU. The study included 65 patients with ET and 50 patients with PV. The overall response rates (ORRs; CR/PR) at 12 months were 69.2% (43.1% and 26.2%) in ET patients and 60% (22% and 38%) in PV patients. CR rates were higher in CALR-mutated ET patients (56.5% vs 28.0%; P = .01), compared with those in subjects lacking a CALR mutation. The median absolute reduction in JAK2V617F variant allele fraction was -6% (range, -84% to 47%) in patients achieving a CR vs +4% (range, -18% to 56%) in patients with PR or nonresponse (NR). Therapy was associated with a significant rate of adverse events (AEs); most were manageable, and PEG discontinuation related to AEs occurred in only 13.9% of subjects. We conclude that PEG is an effective therapy for patients with ET or PV who were previously refractory and/or intolerant of HU. This trial was registered at www.clinicaltrials.gov as #NCT01259856., (© 2019 by The American Society of Hematology.)

Purpose: To assess the efficacy of placing a polyethylene glycol (PEG) spacing hydrogel in patients undergoing proton beam radiation therapy for prostate cancer. This study also aims to assess the effect on rectal radiation dose of prostate-rectum separation in various anatomic planes., Methods and Materials: Seventy-two consecutive prostate cancer patients undergoing conventionally fractionated pencil beam scanning proton radiation therapy with and without hydrogel placement were compared. Magnetic resonance images taken after hydrogel placement measured prostate-rectum separation and were correlated to rectal dosing and rectal toxicity. Univariate analysis of clinical variables and radiation dosing was conducted using nonparametric Wilcoxon rank-sum test with continuity correction between groups (hydrogel spacer vs controls). Spearman's rank correlation coefficient assessed relationships between the various anatomic dimensions of perirectal space and rectal radiation dosing., Results: Fifty-one patients had hydrogel placement before therapy and 21 did not. There was a 42.2% reduction in rectal dosing (mL 3 rectum) in hydrogel patients ( P  < .001). Increasing midline sagittal lift resulted in a greater mitigation of total rectal dose ( P  = .031). The degree of prostate surface area coverage on coronal plane did not correlate with further reductions in rectal radiation dose ( P  = .673). Patients who had PEG hydrogels placed reported more rectal side effects during treatment compared with those patients who did not (35.3% vs 9.5%, P  = .061). At median 9.5-month follow-up, there was no difference in reporting of grade ≤2 rectal toxicity between the 2 groups (7.7% vs 7.1%, P  = .145)., Conclusions: Polyethylene glycol hydrogel placement before pencil proton beam radiation therapy for prostate cancer reduced rectal radiation dose. The most important factor reducing total rectal dose was the degree of sagittal midline separation created by the PEG hydrogel. This is the largest study with the longest follow-up to investigate hydrogel placement in the proton beam radiation setting., (© 2019 The Author(s).)

A limited number of drugs are available to treat patients with polycythemia vera (PV) and essential thrombocythemia (ET). We attempted to identify alternative agents that may target abnormalities within malignant hematopoietic stem (HSCs) and progenitor cells (HPCs). Previously, MDM2 protein levels were shown to be upregulated in PV/ET CD34 + cells, and exposure to a nutlin, an MDM2 antagonist, induced activation of the TP53 pathway and selective depletion of PV HPCs/HSCs. This anticlonal activity was mediated by upregulation of p53 and potentiated by the addition of interferon-α2a (IFN-α2a). Therefore, we performed an investigator-initiated phase 1 trial of the oral MDM2 antagonist idasanutlin (RG7388; Roche) in patients with high-risk PV/ET for whom at least 1 prior therapy had failed. Patients not attaining at least a partial response by European LeukemiaNet criteria after 6 cycles were then allowed to receive combination therapy with low-dose pegylated IFN-α2a. Thirteen patients with JAK2 V617F + PV/ET were enrolled, and 12 (PV, n = 11; ET, n = 1) were treated with idasanutlin at 100 and 150 mg daily, respectively, for 5 consecutive days of a 28-day cycle. Idasanutlin was well tolerated; no dose-limiting toxicity was observed, but low-grade gastrointestinal toxicity was common. Overall response rate after 6 cycles was 58% (7 of 12) with idasanutlin monotherapy and 50% (2 of 4) with combination therapy. Median duration of response was 16.8 months (range, 3.5-26.7). Hematologic, symptomatic, pathologic, and molecular responses were observed. These data indicate that idasanutlin is a promising novel agent for PV; it is currently being evaluated in a global phase 2 trial. This trial was registered at www.clinicaltrials.gov as #NCT02407080., (© 2019 by The American Society of Hematology.)

Background: Myeloproliferative neoplasm (MPN) patients suffer from significant symptoms, inflammation and reduced quality of life. Yoga improves these outcomes in other cancers, but this hasn't been demonstrated in MPNs. The purpose of this study was to: (1) explore the limited efficacy (does the program show promise of success) of a 12-week online yoga intervention among MPN patients on symptom burden and quality of life and (2) determine feasibility (practicality: to what extent a measure can be carried out) of remotely collecting inflammatory biomarkers., Methods: Patients were recruited nationally and randomized to online yoga (60 min/week of yoga) or wait-list control (asked to maintain normal activity). Weekly yoga minutes were collected with Clicky (online web analytics tool) and self-report. Those in online yoga completed a blood draw at baseline and week 12 to assess inflammation (interleukin-6, tumor necrosis factor-alpha [TNF-α]). All participants completed questionnaires assessing depression, anxiety, fatigue, pain, sleep disturbance, sexual function, total symptom burden, global health, and quality of life at baseline, week seven, 12, and 16. Change from baseline at each time point was computed by group and effect sizes were calculated. Pre-post intervention change in inflammation for the yoga group was compared by t-test., Results: Sixty-two MPN patients enrolled and 48 completed the intervention (online yoga = 27; control group = 21). Yoga participation averaged 40.8 min/week via Clicky and 56.1 min/week via self-report. Small/moderate effect sizes were generated from the yoga intervention for sleep disturbance (d = - 0.26 to - 0.61), pain intensity (d = - 0.34 to - 0.51), anxiety (d = - 0.27 to - 0.37), and depression (d = - 0.53 to - 0.78). A total of 92.6 and 70.4% of online yoga participants completed the blood draw at baseline and week 12, respectively, and there was a decrease in TNF-α from baseline to week 12 (- 1.3 ± 1.5 pg/ml)., Conclusions: Online yoga demonstrated small effects on sleep, pain, and anxiety as well as a moderate effect on depression. Remote blood draw procedures are feasible and the effect size of the intervention on TNF-α was large. Future fully powered randomized controlled trials are needed to test for efficacy., Trial Registration: This trial was retrospectively registered with clinicaltrials.gov (ID: NCT03503838 ) on 4/19/2018.

Background: Upstaging from DCIS to invasive ductal carcinoma varies widely from 0 to 59%. We aim to identify risk factors associated with upstaging in all DCIS patients and based on specific surgical intervention., Methods: Patients with a pre-operative diagnosis of DCIS undergoing BCT or mastectomy were reviewed. Multivariable analysis was performed to identify risk factors for upstaging., Results: In total, 623 patients had a preoperative diagnosis of DCIS. Upstaging occurred in 74 patients (12%) overall. There was no difference in upstaging rates between mastectomy and BCT (11% v 14% p = 0.27). Sentinel lymph node biopsy was positive in 4/212 patients (1%). Multivariable analysis revealed suspicion of microinvasion (OR 5.7 95%CI2.2-14.9), surgeon suspicion of invasive disease (OR 2.7, 95% CI 1.2-6.4) and larger size/multicentric/extensive tumor (OR 1.9 95% CI 1.1-3.4) increase risk of upstaging., Conclusions: Suspicion of microinvasion, surgeon suspicion, and tumor size can be used to help guide the use of sentinel lymph node biopsy. For patients without these high risk characteristics, it is hard to justify the use of concurrent SLN biopsy for patients who undergo BCT., (Copyright © 2019. Published by Elsevier Inc.)

Hematopoietic stem cell transplantation (HCT) is a curative treatment for patients with myelofibrosis (MF); however, many HCT-eligible patients decline this potentially life-saving procedure. The reasons behind this decision are not clear. We sought to survey patients with MF to understand their perspective on HCT. A 63-question survey was posted on myeloproliferative neoplasm patient advocacy websites. A total of 129 patients with MF responded to the survey. Among these patients, 49 (41%) were referred for HCT, and 41(32%) attended the transplantation consult. Of the patients who attended the transplantation consult, 24 (59%) did not plan on going on to HCT, and 16 (41%) intended to proceed with HCT. Reasons for the decision to not undergo transplantation included the desire to not be ill, desire to not spend time in the hospital, and concerns about overall quality of life. Specifically, concerns related to financial impact and the risk of graft-versus-host disease (GVHD) were expressed. Patients who decided to proceed with HCT felt that this would extend their survival and allow them to be around family for longer. This is the first survey to investigate patient perceptions regarding HCT for MF. Less than one-half of the patients were referred for HCT, and of those, less than one-half planned on proceeding with the transplantation, suggesting that many patients do not receive this life-saving procedure. Further exploration of the basis of patients' reluctance to proceed with HCT is warranted., (Copyright © 2018. Published by Elsevier Inc.)

The Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and the prefibrotic form of primary myelofibrosis (PMF), frequently progress to more overt forms of MF and a type of acute leukemia termed MPN-accelerated phase/blast phase (MPN-AP/BP). Recent evidence indicates that dysregulation of the tumor suppressor tumor protein p53 (TP53) commonly occurs in the MPNs. The proteins MDM2 and MDM4 alter the cellular levels of TP53. We investigated in 1,294 patients whether abnormalities involving chromosomes 1 and 12, which harbor the genes for MDM4 and MDM2 , respectively, and chromosome 17, where the gene for TP53 is located, are associated with MPN disease progression. Gain of 1q occurred not only in individuals with MPN-BP but also in patients with PV and ET, who, with further follow-up, eventually evolve to either MF and/or MPN-BP. These gains of 1q were most prevalent in patients with a history of PV and those who possessed the JAK2 V617F driver mutation. The gains of 1q were accompanied by increased transcript levels of MDM4 In contrast, 12q chromosomal abnormalities were exclusively detected in patients who presented with MF or MPN-BP, but were not accompanied by further increases in MDM2 / MDM4 transcript levels. Furthermore, all patients with a loss of 17p13, which leads to a deletion of TP53 , had either MF or MPN-AP/BP. These findings suggest that gain of 1q, as well as deletions of 17p, are associated with perturbations of the TP53 pathway, which contribute to MPN disease progression., (© 2018 by The American Society of Hematology.)

Background: Invasive lobular carcinoma (ILC) is the second most frequently diagnosed breast cancer, accounting for 5% to 15% of all invasive breast cancers, yet it remains radiologically elusive in many cases. The goal of this study was to compare the ability to accurately assess disease extent with contrast-enhanced digital mammography (CEDM) and full-field digital mammography (FFDM) in patients with biopsy-proven ILC., Patients and Methods: A single-institution retrospective review of patients diagnosed with ILC with preoperative CEDM was performed. One of 3 blinded radiologist readers rereviewed cases within 1 month of another. Final size diameter was based on the largest dimension on recombined CEDM or FFDM and compared to the reference standard histopathology. Bland-Altman plots were used to visualize the differences between tumor size on imaging and pathology., Results: Thirty women were included. Mean tumor diameter was 27.0 mm (range, 7.0-118 mm) on postoperative histology, 26.0 mm on CEDM, and 16.4 mm on standard mammogram. For CEDM versus FFDM, 5 (16.7%) of 30 versus 9 (30.0%) of 30 cases underestimated pathology by > 10 mm and 5 (16.7%) of 30 versus 3 (10.0%) of 30 overestimated histopathology by > 10 mm, respectively. Two (6.7%) of 30 cases required surgical reexcision. Both Lin (0.87 vs. 0.55) and Pearson (0.87 vs. 0.70) correlation coefficient measures were higher for CEDM versus FFDM., Conclusion: CEDM outperforms standard digital mammography in ability to accurately assess disease extent in patients with biopsy-proven ILC, resulting in improved surgical outcomes. Future studies should compare surgical outcomes in patients with preoperative magnetic resonance imaging and CEDM in patients with ILC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and Purpose: Intensity modulated proton therapy (IMPT) allows for modulation parameterized for individual beamlets by position, intensity, and depth. This modulation capability is ideally suited for sparing organs at risk intermediate of the radiation target, such as hippocampal volumes within the whole brain. This work compared IMPT relative to volumetric modulated arc therapy (VMAT) during hippocampal avoidance whole brain radiation therapy (HA WBRT)., Materials and Methods: Ten adult and ten pediatric patients previously treated for central nervous system malignancies were identified. IMPT and VMAT treatment plans employing HA WBRT were generated for each patient, delivering 30 GyE (Gray Equivalent) in 10 fractions for adults and 36 GyE in 20 fractions for pediatrics. Dose indices, including dose volume histogram metrics and homogeneity index HI = [D5% - D95%]/[D mean ] × 100, were used to assess plan quality and describe target coverage and normal-tissue sparing., Results: IMPT offered significant benefits relative to VMAT for hippocampal sparing. Hippocampal mean dose was reduced from 13.7 ± 0.8 Gy with VMAT to 5.4 ± 0.3 GyE using IMPT for pediatrics, and was reduced from 11.7 ± 0.9 Gy with VMAT to 4.4 ± 0.2 GyE using IMPT for adults. IMPT similarly lowered left hippocampal mean dose. Dose to 95% of the clinical target volume was statistically equivalent for both groups; however IMPT reduced the homogeneity index by roughly half., Conclusion: This manuscript demonstrates that HA IMPT can match or exceed dosimetric benefits offered with modulated X-rays. Inclusion of IMPT in future prospective studies is warranted., (© 2018 The Authors.)